Research Study to Look at How Well the Drug Concizumab Wo... | NCT04082429 | Trialant
NCT04082429
Sponsor
Novo Nordisk A/S
Status
Active, not recruiting
Last Update Posted
Jun 12, 2026Actual
Enrollment
156Actual
Phase
Phase 3
Conditions
Haemophilia A Without Inhibitors
Haemophilia B Without Inhibitors
Interventions
Concizumab
Countries
United States
Algeria
Australia
Bosnia and Herzegovina
Bulgaria
Canada
Croatia
Denmark
Estonia
France
Germany
Hungary
India
Israel
Italy
Japan
Lithuania
Malaysia
Mexico
Poland
Portugal
Russia
Serbia
Slovakia
South Africa
South Korea
Spain
Sweden
Switzerland
Thailand
Turkey (Türkiye)
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04082429
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
NN7415-4307
Secondary IDs
ID
Type
Description
Link
U1111-1225-9722
Other Identifier
World Health Organization (WHO)
2018-004891-36
Registry Identifier
European Medicines Agency (EudraCT)
Brief Title
Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors
Official Title
Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors
Acronym
explorer8
Organization
Novo Nordisk A/SINDUSTRY
Status Module
Record Verification Date
Jun 2026
Overall Recruitment Status or Expanded Access Status
Active, not recruiting
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT04921956Available
Start Date
Nov 13, 2019Actual
Primary Completion Date
Jul 12, 2022Actual
Completion Date
Feb 21, 2028Estimated
First Submitted Date
Sep 5, 2019
First Submission Date that Met QC Criteria
Sep 5, 2019
First Posted Date
Sep 9, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Jul 11, 2025
Results First Submitted that Met QC Criteria
Oct 16, 2025
Results First Posted Date
Oct 31, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jul 10, 2023
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Oct 31, 2025Actual
Last Update Submitted Date
Jun 11, 2026
Last Update Posted Date
Jun 12, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novo Nordisk A/SINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study will test how well a new medicine called concizumab works in the body of people with haemophilia A or B without inhibitors. The purpose is to show that concizumab can prevent bleeds in the body and is safe to use. Participants who usually only take medicine to treat bleeds (on-demand) will be placed in one of two groups. In one group participants will get study medicine from the start of the study. In the other group participants will continue with their normal medicine and get study medicine after 6 months. Which treatment the participant gets is decided by chance. Participants who usually take medicine to prevent bleeds (prophylaxis treatment) or who are already being treated with concizumab (study medicine) will receive the study medicine from the start of the study. Participants will have to inject themselves with the study medicine 1 time every day under the skin. This can be done at home. The study doctor will hand out the medicine in the form of a pen-injector. The pen-injector will contain the study medicine. The study will last for up to 8 years. The length of time the participant will be in the study depends on when they agreed to take part and when the medicine is available for purchase in their country (or 31 December 2027 at the latest). The time between visits will be approximately 4 weeks for the first 6 to 12 months depending on the group participants are in, and approximately 8 weeks for the rest of the study. If the participant attends extra visits due to the prescription medicine not being available for purchase in their country, these will be 14 weeks apart. Participants will be asked to record information in an electronic diary during the study and may also be asked to wear an activity tracker.
Detailed Description
Not provided
Conditions Module
Conditions
Haemophilia A Without Inhibitors
Haemophilia B Without Inhibitors
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
156Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm 1: No prophylaxis (PPX)
Experimental
Haemophilia A (HA) and haemophilia B (HB) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension phase, this group will receive treatment with concizumab.
Drug: Concizumab
Arm 2: Concizumab prophylaxis
Experimental
HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.
Drug: Concizumab
Arm 3: Concizumab prophylaxis
Experimental
The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.
Drug: Concizumab
Arm 4: Concizumab prophylaxis
Experimental
Arm 4 will include patients previously on prophylaxis with factor products with a minimum of 24 weeks observation in NN7415-4322 (explorer 6) (at least 30 HA and 30 HB patients).
In addition, arm 4 will also include: 1) Patients who were randomised to arms 1 and 2 before the treatment pause. 2) HA patients who were in NN7415-4255 (explorer 5) at the time of the treatment pause, and who have now completed explorer 5. 3) On demand patients included after arms 1 and 2 are closed.
Drug: Concizumab
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Concizumab
Drug
When patients are randomised/allocated to concizumab prophylaxis, they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week (Wk) 0) (arm 2, 3 and 4) or visit 9a (Wk 24) (arm 1) followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week dose adjustment period on 0.20 mg/kg concizumab, the patients can be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab. A potential dose adjustment will take place at visit 4a.1 (Wk 6) or 9a.3 (Wk 30) and will be based on the concizumab exposure level measured at the previous visit 4a (Wk 6) or 9a.2 (Wk 28). Patients who have concizumab exposure levels of 200-4000 ng/mL will stay at 0.20 mg/kg concizumab. Patients in arm 1 will continue on-demand treatment with their usual replacement therapy until visit 9a (week 24; end of main part). In the extension part, patients in arm 1 will receive daily concizumab subcutaneous injections.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excluding data before restart (OTwoATexBR). It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
Secondary Outcomes
Measure
Description
Time Frame
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is on stable treatment without ancillary therapy excluding data before restart (OT stable woATexBR). It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
Male aged 12 years or older at the time of signing informed consent.
Congenital severe haemophilia A (FVIII below 1%) or B (FIX equal to or below 2%).
Exclusion Criteria:
Known or suspected hypersensitivity to any constituent of the trial product or related products.
Known inherited or acquired coagulation disorder other than congenital haemophilia.
Presence of confirmed inhibitors 0.6 BU or greater at screening.
History of thromboembolic disease (includes arterial and venous thrombosis including myocardial infarction, pulmonary embolism, cerebral infarction/thrombosis, deep vein thrombosis, other clinically significant thromboembolic events and peripheral artery occlusion). Current clinical signs of, or treatment for thromboembolic disease. Patients who in the judgement of the investigator are considered at high risk of thromboembolic events (thromboembolic risk factors could include, but are not limited to, hypercholesterolemia, diabetes mellitus, hypertension, obesity, smoking, family history of thromboembolic events, arteriosclerosis, other conditions associated with increased risk of thromboembolic events.)
Young G, Angchaisuksiri P, Apte SJ, Brown Frandsen R, Chan AK, Chowdary P, Eichler H, Lyu CJ, Martinez Garcia MF, Matsushita T, Trakymiene SS, Tran HA, Trinchero A, Windyga J, Astermark J. Concizumab in patients with hemophilia A or B without inhibitors: 56-week cut-off results of the phase 3 explorer8 study. Blood Adv. 2026 Jun 24:bloodadvances.2026019931. doi: 10.1182/bloodadvances.2026019931. Online ahead of print.
Data is reported till cutoff date 27-Dec-2022 and study is still ongoing. Initially, participants were randomised to arm 1 or 2 or to non-randomised arms 3 or 4. There was a treatment pause due to investigation of thromboembolic events. After treatment pause, participants randomised to arms 1 or 2 before pause entered arm 4. Participants allocated to arms 3 and 4 before pause re-entered arms initially allocated to. New participants were randomized in arms 1and 2.
Recruitment Details
The trial was conducted at 68 sites in 31 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Periods
Title
Milestones
Reasons Not Completed
Main Part (Before the Treatment Pause)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 25, 2021
Jul 11, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Patients will be randomised to concizumab PPX/no PPX/ assigned into non-randomised arms, based on treatment before trial. Upon restart, patients randomised to arms 1/2 before pause will enter arm 4. Patients allocated to arms 3 & 4 before pause will re-enter initially allocated arm. Randomisation into arms 1/2 will be restarted with new patients. Main part is completed when patient completed 24 wks (excluding screening) in arm 1 or 32 wks (excluding screening) in arms 2-4. After main part, patients will have offer to continue in extension (ext.) part and receive treatment with product until concizumab is commercially available in their countries or until 31-Dec-2027 at latest. Patients will be in the extension part for up to 345 weeks (arms 2-4) or up to 353 weeks (arm 1). Patient will receive last dose at home on day prior to visit 26a. Follow-up part will start on visit 26a and lasts for 7 wks and include reporting of bleeding episodes until visit 27a.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Arm 1: No prophylaxis (PPX)
Arm 2: Concizumab prophylaxis
Arm 3: Concizumab prophylaxis
Arm 4: Concizumab prophylaxis
For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is OT stable woATexBR. It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes
Rate of treated spontaneous bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes
Rate of treated spontaneous bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes
Rate of treated spontaneous and traumatic joint bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes
Rate of treated spontaneous and traumatic joint bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes
Rate of treated spontaneous and traumatic target joint bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes
Rate of treated spontaneous and traumatic target joint bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events
Number of thromboembolic events in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment (OT). It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events
From week 0 to end of trial (up to 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions
Number of hypersensitivity type reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions
From week 0 to end of trial (up until 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions
Number of injection site reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
On demand (arm 1 main part): from randomisation (week 0) until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From week 25 up until the 56 week cut-off
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions
From week 0 to end of trial (up until 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab
Concizumab (arms 2-4): From start of concizumab treatment (week 0) up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab
From week 0 to end of trial (up until 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)
Ctrough for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without data before re-start (OTexBR). It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Pre-dose (prior to the concizumab administration at week 24)
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Thrombin Peak
Pre-dose thrombin peak for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Pre-dose (prior to the concizumab administration at week 24)
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration
Pre-dose free TFPI for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Pre-dose (prior to the concizumab administration at week 24)
Haemophila A and Haemophilia B Participants Without Inhibitors: Maximum Concizumab Plasma Concentration (Cmax)
Cmax for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h
Haemophila A and Haemophilia B Participants Without Inhibitors: Area Under the Concizumab Plasma Concentration-time Curve (AUC)
AUC for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h
Orange
California
92868
United States
Center for Blood Disorders Augusta University
Augusta
Georgia
30912
United States
Indiana Hemophilia-Thromb Ctr
Indianapolis
Indiana
46260
United States
University of Iowa_Iowa City
Iowa City
Iowa
52242
United States
Children's Hospital of Michigan
Detroit
Michigan
48201
United States
Michigan State University
Lansing
Michigan
48911
United States
Novant Hlth Vasc Ins Charlotte
Charlotte
North Carolina
28204
United States
M.S. Hershey Medical Center
Hershey
Pennsylvania
17033
United States
Vanderbilt University Medical Center_Nashville_0
Nashville
Tennessee
37212
United States
University of Texas San Antonio
San Antonio
Texas
78229
United States
Versiti, CCBD
Milwaukee
Wisconsin
53226
United States
Haematology and Blood Bank Department
Algiers
16000
Algeria
CHU Constantine BEN BADIS/ Hematology department
Constantine
25000
Algeria
The Alfred
Melbourne
Victoria
3004
Australia
Royal Children's Hospital
Parkville
Victoria
3052
Australia
The Royal Children's Hospital
Parkville
Victoria
3052
Australia
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
Murdoch
Western Australia
6150
Australia
University Clinical Center of Republic Srpska (205)
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Wroclaw
50-367
Poland
ULS São João, E.P.E._H.São João_Imunohemoterapia
Porto
4200-319
Portugal
Children Regional Clinical Hospital
Krasnodar
350007
Russia
Morozovskaya municipal children hospital
Moscow
119049
Russia
National Medical Research institution of haemotology
Moscow
125167
Russia
Republican Hospital n.a. V. A. Baranov
Petrozavodsk
185019
Russia
City out-patient clinic 37, City Hemophilia Centre
Saint Petersburg
191186
Russia
Clinical Centre of Serbia, Institute for Haematology
Belgrade
11000
Serbia
Institute for Mother and Child Health Care of Serbia
Belgrade
11070
Serbia
University Clinical Centre Kragujevac
Kragujevac
34000
Serbia
Clinical Centre of Vojvodina
Novi Sad
21000
Serbia
Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz
Bratislava
851 07
Slovakia
Charlotte Maxeke Johannesburg Academic Hospital
Parktown, Johannesburg
Gauteng
2193
South Africa
Pietersburg Hospital
Polokwane
Limpopo
0699
South Africa
Daejeon Eulji Medical Center, Eulji University
Daejeon
35233
South Korea
Daejeon Eulji University Hospital
Daejeon
35233
South Korea
Jeju National University Hospital
Jeju City
63241
South Korea
Jeju National University Hospital
Jeju-do
63241
South Korea
Severance Hospital, Yonsei University Health System
Seoul
03722
South Korea
Hospital Universitario La Paz
Madrid
28046
Spain
Hospital Regional Universitario de Málaga
Málaga
29010
Spain
Hospital Univ. Central de Asturias
Oviedo
33011
Spain
Hospital Virgen del Rocío
Seville
41013
Spain
Hospital Universitario y Politécnico La Fe
Valencia
46026
Spain
Skåne US - Koagulationsmottagning
Malmö
214 28
Sweden
Koagulationsmottagningen
Solna
171 64
Sweden
Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie
Zurich
8091
Switzerland
Ramathibodi Hospital_Department of Haematology
Bangkok
10400
Thailand
Gazi University
Ankara
Beşevler/Ankara
06500
Turkey (Türkiye)
Gazi Üniversitesi Hastanesi- Hematoloji
Ankara
Beşevler/Ankara
06500
Turkey (Türkiye)
İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü
Capa-ISTANBUL
Capa-ISTANBUL
34093
Turkey (Türkiye)
Acıbadem Adana Hastanesi-Hematoloji
Adana
01130
Turkey (Türkiye)
Hacettepe University Medical Faculty
Ankara
06230
Turkey (Türkiye)
Hacettepe Üniversitesi Hastanesi- Endokrinoloji
Ankara
06230
Turkey (Türkiye)
Trakya Üniversitesi Tıp Fakültesi Hastanesi-Hematoloji
Edirne
22030
Turkey (Türkiye)
Ege Üniversitesi Hastanesi- Hematoloji
Izmir
35100
Turkey (Türkiye)
Ondokuz Mayıs Üniversitesi Hastanesi - Hematoloji
Samsun
55139
Turkey (Türkiye)
National specialized children's hospital 'OHMATDYT' - Haemostasis centre
Kyiv
01135
Ukraine
Institute of blood pathology and transfusion medicine of NAMSU - General and haematol. surgery
Lviv
79044
Ukraine
Belfast City Hospital
Belfast
BT9 7AB
United Kingdom
Royal Free Haemophilia Comprehensive Care Center
London
NW3 2QG
United Kingdom
Royal Free Hospital - Haemophilia
London
NW3 2QG
United Kingdom
Royal Hallamshire Hospital
Sheffield
S10 2JF
United Kingdom
Derived
Angchaisuksiri P, von Mackensen S, Apte S, Benson G, Eichler H, Findley A, Matsushita T, Mazini Tavares CM, Puggaard Ravn M, Sathar J, Villarreal Martinez L, Young G. Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study. Res Pract Thromb Haemost. 2025 Feb 20;9(2):102705. doi: 10.1016/j.rpth.2025.102705. eCollection 2025 Feb.
Chowdary P, Angchaisuksiri P, Apte S, Astermark J, Benson G, Chan AKC, Jimenez Yuste V, Matsushita T, Hogh Nielsen AR, Sathar J, Sutton C, Saulyte Trakymiene S, Tran H, Villarreal Martinez L, Wheeler AP, Windyga J, Young G, Thaung Zaw JJ, Eichler H. Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial. Lancet Haematol. 2024 Dec;11(12):e891-e904. doi: 10.1016/S2352-3026(24)00307-7. Epub 2024 Nov 6.
FG001
Extension Phase Arm 1: Concizumab PPX - Participants With HA
Participants with HA who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
FG002
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
FG003
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
FG004
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
FG005
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
FG006
Extension Phase Arm 1: Concizumab PPX - Participants With HB
Participants with HB who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
FG007
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
FG008
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
FG0001 subjects
FG0010 subjects
FG0023 subjects
FG00310 subjects
FG00418 subjects
FG0051 subjects
FG0060 subjects
FG0072 subjects
FG0082 subjects
COMPLETED
FG0000 subjectsParticipant discontinued from arm 1 was allocated to arm 4, however was not exposed to concizumab treatment in arm 4- concizumab PPX: participants with HA. This participant was included in the safety analysis set (SAS).
FG0010 subjects
FG0022 subjects
FG0039 subjects
FG00413 subjects
FG0051 subjects
FG0060 subjects
FG0072 subjects
FG0082 subjects
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG0045 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG0043 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Main Part (After the Treatment Pause)
Type
Comment
Milestone Data
STARTED
FG0009 subjects
FG0010 subjects
FG00218 subjects
FG0039 subjects
FG00446 subjectsParticipants restarting from before treatment pause = 13 Participants moved from old arm 1+2 = 2 (0+2) Participants allocated after restart = 31
FG00512 subjects
FG0060 subjects
FG00724 subjects
FG00830 subjectsParticipants restarting from before treatment pause = 2 Participants moved from old arm 1+2 = 3 (1+2) Participants allocated after restart = 25
COMPLETED
FG0007 subjects
FG0010 subjects
FG00217 subjects
FG0036 subjects
FG004
NOT COMPLETED
FG0002 subjects
FG0010 subjects
FG0021 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Extension Part
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0017 subjects
FG00217 subjects
FG0036 subjects
FG00445 subjects
FG0050 subjects
FG00610 subjects
FG00723 subjects
FG00825 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0017 subjects
FG00217 subjects
FG0036 subjects
FG004
Type
Comment
Reasons
Ongoing
FG0000 subjects
FG0017 subjects
FG00217 subjects
FG003
Baseline characteristics were analysed based on the on-treatment without data before restart (OTexBR) analysis set. OTexBR analysis data set was defined as the observation period after the restart of treatment where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX with the new concizumab dosing regimen.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
BG001
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
BG002
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
BG003
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
BG004
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
BG005
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
BG006
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0009
BG00112
BG00218
BG00324
BG0049
BG00546
BG00630
BG007148
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00034.7± 21.3
BG00130.4± 17.5
BG00230.7± 9.6
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0011
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excluding data before restart (OTwoATexBR). It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG0009
OG00118
Title
Denominators
Categories
Title
Measurements
OG00019.6(17.3 to 30.4)
OG0012.9(0.0 to 5.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Negative binomial regression
<0.001
ABR ratio
0.14
2-Sided
95
0.07
0.29
Superiority
Bleeding endpoints were analysed using a negative binomial regression model with the logarithm of the length of the observation period included (in years) as offset with treatment and bleeding frequency prior to screening as factors.
Primary
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
ID
Title
Description
OG000
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is on stable treatment without ancillary therapy excluding data before restart (OT stable woATexBR). It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
Intra-participant analysis set (IPAS) included participants in arm 4 that were on a stable PPX regimen for at least 24 weeks in NN7415-4322 and who entered the maintenance period in this trial NN7415-4307. The participants reported in both arms/groups represent the same 29 participants, with results reported from Study 4322 and this study (Study 4307). The endpoint is only defined for arm 4 (previous PPX-study 4322) and arm 4 (concizumab PPX-study 4307) as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off
ID
Title
Description
OG000
Arm 4: Previous PPX (Study 4322) - Participants With HA
Arm 4 participants with haemophilia A who were on stable PPX for atleast 24 weeks in study 4322 and continued till end of study (until 115 weeks).
Secondary
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is OT stable woATexBR. It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
IPAS included participants in arm 4 that were on a stable PPX regimen for at least 24 weeks in NN7415-4322 and who entered the maintenance period in this trial NN7415-4307. The participants reported in both arms/groups represent the same 29 participants, with results reported from Study 4322 and this study (Study 4307). The endpoint is only defined for arm 4 (previous PPX-study 4322) and arm 4 (concizumab PPX-study 4307) as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off
ID
Title
Description
OG000
Arm 4: Previous PPX (Study 4322) - Participants With HB
Arm 4 participants with haemophilia B who were on stable PPX for atleast 24 weeks in study 4322 and continued till end of study (until 115 weeks).
Secondary
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes
Rate of treated spontaneous bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes
Rate of treated spontaneous bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes
Rate of treated spontaneous and traumatic joint bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes
Rate of treated spontaneous and traumatic joint bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes
Rate of treated spontaneous and traumatic target joint bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes
Rate of treated spontaneous and traumatic target joint bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
FAS included all participants randomised to the new concizumab PPX dosing regimen or on-demand treatment after the treatment pause or allocated to arm 3 or 4 with the new concizumab PPX dosing regimen. This endpoint is only defined for arms 1 and 2 as per protocol.
Posted
Median
Inter-Quartile Range
Events per year
On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events
Number of thromboembolic events in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment (OT). It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm1, arm 2, arm 3, arm 4, arm 1 extension part) and participants with HB (arm 1, arm 2, arm 4, arm 1 extension part)] only.
Posted
Number
Events
On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events
Not Posted
Dec 2028
From week 0 to end of trial (up to 384 weeks)
Participants
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions
Number of hypersensitivity type reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm1, arm 2, arm 3, arm 4, arm 1 extension part) and participants with HB (arm 1, arm 2, arm 4, arm 1 extension part)] only.
Posted
Number
Reactions
On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions
Not Posted
Dec 2028
From week 0 to end of trial (up until 384 weeks)
Participants
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions
Number of injection site reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm1, arm 2, arm 3, arm 4, arm 1 extension part) and participants with HB (arm 1, arm 2, arm 4, arm 1 extension part)] only.
Posted
Number
Reactions
On demand (arm 1 main part): from randomisation (week 0) until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From week 25 up until the 56 week cut-off
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions
Not Posted
Dec 2028
From week 0 to end of trial (up until 384 weeks)
Participants
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab
Not Posted
May 2028
Concizumab (arms 2-4): From start of concizumab treatment (week 0) up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off
Participants
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab
Not Posted
Dec 2028
From week 0 to end of trial (up until 384 weeks)
Participants
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)
Ctrough for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without data before re-start (OTexBR). It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm 2, arm 3, arm 4) and participants with HB (arm 2, arm 4)] only.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter (ng/mL)
Pre-dose (prior to the concizumab administration at week 24)
ID
Title
Description
OG000
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG001
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Thrombin Peak
Pre-dose thrombin peak for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm 1, arm 2, arm 3, arm 4) and participants with HB (arm 1, arm 2, arm 4)] only.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanomoles per liter (nmol/L)
Pre-dose (prior to the concizumab administration at week 24)
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration
Pre-dose free TFPI for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm 1, arm 2, arm 3, arm 4) and participants with HB (arm 1, arm 2, arm 4)] only.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose (prior to the concizumab administration at week 24)
ID
Title
Description
OG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Maximum Concizumab Plasma Concentration (Cmax)
Cmax for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm 2, arm 3, arm 4) and participants with HB (arm 2, arm 4)] only.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h
ID
Title
Description
OG000
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG001
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Secondary
Haemophila A and Haemophilia B Participants Without Inhibitors: Area Under the Concizumab Plasma Concentration-time Curve (AUC)
AUC for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
SAS was defined as all participants exposed to concizumab PPX or randomised to on-demand treatment. Overall number of participants analysed = Participants with available data for the outcome measure. The endpoint is applicable for reported arms [for participants with HA (arm 2, arm 3, arm 4) and participants with HB (arm 2, arm 4)] only.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms*hour/milliliter (ng*hr/mL)
Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h
ID
Title
Description
OG000
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG001
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Time Frame
Up to week 56 cut-off
Description
Safety analysis set (SAS) included all participants exposed to concizumab prophylaxis (PPX) or randomised to on-demand treatment. All presented AEs were treatment emergent AEs (TEAEs). TEAEs were defined as AEs which initiated or worsened during the time period where participants were considered to be affected by on demand treatment or concizumab treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Arm 1: Previous On Demand (OnD) Treatment: No Prophylaxis (PPX) - Participants With HA
Participants with HA received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
0
9
0
9
2
9
EG001
Extension Phase Arm 1: Concizumab PPX - Participants With HA
Participants with HA who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
0
7
0
7
5
7
EG002
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
0
18
1
18
10
18
EG003
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
0
10
1
10
8
10
EG004
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
1
52
10
52
40
52
EG005
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
0
12
2
12
2
12
EG006
Extension Phase Arm 1: Concizumab PPX - Participants With HB
Participants with HB who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
0
10
0
10
5
10
EG007
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
0
24
6
24
12
24
EG008
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
0
30
2
30
24
30
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal injury
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG0030 events0 affected10 at risk
EG004
Acute myocardial infarction
Cardiac disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
COVID-19
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Craniocerebral injury
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Haematoma muscle
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Haemophilic arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hemiparesis
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hepatorenal syndrome
Hepatobiliary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Intra-abdominal haemorrhage
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Liver disorder
Hepatobiliary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Post procedural haematoma
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Retroperitoneal haemorrhage
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Superficial vein thrombosis
Vascular disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Cartilage injury
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Gastroenteritis rotavirus
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Renal haematoma
Renal and urinary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Traumatic haematoma
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Ureterolithiasis
Renal and urinary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain upper
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG0030 events0 affected10 at risk
EG0043 events3 affected52 at risk
EG0050 events0 affected12 at risk
EG0060 events0 affected10 at risk
EG0070 events0 affected24 at risk
EG0081 events1 affected30 at risk
Acne
Skin and subcutaneous tissue disorders
MedDRA 25
Systematic Assessment
EG0001 events1 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Aphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Bacterial test positive
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
COVID-19
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0022 events2 affected18 at risk
EG003
Cognitive disorder
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Device physical property issue
Product Issues
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Fibrin D dimer increased
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Fibrinolysis
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Headache
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hypertension
Vascular disorders
MedDRA 25
Systematic Assessment
EG0001 events1 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Inflammatory bowel disease
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Influenza
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Injection site erythema
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Injection site haematoma
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Injection site rash
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Injection site reaction
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Keratitis
Eye disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Musculoskeletal discomfort
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Oedema peripheral
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Prostatitis
Reproductive system and breast disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Prothrombin fragment 1.2 increased
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pyoderma
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Subcutaneous haematoma
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0022 events2 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Allergy to arthropod bite
Immune system disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected18 at risk
EG003
Excessive cerumen production
Ear and labyrinth disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Hepatic steatosis
Hepatobiliary disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Injection site mass
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Injection site pain
General disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Laryngitis
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Nasal septum deviation
Respiratory, thoracic and mediastinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Pruritus allergic
Skin and subcutaneous tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0022 events1 affected18 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Rosacea
Skin and subcutaneous tissue disorders
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected18 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA 25
Systematic Assessment
EG0000 events0 affected9 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected18 at risk
EG003
There was a pause in the concizumab clinical development programme during the period from March to August 2020, while thromboembolic events were investigated. As of 19 March 2020, all participants on concizumab had stopped treatment and switched to another available treatment as per investigator's discretion. Based on the investigation, risk mitigation actions (including new concizumab dosing regimen) were implemented and trial protocols updated before resuming.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG00012
OG00124
Title
Denominators
Categories
Title
Measurements
OG00014.9(3.3 to 22.1)
OG0011.6(0.0 to 4.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Negative binomial regression
<0.001
ABR ratio
0.21
2-Sided
95
0.10
0.45
Superiority
Bleeding endpoints were analysed using a negative binomial regression model with the logarithm of the length of the observation period included (in years) as offset with treatment and bleeding frequency prior to screening as factors.
OG001
Arm 4: Concizumab PPX (Study 4307) - Participants With HA
Arm 4 participants with haemophilia A who were on stable PPX for atleast 24 weeks in study 4322 and who entered the maintenance period in 4307.
Units
Counts
Participants
OG00029
OG00129
Title
Denominators
Categories
Title
Measurements
OG0002.2(0.8 to 6.2)
OG0011.7(0.5 to 4.8)
OG001
Arm 4: Concizumab PPX (Study 4307) - Participants With HA
Arm 4 participants with haemophilia B who were on stable PPX for atleast 24 weeks in study 4322 and who entered the maintenance period in 4307.
Units
Counts
Participants
OG00022
OG00122
Title
Denominators
Categories
Title
Measurements
OG0002.1(0.9 to 4.2)
OG0011.3(0.0 to 6.4)
OG001
Arm 2: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG0009
OG00118
Title
Denominators
Categories
Title
Measurements
OG00019.3(7.2 to 20.5)
OG0011.0(0.0 to 3.6)
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG00012
OG00124
Title
Denominators
Categories
Title
Measurements
OG00010.8(3.3 to 17.8)
OG0011.0(0.0 to 2.5)
OG001
Arm 2: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG0009
OG00118
Title
Denominators
Categories
Title
Measurements
OG00013.0(10.7 to 28.3)
OG0012.0(0.0 to 4.0)
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG00012
OG00124
Title
Denominators
Categories
Title
Measurements
OG00010.0(3.3 to 18.0)
OG0012.0(0.0 to 3.7)
OG001
Arm 2: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG0009
OG00118
Title
Denominators
Categories
Title
Measurements
OG0004.3(1.6 to 13.0)
OG0011.7(0.0 to 3.0)
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
Units
Counts
Participants
OG00012
OG00124
Title
Denominators
Categories
Title
Measurements
OG0002.2(0.0 to 8.1)
OG0010.7(0.0 to 1.5)
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG002
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG004
Extension Phase Arm 1: Concizumab PPX - Participants With HA
Participants with HA who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
OG005
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG006
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG007
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG008
Extension Phase Arm 1: Concizumab PPX - Participants With HB
Participants with HB who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
Units
Counts
Participants
OG0009
OG00118
OG00210
OG00352
OG0047
OG00512
OG00624
OG00730
OG00810
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0034
OG0040
OG0050
OG0060
OG0070
OG0080
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4
OG002
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG004
Extension Phase Arm 1: Concizumab PPX - Participants With HA
Participants with HA who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
OG005
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG006
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4
OG007
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG008
Extension Phase Arm 1: Concizumab PPX - Participants With HB
Participants with HB who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
Units
Counts
Participants
OG0009
OG00118
OG00210
OG00352
OG0047
OG00512
OG00624
OG00730
OG00810
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG001
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HA
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4
OG002
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 4: Concizumab PPX - Participants With HA
Participants with HA previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG004
Extension Phase Arm 1: Concizumab PPX - Participants With HA
Participants with HA who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
OG005
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4. Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG006
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG007
Arm 4: Concizumab PPX - Participants With HB
Participants with HB previously on PPX with factor products and a minimum of 24 weeks of observation in the non interventional study 4322 (NCT03741881) were allocated to Arm 4. Additionally, Arm 4 also included participants who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed. The original dosing regimen was a loading s.c. dose of 1.0 mg/kg concizumab on the first day of treatment, followed by a maintenance dose of 0.25 mg/kg concizumab given as a daily s.c. injection from the second day and onwards. After the concizumab treatment pause and the treatment restart, participants received a loading dose of 1.0 mg/kg concizumab at visit 2a followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could have their dose increased to 0.25 mg/kg or decreased to 0.15 mg/kg concizumab or they could remain at a dose of 0.20 mg/kg.
OG008
Extension Phase Arm 1: Concizumab PPX - Participants With HB
Participants with HB who completed the main part were offered concizumab PPX in the extension part for up to an additional 353 weeks.
Units
Counts
Participants
OG0009
OG00118
OG00210
OG00352
OG0047
OG00512
OG00624
OG00730
OG00810
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
OG00314
OG0041
OG0050
OG0062
OG00728
OG0080
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG002
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HA
Participants with HA who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG004
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HB
Participants with HB who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
Units
Counts
Participants
OG00015
OG0017
OG00245
OG00323
OG00426
Title
Denominators
Categories
Title
Measurements
OG000767.7± 112.4
OG001612.3± 274.9
OG002729.3± 158.6
OG003413.6± 234.7
OG004719.7± 189.7
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG002
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HA
Participants with HA who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG004
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4.
Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG005
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG006
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HB
Participants with HB who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
Units
Counts
Participants
OG0007
OG00115
OG0027
OG00343
OG0049
OG00522
OG00626
Title
Denominators
Categories
Title
Measurements
OG00019.9± 117.7
OG00198.3± 53.3
OG00292.3± 69.0
OG00392.1± 57.8
OG0049.6± 110.7
OG00554.6± 111.9
OG00679.4± 57.1
Participants with HA received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG002
Arm 3: Concizumab Non-naive: Concizumab PPX - Participants With HA
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HA
Participants with HA who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG004
Arm 1: Previous OnD Treatment: No PPX - Participants With HB
Participants with HB received their on-demand treatment for a minimum of 24 weeks. After treatment pause, participants initially randomised to arm 1 were to enter arm 4.
Subsequently, following the main phase, participants transitioned to the new dosing regimen for concizumab and were scheduled to undergo concizumab prophylaxis in the trial's extension phase.
OG005
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG006
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HB
Participants with HB who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
Units
Counts
Participants
OG0007
OG00116
OG0027
OG00344
OG00411
OG00523
OG00626
Title
Denominators
Categories
Title
Measurements
OG00070.1± 12.3
OG00111.1± 74.8
OG00215.9± 75.8
OG0039.6± 87.9
OG00488.1± 14.6
OG00516.3± 130.3
OG00610.5± 107.4
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG002
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HA
Participants with HA who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG004
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HB
Participants with HB who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
Units
Counts
Participants
OG00010
OG0015
OG00236
OG00311
OG00422
Title
Denominators
Categories
Title
Measurements
OG0001158.2± 61.9
OG001583.4± 282.2
OG0021029.7± 130.9
OG003689.2± 190.5
OG004828.0± 111.2
Participants with HA received a loading dose (participants entering from the phase 2 trial [N7415-4255] (NCT03196297) were not to receive a loading dose) of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG002
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HA
Participants with HA who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.
OG003
Arm 2: Previous OnD Treatment: Concizumab PPX - Participants With HB
Participants with HB received a loading dose of 1.0 milligrams per kilograms (mg/kg) concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg. After treatment pause, participants initially randomised to arm 2 were to enter arm 4.
OG004
Arm 4: Concizumab PPX (IPAS) + Concizumab PPX (Others) - Participants With HB
Participants with HB who were on a stable PPX regimen for at least 24 weeks in study 4322 and who entered the maintenance period in the present trial, who were randomised to arms 1 (no PPX) and 2 (concizumab PPX) before the treatment pause, participants who were in the phase 2 trial 4255 at the time of the treatment pause, and who had subsequently completed the trial when concizumab treatment was restarted and on-demand participants included after arms 1 and 2 were closed were all allocated to Arm 4 and received a loading dose of 1.0 mg/kg concizumab subcutaneously followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week maintenance dose setting period on 0.20 mg/kg concizumab, the participants could be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab or stayed at 0.20mg/kg.