Safety and Efficacy of BAY94-9027 in Previously Treated Male Children With Haemophilia A

Phase 3

Completed

• Conditions: Hemophilia A
• Interventions: Biological: BAY94-9027

• Registration Number: NCT01775618
• Lead Sponsor: Bayer

Brief Summary

Hemophilia A is an inherited blood disorder in which one protein, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. Hemophilia A causes the clotting process to be slowed and the person experiences bleeds causing serious problems that could lead to disability. The current standard treatment for severe hemophilia A is infusion of FVIII to stop bleeding, or regular scheduled treatment to prevent bleeds from occuring. Due to the short half-life of FVIII, prophylaxis may require treatment as often as every other day.

In this trial safety and efficacy of a long-acting recombinant Factor VIII molecule is being evaluated in 50 male subjects, \< 12 years of age, with severe Hemophilia A. These subjects will receive open label treatment with long-acting rFVIII for approximately 6 months (or longer until 50 exposure days) on a regular schedule at least once every 7-days. Doses and dose intervals may be adapted to the subject's clinical need. A second group of patients will receive open label treatment with the same drug for 12 weeks on a regular schedule of 2x/week. Patients will attend the treatment center for routine blood samples and will be required to keep an electronic diary.

Subjects will be offered participation in an optional extension study to collect observations for at least an additional 50 exposure days.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-01-23
• Study First Submitted QC: 2013-01-23
• Study First Posted: 2013-01-25
• Study Start: 2013-05-29
• Primary Completion: 2015-03-19
• Study Completion: 2020-02-19
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-19
• Last Update Posted: 2020-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 73

Inclusion Criteria

• Males < 12 years of age
• Subjects with severe hemophilia A
• Previously treated with FVIII for > 50 exposure days

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Exclusion Criteria

• Subjects with current evidence of or history of inhibitors to FVIII
• Any other inherited or acquired bleeding disorder
• Platelet counts < 100,000/mm^3
• Creatinine > 2x the upper limit of normal
• Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) > 5x the upper limit of normal

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 2 (Expansion group)	BAY94-9027	Participants were administered with BAY94-9027 at a dose of 25-60 IU/kg twice per week for prophylaxis for 12 weeks.
Main study	BAY94-9027	Participants were treated and prophylaxis administered with BAY94-9027 at a dose of 25-60 international units/kilogram (IU/kg) twice per week or 45-60 IU/kg every 5 days or 60 IU/kg every 7 days as an intravenous (IV) infusion as per clinical needs of each subject up to at least 50 exposure days (EDs) and a minimum of at least 6 months.
Extension study	BAY94-9027	Participants were treated and prophylaxis administered with BAY94-9027 at a dose of 25- 60 IU/kg twice per week or 45-60 IU/kg every 5 days or 60 IU/kg every 7 days as an IV infusion as per clinical needs of each subject for at least 50 EDs or until marketing authorization of the drug.

Primary Outcome Measures

Name	Time	Method
Characterization of a potential immune response	12 weeks
Annualized number of all bleeds	At least 50 exposure days (ED) over 6 months, on average 245 days
Pharmacokinetics profile of BAY94-9027 based on blood concentration over the defined time period	Pre-dose to 72 hours post-dose	Pharmacokinetics profile includes maximum concentration (Cmax), half-life (t1/2), area under the concentration versus time curve (AUC), mean residence time (MRT), volume of distribution at steady state (Vss), and clearance (CL)
Response of acute bleeding events to treatment based on a 4-point scale (poor, moderate, good, or excellent)	At least 50 exposure days (ED) over 6 months, on average 245 days
Inhibitor development in the extension study	At least 50 additional EDs to achieve at least 100 cumulative EDs, on average 5 years

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events as a measure of safety and tolerability	From the start of study treatment up to 7 days after the last dose (Main study: on average 245+7 days; Part 2: 12 weeks+7 days; Extension study: on average 5 years+7 days)
Assessment of incremental recovery in main study	At least 50 exposure days (ED) over 6 months, on average 245 days
Inhibitor development in the main study	After 10 to 15 and 50 exposure days (ED) over 6 months, on average 245 days