A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A

NCT01580293 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 130242011-005210-11
• Study Type: interventional
• Target: 145
• Locations: 20 countries
• Sites: 59

Brief Summary

Haemophilia A is an inherited disorder in which one of the proteins, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. In a person with haemophilia A, the clotting process is slowed and the person experiences bleeds that can result in serious problems and potential disability. The current standard treatment for severe haemophilia A is regularly scheduled infusion of FVIII to keep levels high enough to prevent bleeding. 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 evaluated in subjects with severe Hemophilia A. 120-140 patients will receive open label treatment with long-acting rFVIII either on-demand to treat bleeds or prophylactically for 36 weeks in the main trial plus an optional extension to continue treatment for at least 100 total exposure days (ED). Patients on prophylactic treatment will receive study drug at dosing intervals between once and twice a week depending on their observed bleeding. Patients will attend the treatment centre for routine blood samples and be required to keep an electronic diary. Male patients aged 12-65, with severe hemophilia A, previously treated with FVIII for at least 50 exposure days may be eligible for this study.

Conditions

Hemophilia A

Keywords

Hemophilia A, factor VIII, prophylaxis

Outcome Measures

Primary Outcomes (1)

• Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial

  Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).

  On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Secondary Outcomes (18)

• Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A

  On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

• Annualized Number of Total Bleeds in On-demand Treatment Arm and in Each Prophylaxis Arm, Part A, Extension

  at least 100 total exposure days acquired, median time 3.9 years up to 7 years maximum

• Number of Participants Developed Human Coagulation Factor VIII (FVIII) Inhibitor - Part A

  Weeks 0 to 36 during Part A

• Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A

  Weeks 0 to 36

• Number of Bleeds According to Locations - Part A

  Weeks 0 -36

Other Outcomes (10)

• Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 - Part A

  Week 0 (baseline) and Week 36 during Part A

• Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 - Part A

  Week 0 (baseline) and Week 36 during Part A

• Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions- Part A

  On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Study Arms (4)

Arm 1

EXPERIMENTAL

On-demand treatment of BAY94-9027 at individual dose and number of infusions based upon location and severity of bleeds

Biological: BAY94-9027

Arm 2

EXPERIMENTAL

Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by 2 infusions per week over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED

Biological: BAY94-9027

Arm 3

EXPERIMENTAL

Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 5 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED

Biological: BAY94-9027

Arm 4

EXPERIMENTAL

Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 7 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED

Biological: BAY94-9027

Interventions

BAY94-9027 BIOLOGICAL

Intravenous infusion of BAY94-9027

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male; 12-65 years of age
• Subjects with severe hemophilia A
• Previously treated with factor VIII for a minimum of 150 exposure days

You may not qualify if:

• Inhibitors to FVIII (current evidence or history)
• Any other inherited or acquired bleeding disorder in addition to Hemophilia A
• Platelet count \< 100,000/mm3
• Creatinine \> 2x upper limit of normal or AST/ALT (aspartate aminotransferase/alanine aminotransferase) \> 5x upper limit of normal

Sponsors & Collaborators

• Bayer: lead

Study Sites (59)

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Tucson, Arizona, 85724-5024, United States

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Sacramento, California, 95817, United States

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San Diego, California, 92103-8651, United States

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Jacksonville, Florida, 32207, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60612, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55455, United States

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Syracuse, New York, 13210, United States

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Cincinnati, Ohio, 45229-3039, United States

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Cleveland, Ohio, 44106-6007, United States

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Columbus, Ohio, 43205, United States

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Hershey, Pennsylvania, 17033, United States

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Richmond, Virginia, 23298-0155, United States

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Vienna, 1090, Austria

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Bruges, 8000, Belgium

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London, Ontario, N6A 5W9, Canada

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Medellín, Antioquia, 050030, Colombia

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Baranquilla, Atlántico, 080020, Colombia

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Aarhus N, 8200, Denmark

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Bron, 69677, France

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Marseille, 13005, France

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Reims, 51092, France

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Rennes, 35033, France

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Heidelberg, Baden-Wurttemberg, 69004, Germany

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Bonn, North Rhine-Westphalia, 53127, Germany

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Ramat Gan, 5262000, Israel

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Napoli, Campania, 80131, Italy

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Rome, Lazio, 00161, Italy

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Milan, Lombardy, 20122, Italy

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Turin, Piedmont, 10126, Italy

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Nagoya, Aichi-ken, 466-8560, Japan

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Nishinomiya, Hyōgo, 663-8501, Japan

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Kashihara, Nara, 634-8522, Japan

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Shinjuku-ku, Tokyo, 160-0023, Japan

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Suginami, Tokyo, 167-0035, Japan

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Hiroshima, 734-8551, Japan

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Amsterdam, 1105 AZ, Netherlands

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Groningen, 9713 GZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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The Hague, 2545 CH, Netherlands

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Oslo, 0372, Norway

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Wroclaw, 50-367, Poland

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Timișoara, 300011, Romania

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Singapore, 119228, Singapore

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Singapore, 169608, Singapore

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Singapore, 229 899, Singapore

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Busan, Busan Gwang''yeogsi, 49241, South Korea

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Daejeon, 35233, South Korea

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Seoul, 03722, South Korea

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Seoul, 05278, South Korea

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Changhua, 50006, Taiwan

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Taipei, 100, Taiwan

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Taipei, 11217, Taiwan

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Ankara, 06100, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Newcastle upon Tyne, Vale of Glamorgan, the, NE1 4LP, United Kingdom

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London, SE1 7EH, United Kingdom

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Sheffield, S10 2JF, United Kingdom

Location

Related Publications (4)

• Baumann A, Piel I, Hucke F, Sandmann S, Hetzel T, Schwarz T. Pharmacokinetics, excretion, distribution, and metabolism of 60-kDa polyethylene glycol used in BAY 94-9027 in rats and its value for human prediction. Eur J Pharm Sci. 2019 Mar 15;130:11-20. doi: 10.1016/j.ejps.2019.01.015. Epub 2019 Jan 14.

  PMID: 30654111 BACKGROUND

• Lalezari S, Reding MT, Pabinger I, Holme PA, Negrier C, Chalasani P, Shin HJ, Wang M, Tseneklidou-Stoeter D, Maas Enriquez M. BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results. Haemophilia. 2019 Nov;25(6):1011-1019. doi: 10.1111/hae.13853. Epub 2019 Oct 17.

  PMID: 31621991 BACKGROUND

• Reding MT, Ng HJ, Poulsen LH, Eyster ME, Pabinger I, Shin HJ, Walsch R, Lederman M, Wang M, Hardtke M, Michaels LA. Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII. J Thromb Haemost. 2017 Mar;15(3):411-419. doi: 10.1111/jth.13597. Epub 2017 Feb 22.

  PMID: 27992112 BACKGROUND

• Reding MT, Pabinger I, Holme PA, Maas Enriquez M, Mancuso ME, Lalezari S, Miesbach W, Di Minno G, Klamroth R, Hermans C. Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: post hoc analysis from the PROTECT VIII study. Ther Adv Hematol. 2023 Apr 22;14:20406207231166779. doi: 10.1177/20406207231166779. eCollection 2023.

  PMID: 37113811 RESULT

Related Links

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

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Limitations and Caveats

Some registered "Secondary outcome measure" were re-classified as "Other Pre-specified" in line with protocol.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: April 19, 2012
• Study Start: April 23, 2012
• Primary Completion: June 13, 2014
• Study Completion: November 21, 2019
• Last Updated: November 7, 2023
• Results First Posted: December 6, 2018

Record last verified: 2023-11

Locations

SG (3); US (14); FR (4); AU (1); KR (4); CO (2); PL (1); NO (1); BE (1); CA (1); RO (1); IT (4); TW (3); GB (3); JP (6); TU (2); DE (2); IL (1); NL (4); DK (1)