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

NCT03597022 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 195802017-003324-67
• Study Type: interventional
• Target: 24
• Locations: 10 countries
• Sites: 16

Brief Summary

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.

Conditions

Hemophilia A and B

Keywords

Subcutaneous; Prophylaxis; Non-Inhibitors; Inhibitors

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (3)

BAY1093884 100mg

EXPERIMENTAL

Subjects received BAY1093884 100 mg once a week until premature termination of the study

Drug: Befovacimab (BAY1093884)

BAY1093884 225mg

EXPERIMENTAL

Subjects received BAY1093884 225 mg once a week until premature termination of the study

Drug: Befovacimab (BAY1093884)

BAY1093884 400mg

EXPERIMENTAL

Subjects received BAY1093884 400mg once a week until premature termination of the study

Drug: Befovacimab (BAY1093884)

Interventions

Befovacimab (BAY1093884) DRUG

Once weekly doses until premature termination of the study, subcutaneous injection

Also known as: Anti-TFPI (Tissue Factor Pathway Inhibitor) monoclonal antibody (immunoglobulin G2; IgG2)

BAY1093884 100mg; BAY1093884 225mg; BAY1093884 400mg

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (17)

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Medical centre Hipokrat - N EOOD

Plovdiv, 4000, Bulgaria

Location

SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD

Sofia, 1756, Bulgaria

Location

MHAT Sveta Marina EAD

Varna, 9010, Bulgaria

Location

Hôpital Louis Pradel - Bron

Bron, 69500, France

Location

Hôpital Robert Debré - Reims Cedex

Reims, 51092, France

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Ogikubo Hospital

Suginami, Tokyo, 167-0035, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Haematology Service, Canterbury Health Laboratories

Christchurch, 8011, New Zealand

Location

Eulji University Hospital

Daejeon, 35233, South Korea

Location

Changhua Christian Hospital

Changhua, 50006, Taiwan

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Hemophilia A

Interventions

lipoprotein-associated coagulation inhibitor; Antibodies, Monoclonal; Immunoglobulin G

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes

Limitations and Caveats

Acceptable safety and tolerability of befovacimab was not demonstrated in the study, prompting early termination of the study. The "post-hoc" SAP was used for analyses. The other SAP was pre-specified but became not applicable after the termination.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

1-888-8422937

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 24, 2018
• Study Start: July 24, 2018
• Primary Completion: October 15, 2019
• Study Completion: October 15, 2019
• Last Updated: November 30, 2020
• Results First Posted: November 30, 2020

Record last verified: 2020-11

Locations

BU (3); FR (2); GB (3); AU (1); NZ (1); IT (1); KR (1); TW (1); JP (2); HU (1)