A Single Escalating Dose and Multiple Dose Study of BAY 1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors

A Phase 1, First in Man, Multicenter, Open Label, Single Escalating Dose Study of BAY1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors

Investigate the safety, tolerability and pharmacokinetics of BAY1093884 after Intravenous (IV) and subcutaneous (SC) administration of increasing single doses and SC administration of multiple doses.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
  • Sofia, Bulgaria, 1756
  • Varna, Bulgaria, 9010
• Germany
  • Berlin, Germany, 10249
  • Hessen
    • Gießen, Hessen, Germany, 35392
• Japan
  • Tokyo
    • Suginami, Tokyo, Japan, 167-0035
• Ukraine
  • Kiev, Ukraine
  • Lviv, Ukraine, 79044
• United Kingdom
  • London, United Kingdom, NW3 2QG
  • Manchester, United Kingdom, M13 9WL

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 Factor IX (FIX) concentration by measurement at the time of screening or from reliable prior documentation
• For subjects in Cohorts I-IV, I-SC1 and I-SC2; If history of inhibitors is evident, inhibitor titer of ≥5 Bethesda Units (BU) at screening or prior to screening at any time from medical records.
• Age: 18 to 65 years of age at screening
• Body mass index (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 (clinically relevant) allergies, non-allergic drug reactions, or multiple drug allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Without inhibitors; Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection	Drug: BAY1093884; Single escalating dose with a starting dose of 0.3 mg/kg for the first cohort. Drug will be administered via IV infusion over 1 hour and SC injection. Based on safety, PK and PD results the doses for the other cohorts will be determined.; Drug: BAY1093884; Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.
Experimental: With inhibitors; Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection	Drug: BAY1093884; Single escalating dose with a starting dose of 0.3 mg/kg for the first cohort. Drug will be administered via IV infusion over 1 hour and SC injection. Based on safety, PK and PD results the doses for the other cohorts will be determined.; Drug: BAY1093884; Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.
Experimental: Without inhibitors_multiple dose; Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks	Drug: BAY1093884; Single escalating dose with a starting dose of 0.3 mg/kg for the first cohort. Drug will be administered via IV infusion over 1 hour and SC injection. Based on safety, PK and PD results the doses for the other cohorts will be determined.; Drug: BAY1093884; Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants (single dose cohors) with adverse events as measure of safety and tolerability	Adverse events including abnormal laboratory findings and local injection site reactions	Up to 56 days
Plasma levels of anti-BAY1093884 antibodies		Pre-dose, Day 14, 21,28, 43 and 56
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)	AUC from time 0 to the last data point > LLOQ (lower limit of quantitation)	Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D	AUC(0-last) divided by dose	Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
Plasma concentration of BAY1093884 characterized by Cmax	Maximum observed drug concentration in measured matrix after single dose administration	Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
Plasma concentration of BAY1093884 characterized by Cmax/D	Cmax divided by dose	Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue factor pathway inhibitor (TFPI) activity		Up to 77 days
Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability	Adverse events including abnormal laboratory findings and local injection site reactions	Up to 77 days
Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)		Pre-dose, Day 14, 28, 49 and 77
Plasma concentration of BAY1093884 characterized by AUC(0-7d and AUC(0-tau) (multiple dose cohort)	AUC from time 0 to 7d after first and last dose (AUC(0-tau)	Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42
Plasma concentration of BAY1093884 characterized by AUC(0-7d/D and AUC(0-tau)/D after multiple dose	AUC(0-7d) after first dose and AUC(0-tau) after last dose divided by dose	Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42
Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md)	maximum observed drug concentration in measured matrix after first and last dose	Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42
Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D)	Cmax after first and last dose divided by dose	Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42
Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (after first and last dose)	Cmax after last dose divided by Cmax after first dose, AUC after last dose divided by AUC after first dose	Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Actual): July 9, 2018
• Study Completion (Actual): October 11, 2018

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 7, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

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: 16144; 2014-003283-20 (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