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

Bayer32 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Hemophilia A Hemophilia B

Interventions

BAY1093884DRUG

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.

BAY1093884DRUG

Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (10)

Unnamed facility

Plovdiv, Bulgaria

Unnamed facility

Sofia, Bulgaria

Unnamed facility

Varna, Bulgaria

Unnamed facility

Giessen, Hesse, Germany

Outcomes

Primary Outcomes

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

Time frame: Up to 56 days

Plasma levels of anti-BAY1093884 antibodies

Time frame: 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)

Time frame: 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

Plasma concentration of BAY1093884 characterized by Cmax

Maximum observed drug concentration in measured matrix after single dose administration

Plasma concentration of BAY1093884 characterized by Cmax/D

Cmax divided by dose

Secondary Outcomes

Data from ClinicalTrials.gov

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Tissue factor pathway inhibitor (TFPI) activity

Time frame: 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

Time frame: Up to 77 days

Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)

Time frame: 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)

Time frame: 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

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

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

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