Safety and Pharmacokinetics of Subcutaneous Injection of OCTA101 in Adult Patients With Severe Hemophilia A

NCT ID: NCT04046848

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-03
• Study Completion Date: 2022-02-18

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.

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

OCTA101

Intervention Type: DRUG

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

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.

Group Type: EXPERIMENTAL

OCTA101

Intervention Type: DRUG

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

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.

Group Type: EXPERIMENTAL

OCTA101

Intervention Type: DRUG

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

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.

Group Type: EXPERIMENTAL

OCTA101

Intervention Type: DRUG

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

Cohort 6

(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.

Group Type: EXPERIMENTAL

OCTA101

Intervention Type: DRUG

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

Interventions

OCTA101

OCTA101 is composed of OCTA8 (human-cl rhFVIII - Nuwiq Intermediate 2 Q-Eluate) and OCTA12 (recombinant human VWF fragment dimer).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Severe hemophilia A (<1% FVIII:C) as documented in medical records

2. Males ≥18 years of age

3. Subjects who have had ≥150 exposure days (EDs) with a FVIII product

4. Written informed consent for study participation obtained before undergoing any study specific procedures

Exclusion Criteria

1. Previous participation in this trial

2. Use of an Investigational Medicinal Product within 30 days prior to the first OCTA101 injection

3. History of FVIII inhibitors titre ≥0.6 BU/mL defined by medical records

4. Inhibitors to FVIII (≥0.6 BU/mL) at screening measured by Nijmegen modified Bethesda method at central laboratory

5. Human immunodeficiency virus (HIV) positive subjects with a CD4+ count <200/mL

6. Clinically significant anemia at screening (hemoglobin <8 g/dL)

7. 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

8. Any coagulation disorder other than hemophilia A

9. AST or ALT levels >3 times the upper limit of normal

10. Creatinine >120 μmol/L

11. Platelet count <100,000 μL

12. BMI ≥30 kg/m²

13. For Cohort 6, patients with a positive LumiTope test at screening will be excluded

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Octapharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Specialized Hospital for Active Treatment of Hematological Diseases EAD Clinic of Clinical Hematology

Sofia, , Bulgaria

Countries

Bulgaria

References

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.

Reference Type: BACKGROUND

PMID: 28034891 (View on PubMed)

Gibaldi M. (1991) Biopharmaceutics and Clinical Pharmacokinetics. 4th Edition, Lea and Febiger, Philadelphia, Appendix II.

Reference Type: 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.

Reference Type: BACKGROUND

PMID: 28815880 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11145235 (View on PubMed)

Wagner JG (1975) Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications, Inc. Hamilton, IL, USA

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SubQ8-01

Identifier Type: -

Identifier Source: org_study_id