A Study to Assess Pharmacokinetics and Pharmacodynamics Following Administration of BAY1093884 in Patients With Severe Hemophilia

A Phase 1 Study to Assess Pharmacokinetics and Pharmacodynamics Following Administration of BAY1093884 in Patients With Severe Hemophilia

The primary objective of this study is to assess the pharmacokinetics in patients with severe hemophilia.

The secondary objective is to assess the pharmacodynamics of BAY1093884 based on tissue factor pathway inhibitor activity

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Drug: BAY1093884; Drug: BAY1093884

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center

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:

• Males with severe congenital hemophilia A or B defined as <1% FVIII or <2% FIX concentration by measurement at the time of screening or from reliable prior documentation (e.g., measurement in other clinical Bayer trials, or diagnostic genetic testing)
• Male with any inhibitor titer at screening or prior to screening at any time from medical records. Subjects may be receiving a bypassing agent (rFVIIa; NovoSeven and/or aPCC; FEIBA) for treatment.
• Age: 18 to 65 years at screening
• BMI: 18 to 29.9 kg/m2

Exclusion Criteria:

• Subjects with known bleeding disorders (such as von Willebrand factor [vWF] deficiency, FXI deficiency, platelet disorders, or known acquired or inherited thrombophilia etc.) other than congenital Hemophilia A or B with or without inhibitors
• History of angina pectoris or treatment for angina pectoris
• History of coronary and/or peripheral atherosclerotic disease, congestive heart failure, disseminated intravascular coagulopathy, or stage 2 hypertension defined as systolic blood pressure (SBP) ≥160 mmHg or diastolic blood pressure (DBP) ≥100 mmHg even if controlled
• History of thrombophlebitis, venous/arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, cerebrovascular accident, ischemic heart disease, transient ischemic attack)
• Known or suspected hypersensitivity of the immune system, history of anaphylactic reaction, known severe allergies, non-allergic drug reactions, or multiple drug allergies
• Subjects with inhibitors treated with FEIBA, who are not willing to accept rFVIIa (NovoSeven) for the treatment of any bleeds occurring either between screening and dosing or after study drug administration, and until the end of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1093884 in subjects with Hemophilia; Single dose of BAY1093884 over 30 minutes administered in subjects with severe congenital Hemophilia A or B, with inhibitors or without inhibitors	Drug: BAY1093884; 0.3 mg/kg given intravenously; Drug: BAY1093884; 1 mg/kg given intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (0-tlast) of BAY1093884 in plasma	Area under the concentration vs. time curve from time 0 to the last data point > LLOQ	Up to 15 days after drug administration
AUC(0-tlast)/D of BAY1093884 in plasma	AUC(0-tlast) divided by dose	Up to 15 days after drug administration
Cmax of BAY1093884 in plasma	Maximum observed drug concentration in measured matrix after single dose administration	Up to 15 days after drug administration
Cmax/D of BAY1093884 in plasma	Cmax divided by dose	Up to 15 days after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Tissue factor plasma inhibitor activity: effect of BAY1093884 to inhibit the anticoagulatory activity of plasma TFPI as assessed by a chromogenic assay	Up to 15 days after drug administration

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2018
• Primary Completion (Actual): October 17, 2018
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

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: 19592

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