A Study of Fitusiran in Severe Hemophilia A and B Patient... | NCT03549871 | Trialant
NCT03549871
Sponsor
Genzyme, a Sanofi Company
Status
Completed
Last Update Posted
Feb 6, 2023Actual
Enrollment
80Actual
Phase
Phase 3
Conditions
Hemophilia
Interventions
Fitusiran
BPA prophylaxis
Factor (FVIII or FIX) prophylaxis
Countries
United States
Australia
China
Denmark
France
Ireland
Israel
Italy
Japan
Malaysia
Mexico
South Korea
Turkey (Türkiye)
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03549871
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
EFC15110
Secondary IDs
ID
Type
Description
Link
2016-004087-19
EudraCT Number
ALN-AT3SC-009
Other Identifier
Alnylam
U1111-1217-3270
Registry Identifier
WHO Universal Trial Number (UTN)
Brief Title
A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
Official Title
ATLAS-PPX: an Open-label, Multinational, Switching Study to Describe the Efficacy and Safety of Fitusiran Prophylaxis in Patients With Hemophilia A and B Previously Receiving Factor or Bypassing Agent Prophylaxis.
Acronym
ATLAS-PPX
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Jan 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 25, 2018Actual
Primary Completion Date
Jan 20, 2022Actual
Completion Date
Mar 25, 2022Actual
First Submitted Date
May 25, 2018
First Submission Date that Met QC Criteria
Jun 6, 2018
First Posted Date
Jun 8, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Jan 10, 2023
Results First Submitted that Met QC Criteria
Jan 10, 2023
Results First Posted Date
Feb 6, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 10, 2023
Last Update Posted Date
Feb 6, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Genzyme, a Sanofi CompanyINDUSTRY
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
Yes
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Primary Objective:
To characterize the frequency of bleeding episodes (BE) while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor concentrate or bypassing agent (BPA) prophylaxis.
Secondary Objectives:
To characterize the following while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis:
the frequency of spontaneous bleeding episodes
the frequency of joint bleeding episodes
health related quality of life (HRQOL) in participants greater than or equal to (>=) 17 years of age
To characterize the frequency of bleeding episodes during the onset and treatment periods in participants receiving fitusiran.
To characterize the safety and tolerability of fitusiran.
To characterize the annualized weight-adjusted consumption of factor/BPA while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis.
Detailed Description
The estimated total time on study, inclusive of Screening, for each participant was up to 15 months for participants who were enrolled in the extension study except for participants in the subgroup of Cohort A, for whom it was up to 9 months. The estimated total time on study was up to 21 months (up to 15 months in participants in the subgroup of Cohort A) in participants who did not enroll in the extension study due to the requirement for an additional up to 6 months of follow-up for monitoring of antithrombin (AT) levels.
Conditions Module
Conditions
Hemophilia
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
80Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Fitusiran
Experimental
Cohort A [inhibitor]: participants with severe hemophilia A/B and inhibitory antibodies to coagulation factor VIII (FVIII)/factor IX (FIX) previously received BPA prophylaxis. Cohort B [non-inhibitor]: participants with severe hemophilia A/B without inhibitory antibodies to FVIII/FIX previously received factor prophylaxis. Participants from both cohorts was enrolled into 6-month factor/BPA prophylaxis period and continued their pre-study, regularly scheduled prophylaxis regimen with factor/BPAs. This period could be skipped by subgroup of Cohort A (hemophilia B with inhibitors to FIX and historical annualized bleeding rate [ABR] >=20) that started directly with fitusiran. Post completing factor/BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset+6-month efficacy) followed by AT follow-up/roll-over into LTE15174 (NCT03754790). Throughout study, participants could receive on-demand treatment for breakthrough BE with factor/BPAs, as appropriate.
Drug: Fitusiran
Drug: BPA prophylaxis
Drug: Factor (FVIII or FIX) prophylaxis
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Fitusiran
Drug
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Fitusiran
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Estimated Annualized Bleeding Rate (ABR)
Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Bleeding Rate (ABR)
A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period *365.25.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary Outcomes
Measure
Description
Time Frame
Estimated Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA infusion. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. Spontaneous BE: BE occurrence for no apparent/known reason, particularly into joints, muscles, and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data was derived using repeated measures NB regression model.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Males, >=12 years of age.
Severe hemophilia A or B (as evidenced by a central laboratory measurement at screening or documented medical record evidence of FVIII less than (<) 1 percent (%) or FIX level less than or equal to (<=) 2%).
A minimum of 2 bleeding episodes required BPA treatment within the last 6 months prior to screening for participants with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode required factor treatment within the last 12 months prior to screening for participants without inhibitory antibodies to factor VIII or factor IX (Cohort B).
Met either the definition of inhibitor or non-inhibitor participant as below:
Inhibitor: Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met one of the following Nijmegen-modified Bethesda assay results criteria:
Inhibitor titer of >=0.6 Bethesda Unit per milliliter (BU/mL) at screening, or
Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of 2 consecutive titers >=0.6 BU/mL, or
Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of anamnestic response
The subgroup of participants in Cohort A participants might additionally meet the following criteria to be eligible to start treatment with fitusiran directly after the screening period:
Hemophilia B with inhibitory antibody to Factor IX as defined above
Not responding adequately to BPA treatment (historical ABR >=20) prior to enrollment
In the opinion of the Investigator, with approval of Sponsor Medical Monitor, 6-month BPA prophylaxis period should be omitted.
Non-inhibitor: Use of factor concentrates for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met each of the following criterion:
Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at screening and
No use of BPAs to treat bleeding episodes for at least the last 6 months prior to screening and
No history of immune tolerance induction therapy within the past 3 years prior to screening.
Documented prophylactic treatment with factor concentrates or BPAs for the treatment of hemophilia A or B for at least 6 months prior to screening.
Adherent to the prescribed prophylactic therapy for at least 6 months prior to screening per Investigator assessment.
Willed and complied with the study requirements and to provide written informed consent and assent.
Exclusion Criteria:
Known co-existing bleeding disorders other than hemophilia A or B.
AT activity <60% at screening.
Co-existing thrombophilic disorder.
Clinically significant liver disease.
Active Hepatitis C virus infection.
Acute or chronic Hepatitis B virus infection.
HIV positive with a CD4 count of <200 cells per microliter.
History of arterial or venous thromboembolism.
Inadequate renal function.
History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc).
History of intolerance to subcutaneous injection(s).
Any other conditions or comorbidities that made the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment.
Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You CW, Vilchevska K, Bagot CN, Sharif A, Peyvandi F, Young G, Negrier C, Chi J, Kittner B, Sussebach C, Shammas F, Mei B, Andersson S, Kavakli K. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood. 2024 May 30;143(22):2256-2269. doi: 10.1182/blood.2023021864.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Subgroup of Cohort A: Participants with hemophilia B with inhibitors and inadequate response to BPA treatment (historical annualized bleeding rate [ABR] greater than or equal to [>=] 20) prior to enrollment did not participate in 6-month prophylaxis period and they entered directly into fitusiran treatment period.
Recruitment Details
Study was conducted at 35 active sites in 15 countries. Total of 99 participants were screened from 25 July 2018 to 19 March 2021, of which 19 were screen failure due to not meeting eligibility criteria. Study had 2 main periods: 6-month factor/bypassing agent (BPA) prophylaxis period & 7-month fitusiran treatment period (1-month onset and 6-month fitusiran efficacy period).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort A: Inhibitor
Participants with hemophilia A or B and inhibitory antibodies to coagulation factor VIII (FVIII) or coagulation factor IX (FIX) and who were receiving BPA prophylaxis were enrolled in the study and entered into 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs (twice weekly [activated prothrombin complex concentrates {aPCC}] or every other day [recombinant factor VIIa {rFVIIa}]). This period was skipped by a subgroup of Cohort A (hemophilia B with inhibitors and historical ABR >= 20) and they entered directly in to fitusiran treatment period. Post completion of BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 milligrams (mg) once monthly (QM) as subcutaneous (SC) injection for 7 months until the sponsor initiated a voluntary dose pause. After dose pause and protocol amendment, the fitusiran dose was changed to 50 mg once every other month (Q2M) as SC injection. Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout study, participants in fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs, as appropriate.
Periods
Title
Milestones
Reasons Not Completed
Factor/BPA Prophylaxis: Day -168 to -1
Type
Comment
Milestone Data
STARTED
Enrolled
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
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
Dec 8, 2020
Jan 10, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Canada
Germany
South Africa
Spain
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Single Group Assignment
Intervention Model Description
Not provided
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
BPA prophylaxis
Drug
Pharmaceutical form: solution for injection Route of administration: Intravenous
Fitusiran
Factor (FVIII or FIX) prophylaxis
Drug
Pharmaceutical form: solution for injection Route of administration: Intravenous
Fitusiran
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Spontaneous BE: bleeding event occurred for no apparent or known reason, particularly into joints, muscles and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Estimated Annualized Joint Bleeding Rate
BE: any hemorrhage that required administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection to treat BE at that location was considered part of original BE; counted as 1 BE towards ABR. Bleeding after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint ("aura") + increasing swelling/warmth over joint skin, increasing pain/progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data were derived by using repeated measures NB regression model.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Joint Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint (aura) increasing swelling/warmth over joint skin, increasing pain or progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of joint BE/number of days in respective period*365.25.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: participant-reported questionnaire for adults aged >=17 years with hemophilia and comprised of 46 items covering 10 domains. Physical health domain (PHD) is assessed with 5 items rated on 5-point Likert scale: never, rarely, sometimes, often or all the time. Raw score for PHD were transformed to scale ranged from 0 to 100, where lower scores = better physical health. Least square (LS) mean and 95% confidence interval (CI) by mixed model for repeated measure (MMRM) analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis & fitusiran treatment) & Baseline score (Month -6) as fixed effects.
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: questionnaire for adults aged >= 17 years with hemophilia; and comprised of 46 items covering 10 domains: physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality. Items were rated on 5-point Likert scale: never, rarely, sometimes, often or all time. Domain raw score was transformed to scale ranged from 0 to 100, where lower scores=better health. LS mean & 95% CI by MMRM analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis & fitusiran treatment) & Baseline score (Month -6) as fixed effects.
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Estimated Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Estimated ABR and 95% CI was derived by using repeated measures NB regression model with logarithm of duration (years) that each participant spends in 1-Month fitusiran onset period matching BE data being analyzed as offset variable. ABR = total number of qualifying BE/number of days in respective period *365.25.
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Observed Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and was counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in the 1-month onset period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in 1-month onset period and excluded any bleeding events in period of intercurrent events.
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Estimated Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: defined as any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in the period of intercurrent events. ABR = total number of qualifying BE/number of days in respective period *365.25.
From Day 1 up to Day 190
Observed Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original bleeding event and was counted as one BE towards ABR. Any bleeding that began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in treatment period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in period of intercurrent events.
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: [Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period]*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agent: aPCC (unit per kilogram [U/kg]) were reported.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort A: Annualized Weight-adjusted Consumption of BPA (Recombinant Factor VIIa)
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: rFVIIa (unit: micrograms per kg [mcg/kg]) were reported. Combined data of annualized weight-adjusted BPA consumption (mcg/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort B: Annualized Weight-adjusted Consumption of Factor
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: FVIII and FIX (unit: international Units [IU] per kg [IU/kg]) were reported.
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Prahran
3181
Australia
Investigational Site Number 8604
Beijing
100045
China
Investigational Site Number 4501
Copenhagen
2100
Denmark
Investigational Site Number 3303
Lyon
69677
France
Investigational Site Number 5301
Crumlin
12
Ireland
Investigational Site Number 9701
Ramat Gan
52621
Israel
Investigational Site Number 3902
Milan
20122
Italy
Investigational Site Number 8101
Nagoya
Japan
Investigational Site Number 8102
Nishinomiya
Japan
Investigational Site Number 8104
Saitama
Japan
Investigational Site Number 8109
Tokyo
Japan
Investigational Site Number 6004
Ampang
68000
Malaysia
Investigational Site Number 6002
Johor Bahru
80100
Malaysia
Investigational Site Number 6003
Kota Kinabalu
88586
Malaysia
Investigational Site Number 5201
San Pablo
Mexico
Investigational Site Number 8201
Busan
602-739
South Korea
Investigational Site Number 8202
Daejeon
35233
South Korea
Investigational Site Number 8204
Seoul
3722
South Korea
Investigational Site Number 9002
Adana
?01130
Turkey (Türkiye)
Investigational Site Number 9001
Ankara
06100
Turkey (Türkiye)
Investigational Site Number 9004
Antalya
07059
Turkey (Türkiye)
Investigational Site Number 9008
Gaziantep
27100
Turkey (Türkiye)
Investigational Site Number 9005
Istanbul
34093
Turkey (Türkiye)
Investigational Site Number 9010
Izmir
35040
Turkey (Türkiye)
Investigational Site Number 9003
Izmir
TR-35100
Turkey (Türkiye)
Investigational Site Number 9009
Kayseri
38039
Turkey (Türkiye)
Investigational Site Number 9006
Samsun
55200
Turkey (Türkiye)
Investigational site number 9013
Van
65080
Turkey (Türkiye)
Investigational Site Number 8003
Kyiv
?01135
Ukraine
Investigational Site Number 8002
Lviv
79044
Ukraine
Investigational Site Number 4402
Glasgow
G4 0SF
United Kingdom
Investigational Site Number 4407
London
E1 2ES
United Kingdom
Investigational Site Number 4403
London
NW3 2QG
United Kingdom
Investigational Site Number 4401
London
SE1 9RT
United Kingdom
FG001
Cohort B: Non-inhibitor
Participants with hemophilia A or B, without inhibitory antibodies to FVIII or FIX who were receiving factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with factor concentrates (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]). Post completion of factor prophylaxis period, participants entered in to 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until the sponsor initiated a voluntary dose pause. Participants could continue to receive their factor prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with factor, as appropriate.
FG00030 subjects
FG00150 subjects
Started Directly With Fitusiran
FG0002 subjects
FG0010 subjects
Started With Factor or BPA Prophylaxis
FG00028 subjects
FG00150 subjects
COMPLETED
FG00023 subjects
FG00146 subjects
NOT COMPLETED
FG0007 subjects
FG0014 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0012 subjects
Adverse Event
FG0001 subjects
FG0010 subjects
Parent withdrew consent
FG0001 subjects
FG0010 subjects
Switched to treatment not per protocol
FG0004 subjects
FG0010 subjects
Related to Coronavrus Disease 2019
FG0001 subjects
FG0010 subjects
Did not meet trial eligibility
FG0000 subjects
FG0012 subjects
Fitusiran Treatment: Day 1 to Day 190
Type
Comment
Milestone Data
STARTED
FG00023 subjects
FG00146 subjects
Received 80mg QM & Part of Safety Analysis Set 1 (SAS 1)
FG00021 subjects
FG00146 subjects
Received 50 mg Q2M & Part of Safety Analysis Set 2 (SAS 2)
FG0002 subjectsParticipants received fitusiran 50mg Q2M dosing regimen after dose pause and amended protocol 5, dated 25-Nov-2020. They were considered as safety analysis set 2 (SAS 2) and were subjected only to safety analysis and not to main efficacy analysis (Efficacy Set 1).
FG0010 subjects
Efficacy Analysis Set 1 (EAS 1)
FG00019 subjects
FG00146 subjects
Efficacy Analysis Set 2 (EAS 2)
FG0002 subjectsEfficacy Analysis Set 2 (EAS 2) included all participants in the SAS 2 who received BPA prophylaxis and fitusiran 50 mg Q2M after dose pause, protocol amendment 5 (dated 25-Nov-2020) and dose resumption.
FG0010 subjects
COMPLETED
FG00017 subjects
FG00137 subjects
NOT COMPLETED
FG0006 subjects
FG0019 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
More than 1 antithrombin (AT) measurement less than 15%
FG0001 subjects
FG001
Baseline analysis population included all completed participants from BPA/factor prophylaxis period + 2 participants from Cohort A subgroup who directly enrolled to fitusiran treatment period.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort A: Inhibitor
Participants with hemophilia A or B and inhibitory antibodies to FVIII or FIX and who were receiving BPA prophylaxis were enrolled in the study and entered into 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]). This period was skipped by a subgroup of Cohort A (hemophilia B with inhibitors and historical ABR >= 20) and they entered directly in to fitusiran treatment period. Post completion of BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection for 7 months until the sponsor initiated a voluntary dose pause. After dose pause and protocol amendment, the fitusiran dose was changed to 50 mg Q2M as SC injection. Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout the study, participants in fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs, as appropriate.
BG001
Cohort B: Non-inhibitor
Participants with hemophilia A or B, without inhibitory antibodies to FVIII or FIX who were receiving factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with factor concentrates (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]). Post completion of factor prophylaxis period, participants entered in to 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until the sponsor initiated a voluntary dose pause. Participants could continue to receive their factor prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with factor, as appropriate.
BG002
Total Title
Denominators
Units
Counts
Participants
BG00023
BG00146
BG00269
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
BG00027.7± 15.9
BG00123.5± 7.3
BG00224.9± 11.0
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
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
Estimated Annualized Bleeding Rate (ABR)
Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model.
Analysis was performed on efficacy analysis set 1 (EAS1) which included participants who received factor/BPA prophylaxis and any dose of fitusiran before dose resumption. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Number
95% Confidence Interval
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0007.482(5.520 to 10.141)
OG0012.908(1.727 to 4.898)
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
Analyzed using repeated measures NB model with fixed effect of treatment period (fitusiran efficacy period or factor/BPA prophylaxis period) and robust sandwich covariance matrix was constructed to account for within participant dependence, logarithm of duration (in years) that each participant spends in each study period matching BE data being analyzed as an offset variable.
Repeated measures NB regression model
=0.0008
The threshold for significance was <0.05.
ABR ratio
0.389
2-Sided
95
0.224
0.675
Superiority
Primary
Observed Annualized Bleeding Rate (ABR)
A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period *365.25.
Analysis was performed on EAS1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Mean
Standard Deviation
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Estimated Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA infusion. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. Spontaneous BE: BE occurrence for no apparent/known reason, particularly into joints, muscles, and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data was derived using repeated measures NB regression model.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Number
95% Confidence Interval
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Observed Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Spontaneous BE: bleeding event occurred for no apparent or known reason, particularly into joints, muscles and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Mean
Standard Deviation
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Estimated Annualized Joint Bleeding Rate
BE: any hemorrhage that required administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection to treat BE at that location was considered part of original BE; counted as 1 BE towards ABR. Bleeding after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint ("aura") + increasing swelling/warmth over joint skin, increasing pain/progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data were derived by using repeated measures NB regression model.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Number
95% Confidence Interval
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Observed Annualized Joint Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint (aura) increasing swelling/warmth over joint skin, increasing pain or progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of joint BE/number of days in respective period*365.25.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Mean
Standard Deviation
episodes per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: participant-reported questionnaire for adults aged >=17 years with hemophilia and comprised of 46 items covering 10 domains. Physical health domain (PHD) is assessed with 5 items rated on 5-point Likert scale: never, rarely, sometimes, often or all the time. Raw score for PHD were transformed to scale ranged from 0 to 100, where lower scores = better physical health. Least square (LS) mean and 95% confidence interval (CI) by mixed model for repeated measure (MMRM) analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis & fitusiran treatment) & Baseline score (Month -6) as fixed effects.
Analysis was performed on EAS 1 population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Least Squares Mean
95% Confidence Interval
score on a scale
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: questionnaire for adults aged >= 17 years with hemophilia; and comprised of 46 items covering 10 domains: physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality. Items were rated on 5-point Likert scale: never, rarely, sometimes, often or all time. Domain raw score was transformed to scale ranged from 0 to 100, where lower scores=better health. LS mean & 95% CI by MMRM analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis & fitusiran treatment) & Baseline score (Month -6) as fixed effects.
Analysis was performed on EAS1 population. Here, 'overall number of participants analyzed = participants with available data for this outcome measure. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure.
Posted
Least Squares Mean
95% Confidence Interval
score on a scale
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
ID
Title
Description
OG000
Overall Factor/BPA Prophylaxis Period
All participants, whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Estimated Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Estimated ABR and 95% CI was derived by using repeated measures NB regression model with logarithm of duration (years) that each participant spends in 1-Month fitusiran onset period matching BE data being analyzed as offset variable. ABR = total number of qualifying BE/number of days in respective period *365.25.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran 1-month onset period was planned and performed for this outcome measure.
Posted
Number
95% Confidence Interval
episodes per participant per year
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
ID
Title
Description
OG000
Overall Fitusiran 80 mg 1-Month Onset Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran 1-month onset period and were considered for the efficacy analysis during fitusiran 1-month onset period.
Secondary
Observed Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and was counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in the 1-month onset period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in 1-month onset period and excluded any bleeding events in period of intercurrent events.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran 1-month onset period was planned and performed for this outcome measure.
Posted
Mean
Standard Deviation
episodes per participant per year
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
ID
Title
Description
OG000
Overall Fitusiran 80 mg 1-Month Onset Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran 1-month onset period and were considered for the efficacy analysis during fitusiran 1-month onset period.
Secondary
Estimated Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: defined as any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in the period of intercurrent events. ABR = total number of qualifying BE/number of days in respective period *365.25.
Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran treatment period was planned and performed for this outcome measure.
Posted
Number
95% Confidence Interval
episodes per participant per year
From Day 1 up to Day 190
ID
Title
Description
OG000
Overall Fitusiran 80 mg Treatment Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran treatment period (i.e., 1-month onset period + 6-month efficacy period) and were considered for efficacy analysis during fitusiran treatment period.
Units
Secondary
Observed Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original bleeding event and was counted as one BE towards ABR. Any bleeding that began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in treatment period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in period of intercurrent events.
Analysis was performed on EAS1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran treatment period was planned and performed for this outcome measure.
Posted
Mean
Standard Deviation
episodes per participant per year
from Day 1 up to Day 190
ID
Title
Description
OG000
Overall Fitusiran 80 mg Treatment Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran treatment period (i.e., 1-month onset period + 6-month efficacy period) and were considered for efficacy analysis during fitusiran treatment period.
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: [Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period]*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agent: aPCC (unit per kilogram [U/kg]) were reported.
Analysis was performed on EAS 1 population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Combined data of annualized weight-adjusted BPA consumption (U/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Posted
Mean
Standard Deviation
U/kg per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
BPA Prophylaxis: Cohort: A Inhibitor
Participants with hemophilia A or B, with inhibitory antibodies to FVIII or FIX and who were receiving BPA prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs ((twice weekly [aPCC] or every other day [rFVIIa]). This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Cohort A: Annualized Weight-adjusted Consumption of BPA (Recombinant Factor VIIa)
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: rFVIIa (unit: micrograms per kg [mcg/kg]) were reported. Combined data of annualized weight-adjusted BPA consumption (mcg/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Analysis was performed on EAS 1 population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Combined data of annualized weight-adjusted BPA consumption (mcg/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Posted
Mean
Standard Deviation
mcg/kg per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
BPA Prophylaxis: Cohort: A Inhibitor
Participants with hemophilia A or B, with inhibitory antibodies to FVIII or FIX and who were receiving BPA prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]). This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).
Secondary
Cohort B: Annualized Weight-adjusted Consumption of Factor
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: FVIII and FIX (unit: international Units [IU] per kg [IU/kg]) were reported.
Analysis was performed on EAS 1 population. Here, 'number analyzed' = participants with available data for each specified category. Combined data of annualized weight-adjusted factor consumption (IU/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Posted
Mean
Standard Deviation
IU/kg per participant per year
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
ID
Title
Description
OG000
Factor Prophylaxis: Cohort B: Non-inhibitor
Participants with hemophilia A or B, without inhibitory antibodies to FVIII or FIX who were receiving factor prophylaxis were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with factor concentrates (twice weekly [standard half-life FVIII], once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]).
OG001
Time Frame
Factor/BPA prophylaxis period: from Day -168 to Day -1; Fitusiran 80 mg QM/50 mg Q2M period: from Day 1 of fitusiran treatment period (i.e., 1 month onset+ 6 months efficacy) until AT follow up (i.e. up to 21 months)
Description
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug which did not necessarily have a causal relationship with the treatment. Safety analysis set (SAS): all participants who were enrolled and received any dose of fitusiran (80 mg, QM before dose pause; SAS 1)/(50 mg, Q2M after dose pause; SAS 2).
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
Cohort A: SAS 1 - BPA Prophylaxis
Participants with hemophilia A or B, with inhibitory antibodies to FVIII or FIX and who were receiving BPA prophylaxis were enrolled in the study and entered the 6-month BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]).
0
19
5
19
10
19
EG001
Cohort A: SAS 1 - Fitusiran 80 mg QM
Post completion of BPA prophylaxis period, participants entered into the 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until sponsor initiated a voluntary dose pause. Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. A subgroup of Cohort A (participants with hemophilia B and inhibitory antibodies to FIX who had not responded adequately to BPA prophylaxis prior to study entry [historical ABR >=20]) entered directly into fitusiran treatment period. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs, as appropriate. Post last fitusiran dose, participants had a safety follow-up/AT activity level follow-up up to 6 months (monthly monitor until AT activity levels return to approximately 60% or per Investigator discretion).
0
21
5
21
13
21
EG002
Cohort B: SAS 1 - Factor Prophylaxis
Participants with hemophilia A or B, without inhibitory antibodies to FVIII or FIX and who were receiving factor prophylaxis were enrolled in the study and entered the 6-month BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with factor concentrates (twice weekly [standard half-life FVIII), once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]).](streamdown:incomplete-link)
0
46
0
46
9
46
EG003
Cohort B: SAS 1 - Fitusiran 80 mg QM
Post completion of Factor prophylaxis period, participants entered into the 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until sponsor initiated a voluntary dose pause (up to maximum of 7 months). Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with factor, as appropriate. Post last fitusiran dose, participants had a safety follow-up/AT activity level follow-up up to 6 months (monthly monitor until AT activity levels return to approximately 60% or per Investigator discretion).
0
46
4
46
28
46
EG004
Overall: SAS 1 - Factor/BPA Prophylaxis
All participants whether with inhibitory antibodies (Cohort A) or without inhibitory antibodies (Cohort B) to FVIII or FIX and who were receiving BPA or factor prophylaxis, respectively, were enrolled in the study and entered the 6-month factor or BPA prophylaxis period in this study and continued their pre-study regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]) or factors (twice weekly [standard half-life FVIII), once weekly [extended half-life FVIII; standard half-life FIX], and once biweekly [extended half-life FIX]) in 6-month factor or BPA prophylaxis period. This period was skipped by a subgroup of Cohort A which included participants with hemophilia B with inhibitory antibodies to FIX and who had not responded adequately to BPA prophylaxis prior to study entry (historical ABR >=20).](streamdown:incomplete-link)
0
65
5
65
19
65
EG005
Overall: SAS 1 - Fitusiran 80 mg QM
Post completion of BPA prophylaxis period, all participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause (up to maximum of 7 months). Participants could continue to receive BPA/factor prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. A subgroup of Cohort A (participants with hemophilia B and inhibitory antibodies to FIX who had not responded adequately to BPA prophylaxis treatment [historical ABR >=20]) entered directly into fitusiran treatment period. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs or factors, as appropriate. Post last fitusiran dose, participants had a safety follow-up/AT activity level follow-up up to 6 months (monthly monitor until AT activity levels return to approximately 60% or per Investigator discretion).
0
67
9
67
41
67
EG006
Cohort A: SAS 2 - BPA Prophylaxis
Participants with hemophilia A or B, with inhibitory antibodies to FVIII or FIX and who were receiving BPA prophylaxis were enrolled in the study and entered the 6-month BPA prophylaxis period in this study and continued their pre-study, regularly scheduled prophylaxis regimen with BPAs (twice weekly [aPCC] or every other day [rFVIIa]).
0
2
1
2
1
2
EG007
Cohort A: SAS 2 - Fitusiran 50 mg Q2M
Post completion of BPA prophylaxis period, participants entered into the 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 50 mg Q2M as SC injection after sponsor initiated voluntary dose pause and protocol amendment. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs (twice weekly [aPCC] or every other day [rFVIIa]), as appropriate. Post last fitusiran dose, participants had a safety follow-up/AT activity level follow-up up to 6 months (monthly monitor until AT activity levels return to approximately 60% or per Investigator discretion).
0
2
1
2
2
2
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Fall
Injury, poisoning and procedural complications
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG0030 events0 affected46 at risk
EG0040 events0 affected65 at risk
EG0051 events1 affected67 at risk
EG0060 events0 affected2 at risk
EG0070 events0 affected2 at risk
Femur Fracture
Injury, poisoning and procedural complications
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
C-Reactive Protein Increased
Investigations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Cerebrovascular Accident
Nervous system disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Pancreatitis Acute
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Stevens-Johnson Syndrome
Skin and subcutaneous tissue disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Haemarthrosis
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Haemophilic Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0002 events2 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Muscle Haemorrhage
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Covid-19 Pneumonia
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Vascular Device Infection
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Central Venous Catheter Removal
Surgical and medical procedures
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Biliary Neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Asthma Late Onset
Respiratory, thoracic and mediastinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Arthropod Bite
Injury, poisoning and procedural complications
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG0030 events0 affected46 at risk
EG0041 events1 affected65 at risk
EG0051 events1 affected67 at risk
EG0060 events0 affected2 at risk
EG0070 events0 affected2 at risk
Buttock Injury
Injury, poisoning and procedural complications
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA24.1
Systematic Assessment
EG0002 events2 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDRA24.1
Systematic Assessment
EG0003 events1 affected19 at risk
EG0013 events3 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Aspartate Aminotransferase Increased
Investigations
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0013 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Fibrin D Dimer Increased
Investigations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0013 events3 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Lymphocyte Count Increased
Investigations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Neutrophil Count Decreased
Investigations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
White Blood Cell Count Decreased
Investigations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA24.1
Systematic Assessment
EG0002 events2 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Headache
Nervous system disorders
MedDRA24.1
Systematic Assessment
EG0002 events2 affected19 at risk
EG0012 events1 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0013 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Dental Caries
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0002 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Eosinophilic Oesophagitis
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Gastrointestinal Motility Disorder
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Teething
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Dermatitis Allergic
Skin and subcutaneous tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0011 events1 affected21 at risk
EG0024 events3 affected46 at risk
EG003
Joint Swelling
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Synovitis
Musculoskeletal and connective tissue disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0011 events1 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Iron Deficiency
Metabolism and nutrition disorders
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Genital Herpes Simplex
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Influenza
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0011 events1 affected21 at risk
EG0022 events2 affected46 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0011 events1 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Tinea Pedis
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0001 events1 affected19 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA24.1
Systematic Assessment
EG0004 events3 affected19 at risk
EG0015 events4 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Injection Site Erythema
General disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0012 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Injection Site Pain
General disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0012 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0013 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0012 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0012 events2 affected21 at risk
EG0020 events0 affected46 at risk
EG003
Hepatic Steatosis
Hepatobiliary disorders
MedDRA24.1
Systematic Assessment
EG0000 events0 affected19 at risk
EG0012 events2 affected21 at risk
EG0021 events1 affected46 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000632624
fitusiran
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
Study drug on hold
FG0004 subjects
FG0015 subjects
Participant's decision
FG0000 subjects
FG0012 subjects
Adverse Event
FG0000 subjects
FG0012 subjects
0
Male
BG00023
BG00146
BG00269
0
Asian
BG0004
BG00117
BG00221
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
Black or African American
BG0001
BG0010
BG0021
White
BG00018
BG00127
BG00245
More than one race
BG0000
BG0010
BG0020
Unknown or Not Reported
BG0000
BG0012
BG0022
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0007.56± 9.49
OG0013.19± 7.75
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0005.002(3.424 to 7.305)
OG0012.222(1.190 to 4.152)
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
ABR ratio
0.444
2-Sided
95
0.234
0.842
Superiority
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0005.09± 7.93
OG0012.51± 7.33
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0005.282(3.647 to 7.651)
OG0012.564(1.440 to 4.566)
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
ABR ratio
0.485
2-Sided
95
0.259
0.910
Superiority
OG001
Overall Fitusiran 80 mg Efficacy Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran efficacy period (i.e., from Day 29 to Day 190 of fitusiran treatment period) and were considered for efficacy analysis during fitusiran efficacy period.
Units
Counts
Participants
OG00065
OG00165
Title
Denominators
Categories
Title
Measurements
OG0005.35± 8.19
OG0012.82± 7.54
OG001
Overall Fitusiran 80 mg Treatment Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran treatment period (i.e., 1-month onset period + 6-month efficacy period) and were considered for efficacy analysis during fitusiran treatment period.
Units
Counts
Participants
OG00048
OG00148
Title
Denominators
Categories
Title
Measurements
OG000-6.00(-10.19 to -1.81)
OG001-9.60(-15.35 to -3.84)
OG001
Overall Fitusiran 80 mg Treatment Period
All participants who received fitusiran 80 mg QM as SC injection (either in Cohort A or Cohort B) until sponsor initiated a voluntary dose pause during fitusiran treatment period (i.e., 1-month onset period + 6-month efficacy period) and were considered for efficacy analysis during fitusiran treatment period.
Units
Counts
Participants
OG00048
OG00148
Title
Denominators
Categories
Title
Measurements
OG000-3.07(-5.56 to -0.58)
OG001-7.62(-10.26 to -4.98)
Units
Counts
Participants
OG00065
Title
Denominators
Categories
Title
Measurements
OG0005.419(3.716 to 7.901)
Units
Counts
Participants
OG00065
Title
Denominators
Categories
Title
Measurements
OG0005.42± 8.28
Counts
Participants
OG00065
Title
Denominators
Categories
Title
Measurements
OG0003.317(2.111 to 5.211)
Counts
Participants
OG00065
Title
Denominators
Categories
Title
Measurements
OG0003.48± 6.98
OG001
Fitusiran 80 mg Prophylaxis: Cohort A: Inhibitor
Post completion of BPA prophylaxis period, participants entered into the 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until the sponsor initiated a voluntary dose pause (up to maximum of 7 months). Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. A subgroup of Cohort A (hemophilia B participants with inhibitory antibodies to Factor IX who were not responding adequately to BPA prophylaxis prior to study entry: historical ABR >=20) entered directly into fitusiran treatment period. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs, as appropriate.
Units
Counts
Participants
OG00015
OG00115
Title
Denominators
Categories
Title
Measurements
OG0007912.7± 5507.6
OG00139.7± 87.0
OG001
Fitusiran 80 mg Prophylaxis: Cohort A: Inhibitor
Post completion of BPA prophylaxis period, participants entered into the 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until the sponsor initiated a voluntary dose pause (up to maximum of 7 months). Participants could continue to receive BPA prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. A subgroup of Cohort A (hemophilia B participants with inhibitory antibodies to FIX who were not responding adequately to BPA prophylaxis prior to study entry: historical ABR >=20) entered directly into fitusiran treatment period. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with BPAs, as appropriate.
Post completion of factor prophylaxis period, participants entered in to 7-month fitusiran treatment period (1-month onset period + 6-month efficacy period) and received fitusiran 80 mg QM as SC injection until the sponsor initiated a voluntary dose pause (up to maximum of 7 months). Participants could continue to receive their factor prophylaxis for up to 7 days after start of fitusiran treatment on Day 1. Throughout the study, participants in the fitusiran treatment period could receive on-demand treatment for breakthrough bleeding episodes with factor, as appropriate.