Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A

NCT01029340 | Completed Phase 3 Results DMC

• 2 other identifiers: 129542009-012149-43
• Study Type: interventional
• Target: 74
• Locations: 21 countries
• Sites: 57

Brief Summary

The study will assess the pharmacokinetics (part A) safety, tolerability, and efficacy of prophylaxis treatment (2 to 3 times a week) (part B) with BAY81-8973 over a one year period (split into two six month treatment periods). The study will compare 2 different methods (assays) for measuring the amount of study drug, the chromogenic substrate assay per European Pharmacopeia (CS/EP) with the classical assay (Chromogenic Substrate Adjusted, CS/ADJ). During one six month period patients will receive the study drug where the dose has been measured using the" (CS/EP) and during the other six months period the dose will be measured based on the Chromogenic Substrate Adjusted assay CS/ADJ)

Conditions

Blood Coagulation Disorders; Hemophilia A

Keywords

Hemophilia A; Factor VIII; Prophylaxis

Outcome Measures

Primary Outcomes (3)

• Part A - Area Under the Drug Concentration-time Curve (AUC)

  To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.

  Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.

• Part A - Half-life (t 1/2)

  To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.

  Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.

• Part B - Annualized Number of Total Bleeds

  The annualized number of bleeds experienced by participants

  12 months after randomization

Secondary Outcomes (16)

• Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)

  15-30 minutes after the injection

• Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period

  6 months on each potency

• Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed

  6 months on each potency

• Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire

  Baseline and 12 months

• Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire

  Baseline and 12 months

Study Arms (5)

Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS

EXPERIMENTAL

Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)

EXPERIMENTAL

Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between

Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ

EXPERIMENTAL

Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP

EXPERIMENTAL

Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 5: Recombinant Factor VIII by CS/EP

EXPERIMENTAL

Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks

Biological: Recombinant Factor VIII (BAY81-8973)

Interventions

Recombinant Factor VIII (BAY81-8973) BIOLOGICAL

Single dose of BAY81-8973 crossed over to single dose of Kogenate FS

Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS

Recombinant Factor VIII (Kogenate FS, BAY14-2222) BIOLOGICAL

Single dose of Kogenate FS crossed over to Single dose of BAY81-8973

Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)

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, aged 12 to 65 years
• Severe hemophilia A defined as \< 1% FVIII:C
• \>/= 150 days of previous treatment with FVIII in lifetime
• Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
• No history of or current FVIII inhibitors

You may not qualify if:

• Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
• Low platelet count, abnormal kidney function, or liver disease
• Received treatment with immune suppressing drugs within the last 3 months prior or requires treatment during the study. (Some drugs for hepatitis C, Human immunodeficiency virus (HIV), and steroids are allowed)
• Receiving or has received other experimental drugs within 3 months prior to study entry
• Allergy to Factor VIII or hamsters or mouse protein

Sponsors & Collaborators

• Bayer: lead

Study Sites (60)

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Orange, California, 92868, United States

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Sacramento, California, 95817, United States

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Tampa, Florida, 33607, United States

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Boston, Massachusetts, 02115, United States

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East Lansing, Michigan, 48823, United States

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Kansas City, Missouri, 64108-9898, United States

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Cleveland, Ohio, 44106-2602, United States

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Bahía Blanca, Buenos Aires, B8001HXM, Argentina

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Rosario, Santa Fe Province, S2000CKF, Argentina

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Vienna, Vienna, 1090, Austria

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Graz, 8036, Austria

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Zagreb, 10000, Croatia

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DK-Aarhus N, 8200, Denmark

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Frankfurt am Main, Hesse, 60596, Germany

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Bonn, North Rhine-Westphalia, 53127, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Homburg, Saarland, 66421, Germany

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Magdeburg, Saxony-Anhalt, 39112, Germany

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Hong Kong, Hong Kong

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Bangalore, 34, India

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Mumbai, 400012, India

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Pune, 411005, India

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Jakarta, 10430, Indonesia

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Ramat Gan, 5262000, Israel

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Catanzaro, Calabria, 88100, Italy

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Napoli, Campania, 80131, Italy

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Napoli, Campania, 80144, Italy

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Rome, Lazio, 00168, Italy

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Milan, Lombardy, 20122, Italy

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Vicenza, Veneto, 36100, Italy

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Oslo, 0027, Norway

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Karachi, 75300, Pakistan

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Krakow, 31-501, Poland

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Warsaw, 02-776, Poland

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Belgrade, 11000, Serbia

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Niš, 18000, Serbia

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Novi Sad, 21000, Serbia

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Pretoria, Gauteng, 0001, South Africa

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Parktown, 2132, South Africa

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A Coruña, A Coruña, 15006, Spain

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Barcelona, Barcelona, 08035, Spain

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Santander, Cantabria, 39008, Spain

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Jaén, Jaén, 23007, Spain

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Oviedo, Principality of Asturias, 33006, Spain

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Valencia, Valencia, 46026, Spain

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Gothenburg, 413 45, Sweden

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Malmo, 205 02, Sweden

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Karolinska Universitetssjukhuset i Solna

Stockholm, 171 76, Sweden

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Taipei, Taipei, 10016, Taiwan

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Changhua, 500, Taiwan

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Taipei, 11217, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Adana, 01330, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Izmir, 35-100, Turkey (Türkiye)

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Dundee, Dundee City, DD1 9SY, United Kingdom

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Oxford, Oxfordshire, OX3 7LJ, United Kingdom

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Sheffield, South Yorkshire, S10 2JF, United Kingdom

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London, SE1 7EH, United Kingdom

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Related Publications (3)

• Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.

  PMID: 27002680 RESULT

• Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.

  PMID: 26931631 RESULT

• Saxena K, Lalezari S, Oldenburg J, Tseneklidou-Stoeter D, Beckmann H, Yoon M, Maas Enriquez M. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial. Haemophilia. 2016 Sep;22(5):706-12. doi: 10.1111/hae.12952. Epub 2016 Jun 24.

  PMID: 27339736 DERIVED

Related Links

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

MeSH Terms

Conditions

Blood Coagulation Disorders; Hemophilia A

Interventions

Factor VIII; F8 protein, human; BAY 14-2222

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders, Inherited; 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

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trial-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 9, 2009
• Study Start: December 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: March 1, 2013
• Last Updated: November 28, 2016
• Results First Posted: November 18, 2013

Record last verified: 2016-10

Locations

GB (4); CR (1); ID (1); IT (6); NO (1); TW (3); PA (1); PL (2); TU (3); US (7); SE (3); ZA (2); TH (2); AU (2); ES (6); AR (2); HK (1); DK (1); IN (3); IL (1); DE (5)