Severe hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). MedDRA version: 20.1 Level: LLT Classification code 10053754 Term: Hemophilia B without inhibitors System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System
Conditions
Interventions
Product Name: PF-06741086 100 mg/ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PF-06741086
Other descriptive name: PF-06741086
Sponsors
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: 1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative/parent(s)/legal guardian) has been informed of all pertinent aspects of the study. 2. Males =18 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects with any of the following characteristics/conditions will not be included in the study: 1. Females. 2. Known coronary artery, thrombotic, or ischemic disease. 3. Known hemostatic defect other than hemophilia A or B. 4. ATIII, Protein C, or Protein S deficiency, Factor V Leiden, Prothrombin 20210 mutation, or other known pro thrombotic condition 5. Currently receiving treatment for acute bleeding episodes with APCC (eg, Factor Eight Inhibitor Bypass Agent [FEIBA]) and cannot substitute treatment with rFVIIa at a dose level of approximately 90 µg/kg for the duration of the study. 6. Regular, concomitant therapy with immunomodulating drugs (eg, intravenous immunoglobulin [IVIG], and routine systemic corticosteroids). 7. Abnormal renal or hepatic function as defined by the following laboratory results at Screening: • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >3 times the upper limit of normal (ULN). • Total bilirubin level >2 mg/dL (>35 µmol/L). • Serum albumin 1.25 times the ULN. 8. Abnormal hematology values as defined by the following laboratory results at Screening: • Platelet count 1.25 times the ULN. 10. CD4 cell count =200/µL. 11. Known hypersensitivity or allergic reaction to hamster protein. 12. Known sensitivity to heparin or heparin induced thrombocytopenia. 13. Investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study. 14. Participation in other studies involving investigational drug(s) within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives prior to study entry and/or during study participation. 15. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 16. With partners currently pregnant or able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. 17. Had major surgery, as judged by the investigator, within 3 months prior to the study or have elective surgery planned during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of multiple doses of PF-06741086 administered to severe hemophilia A and B subjects with and without inhibitors against FVIII and FIX.;Timepoint(s) of evaluation of this end point: Timepoints are all listed in the list of primary endpoints.; Secondary Objective: •To assess the clinical efficacy of repeat dosing of PF-06741086. •To characterize the PK profile of PF-06741086. •To characterize the PD profile of PF-06741086. •To characterize the immunogenicity of PF-06741086. ; Primary end point(s): •Frequency, severity and causal relationship of treatment emergent adverse events (AEs) (treatment emergent adverse events [TEAEs]) and withdrawals due to TEAEs; Day 1 up to Day 113. •Frequency and magnitude of abnormal laboratory findings (including hematology, PT/INR, aPTT, chemistry, urinalysis, fibrinogen, ATIII activity and cardiac troponin I); Day 1 up to Day 113. •Changes from baseline in vital sign (blood pressure, pulse rate, temperature and respiration rate) measurements 12 lead electrocardiogram (ECG) parameters and physical examination; Day 1 up to Day 113. •Frequency, severity and causal relationship of infusion and injection site reactions; Day 1 up to Day 113. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Efficacy: -Frequency and annualized rate of bleeding episodes; Day 1 up to Day 85. -Pharmacokinetics: •Plasma PF-06741086 concentrations (Day 1 up to Day 113) and noncompartmental parameters will be calculated as determined by a validated assay: o Single-dose o Day 1 to Day 7 (QW): Cmax, Tmax, AUClast, C168h o Day 1 to Day 28 (QM): Cmax, Tmax, AUClast, C672h. o Multiple-dose Day 29 to Day 36 (QW) or Day 29 to Day 57 (QM) Cmax,ss, Tmax,ss, AUCt, Vss (for IV administration only), CL (for IV administration only) or CL/F (for SC administration only), and Cmin. -Pharmacodynamics •Total TFPI; Day 1 up to Day 113. •Thrombin generation (including lag time, peak thrombin generation and endogenous thrombin generation potential); Day 1 up to Day 113. •Prothrombin fragment 1+2; Day 1 up to Day 113. •D-dimer; Day 1 up to Day 113. •Dilute prothrombin time; Day 1 up to Day 113. -Immunogenicity •Frequency of anti drug antibody (ADA) and neutralizing antibody (NAb) production against PF-06741086; Day 1 up to Day 113. Only positive ADA samples and the corresponding baseline sample will be tested in the NAb assay. ;Timepoint(s) of evaluation of this end point: Timepoints are all listed in the list of secondary endpoints. | — |
Countries
Brazil, Bulgaria, Chile, Croatia, France, Poland, South Africa, Spain, Switzerland, United States
Contacts
Public ContactClinical Trials.gov Call center
Pfizer Inc.
Outcome results
None listed