Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 4 for:    BAY1093884

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02571569
Recruitment Status : Completed
First Posted : October 8, 2015
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hemophilia A Hemophilia B Drug: BAY1093884 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : October 28, 2015
Actual Primary Completion Date : July 9, 2018
Actual Study Completion Date : October 11, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Without inhibitors
Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection
Drug: BAY1093884
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.

Experimental: With inhibitors
Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection
Drug: BAY1093884
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.

Experimental: Without inhibitors_multiple dose
Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks
Drug: BAY1093884
Multiple dose cohort with a single 150-mg SC injection once a week for 6 weeks.




Primary Outcome Measures :
  1. Number of participants (single dose cohors) with adverse events as measure of safety and tolerability [ Time Frame: Up to 56 days ]
    Adverse events including abnormal laboratory findings and local injection site reactions

  2. Plasma levels of anti-BAY1093884 antibodies [ Time Frame: Pre-dose, Day 14, 21,28, 43 and 56 ]
  3. Plasma concentration of BAY1093884 characterized by AUC(0-tlast) [ 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 ]
    AUC from time 0 to the last data point > LLOQ (lower limit of quantitation)

  4. Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D [ 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 ]
    AUC(0-last) divided by dose

  5. Plasma concentration of BAY1093884 characterized by Cmax [ 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 ]
    Maximum observed drug concentration in measured matrix after single dose administration

  6. Plasma concentration of BAY1093884 characterized by Cmax/D [ 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 ]
    Cmax divided by dose


Secondary Outcome Measures :
  1. Tissue factor pathway inhibitor (TFPI) activity [ Time Frame: Up to 77 days ]
  2. Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability [ Time Frame: Up to 77 days ]
    Adverse events including abnormal laboratory findings and local injection site reactions

  3. Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort) [ Time Frame: Pre-dose, Day 14, 28, 49 and 77 ]
  4. Plasma concentration of BAY1093884 characterized by AUC(0-7d and AUC(0-tau) (multiple dose cohort) [ 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 ]
    AUC from time 0 to 7d after first and last dose (AUC(0-tau)

  5. Plasma concentration of BAY1093884 characterized by AUC(0-7d/D and AUC(0-tau)/D after multiple 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 ]
    AUC(0-7d) after first dose and AUC(0-tau) after last dose divided by dose

  6. Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md) [ 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 ]
    maximum observed drug concentration in measured matrix after first and last dose

  7. Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D) [ 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 ]
    Cmax after first and last dose divided by dose

  8. Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (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 ]
    Cmax after last dose divided by Cmax after first dose, AUC after last dose divided by AUC after first dose



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02571569


Locations
Layout table for location information
Bulgaria
Plovdiv, Bulgaria, 4002
Sofia, Bulgaria, 1756
Varna, Bulgaria, 9010
Germany
Gießen, Hessen, Germany, 35392
Berlin, Germany, 10249
Japan
Suginami, Tokyo, Japan, 167-0035
Ukraine
Kiev, Ukraine
Lviv, Ukraine, 79044
United Kingdom
London, United Kingdom, NW3 2QG
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Bayer
Investigators
Layout table for investigator information
Study Director: Bayer Study Director Bayer

Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02571569     History of Changes
Other Study ID Numbers: 16144
2014-003283-20 ( EudraCT Number )
First Posted: October 8, 2015    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018

Layout table for additional information
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked