Hemophilia A, Hemophilia B
Conditions
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.
Interventions
DRUGBAY1093884
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.
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 |
| 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 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 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 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 |
Countries
Bulgaria, Germany, Japan, Ukraine, United Kingdom
Outcome results
None listed