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

Phase 1

Completed

• Conditions: Hemophilia A; Hemophilia B
• Interventions: Drug: BAY1093884

• Registration Number: NCT02571569
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-10-07
• Study First Submitted QC: 2015-10-07
• Study First Posted: 2015-10-08
• Study Start: 2015-10-28
• Primary Completion: 2018-07-09
• Status Verified: 2018-10
• Study Completion: 2018-10-11
• Last Update Submitted: 2018-10-17
• Last Update Posted: 2018-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 32

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Without inhibitors	BAY1093884	Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection
Without inhibitors_multiple dose	BAY1093884	Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks
With inhibitors	BAY1093884	Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Number of participants (single dose cohors) with adverse events as measure of safety and tolerability	Up to 56 days	Adverse events including abnormal laboratory findings and local injection site reactions
Plasma levels of anti-BAY1093884 antibodies	Pre-dose, Day 14, 21,28, 43 and 56
Plasma concentration of BAY1093884 characterized by Cmax/D	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	Cmax divided by dose
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)	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	AUC from time 0 to the last data point \> LLOQ (lower limit of quantitation)
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D	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	AUC(0-last) divided by dose
Plasma concentration of BAY1093884 characterized by Cmax	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	Maximum observed drug concentration in measured matrix after single dose administration

Secondary Outcome Measures

Name	Time	Method
Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability	Up to 77 days	Adverse events including abnormal laboratory findings and local injection site reactions
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	AUC(0-7d) after first dose and AUC(0-tau) after last dose divided by dose
Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D)	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	Cmax after first and last dose divided by dose
Tissue factor pathway inhibitor (TFPI) activity	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	AUC from time 0 to 7d after first and last dose (AUC(0-tau)
Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md)	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	maximum observed drug concentration in measured matrix after first and last dose
Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (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	Cmax after last dose divided by Cmax after first dose, AUC after last dose divided by AUC after first dose