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

• ClinicalTrials.gov Identifier: NCT01775618
• Recruitment Status: Completed
• First Posted: January 25, 2013
• Last Update Posted: August 21, 2020
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: January 23, 2013
• First Posted Date: January 25, 2013
• Last Update Posted Date: August 21, 2020
• Actual Study Start Date: May 29, 2013
• Actual Primary Completion Date: March 19, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2020)

• Annualized number of all bleeds [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: At least 50 exposure days (ED) over 6 months, on average 245 days ]
• Characterization of a potential immune response [ Time Frame: 12 weeks ]
• Inhibitor development in the extension study [ Time Frame: At least 50 additional EDs to achieve at least 100 cumulative EDs, on average 5 years ]

Original Primary Outcome Measures (submitted: January 23, 2013)

• Annualized number of all bleeds [ Time Frame: Up to 11 months ]
• Pharmacokinetic profile of BAY94-9027 based on blood concentration over the defined time period [ Time Frame: 6 time points from pre-infusion to 72 hours post-infusion ]
• Response of acute bleeding events to treatment based on a 4-point scale (poor, moderate, good, or excellent) [ Time Frame: Up to 11 months ]

Current Secondary Outcome Measures (submitted: August 19, 2020)

• Inhibitor development in the main study [ Time Frame: After 10 to 15 and 50 exposure days (ED) over 6 months, on average 245 days ]
• Assessment of incremental recovery in main study [ Time Frame: At least 50 exposure days (ED) over 6 months, on average 245 days ]
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 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) ]

Original Secondary Outcome Measures (submitted: January 23, 2013)

• Inhibitor development after 10 to 15 EDs (exposure days) [ Time Frame: Up to 15 weeks ]
• Inhibitor development after 50 EDs [ Time Frame: Up to 11 months ]
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 11 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of BAY94-9027 in Previously Treated Male Children With Haemophilia A
• Official Title: A Multi-center, Phase III, Non-controlled, Open-label Trial to Evaluate the Pharmacokinetics, Safety, and Efficacy of BAY94-9027 for Prophylaxis and Treatment of Bleeding in Previously Treated Children (Age <12 Years) With Severe Hemophilia A

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia A

Intervention

• Biological: BAY94-9027
  Study drug dosing was adjusted to the clinical needs of each subject in the range of 25-60 IU/kg/administration, intravenous infusion, at least 50 EDs and a minimum of at least 6 months
• Biological: BAY94-9027
  Twice per week prophylaxis: 25-60 IU/kg, intravenous infusion, for 12 weeks
• Biological: BAY94-9027
  Study drug dosing was adjusted to the clinical needs of each subject in the range of 25-60 IU/kg/administration, intravenous infusion, at least 50 additional EDs to achieve at least 100 cumulative EDs, or until marketing authorization of the drug

Study Arms

• Experimental: Main study
  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.
  Intervention: Biological: BAY94-9027
• Experimental: Part 2 (Expansion group)
  Participants were administered with BAY94-9027 at a dose of 25-60 IU/kg twice per week for prophylaxis for 12 weeks.
  Intervention: Biological: BAY94-9027
• Experimental: Extension study
  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.
  Intervention: Biological: BAY94-9027

• Publications *: Mancuso ME, Biss T, Fischer K, Maas Enriquez M, Steele M, Wang M, Tseneklidou-Stoeter D, Ahuja S, Kenet G. PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A. Haemophilia. 2021 May;27(3):434-444. doi: 10.1111/hae.14294. Epub 2021 Mar 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 23, 2017): 73
• Original Estimated Enrollment (submitted: January 23, 2013): 50
• Actual Study Completion Date: February 19, 2020
• Actual Primary Completion Date: March 19, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: up to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Bulgaria, Canada, Greece, Israel, Italy, Lithuania, Netherlands, New Zealand, Norway, Poland, Romania, Spain, United Kingdom, United States
• Removed Location Countries: Germany, Hungary, Slovenia

Administrative Information

• NCT Number: NCT01775618
• Other Study ID Numbers: 15912; 2012-004434-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: August 2020