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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hemophilia A	Biological: BAY94-9027	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 29, 2013
• Actual Primary Completion Date: March 19, 2015
• Actual Study Completion Date: February 19, 2020

Arms and Interventions

Arm	Intervention/treatment
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.	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
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.	Biological: BAY94-9027; Twice per week prophylaxis: 25-60 IU/kg, intravenous infusion, for 12 weeks
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.	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

Outcome Measures

Primary Outcome Measures :

1. Annualized number of all bleeds [ Time Frame: At least 50 exposure days (ED) over 6 months, on average 245 days ]
2. 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)
3. 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 ]
4. Characterization of a potential immune response [ Time Frame: 12 weeks ]
5. Inhibitor development in the extension study [ Time Frame: At least 50 additional EDs to achieve at least 100 cumulative EDs, on average 5 years ]

Secondary Outcome Measures :

1. Inhibitor development in the main study [ Time Frame: After 10 to 15 and 50 exposure days (ED) over 6 months, on average 245 days ]
2. Assessment of incremental recovery in main study [ Time Frame: At least 50 exposure days (ED) over 6 months, on average 245 days ]
3. 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) ]

Eligibility Criteria

• Ages Eligible for Study: up to 12 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Sacramento, California, United States, 95817

United States, Florida

Pensacola, Florida, United States, 32504

United States, Ohio

Cincinnati, Ohio, United States, 45229

Cleveland, Ohio, United States, 44106-6007

Columbus, Ohio, United States, 43205-2696

United States, Pennsylvania

Hershey, Pennsylvania, United States, 17033

United States, Utah

Salt Lake City, Utah, United States, 84113

Argentina

La Plata, Buenos Aires, Argentina, 1900

Austria

Wien, Austria, 1090

Belgium

Gent, Belgium, 9000

Leuven, Belgium, 3000

Bulgaria

Plovdiv, Bulgaria, 4002

Sofia, Bulgaria, 1527

Varna, Bulgaria, 9010

Canada, Alberta

Calgary, Alberta, Canada, T3B 6A8

Canada, Ontario

Toronto, Ontario, Canada, M5G 1X8

Greece

Thessaloniki, Greece, 54642

Israel

Ramat Gan, Israel, 5262000

Italy

Milano, Lombardia, Italy, 20122

Palermo, Sicilia, Italy, 90127

Padova, Veneto, Italy, 35128

Lithuania

Vilnius, Lithuania, 08661

Netherlands

Amsterdam, Netherlands

Utrecht, Netherlands, 3584 CX

New Zealand

Christchurch, New Zealand, 8011

Hamilton, New Zealand, 3204

Norway

Oslo, Norway, 0027

Poland

Lodz, Poland, 91-738

Olsztyn, Poland, 10-561

Romania

Bucharest, Romania, 011026

Bucharest, Romania, 022328

Timisoara, Romania, 300011

Spain

Esplugues de LLobregat, Barcelona, Spain, 08950

United Kingdom

Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP

Bristol, United Kingdom, BS2 8AE

Manchester, United Kingdom, M13 9WL

Sheffield, United Kingdom, S10 2TH

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here to find information about studies related to Bayer Healthcare products conducted in Europe. 

Click here to find results for studies related to Bayer products. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01775618
• Other Study ID Numbers: 15912; 2012-004434-42 ( EudraCT Number )
• First Posted: January 25, 2013
• Last Update Posted: August 21, 2020
• Last Verified: August 2020

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

Keywords provided by Bayer:

Hemophilia A; Factor VIII; Prophylaxis; Pediatric

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Factor VIII; Coagulants