A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Congenital Hemophilia A
- Sponsor
- CSL Behring
- Enrollment
- 84
- Locations
- 1
- Primary Endpoint
- Treatment Success
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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 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.
Investigators
Eligibility Criteria
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.
Outcomes
Primary Outcomes
Treatment Success
Time Frame: Up to 1 year
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) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
Secondary Outcomes
- Annualized Bleeding Rate(Up to 1 year)
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year(Up to 1 year)
- Incremental Recovery(At 1 hour after the start of infusion)
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month(Up to 1 year)
- Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event(Up to 1 year)
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month(Up to 1 year)
- Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.(Up to 1 year)
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year(Up to 1 year)
- Half-life (t1/2) of rVIII-SingleChain(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)
- Number of Subjects With Inhibitor Formation to rVIII-SingleChain(At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).)
- Area Under the Concentration Curve (AUC)(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)
- Clearance (Cl) of rVIII-SingleChain(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)