Multiple Escalating Dose Study of BAY1093884 in Adults With Hemophilia A or B With or Without Inhibitors

The purpose of this study was to assess the safety and tolerability of multiple doses of a human monoclonal antibody (BAY1093884) given under the skin in subjects with hemophilia A or B. This antibody was intended to protect from bleeds by inhibiting a substance (Tissue Factor Pathway Inhibitor, TFPI) that reduces the ability of the body to form blood clots.

Study Overview

• Status: Terminated
• Conditions: Hemophilia A and B
• Intervention / Treatment: Drug: Befovacimab (BAY1093884)

Detailed Description

The primary objective of the study was to assess the safety and tolerability of multiple subcutaneous injections of BAY1093884 (anti-TFPI monoclonal antibody, immunoglobulin G2, IgG2) in patients with hemophilia A or B with or without inhibitors.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Wien, Austria, 1090
    • Universitätsklinikum AKH Wien
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Medical centre Hipokrat - N EOOD
  • Sofia, Bulgaria, 1756
    • SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
  • Varna, Bulgaria, 9010
    • MHAT Sveta Marina EAD
• France
  • Bron, France, 69500
    • Hôpital Louis Pradel - Bron
  • Reims Cedex, France, 51092
    • Hôpital Robert Debré - Reims Cedex
• Hungary
  • Pecs, Hungary, 7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
• Japan
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Tokyo
    • Suginami, Tokyo, Japan, 167-0035
      • Ogikubo Hospital
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35233
    • Eulji University Hospital
• New Zealand
  • Christchurch, New Zealand, 8011
    • Haematology Service, Canterbury Health Laboratories
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male severe hemophilic patients with undetectable FVIII activity <1% or FIX activity <2%, with or without inhibitors (any titer) are eligible.
• Subjects with a past history of inhibitors (any inhibitor titer) are eligible.
• Age ≥18 years.
• Documentation of ≥4 bleeding episodes (any type or location of bleeds, treated or not) within the 6 months prior to screening.
• For subjects on prophylaxis: Willingness to interrupt ongoing prophylaxis.
• For subjects on immune tolerance induction (ITI): Willingness to interrupt ongoing ITI.

Exclusion Criteria:

• History of any other coagulation disorder (particularly disseminated intravascular coagulopathy or combined FVIII/FV deficiency) or platelet disorder.
• History of diseases related to venous thromboembolic events (e.g., pulmonary embolism, deep vein thrombosis, thrombophlebitis) or thrombotic microangiopathy.
• Risk factors for venous or arterial diseases (e.g., uncontrolled hypertension, uncontrolled diabetes).
• History of cardiac, coronary and/or arterial peripheral atherosclerotic disease
• Platelet count <100,000/μL.
• Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm^3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1093884 100mg; Subjects received BAY1093884 100 mg once a week until premature termination of the study	Drug: Befovacimab (BAY1093884); Once weekly doses until premature termination of the study, subcutaneous injection; Other Names: Anti-TFPI (Tissue Factor Pathway Inhibitor) monoclonal antibody (immunoglobulin G2; IgG2)
Experimental: BAY1093884 225mg; Subjects received BAY1093884 225 mg once a week until premature termination of the study	Drug: Befovacimab (BAY1093884); Once weekly doses until premature termination of the study, subcutaneous injection; Other Names: Anti-TFPI (Tissue Factor Pathway Inhibitor) monoclonal antibody (immunoglobulin G2; IgG2)
Experimental: BAY1093884 400mg; Subjects received BAY1093884 400mg once a week until premature termination of the study	Drug: Befovacimab (BAY1093884); Once weekly doses until premature termination of the study, subcutaneous injection; Other Names: Anti-TFPI (Tissue Factor Pathway Inhibitor) monoclonal antibody (immunoglobulin G2; IgG2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Drug-related Treatment-emergent Adverse Events	An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AEs (TEAEs). Drug-related TEAEs were TEAEs that had "reasonable causal relationship" to the study treatment decided by the investigators.	After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Number of Participants With Serious Treatment-emergent Adverse Events	A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. SAEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as serious treatment-emergent AEs (TESAEs). Drug-related TESAEs were TESAEs that had "reasonable causal relationship" to the study treatment decided by the investigators.	After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Number of Participants With Treatment-emergent Adverse Events of Special Interest	Any thromboembolic or thrombotic microangiopathic event or any hypersensitivity reaction was an adverse event of special interest (AESI). AESIs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AESIs.	After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Number of Participants With Clinically Relevant Abnormalities in Laboratory Values	"Clinically relevant "implied the presence of a clinical sign or symptom that required medical action.	After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): October 15, 2019
• Study Completion (Actual): October 15, 2019

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Subcutaneous; Prophylaxis; Inhibitors; Non-Inhibitors
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Immunologic Factors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Immunoglobulins; Immunoglobulin G; Lipoprotein-associated coagulation inhibitor
• Other Study ID Numbers: 19580; 2017-003324-67 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes