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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hemophilia A and B

Intervention / Treatment
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* Drug: Befovacimab (BAY1093884)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous, Prophylaxis, Non-Inhibitors, Inhibitors