A Phase 2/ 3 Trial to Evaluate the Efficacy and Safety of BAY86-6150

A Phase 2/3, Multicenter, Open-label Clinical Study to Assess the Safety and Efficacy of BAY86-6150 in Subjects With Hemophilia A or B With Inhibitors, Composed of 2 Parts (A & B). Part A: Sequential Cohorts of Four Dose Levels of the Modified rFVIIa BAY86-6150 Assessed in a Non-controlled Dose Response Design in Acutely Bleeding Subjects and for PK/ PD in an Intra-individual Crossover Design Compared With One Fixed Dose of Eptacog Alfa in Non-bleeding Subjects. Part B: Confirmatory Study to Further Investigate the Efficacy and Safety of BAY86-6150

Haemophilia is a disorder, usually genetic, affecting mostly male individuals, in which one of the proteins needed to form blood clots (FVIII) is missing or not present in sufficient levels. In a person with haemophilia, the clotting process is much slower and the person experiences bleeding episodes that can result in serious problems and potential disability.

The current haemophilia standard of care is to maintain FVIII activity level above 1%. Sometimes, patients can develop antibodies (so called "inhibitors") against FVIII and it is no longer effective at controlling bleeds. Bleeds in these patients are currently treated using other proteins involved in the clotting process.

The purpose of this study is to investigate how effectively BAY86-6150 may stop acute bleeds in "inhibitor" patients. This study consists of two parts, A and B. The purpose of part A is to find the most effective yet tolerable out of four doses of BAY86-6150 with regard to efficacy and safety (dose-finding part). Part A is expected to last 9 - 29 months. The purpose of part B is to confirm efficacy and safety of the dose found in part A in all participating patients (confirmatory part). Part B is expected to last 12-32 months.

Approximately 60 male subjects 12 to 62 years-of-age with moderate or severe haemophilia A or B, with inhibitors to FVIII or FIX, who have had 4 or more bleeding episodes in the last 6 months, will participate in this study.

Patient's bleeds will be treated with BAY86-6150 and with a rescue medication if no response is made to BAY86-6150. Patients will attend the treatment centre at regular intervals and be required to keep an electronic diary.

Study Overview

• Status: Completed
• Conditions: Hemophilia A, Hemophilia B
• Intervention / Treatment: Drug: BAY86-6150; Drug: BAY86-6150; Drug: eptacog alfa [activated]

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
• Brazil
  • Rio de Janeiro, Brazil, 20211030
  • Sao Paulo, Brazil, 04023-061
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01401901
• Bulgaria
  • Sofia, Bulgaria, 1756
• Chile
  • Santiago, Chile, 836-0156
• China
  • Beijing, China, 100730
  • Tianjin, China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
• Colombia
  • Bogotá, Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia
• Denmark
  • Aarhus N, Denmark, 8200
• France
  • Lyon Cedex, France, 69437
  • Tours, France, 37044
• Germany
  • Baden-Württemberg
    • Villingen-Schwenningen, Baden-Württemberg, Germany, 78050
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
• Hungary
  • Budapest, Hungary, 1134
  • Debrecen, Hungary, 4032
• India
  • Bangalore, India, 34
  • Pune, India, 411004
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500034
  • Punjab
    • Ludhiana, Punjab, India, 141008
• Israel
  • Tel Hashomer, Israel, 5262000
• Italy
  • Firenze, Italy, 50134
  • Milano, Italy, 20122
• Japan
  • Nara
    • Kashihara, Nara, Japan, 634-8522
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-0023
    • Suginami, Tokyo, Japan, 167-0035
• Korea, Republic of
  • Seoul, Korea, Republic of, 134-727
• Mexico
  • México D. F., Mexico, 04530
  • Oaxaca, Mexico, 68000
  • San Luis Potosí, Mexico, 78216
  • Jalisco
    • Guadalajara, Jalisco, Mexico
• Netherlands
  • Utrecht, Netherlands, 3508 GA
• New Zealand
  • Christchurch, New Zealand, 8011
• Poland
  • Warszawa, Poland, 02-776
• Romania
  • Bucharest, Romania, 022328
  • Bucharest, Romania, 11026
  • Timis
    • Timisoara, Timis, Romania, 300011
• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
  • Khabarovsk, Russian Federation, 680009
  • Samara, Russian Federation, 443079
  • St. Petersburg, Russian Federation, 191186
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 169608
• South Africa
  • Freestate
    • Bloemfontein, Freestate, South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2132
    • Pretoria, Gauteng, South Africa, 0001
• Sweden
  • Göteborg, Sweden, 413 45
• Taiwan
  • Changhua, Taiwan, 500
  • Taipei, Taiwan, 110
  • Taipei, Taiwan, 10016
• Turkey
  • Istanbul, Turkey, 34098
  • Izmir, Turkey, 35100
• Ukraine
  • Donetsk, Ukraine, 83045
  • Lviv, Ukraine, 79044
  • Odessa, Ukraine, 65025
• United Kingdom
  • London, United Kingdom, SE1 7EH
  • Truro, United Kingdom, TR1 3LJ
• United States
  • California
    • Sacramento, California, United States, 95817
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 62 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male subjects
• 12 to 62 years-of-age
• History of moderate or severe congenital hemophilia A or B with inhibitors to FVIII or FIX
• 4 or more bleeding episodes in the last 6 months before enrollment.

Exclusion Criteria:

• Clinically relevant coagulation disorder other than congenital hemophilia A or B with inhibitors
• History of coronary and/or peripheral atherosclerotic disease
• Disseminated intravascular coagulopathy, or stage 2 hypertension
• Angina pectoris
• Myocardial infarction
• Transient ischemic attack
• Stroke
• Congestive heart failure
• Thromboembolic event

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: BAY86-6150; Four dose levels (6.5 µg/kg, 20 µg/kg, 50 µg/kg and 90 µg/kg) of BAY86-6150 will be studied.; Drug: BAY86-6150; Confirmation of recommended dose of BAY86-6150 to be evaluated further as determined in Part A.
ACTIVE_COMPARATOR: Arm 2	Drug: eptacog alfa [activated]; comparative PK/PD (pharmacokinetics/pharmacodynamics) evaluation
EXPERIMENTAL: Arm 3	Drug: BAY86-6150; Four dose levels (6.5 µg/kg, 20 µg/kg, 50 µg/kg and 90 µg/kg) of BAY86-6150 will be studied.; Drug: BAY86-6150; Confirmation of recommended dose of BAY86-6150 to be evaluated further as determined in Part A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful treatments of bleeding episodes.	A bleed was defined as successfully treated, if no administration of rescue medication was required.	10 hours after each bleed
Proportion of successful treatments of bleeding episodes on subject level.	Proportion of successful treatments of bleeding episodes was calculated as number of bleeding episodes treated successfully - without rescue medication - divided by the total number of bleeding episodes on a dose level.	10 hours after each bleed

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to stop the bleed	10 hours after each bleed
Number of injections needed to stop the bleeding episode.	10 hours after each bleed
Effectiveness of treatment as rated by the subject's assessment (very effective, effective, partially effective, not effective).	10 hours after each bleed
Participant's reported outcome as assessed by Euro QoL (EQ-5D).	14 days after last exposure to BAY86-6150
Participant's reported outcome as assessed by Brief Pain Inventory.	7 days after last exposure to BAY86-6150
Participant's reported outcome as assessed by Work Productivity and Activity Impairment Questionaire.	14 days after last exposure to BAY86-6150

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (ESTIMATE): June 21, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: hemophilia, haemophilia, inhibitor, FVIIa, Factor VII activated, bypassing
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: 15534; 2011-000323-33 (EUDRACT_NUMBER); U1111-1133-2156 (OTHER: WHO - Universal Trial Number (UTN))