Back to resultsA Single Escalating Dose and Multiple Dose Study of BAY 1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors
Primary Purpose
Hemophilia A, Hemophilia B
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BAY1093884
BAY1093884
Sponsored by
About this trial
This is an interventional basic science trial for Hemophilia A
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Without inhibitors
With inhibitors
Without inhibitors_multiple dose
Arm Description
Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection
Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection
Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks
Outcomes
Primary Outcome Measures
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
Plasma levels of anti-BAY1093884 antibodies
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)
AUC from time 0 to the last data point > LLOQ (lower limit of quantitation)
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 Outcome Measures
Tissue factor pathway inhibitor (TFPI) activity
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
Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)
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)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02571569
Brief Title
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
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 28, 2015 (Actual)
Primary Completion Date
July 9, 2018 (Actual)
Study Completion Date
October 11, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A, Hemophilia B
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Without inhibitors
Arm Type
Experimental
Arm Description
Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection
Arm Title
With inhibitors
Arm Type
Experimental
Arm Description
Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection
Arm Title
Without inhibitors_multiple dose
Arm Type
Experimental
Arm Description
Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks
Intervention Type
Drug
Intervention Name(s)
BAY1093884
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BAY1093884
Intervention Description
Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.
Primary Outcome Measure Information:
Title
Number of participants (single dose cohors) with adverse events as measure of safety and tolerability
Description
Adverse events including abnormal laboratory findings and local injection site reactions
Time Frame
Up to 56 days
Title
Plasma levels of anti-BAY1093884 antibodies
Time Frame
Pre-dose, Day 14, 21,28, 43 and 56
Title
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)
Description
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
Title
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D
Description
AUC(0-last) divided by dose
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
Title
Plasma concentration of BAY1093884 characterized by Cmax
Description
Maximum observed drug concentration in measured matrix after single dose administration
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
Title
Plasma concentration of BAY1093884 characterized by Cmax/D
Description
Cmax divided by dose
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
Secondary Outcome Measure Information:
Title
Tissue factor pathway inhibitor (TFPI) activity
Time Frame
Up to 77 days
Title
Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability
Description
Adverse events including abnormal laboratory findings and local injection site reactions
Time Frame
Up to 77 days
Title
Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)
Time Frame
Pre-dose, Day 14, 28, 49 and 77
Title
Plasma concentration of BAY1093884 characterized by AUC(0-7d and AUC(0-tau) (multiple dose cohort)
Description
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
Title
Plasma concentration of BAY1093884 characterized by AUC(0-7d/D and AUC(0-tau)/D after multiple dose
Description
AUC(0-7d) after first dose and AUC(0-tau) after last dose divided by dose
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
Title
Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md)
Description
maximum observed drug concentration in measured matrix after first and last dose
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
Title
Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D)
Description
Cmax after first and last dose divided by dose
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
Title
Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (after first and last dose)
Description
Cmax after last dose divided by Cmax after first dose, AUC after last dose divided by AUC after first dose
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
City
Gießen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
City
Berlin
ZIP/Postal Code
10249
Country
Germany
City
Suginami
State/Province
Tokyo
ZIP/Postal Code
167-0035
Country
Japan
City
Kiev
Country
Ukraine
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Single Escalating Dose and Multiple Dose Study of BAY 1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors
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