Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors

CSL Behring

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Hemophilia B With Inhibitors

Hemophilia A With Inhibitors

Treatments

Drug: CSL689

Drug: Eptacog alfa (activated)

Study type

Interventional

Funder types

Industry

Identifiers

NCT02484638

2012-001309-26 (EudraCT Number)

CSL689_2001

Details and patient eligibility

About

The purpose of this study is to investigate the pharmacokinetics (PK), efficacy, and safety of rVIIa-FP (CSL689). The study will enroll approximately 54 male subjects, 12 to 65 years of age, with hemophilia types A or B who have developed inhibitors to FVIII or FIX. The study consists of 3 sequential parts (Parts 1, 2, 3): The purpose of Part 1 (PK part) is to evaluate the PK of a single treatment of CSL689 (low dose or high dose) and compare with the PK of a single treatment of Eptacog alfa (low dose or high dose). In Part 1, CSL689 and Eptacog alfa will be given by the doctor at the study center. The purpose of Part 2 (Dose-evaluation part) is to identify which of the 2 tested dose levels of CSL689 shows the best efficacy and safety in stopping acute bleeding events (this dose will be called the "population best dose"). The purpose of the final Part 3 (Repeated-dose part) is to confirm the efficacy and safety of the "population best dose" identified in Part 2. In Parts 2 and 3, subjects will self-administer a specified number of CSL689 infusions at home on-demand (ie, when a bleeding event occurs), will keep an electronic diary, and will visit the center at monthly intervals. This study is expected to last for up to 16 months for the subjects participating in all 3 parts, and up to 9 months for the subjects participating in Part 3 only.

Enrollment

25 patients

Sex

Male

Ages

12 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male subjects with hemophilia A or B and inhibitors.
Age ≥ 12 and ≤ 65 years.
High responding inhibitor with documented historical inhibitor titer > 5 Bethesda Units/mL.

Exclusion criteria

Congenital or acquired coagulation disorders other than hemophilia A or B.
Ongoing immune tolerance induction therapy or planned during study.
Known or suspected hypersensitivity to activated recombinant human FVII or to any excipient of CSL689.
Body mass index > 30 kg/m².
Major surgery within 28 days before screening or scheduled major and / or orthopedic surgery during the study.
Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
Any clinical signs or known history of thromboembolic events, including known deep vein thrombosis.
Human immunodeficiency virus (HIV)-positive subjects who have low cluster of differentiation 4 (CD4)+ lymphocyte count (200/μL or less) at screening.
Use of the following within the screening period or planned during study: a) plasma or coagulation factor concentrates other than rescue therapy or therapy during Part 1, b) other platelet inhibitors, c) desmopressin, and d) fibrinolysis inhibitors, except if used as local treatment (eg, for oral bleeds).

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

25 participants in 4 patient groups

CSL689 low-dose

Experimental group

Description:

* Part 1: single injection of low-dose CSL689 for PK evaluation * Part 2: up to 2 injections of low-dose CSL689 per bleeding event (bleeding events 1 to 3\*) * Part 3: up to 3 injections of low-dose CSL689 per bleeding event \* Note: All subjects in the low-dose arm will be treated with high-dose CSL689 for bleeding events 4-6 in Part 2

Treatment:

Drug: CSL689

CSL689 high-dose

Experimental group

Description:

* Part 1: single injection of high-dose CSL689 for PK evaluation * Part 2: up to 2 injections of high-dose CSL689 per bleeding event (bleeding events 4 to 6\*) * Part 3: up to 3 injections of high-dose CSL689 per bleeding event * Note: All subjects in the high-dose arm will be treated with low-dose CSL689 for bleeding events 1-3 in Part 2

Treatment:

Drug: CSL689

Eptacog alfa low-dose

Active Comparator group

Description:

Single injection of low-dose Eptacog alfa in Part 1 for PK evaluation

Treatment:

Drug: Eptacog alfa (activated)

Eptacog alfa high-dose

Active Comparator group

Description:

Single injection of high-dose Eptacog alfa in Part 1 for PK evaluation