Study of FVIIa Variant BAY86-6150 (B0189) in Subjects With Moderate or Severe Hemophilia Types A or B With or Without Inhibitors (MATCHBOX)

A Phase I, Randomized, Double-blind, Placebo Controlled, Single Dose Escalation Study of FVIIa Variant BAY86-6150 (B0189) in Subjects With Moderate or Severe Hemophilia Types A or B With or Without Inhibitors

This is the first in humans study of BAY86-6150 (B0189) in non-bleeding subjects with moderate or severe congenital hemophilia A or B with or without inhibitors. This is a randomized, double-blind, placebo-controlled, single-dose, dose escalation study. It is designed to investigate the safety, tolerability, potential immunogenicity, pharmacokinetic and pharmacodynamic profile of BAY86-6150 (B0189) and to determine a dose or range of doses to be examined in subsequent studies.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Drug: BAY Factor VII (BAY86-6150); Drug: BAY Factor VII (BAY86-6150); Drug: BAY Factor VII (BAY86-6150); Drug: BAY Factor VII (BAY86-6150); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Warszawa, Poland, 02-776
• South Africa
  • Freestate
    • Bloemfontein, Freestate, South Africa, 9300
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
• United Kingdom
  • London, United Kingdom, W12 0HS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• History of moderate or severe congenital hemophilia A or B with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX)
• Male subjects 18-65 years of age inclusive
• Able to dismiss factor replacement therapy during the course of the study unless required for the treatment of an acute bleeding episode
• Written informed consent
• Willing and able to comply with the requirements of the protocol
• Have adequate venous access
• Willing to use an effective method of contraception until Day 30 of their study participation

Exclusion Criteria:

• Received factor replacement therapy or treatment with any other procoagulant therapeutics, or any antifibrinolytic agents, including blood products, at anytime within 5 days prior to administration of investigational medicinal product (IMP)
• Planned administration of factor replacement therapy or treatment with any other procoagulant therapeutics or any antifibrinolytic agents, including blood products, at anytime during the study period
• Acute bleeding episode or any ongoing bleeding episode at any time within 7 days prior to administration IMP
• Clinically relevant coagulation disorder other than congenital hemophilia A or B
• History of angina or receiving treatment for angina
• History of coronary atherosclerotic disease, disseminated intravascular coagulopathy, or stage 2 hypertension defined as systolic blood pressure (SBP) >/= 160 mmHg or diastolic blood pressure (DBP) >/= 90 mmHg
• History of transient ischemic attack, stroke, myocardial infarction, coronary artery disease, congestive heart failure, or thromboembolic event
• Active infection on day of IMP administration or septicemia at any time within 30 days prior to administration of IMP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BAY Factor VII (6.5 µg/kg) / Placebo; n = 4, randomized 3:1; 6.5 µg/kg BAY 86-6150 (B0189):Placebo	Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 6.5 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 20 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 50 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 90 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: Placebo; Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.
EXPERIMENTAL: BAY Factor VII (20 µg/kg) / Placebo; n = 4, randomized 3:1; 20 µg/kg BAY 86-6150 (B0189):Placebo	Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 6.5 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 20 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 50 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 90 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: Placebo; Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.
EXPERIMENTAL: BAY Factor VII (50 µg/kg) / Placebo; n = 4, randomized 3:1; 50 µg/kg BAY 86-6150 (B0189):Placebo	Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 6.5 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 20 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 50 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 90 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: Placebo; Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.
EXPERIMENTAL: BAY Factor VII (90 µg/kg) / Placebo; n = 4, randomized 3:1; 90 µg/kg BAY 86-6150 (B0189):Placebo	Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 6.5 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 20 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 50 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: BAY Factor VII (BAY86-6150); BAY Factor VII (BAY86-6150), 90 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.; Drug: Placebo; Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Up to Day 50

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic assessment, based on plasma concentration of BAY86-6150	9 time points from pre-dosing on Day 1 up to 48 hours post-dosing
Pharmacodynamic assessment, based on plasma hemostasis marker level	9 time points from pre-dosing on Day 1 up to 48 hours post-dosing
Immunogenicity assessment, based on anti-BAY86-6150 binding antibody levels	3 time points from pre-dosing on Day 1 up to Day 50

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Mahlangu JN, Coetzee MJ, Laffan M, Windyga J, Yee TT, Schroeder J, Haaning J, Siegel JE, Lemm G. Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia. J Thromb Haemost. 2012 May;10(5):773-80. doi: 10.1111/j.1538-7836.2012.04667.x.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: August 9, 2013
• First Posted (ESTIMATE): August 13, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 21, 2014
• Last Update Submitted That Met QC Criteria: August 20, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• 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: 13787; 2008-000117-29 (EUDRACT_NUMBER)