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

Octapharma

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Severe Hemophilia A

Treatments: Drug: OCTA101

Study type: Interventional

Funder types: Industry

Identifiers

NCT04046848

SubQ8-01

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 5 patient groups

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: OCTA101

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: OCTA101

Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: OCTA101

Cohort 5

Experimental group

Description:

(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.

Treatment:

Drug: OCTA101

Cohort 6

Experimental group

Description:

(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.

Treatment:

Drug: OCTA101