Congenital Hemophilia A Clinical Trial
Official title:
A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to < 12 years of age and at least 25 subjects < 6 years of age who have undergone > 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen for the treatment of bleeding episodes and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.
| Status | Completed |
| Enrollment | 84 |
| Est. completion date | August 2015 |
| Est. primary completion date | August 2015 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | N/A to 11 Years |
| Eligibility |
Inclusion Criteria: - Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records, - Males < 12 years of age, - Subjects who have received > 50 EDs with a FVIII product, - Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part - Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements. Exclusion Criteria: - Any history of or current FVIII inhibitors - Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration, - Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain, - Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein, - Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment, - Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening, - Subjects with serum creatinine values >2 x ULN at Screening, - Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1, - Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Study Site | Melbourne | Victoria |
| Austria | Study Site | Linz | |
| Austria | Study Site | Vienna | |
| France | Study Site | Brest | |
| France | Study Site | Lille Cedex | |
| France | Study Site | Nantes | |
| France | Study Site | Paris | |
| Georgia | Study Site | Tbilisi | |
| Germany | Study Site | Bonn | |
| Germany | Study Site | Bremen | |
| Germany | Study Site | Duisburg | |
| Germany | Study Site | Frankfurt/Main | |
| Germany | Study Site | Hannover | |
| Germany | Study Site | Munster | |
| Hungary | Study Site | Debrecen | |
| Ireland | Study Site | Dublin | |
| Italy | Study Site | Milano | |
| Korea, Republic of | Study Site | Daejeon | |
| Lebanon | Study Site | Beirut | |
| Malaysia | Study Site | Kuala Lumpur | |
| Netherlands | Study Site | Amsterdam | |
| Netherlands | Study Site | Njmegen | |
| Netherlands | Study Site | Utrecht | |
| Philippines | Study Site | Cebu City | |
| Philippines | Study Site | Davao City | |
| Philippines | Study Site | Manila | |
| Poland | Study Site | Rzeszow | |
| Portugal | Study Site | Coimbra | |
| Portugal | Study Site | Oporto | |
| Romania | Study Site | Bucharest | |
| Romania | Study Site | Bucharest | |
| Romania | Study Site | Timisoara | |
| Spain | Study Site | Madrid | |
| Switzerland | Study Site | Lucerne | |
| Thailand | Study Site | Bangkok | |
| Thailand | Study Site | Bangkok | |
| Thailand | Study Site | Chiang Mai | |
| Thailand | Study Site | Khon Kaen | |
| Thailand | Study Site | Songkla | |
| Turkey | Study Site | Adana | |
| Turkey | Study Site | Istanbul | |
| Turkey | Study Site | Izmir | |
| Ukraine | Study Site | Donetsk | |
| Ukraine | Study Site | Lviv | |
| United States | Study Site | Aurora | Colorado |
| United States | Study Site | Chicago | Illinois |
| United States | Study Site | Dallas | Texas |
| United States | Study Site | Milwaukee | Wisconsin |
| Lead Sponsor | Collaborator |
|---|---|
| CSL Behring |
United States, Australia, Austria, France, Georgia, Germany, Hungary, Ireland, Italy, Korea, Republic of, Lebanon, Malaysia, Netherlands, Philippines, Poland, Portugal, Romania, Spain, Switzerland, Thailand, Turkey, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Treatment success | Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response). | Up to two years | No |
| Secondary | Annualized bleeding rate | The annualized bleeding rate is defined as the number of bleeds from all causes (traumatic and non-traumatic) divided by the treatment period in years. | Up to two years | No |
| Secondary | Proportion of bleeding episodes requiring 1, 2, 3, or more than 3 infusions of rVIII-SingleChain to achieve hemostasis. | Up to two years | No | |
| Secondary | Consumption of rVIII-SingleChain | rVIII-SingleChain consumed as measured by: number of infusions per month and per year per subject IU/kg per event |
Up to two years | No |
| Secondary | Incremental recovery | Incremental recovery expressed as (IU/mL)/(IU/kg) | 0 to 2 days after infusion | No |
| Secondary | Half-life (t1/2) of rVIII-SingleChain | 0 to 2 days after infusion | No | |
| Secondary | Area under the concentration curve (AUC) | AUC to the last sample with quantifiable drug concentration (AUC0-t). | 0 to 2 days after infusion | No |
| Secondary | Clearance (Cl) of rVIII-SingleChain | 0 to 2 days after infusion | No | |
| Secondary | The number of subjects with inhibitor formation to rVIII-SingleChain | The number of subjects who develop inhibitors to rVIII-SingleChain, defined as a rVIII-SingleChain antibody titer of at least 0.6 Bethesda Units (BU) per mL after receiving study drug. | Up to two years | Yes |