Clinical trial NCT02571569: A Single Escalating Dose and Multiple Dose Study of BAY 1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Hemophilia B
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-10-08
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants (single dose cohors) with adverse events as measure of safety and tolerability
timeFrame: Up to 56 days
measure: Plasma levels of anti-BAY1093884 antibodies
timeFrame: Pre-dose, Day 14, 21,28, 43 and 56
measure: Plasma concentration of BAY1093884 characterized by AUC(0-tlast)
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by Cmax
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by Cmax/D
timeFrame: 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:
measure: Tissue factor pathway inhibitor (TFPI) activity
timeFrame: Up to 77 days
measure: Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability
timeFrame: Up to 77 days
measure: Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)
timeFrame: Pre-dose, Day 14, 28, 49 and 77
measure: Plasma concentration of BAY1093884 characterized by AUC(0-7d and AUC(0-tau) (multiple dose cohort)
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by AUC(0-7d/D and AUC(0-tau)/D after multiple dose
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md)
timeFrame: 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
measure: Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D)
timeFrame: 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
measure: Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (after first and last dose)
timeFrame: 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
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Gießen
country: Germany
state: Hessen
city: Berlin
country: Germany
city: Suginami
country: Japan
state: Tokyo
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: