Hemophilia A with inhibitors, Hemophilia B with inhibitors MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10053752 Term: Hemophilia B with anti factor IX System Organ Class: 100000004850
Conditions
Interventions
Product Name: Recombinant fusion protein, linking activated coagulation factor VII with albumin
Product Code: CSL689
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Pro
Sponsors
CSL Behring GmbH
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male subjects with hemophilia A or B and inhibitors. 2. Age = 12 and = 65 years. 3. High responding inhibitor with documented historical inhibitor titer > 5 Bethesda Units/mL. Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 53 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Congenital or acquired coagulation disorders other than hemophilia A or B. 2. Ongoing immune tolerance induction therapy or planned during study. 3. Known or suspected hypersensitivity to activated recombinant human FVII or to any excipient of CSL689. 4. Body mass index > 30 kg/m². 5. Major surgery within 28 days before screening or scheduled major and / or orthopedic surgery during the study. 6. Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke). 7. Any clinical signs or known history of thromboembolic events, including known deep vein thrombosis. 8. Human immunodeficiency virus (HIV)-positive subjects who have low cluster of differentiation 4 (CD4)+ lymphocyte count (200/µL or less) at screening. 9. 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 the Part 1, b) other platelet inhibitors, c) desmopressin, and d) fibrinolysis inhibitors (except if used as local treatment (eg, for oral bleeds).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 (PK part): To evaluate the single-dose PK of CSL689 (low dose, high dose) in subjects with hemophilia A or B and inhibitors and to compare with the single-dose PK of Eptacog alfa (low dose or high dose). Part 2 (Dose-evaluation part): To determine the best dose ("population-based best dose") of the 2 CSL689 dose levels evaluated. Part 3 (Repeated-dose part): To evaluate the clinical efficacy of the population-based best dose of CSL689 for on-demand therapy of bleeding events in subjects with hemophilia A or B and inhibitors.;Secondary Objective: To evaluate the safety and tolerability of IV administration of CSL689.;Primary end point(s): 1. Area under the curve (AUC0-t); 2. Incremental recovery; 3. Elimination half-life; 4. Total clearance. 5. Treatment success with first CSL689 injection 6. Treatment success with first CSL689 injection at the population best dose; 7. Treatment success with first or second CSL689 injection at the population best dose ;Timepoint(s) of evaluation of this end point: - 1 to 4: Before injection and at up to 6 time points until 24 hours after injection for Eptacog alfa; before injection and at up to 11 time points until up to 120 hours after injection for CSL689. - 5 to 6: Up to 8 hours after first CSL689 injection for each bleeding event - 7: Up to 16 hours after first CSL689 injection for each bleeding event | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Treatment success with first or second CSL689 injection 2. Number of bleeding events requiring > 1 CSL689 injection 3. Number of CSL689 injections per bleeding event 4. Total dose of CSL689 per bleeding event 5. Treatment success with first CSL689 injection at the population best dose 6. Percentage of first bleeding events successfully treated with first CSL689 injection at population best dose in Part 3 7. Treatment success at population best dose 8. Treatment success with CSL689 at the dose level that is not the population best dose 9. Percentage of bleeding events with only “definite” or “abrupt” subject-reported pain relief at the population best dose 10. Percentage of bleeding events with “good” or “excellent” investigator-reported assessment of treatment response at the population best dose of CSL689 11. Proportion of recurrences 12. Proportion of bleeding events with ultrarapid progression. 13. Proportion of bleeding events requiring post-hemostatic maintenance dosing 14. Number of subjects with treatment-emergent adverse events (TEAEs) 15. Percentage of subjects with TEAEs 16. Number of subjects with an antibody response 17. Percentage of subjects with an antibody response 18. AUC(0-inf) 19. Maximum observed plasma FVIIa activity (Cmax) 20. Time of occurrence of maximum observed plasma FVIIa activity (Tmax) 21. Volume of distribution at steady state (Vss) 22. Mean residence time (MRT) ;Timepoint(s) of evaluation of this end point: 1: Up to 16 hours after first CSL689 injection for each bleeding event 2: Up to 8 hours after first CSL689 injection for each bleeding event 3 and 4: Up to 16 hours (Part 2) or up to 24 hours (Part 3) after first CSL689 injection for each bleeding event 5: Up to 8 hours after first CSL689 injection for each bleeding event 6: Up to 8 hours after first CSL689 injection for first bleeding event 7, 8: Up to 24 hours after first CSL689 injection for each bleeding event 9: Up to | — |
Countries
Australia, Canada, European Union, Georgia, Germany, Japan, Korea, Republic of, Malaysia, Russian Federation, Serbia, South Africa, Spain, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Registration Coordinator
CSL Behring GmbH
Outcome results
None listed