Safety and Pharmacokinetics of Subcutaneous Injection of... | NCT04046848 | Trialant
NCT04046848
Sponsor
Octapharma
Status
Terminated
Last Update Posted
Feb 13, 2025Actual
Enrollment
36Actual
Phase
Phase 1Phase 2
Conditions
Severe Hemophilia A
Interventions
OCTA101
Countries
Bulgaria
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT04046848
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
SubQ8-01
Secondary IDs
Not provided
Brief Title
Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Adult Patients With Severe Hemophilia A
Official Title
Phase 1/2 Study to Assess the Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Previously Treated Adult Patients With Severe Hemophilia A
Acronym
Not provided
Organization
OctapharmaINDUSTRY
Status Module
Record Verification Date
Jan 2025
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Study was terminated due to SADRs
Expanded Access Info
No
Start Date
Jul 3, 2019Actual
Primary Completion Date
Feb 18, 2022Actual
Completion Date
Feb 18, 2022Actual
First Submitted Date
Jul 18, 2019
First Submission Date that Met QC Criteria
Aug 2, 2019
First Posted Date
Aug 6, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Feb 7, 2023
Results First Submitted that Met QC Criteria
Jan 20, 2025
Results First Posted Date
Feb 13, 2025Actual
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 20, 2025
Last Update Posted Date
Feb 13, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
OctapharmaINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This Phase 1/2 study will be a dose escalation study in adults in 5 cohorts (named cohorts 1, 2, 3, 5 and 6), with the main purpose to assess the safety of subcutaneous injection of OCTA101 (a human-cl rhFVIII and recombinant human von Willebrand Factor fragment dimer) in previously treated adult patients with severe hemophilia A. The study also aims to assess the pharmacokinetics (PK) characteristics, dose proportionality, and subcutaneous bioavailability of OCTA101 compared with intravenous administration of Nuwiq (Human-cl rh FVIII), in order to define the prophylactic treatment (dose and injection interval) that would result in protective trough levels of FVIII:C for future Phase 3 studies. Cohorts 1, 2, 3 and 5 will undergo a single injection of OCTA101, with cohorts 1, 2 and 3 proceeding to 3-month daily dosing prophylactic treatment for 3 months by Data Monitoring Committee recommendation. Cohorts 1 and 2 will undergo a further PK at the end of the daily injection period. A further cohort, cohort 6, will have an initial 4 to 6-week run-in treatment period with Nuwiq intravenous prophylaxis followed by 12.5 IU/kg OCTA101 subcutaneous daily prophylaxis for >3 up to 6-7 months.
Detailed Description
Not provided
Conditions Module
Conditions
Severe Hemophilia A
Keywords
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
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 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
36Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
Drug: OCTA101
Cohort 2
Experimental
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
Drug: OCTA101
Cohort 3
Experimental
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
Drug: OCTA101
Cohort 5
Experimental
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
OCTA101
Drug
OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Cohort 1
Cohort 2
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Patients Experiencing Adverse Events
Approximately 4 months; up to 11 months for cohort 6
Pre-defined DLTs for this study are: 1. Severe allergic reactions at least possibly related to study drug. 2. Severe vital organ toxicity at least possibly related to study drug that does not resolve to at least mild severity within 48 to 72 hours. 3. Any treatment-emergent severe toxicity at least possibly related to study drug other than the toxicities referenced in 2) that does not decrease to mild or resolve within 7 days
Approximately 4 months; up to 11 months for cohort 6
Patients Experiencing Thromboembolic Events
The definition of the cluster thromboembolic events was based on the standardised MedDRA query (SMQ) "Embolic and thrombotic events":
Definition: Thrombotic disorders are diseases characterized by formation of a thrombus that obstructs vascular blood flow locally or detaches and embolizes to occlude blood flow downstream. Embolism is the sudden blocking of a vessel by a clot or foreign material which has been brought to its site of lodgment by the blood current. (Thrombo-)phlebitis is an inflammation of a vein (phlebitis) associated with thrombus formation (thrombosis).
This SMQ includes 3 sub-SMQ:
Embolic and thrombotic events, venous (SMQ)
Embolic and thrombotic events, arterial (SMQ)
Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ)
Approximately 4 months; up to 11 months for cohort 6
Patients Experiencing Local Injection Site Reactions of Any Grade
Investigator (and patient in case of home treatment) assessed local injection reactivity directly after injection and at 15 ± 5 min post-injection as per the ISO10999-10 standard:
0=no skin reactivity;
mild (subject is aware of the signs/symptoms, but finds it easily tolerated)
moderate (discomfort enough to cause interference with usual activities)
severe (subject is incapacitated and unable to work or participate in many or all usual activities).
Secondary Outcomes
Measure
Description
Time Frame
Efficacy: Area Under the Concentration-time Curve (AUC) of FVIII:C
Mean AUC of FVIII after PK injection of OCTA101 as measured by chromogenic assay.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of FVIII:C
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Severe hemophilia A (<1% FVIII:C) as documented in medical records
Males ≥18 years of age
Subjects who have had ≥150 exposure days (EDs) with a FVIII product
Written informed consent for study participation obtained before undergoing any study specific procedures
Exclusion Criteria:
Previous participation in this trial
Use of an Investigational Medicinal Product within 30 days prior to the first OCTA101 injection
History of FVIII inhibitors titre ≥0.6 BU/mL defined by medical records
Inhibitors to FVIII (≥0.6 BU/mL) at screening measured by Nijmegen modified Bethesda method at central laboratory
Human immunodeficiency virus (HIV) positive subjects with a CD4+ count <200/mL
Clinically significant anemia at screening (hemoglobin <8 g/dL)
Presence of any significant comorbidity (at the discretion of the investigator) that might confound the interpretation of the study data and/or that might put the patient at undue risk by participating in the trial
Any coagulation disorder other than hemophilia A
AST or ALT levels >3 times the upper limit of normal
Creatinine >120 μmol/L
Platelet count <100,000 μL
BMI ≥30 kg/m²
For Cohort 6, patients with a positive LumiTope test at screening will be excluded
Accepts Healthy Volunteers
No
Sex
Male
Sex/Gender Based
Yes
Sex/Gender Description
Male patients only
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Specialized Hospital for Active Treatment of Hematological Diseases EAD Clinic of Clinical Hematology
Cannavo A, Valsecchi C, Garagiola I, Palla R, Mannucci PM, Rosendaal FR, Peyvandi F; SIPPET study group. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A. Blood. 2017 Mar 9;129(10):1245-1250. doi: 10.1182/blood-2016-06-720086. Epub 2016 Dec 29.
Background
Gibaldi M. (1991) Biopharmaceutics and Clinical Pharmacokinetics. 4th Edition, Lea and Febiger, Philadelphia, Appendix II.
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
FG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
FG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
FG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
FG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG0004 subjects
FG0014 subjects
FG0028 subjects
FG0034 subjects
FG00416 subjects
Completed Initial PK Assessment
FG0004 subjects
FG0014 subjects
FG0028 subjects
FG0034 subjects
FG004
Started Daily Prophylaxis With OCTA-101
FG0004 subjects
FG0014 subjects
FG0028 subjects
FG0030 subjectsProphylaxis not planned for this cohort
Completed 3-month Daily Prophylaxis With OCTA-101
FG0004 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG0004 subjects
FG0012 subjects
FG0020 subjects
FG0034 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0012 subjects
FG0028 subjects
FG0030 subjects
FG004
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Outcome Measures Module
Outcome Measures
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
Patients Experiencing Adverse Events
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
Approximately 4 months; up to 11 months for cohort 6
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
Adverse Events Module
Frequency Threshold
0
Time Frame
Approximately 4 months; up to 11 months for cohort 6
Description
An adverse event is any untoward medical occurrence in a study patient receiving an IMP and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not related to the IMP.
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 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Browse Leaves
Not provided
Browse Branches
Not provided
Intervention Browse Module
No data available
No data is available for this block.
Non-Randomized
Intervention Model
Sequential 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
Drug: OCTA101
Cohort 6
Experimental
(n=16): Following an initial 4 to 6-week run-in period with Nuwiq iv prophylaxis, >3-6 months daily prophylactic treatment with 12.5 IU/kg OCTA101 sc, then 25 IU/kg OCTA101 sc for a further 6-7 months (exact dosing depends on available vial sizes). In case of two spontaneous bleeding episodes, after having completed at least 3 months with 12.5 IU/kg OCTA101 daily treatment the individual treatment dose will be increased from 12.5 to 25 IU/kg. Site of administration (abdomen or thigh) to be chosen by the patient. A further treatment phase with 40 IU/kg OCTA101 will be discussed with the DMC, once results of earlier dosing phases are available.
Drug: OCTA101
Cohort 3
Cohort 5
Cohort 6
Approximately 4 months; up to 11 months for cohort 6. Local injection site reactions were captured throughout the period where OCTA-101 was injected subcutaneously (sc).
Inhibitor Formation to FVIII
Development of an inhibitor was defined as a neutralizing antibody value of greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL) identified and confirmed by a second test on an independent sample. In case of positive inhibitor results, inhibitor retesting using a second, separately drawn sample was to be performed, preferably within 15 days of becoming aware of the positive result. Both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
From first injection to 4 months after start of of daily injection (cohorts 1, 2 and 3), 4 weeks after last PK injection (cohort 5), monthly during the daily sc treatment period (cohort 6)
Maximum observed concentration of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of FVIII:C
Time of occurrence of Cmax after PK injection of OCTA101 as measured by chromogenic assay.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
In Vivo Recovery (IVR) of FVIII:C
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in FVIII:C (IU/dL per IU/kg)
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half-life (t1/2) of FVIII:C
Apparent terminal log-linear half-life of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of FVIII:C
The average time at which the number of absorbed FVIII molecules reside in the body, after PK injection of OCTA101 as measured by chromogenic assay.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Area Under the Concentration-time Curve (AUC(0-tz)) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Maximum Plasma Concentration (Cmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: In Vivo Recovery (IVR) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in OCTA-12 (ug/dL per ug/kg).
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Half Life (t1/2) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: t(1/2) could not be determined for OTCA12 as the OCTA12 concentrations had not yet declined during the observation time prior to prior to end of sampling period.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Mean Residence Time (MRT) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Note: MRT could not be determined for OCTA12 as the OCTA12 concentrations had not yet declined during the observation time prior to end of sampling period.
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
Efficacy: Total Annualized Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3 An estimated total annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate for cohort 6.
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93).
Efficacy: Spontaneous Annualized Bleeding Rate
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total spontaneous annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Total Annualized Treated Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total spontaneous annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Traumatic Annualized Bleeding Rate
Traumatic annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total traumatic annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: Joint Annualized Bleeding Rate
Joint annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total joint annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
Efficacy: FVIII:C Trough and Peak Plasma Levels
FVIII:C trough and peak plasma levels during daily dosing for cohorts 1, 2, 3 and 6
3 months; maximally 6 months for cohort 6
Efficacy: Efficacy of Treatment of Bleeding Episodes Using Score (4-point).
Score (4-point) to assess the efficacy of treatment of bleeding episodes with Human-cl rhFVIII. Treatment efficacy will be assessed using predefined criteria to score either 'Excellent', 'Good', 'Moderate' or 'None'. All efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated'.
5 days to approximately 11 months
Safety: Antibody Formation to OCTA12
Samples were checked for the presence of antibodies to OCTA12 by using a validated ELISA in a central lab.
From 0 hours (pre-dose) to 72 hours (cohorts 1,2,3,5) or 96 hours (cohort 2).
Safety: OCTA12 Plasma Levels
OCTA12 plasma levels during daily dosing (cohorts 1, 2, 3 and 6).
3 months; maximally 6 months for cohort 6
Safety: Change in Hemoglobin
Number of Participants with changes in hemoglobin levels that were considered as Adverse Events.
5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Alanine Aminotransferase (ALT)
Alanine aminotransferase (ALT) compared to baseline, measured in U/L. Number of Participants with changes in ALT that were considered as Adverse Events.
5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Safety: Change in Aspartate Transaminase (AST)
Aspartate transaminase (AST) compared to baseline, measured in U/l. Number of Participants with changes in AST that were considered as Adverse Events.
5 days to approximately 11 months
Patients With Changes to Vital Signs
Vitals signs changes from baseline, reported as AEs. Number of Participants with changes to vital signs that were considered as Adverse Events.
5 days to approximately 11 months
Patients With Changes in Physical Examination Results
Number of Participants with changes to their physical examination results from baseline that were considered as Adverse Events
5 days to approximately 11 months
Background
Liesner RJ, Abashidze M, Aleinikova O, Altisent C, Belletrutti MJ, Borel-Derlon A, Carcao M, Chambost H, Chan AKC, Dubey L, Ducore J, Fouzia NA, Gattens M, Gruel Y, Guillet B, Kavardakova N, El Khorassani M, Klukowska A, Lambert T, Lohade S, Sigaud M, Turea V, Wu JKM, Vdovin V, Pavlova A, Jansen M, Belyanskaya L, Walter O, Knaub S, Neufeld EJ. Immunogenicity, efficacy and safety of Nuwiq(R) (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study. Haemophilia. 2018 Mar;24(2):211-220. doi: 10.1111/hae.13320. Epub 2017 Aug 16.
Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, Forgue ST. Confidence interval criteria for assessment of dose proportionality. Pharm Res. 2000 Oct;17(10):1278-83. doi: 10.1023/a:1026451721686.
Background
Wagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications, Inc. Hamilton, IL, USA
0 subjects
PK assessment not carried out in these patients
FG00410 subjects
FG004
10 subjects
1 subjects
15 subjects
BG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
BG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
BG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
BG004
Cohort 6
(n≥16): following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
BG005
Total
Total of all reporting groups
4
BG0014
BG0028
BG0034
BG00416
BG00536
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00037.0± 7.35
BG00140.5± 11.82
BG00243.5± 12.78
BG00329.5± 5.51
BG00441.9± 12.37
BG00538.8± 11.15
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
Male
BG0004
BG0014
BG0028
BG0034
BG004
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White/Non-Hispanic or Latino
Title
Measurements
BG0004
BG0014
BG0028
BG0034
BG00416
BG00536
Region of Enrollment
Number
participants
Title
Denominators
Categories
Bulgaria
Title
Measurements
BG0004
BG0014
BG0028
BG0034
BG00416
BG00536
BMI
Mean
Standard Deviation
kg per m2
Title
Denominators
Categories
Title
Measurements
BG00027.7± 2.79
BG00127.1± 3.14
BG00225.3± 3.89
BG00327.8± 3.59
BG00424.6± 5.03
BG00526.6± 3.42
Haemophilia joint health score
Haemophilia joint health score (HJHS) evaluates six index joints to produce a score between 0-124. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00024.3± 19.65
BG00127.8± 26.11
BG00223.3± 12.61
BG00316.3± 8.14
BG00421.25± 11.38
BG00523.0± 15.89
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Pre-defined DLTs for this study are: 1. Severe allergic reactions at least possibly related to study drug. 2. Severe vital organ toxicity at least possibly related to study drug that does not resolve to at least mild severity within 48 to 72 hours. 3. Any treatment-emergent severe toxicity at least possibly related to study drug other than the toxicities referenced in 2) that does not decrease to mild or resolve within 7 days
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
Approximately 4 months; up to 11 months for cohort 6
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Patients Experiencing Thromboembolic Events
The definition of the cluster thromboembolic events was based on the standardised MedDRA query (SMQ) "Embolic and thrombotic events":
Definition: Thrombotic disorders are diseases characterized by formation of a thrombus that obstructs vascular blood flow locally or detaches and embolizes to occlude blood flow downstream. Embolism is the sudden blocking of a vessel by a clot or foreign material which has been brought to its site of lodgment by the blood current. (Thrombo-)phlebitis is an inflammation of a vein (phlebitis) associated with thrombus formation (thrombosis).
This SMQ includes 3 sub-SMQ:
Embolic and thrombotic events, venous (SMQ)
Embolic and thrombotic events, arterial (SMQ)
Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ)
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
Approximately 4 months; up to 11 months for cohort 6
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Patients Experiencing Local Injection Site Reactions of Any Grade
Investigator (and patient in case of home treatment) assessed local injection reactivity directly after injection and at 15 ± 5 min post-injection as per the ISO10999-10 standard:
0=no skin reactivity;
mild (subject is aware of the signs/symptoms, but finds it easily tolerated)
moderate (discomfort enough to cause interference with usual activities)
severe (subject is incapacitated and unable to work or participate in many or all usual activities).
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
Approximately 4 months; up to 11 months for cohort 6. Local injection site reactions were captured throughout the period where OCTA-101 was injected subcutaneously (sc).
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg: two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
OG003
Primary
Inhibitor Formation to FVIII
Development of an inhibitor was defined as a neutralizing antibody value of greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL) identified and confirmed by a second test on an independent sample. In case of positive inhibitor results, inhibitor retesting using a second, separately drawn sample was to be performed, preferably within 15 days of becoming aware of the positive result. Both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
From first injection to 4 months after start of of daily injection (cohorts 1, 2 and 3), 4 weeks after last PK injection (cohort 5), monthly during the daily sc treatment period (cohort 6)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0012
OG0021
OG003
Secondary
Efficacy: Area Under the Concentration-time Curve (AUC) of FVIII:C
Mean AUC of FVIII after PK injection of OCTA101 as measured by chromogenic assay.
Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6. For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK
Posted
Mean
Standard Deviation
IU*h/mL per IU/kg dosed
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.06265± 0.02606
OG0010.05453± 0.01934
OG0020.06558± 0.04452
OG003
Secondary
Efficacy: Maximum Plasma Concentration (Cmax) of FVIII:C
Maximum observed concentration of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK). Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6.
Posted
Mean
Standard Deviation
IU/mL
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.082± 0.012
OG0010.143± 0.065
OG0020.074± 0.034
OG003
Secondary
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of FVIII:C
Time of occurrence of Cmax after PK injection of OCTA101 as measured by chromogenic assay.
For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK). Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6.
Posted
Mean
Standard Deviation
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
(n≥16): following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0008.04± 0.06
OG00118.92± 10.23
OG00213.56± 6.49
OG003
Secondary
In Vivo Recovery (IVR) of FVIII:C
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in FVIII:C (IU/dL per IU/kg)
For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK). Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6.
Posted
Mean
Standard Deviation
IU/dL per IU/kg
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.146± 0.021
OG0010.132± 0.056
OG0020.135± 0.058
OG003
Secondary
Efficacy: Half-life (t1/2) of FVIII:C
Apparent terminal log-linear half-life of FVIII:C after PK injection of OCTA101 as measured by chromogenic assay.
For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK). Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6.
Posted
Mean
Standard Deviation
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG00022.74± 12.40
OG00124.45± 6.92
OG00226.59± 10.19
OG003
Secondary
Efficacy: Mean Residence Time (MRT) of FVIII:C
The average time at which the number of absorbed FVIII molecules reside in the body, after PK injection of OCTA101 as measured by chromogenic assay.
For 1 patient in cohort 2, the measurable the levels of FVIII:C were very low and not evaluable by conventional non-compartmental PK). Cohort 5 data is given for 40 IU/kg dose. No PK data for cohort 6.
Posted
Mean
Standard Deviation
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
(n≥16): following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0013
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG00037.91± 18.90
OG00140.50± 3.86
OG00243.08± 15.70
OG003
Secondary
Efficacy: Area Under the Concentration-time Curve (AUC(0-tz)) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Posted
Mean
Standard Deviation
ng*h/mL
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0003083.3± 701.3
OG0017061.5± 3436.5
OG0022897.9± 1049.2
OG003
Secondary
Efficacy: Maximum Plasma Concentration (Cmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Posted
Mean
Standard Deviation
ng/ml
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG00059.6± 11.69
OG00195.8± 38.8
OG00254.31± 19.25
OG003
Secondary
Efficacy: Time for Reaching Maximum Plasma Concentration (Tmax) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: OCTA12 was not determined for cohort 6 regarding PK assessment.
Posted
Mean
Standard Deviation
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG00071.46± 1.01
OG00171.39± 19.22
OG00268.15± 8.41
OG003
Secondary
Efficacy: In Vivo Recovery (IVR) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
In vivo recovery (IVR) = dose-normalised and body weight-normalised maximum gain in OCTA-12 (ug/dL per ug/kg).
The total of 20 participants were divided between their assigned cohorts.
Posted
Number
ug/dL per ug/kg
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
In Vivo Recovery
Measure type: number Unit of Measure: ug/dL per ug/kg
Units
Counts
Participants
OG00020
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate IVR
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Half Life (t1/2) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Measurement of OCTA12 plasma concentrations using a validated ELISA in a central lab. Note: t(1/2) could not be determined for OTCA12 as the OCTA12 concentrations had not yet declined during the observation time prior to prior to end of sampling period.
The total of 20 participants were divided between their assigned cohorts.
Posted
Number
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Half Life (t1/2)
Measure type: number Unit of Measure: hours
Units
Counts
Participants
OG00020
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate t1/2
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Mean Residence Time (MRT) of OCTA12 (a Recombinant Von Willebrand Factor Fragment Dimer)
Note: MRT could not be determined for OCTA12 as the OCTA12 concentrations had not yet declined during the observation time prior to end of sampling period.
The total of 20 participants were divided between their assigned cohorts.
Posted
Number
hours
From 0 hours (pre-dose) to 72 hours (cohorts 1,3,5) or 96 hours (cohort 2)
ID
Title
Description
OG000
Mean Residence Time (MRT)
Measure type: number Unit of Measure: hours
Units
Counts
Participants
OG00020
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate MRT
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Total Annualized Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3 An estimated total annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate for cohort 6.
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
Annualized number of bleedings
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93).
ID
Title
Description
OG000
Total Bleeding Rate
Measure type: number Unit of Measure: bleeding events per year
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG0000
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Spontaneous Annualized Bleeding Rate
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total spontaneous annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
Total bleeding events per year
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
ID
Title
Description
OG000
Total Bleeding Rate
Measure type: number Unit of Measure: annualized number of bleedings
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG0000
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Total Annualized Treated Bleeding Rate
Total annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
bleeding events per year
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
ID
Title
Description
OG000
Total Bleeding Rate
Measure type: number Unit of Measure: annualized number of bleedings
Spontaneous annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total spontaneous annualized treated bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
bleeding events per year
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
ID
Title
Description
OG000
Total Bleeding Rates
Measure type: number Unit of Measure: annualized number of bleedings
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG0000
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Traumatic Annualized Bleeding Rate
Traumatic annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3
An estimated total traumatic annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
Total bleeding events per year
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
ID
Title
Description
OG000
Total Bleeding Rate
Measure type: number Unit of Measure: annualized number of bleedings
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG0000
Cohort 2
ParticipantsOG000
Secondary
Efficacy: Joint Annualized Bleeding Rate
Joint annualized bleeding rate during daily subcutaneous treatment with OCTA101 for cohorts 1, 2 and 3.
An estimated total joint annualized bleeding rate was calculated for cohorts 1,2 and 3. As these were estimated rates, there is only one value for each cohort with no measure of spread.
As the study was terminated so soon, it was not considered accurate to extrapolate results to one year for annualized bleeding rate.
The total of 26 participants were divided between their assigned cohorts.
Posted
Number
Total bleeding events per year
The median (min, max) duration of daily sc treatment with OCTA101 in the 16 patients of cohort 1, 2 and 3 was 42 days (22, 93)
ID
Title
Description
OG000
Total Bleeding Rate
Measure type: number Unit of Measure: annualized number of bleedings
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Cohort 1
ParticipantsOG0004
Title
Measurements
OG0000
Cohort 2
ParticipantsOG000
Secondary
Efficacy: FVIII:C Trough and Peak Plasma Levels
FVIII:C trough and peak plasma levels during daily dosing for cohorts 1, 2, 3 and 6
Not all patients in cohort 2 and 3 were analyzed at month 2 and 3 due to study termination. Only 3 patients were analyzed in cohort 6 at month 3 due to study termination. No PK analysis were performed for cohort 6.
Posted
Median
Full Range
IU/mL
3 months; maximally 6 months for cohort 6
ID
Title
Description
OG000
Cohort 1 Predose
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 1 - 3 Hours
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer)
OG002
Cohort 1 - 6 Hours
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer)
OG003
Cohort 2 Predose
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. In months 2 and 3 data could not be collected from all participants.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 2 - 3 Hours
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. In months 2 and 3 data could not be collected from all participants.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG005
Cohort 2 - 6 Hours
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months. In months 2 and 3 data could not be collected from all participants.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG006
Cohort 3 Predose
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
The study was terminated before treatment could be completed, as a result, no data was collected in months 2 and 3.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG007
Cohort 3 - 3 Hours
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
The study was terminated before treatment could be completed, as a result, no data was collected in months 2 and 3.
OG008
Cohort 3 - 6 Hours
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
The study was terminated before treatment could be completed, as a result, no data was collected in months 2 and 3.
OG009
Cohort 6 Predose
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed, so in month 3 data could not be collected from all participants.
OG010
Cohort 6 - 8 Hours
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed, so in month 3 data could not be collected from all participants.
Units
Counts
Participants
OG0004
OG0014
OG0024
OG003
Title
Denominators
Categories
Start of daily treatment
ParticipantsOG0004
ParticipantsOG0014
ParticipantsOG0024
ParticipantsOG003
Secondary
Efficacy: Efficacy of Treatment of Bleeding Episodes Using Score (4-point).
Score (4-point) to assess the efficacy of treatment of bleeding episodes with Human-cl rhFVIII. Treatment efficacy will be assessed using predefined criteria to score either 'Excellent', 'Good', 'Moderate' or 'None'. All efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated'.
Not Posted
5 days to approximately 11 months
Participants
Secondary
Safety: Antibody Formation to OCTA12
Samples were checked for the presence of antibodies to OCTA12 by using a validated ELISA in a central lab.
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
From 0 hours (pre-dose) to 72 hours (cohorts 1,2,3,5) or 96 hours (cohort 2).
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Safety: OCTA12 Plasma Levels
OCTA12 plasma levels during daily dosing (cohorts 1, 2, 3 and 6).
Not Posted
3 months; maximally 6 months for cohort 6
Participants
Secondary
Safety: Change in Hemoglobin
Number of Participants with changes in hemoglobin levels that were considered as Adverse Events.
Not Posted
5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Participants
Secondary
Safety: Change in Alanine Aminotransferase (ALT)
Alanine aminotransferase (ALT) compared to baseline, measured in U/L. Number of Participants with changes in ALT that were considered as Adverse Events.
Not Posted
5 days to approximately 11 months. All routine lab parameters and vital signs were measured at various times, until end of PK and also monthly during daily prophylaxis.)
Participants
Secondary
Safety: Change in Aspartate Transaminase (AST)
Aspartate transaminase (AST) compared to baseline, measured in U/l. Number of Participants with changes in AST that were considered as Adverse Events.
Not Posted
5 days to approximately 11 months
Participants
Secondary
Patients With Changes to Vital Signs
Vitals signs changes from baseline, reported as AEs. Number of Participants with changes to vital signs that were considered as Adverse Events.
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
5 days to approximately 11 months
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Patients With Changes in Physical Examination Results
Number of Participants with changes to their physical examination results from baseline that were considered as Adverse Events
The population included all patients who received at least one dose of IMP.
Posted
Count of Participants
Participants
5 days to approximately 11 months
ID
Title
Description
OG000
Cohort 1
50 IU/kg (n=4): single-period investigation with a single sc dose of 50 IU/kg OCTA101 profiled up to 72 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 2, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
OG004
Cohort 6
Following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
Units
Counts
Participants
OG0004
OG0014
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0012
OG0021
OG003
0
4
0
4
0
4
EG001
Cohort 2
100 IU/kg (n=4): single-period investigation with a single sc dose of 100 IU/kg OCTA101 profiled up to 96 hours after dosing in adult male patients with severe hemophilia A.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 3, alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
1
4
2
4
2
4
EG002
Cohort 3
50 IU/kg (n=8): two-period investigation of a single iv dose of 50 IU/kg Human-cl rhFVIII (Nuwiq) profiled for up to 72 hours after dosing followed by sc dose of 50 IU/kg OCTA101 profiled up to 72 hours in adult male patients with severe hemophilia A.
Treatments will be administered in fixed sequence, with Human-cl rhFVIII first.
Following review of safety and tolerability data by Data Monitoring Committee, proceed with Cohort 4 and 5 alongside daily prophylactic dosing (40-60 IU/kg) for 3 months.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
0
8
1
8
0
8
EG003
Cohort 5
(n=4): Three-period investigation of single sc doses of 20, 40, and 60 IU/kg OCTA101 profiled up to 72 hours after dosing. Treatments were to be administered in fixed dose-ascending sequence.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
0
4
0
4
0
4
EG004
Cohort 6
(n≥16): following an initial 4-6-week run-in period with Nuwiq iv prophylaxis, 6-month prophylactic treatment with 12.5 IU/kg OCTA101 sc daily was planned. Sixteen patients entered the Nuwiq iv run-in and 10 patients went on to receive OCTA101 12.5 IU/kg. The study was terminated before treatment could be completed in all but 1 patient.
OCTA101: OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).
0
16
2
16
2
16
EG0000 events0 affected4 at risk
EG0012 events2 affected4 at risk
EG0021 events1 affected8 at risk
EG0030 events0 affected4 at risk
EG0042 events2 affected16 at risk
Haemoperitoneum
Gastrointestinal disorders
Non-systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected16 at risk
Haematuria
Renal and urinary disorders
Non-systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected16 at risk
Spontaneous hemorrhage
Gastrointestinal disorders
Non-systematic Assessment
Retroperitoneal hematoma
EG0000 events0 affected4 at risk
EG0011 events1 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected16 at risk
EG0000 events0 affected4 at risk
EG0011 events1 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected16 at risk
Roseolovirus test positive
Investigations
Non-systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected16 at risk
Road traffic accident
Social circumstances
Non-systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0041 events1 affected16 at risk
Renal colic
Renal and urinary disorders
Non-systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected4 at risk
EG0020 events0 affected8 at risk
EG0030 events0 affected4 at risk
EG0041 events1 affected16 at risk
Not provided
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Not provided
16
BG00536
4
OG00410
0
OG0040
4
OG00410
0
OG0040
4
OG00410
0
OG0040
4
OG00410
0
OG0042
4
OG0040
0.0695
± 0.0274
4
OG0040
0.107
± 0.014
4
OG0040
11.11
± 0.02
4
OG0040
0.233
± 0.033
4
OG0040
22.77
± 4.88
4
OG0040
37.97
± 7.99
4
1762.9
± 589.9
4
32.95
± 11.5
4
59.26
± 13.71
4
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate IVR
Cohort 3
ParticipantsOG0008
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate IVR
Cohort 5
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate IVR
4
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate t1/2
Cohort 3
ParticipantsOG0008
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate t1/2
Cohort 5
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate t1/2
4
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate MRT
Cohort 3
ParticipantsOG0008
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate MRT
Cohort 5
ParticipantsOG0004
Title
Measurements
OG000NAThe time courses of the plasma concentrations of OCTA12 were not profiled for a sufficiently long time to observe a decline in the OCTA12 plasma concentrations and thus it was not possible to calculate MRT
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.
4
Title
Measurements
OG0000
Cohort 3
ParticipantsOG0008
Title
Measurements
OG0000
Cohort 6
ParticipantsOG00010
Title
Measurements
OG000NADue to study termination this outcome was not calculated for cohort 6.