E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). |
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E.1.1.1 | Medical condition in easily understood language |
Severe Hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053751 |
E.1.2 | Term | Hemophilia A with anti factor VIII |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053754 |
E.1.2 | Term | Hemophilia B without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053752 |
E.1.2 | Term | Hemophilia B with anti factor IX |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To determine the safety and tolerability of long term treatment (up to 365 days) with PF 06741086 in severe hemophilia A and B subjects with or without inhibitors to FVIII or FIX. |
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E.2.2 | Secondary objectives of the trial |
•To determine the efficacy of long term treatment with PF 06741086 in severe hemophilia A and B subjects with or without inhibitors to FVIII or FIX. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must meet the following inclusion criteria to be eligible for enrollment into the study. Subjects continuing from B7841002 within 30 days of the B7841003 Day 1 visit do not require screening procedures to confirm eligibility: 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 <75 years of age. 3.Body Mass Index (BMI) ≥17.5 and ≤30.5 kg/m2 and total body weight ≥50 and ≤100 kg. a. For adolescents, the BMI must be ≥14 kg/m2 and total body weight must be ≥30 kg. 4.Diagnosis of severe hemophilia A or B (FVIII or FIX activity ≤1%). 5.If receiving therapy for human immunodeficiency virus (HIV) or active hepatitis infection, have stable disease and be on a stable regimen at the time of study entry (ie, stable dosing for at least 3 months before consent). 6.Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. The following inclusion criteria only apply to de novo subjects (Cohorts 5 and 6) only: 1. Adolescent males ≥12 to <18 years of age are eligible 2. Patients with an episodic (on-demand) treatment regimen who are willing and able to washout from Factor VIII (for at least 72 hours) or Factor IX (for at least 96 hours) replacement therapy, or bypass agent therapy (for rFVIIa and activated prothrombin complex concentrate [APCC]: at least 72 hours; for other products: at least 5 half-lives) prior to Screening laboratory assessments of factor activity and have no plans to institute prophylactic factor or bypass agent treatment during the study period. 3. Had at least 6 acute bleeding episodes (spontaneous/traumatic) during the 6 month period prior to Screening. Surgical bleeding episodes do not apply to this criterion. 4. Subjects enrolled as Factor VIII or Factor IX inhibitor patients must have a positive inhibitor test result (above the upper limit of normal) at the local laboratory and must receive a bypass agent as primary treatment for bleeding episodes. A positive inhibitor test result will be above the upper limit of normal for the assay. Inhibitor test results from up to 6 months prior to Day 1 may be used to meet this requirement. |
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E.4 | Principal 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, or known severe, uncontrolled hypercholesterolemia. 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.Regular, concomitant therapy with immunomodulating drugs (eg, intravenous immunoglobulin [IVIG], and routine systemic corticosteroids). 6.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. 7.Abnormal renal or hepatic function as defined by the following laboratory results at any time prior to Day 1: •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 < the lower limit of normal (LLN). •Serum creatinine level >1.25 times the ULN. 8.Abnormal hematology values as defined by the following laboratory results at any time prior to Day 1: •Platelet count <100,000/µL. •Fibrinogen level < LLN. •Hemoglobin level <10 gm/dL. 9.Abnormal coagulation activity as defined by the following laboratory results at any time prior to Day 1: •Prothrombin time (PT) >1.25 times the ULN. 10.CD4 cell count ≤200/µL. 11.Known hypersensitivity (eg. latex allergy) or allergic reaction to hamster protein. 12.Known sensitivity to heparin or heparin induced thrombocytopenia. 13.Investigator 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, including their family members, directly involved in the conduct of the study. 14.Participation in other studies involving investigational drug(s) (excluding PF 06741086) within 30 days prior to study entry and/or during study participation. 15.Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior 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.Fertile male subjects 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 (applies only to de novo subjects).
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E.5 End points |
E.5.1 | Primary end point(s) |
•Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs); Day 1 up to Day 393. •Frequency and magnitude of abnormal laboratory findings (including hematology, chemistry, urinalysis); Day 1 up to Day 393. •Changes from baseline in vital sign (blood pressure, pulse rate, temperature and respiration rate) measurements and physical examinations; Day 1 up to Day 393 and ECG Day 1 to Day 29 in de novo subjects only. •Frequency, severity and casual relationship of infusion and injection site reactions; Day 1 up to Day 393. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints are all listed in the list of primary endpoints. |
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E.5.2 | Secondary end point(s) |
•Frequency and annualized rate of bleeding episodes; Day 1 up to Day 393. •Frequency of rescue (FVIII, or FIX) therapy for treatment of breakthrough bleeding episodes.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints are all listed in the list of secondary endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Chile |
Croatia |
France |
Poland |
South Africa |
Spain |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 17 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |