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PF-06741086 Multiple Dose Study in Severe Hemophilia

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ClinicalTrials.gov Identifier: NCT02974855
Recruitment Status : Active, not recruiting
First Posted : November 29, 2016
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous and/or intravenous doses of PF-06741086 in subjects with severe hemophilia.

Condition or disease Intervention/treatment Phase
Hemophilia A or B Biological: PF-06741086 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Open-label, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Efficacy Of Subcutaneous Or Intravenous Pf-06741086 In Subjects With Severe Hemophilia
Actual Study Start Date : March 8, 2017
Estimated Primary Completion Date : November 25, 2018
Estimated Study Completion Date : November 25, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06741086 (Cohort 1) Biological: PF-06741086
PF-06741086 subcutaneous (SC) injection

Experimental: PF-06741086 (Cohort 2) Biological: PF-06741086
PF-06741086 SC injection

Experimental: PF-06741086 (Cohort 3) Biological: PF-06741086
PF-06741086 SC injection

Experimental: PF-06741086 (Cohort 4) Biological: PF-06741086
PF-06741086 intravenous (IV) infusion




Primary Outcome Measures :
  1. Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs [ Time Frame: Day 1 up to Day 113 ]
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  2. Percentage of subjects with laboratory abnormalities [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for laboratory examination: hematology, serum chemistry, and urinalysis.

  3. Number of subjects with changes from baseline in vital signs [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for vital sign examination: blood pressure, pulse rate, temperature, respiration rate.

  4. Number of subjects with change from baseline in electrocardiogram (ECG) parameters [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for ECG examinations: QT interval (QTc), QTcF interval (Fridericia's Correction), QRS complex, PR interval, and RR interval.

  5. Percentage of subjects with changes from baseline in physical examination [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for full physical examinations: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems.

  6. Percentage of subjects with infusion site reactions [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for injection site reaction examinations: induration, erythema, edema, rash, pruritis.

  7. Percentage of subjects with injection site reactions [ Time Frame: Day 1 up to Day 113 ]
    Following parameters were analyzed for injection site reaction examinations: induration, erythema, edema, rash, pruritis.


Secondary Outcome Measures :
  1. Number of bleeding episodes [ Time Frame: Day 1 up to Day 85 ]
    Bleeding episodes requiring treatment with factor replacement.

  2. Thrombin generation (lag time) [ Time Frame: Day 1 up to Day 113 ]
    An ex vivo pharmacodynamic measure of thrombin generation (initiation of thrombin generation).

  3. Thrombin generation (peak thrombin generation) [ Time Frame: Day 1 up to Day 113 ]
    An ex vivo pharmacodynamic measure of thrombin generation (maximum thrombin generation).

  4. Thrombin generation (endogenous thrombin generation potential) [ Time Frame: Day 1 up to Day 113 ]
    An ex vivo pharmacodynamic measure of thrombin generation (area under the thrombin generation curve).

  5. Prothrombin fragment 1+2 [ Time Frame: Day 1 up to Day 113 ]
    An in vivo pharmacodynamic measure of thrombin generation (prothrombin cleavage).

  6. D-dimer [ Time Frame: Day 1 up to Day 113 ]
    An in vivo pharmacodynamic measure of thrombin generation (fibrin degradation).

  7. Dilute prothrombin time [ Time Frame: Day 1 up to Day 113 ]
    An ex vivo pharmacodynamic measure of thrombin generation (via extrinsic pathway).

  8. Total TFPI [ Time Frame: Day 1 up to Day 113 ]
    Total amount of tissue factor pathway inhibitor (bound and unbound) in plasma.

  9. Frequency of anti drug antibody (ADA) and neutralizing antibody (NAb) production against PF 06741086 [ Time Frame: Day 1 up to Day 113 ]
    The percentage of participants with positive ADA and neutralizing antibodies will be summarized for each treatment arm.

  10. Plasma PF-06741086 concentrations [ Time Frame: Day 1 up to Day 113 ]
    Plasma PF-06741086 concentrations over time

  11. Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 up to Day 113 ]
    Maximum observed plasma concentration

  12. Time for Cmax (Tmax) [ Time Frame: Day 1 up to Day 113 ]
    Time to reach Cmax

  13. Area under the curve from time zero to last quantifiable concentration (AUClast) [ Time Frame: Day 1 up to Day 113 ]
    Area under the curve from time zero to last quantifiable concentration

  14. Terminal half-life (t 1/2) [ Time Frame: Day 1 up to Day 113 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  15. Trough concentrations (Ctrough) [ Time Frame: Day 1 up to Day 113 ]
    Minimum observed plasma concentration

  16. Volume of distribution at steady state (Vss) [ Time Frame: Day 1 up to Day 113 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state. IV administration only.

  17. Clearance (CL) [ Time Frame: Day 1 up to Day 113 ]
    Clearance is a quantitative measure of the rate at which a drug substance is removed from the body. IV administration only.

  18. Apparent clearance (CL/F) [ Time Frame: Day 1 up to Day 113 ]
    Apparent clearance is a quantitative measure of the rate at which a drug substance is removed from the body.SC administration only.

  19. Concentrations at steady state (Css) [ Time Frame: Day 1 up to Day 113 ]
    Plasma concentrations at steady state

  20. Time for steady state (Tss) [ Time Frame: Day 1 up to Day 113 ]
    Time to reach steady state plasma concentrations



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe hemophilia A or B (Factor VIII or Factor IX activity ≤ 1%), including patients with inhibitors to Factor VIII or Factor IX
  • Episodic (on-demand) treatment regimen prior to screening
  • At least 6 acute bleeding episodes during the 6-month period prior to screening

Exclusion Criteria:

  • Known coronary artery, thrombotic, or ischemic disease
  • Currently receiving treatment for acute bleeding episodes with APCC and cannot substitute treatment with rFVIIa

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): NCT02974855


Locations
United States, Colorado
UC Denver Hemophilia and Thrombosis Center - Pharmacy
Aurora, Colorado, United States, 80045
UC Denver Hemophilia and Thrombosis Center
Aurora, Colorado, United States, 80045
United States, Illinois
Pharmacy
Chicago, Illinois, United States, 60612
Rush University Medical Center
Chicago, Illinois, United States, 60612
Chile
Hospital Dr. Sotero del Rio
Santiago, Chile, 8207257
Croatia
Klinicki bolnicki centar Zagreb
Zagreb, Croatia, 10000
Poland
Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-952
South Africa
Phoenix Pharma (Pty) Ltd
Port Elizabeth, Eastern CAPE, South Africa, 6001
Haemophilia Comprehensive Care Centre
Johannesburg, Gauteng, South Africa, 2193
Switzerland
UniversitatsSpital Zurich, Klinik fur Hamatologie
Zurich, Switzerland, 8091
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02974855     History of Changes
Other Study ID Numbers: B7841002
2016-001885-27 ( EudraCT Number )
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
hemophilia

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn