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

NCT02571569 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 161442014-003283-20
• Study Type: interventional
• Target: 32
• Locations: 5 countries
• Sites: 10

Brief Summary

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.

Conditions

Hemophilia A; Hemophilia B

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• 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

  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)

  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

  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

Study Arms (3)

Without inhibitors

EXPERIMENTAL

Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection

Drug: BAY1093884

With inhibitors

EXPERIMENTAL

Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection

Drug: BAY1093884

Without inhibitors_multiple dose

EXPERIMENTAL

Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks

Drug: BAY1093884

Interventions

BAY1093884 DRUG

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.

With inhibitors; Without inhibitors

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (10)

Unknown Facility

Plovdiv, 4002, Bulgaria

Location

Unknown Facility

Sofia, 1756, Bulgaria

Location

Unknown Facility

Varna, 9010, Bulgaria

Location

Unknown Facility

Giessen, Hesse, 35392, Germany

Location

Unknown Facility

Berlin, 10249, Germany

Location

Unknown Facility

Suginami, Tokyo, 167-0035, Japan

Location

Unknown Facility

Kiev, Ukraine

Location

Unknown Facility

Lviv, 79044, Ukraine

Location

Unknown Facility

London, NW3 2QG, United Kingdom

Location

Unknown Facility

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

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; Genetic Diseases, X-Linked

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 8, 2015
• Study Start: October 28, 2015
• Primary Completion: July 9, 2018
• Study Completion: October 11, 2018
• Last Updated: October 18, 2018

Record last verified: 2018-10

Locations

BU (3); JP (1); GB (2); DE (2); UA (2)