E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize single dose pharmacokinetic profile of FVIII activity after administration of Xyntha in male Chinese subjects with hemophilia A. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of a single dose of Xyntha in male Chinese subjects with hemophilia A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male Chinese subjects 6 years or older (weight >20kg) with severe hemophilia A (factory VIII activity <1%) previously treated with >150 exposure days to any FVIII-containing products 2. Subjects should not have received an infusion of any FVIII products for at least 3 days (at least 72 hours) before the administration of Xyntha on Day 1 3. Subjects must be in a non-bleeding state before the administration of Xyntha on Day 1 4. Evidence of a personally or legally acceptable representative (legally acceptable representative is only applicable to pediatric subjects) signed and dated informed consent document indicating that the subject or legally acceptable representative has been informed of all pertinent aspects of this study. 5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
1. Current FVIII inhibitor or history of FVIII inhibitor (defined as > upper limit of normal (ULN) of the local reporting laboratory). 2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or clinical findings at Screening. 3. Diagnosed with any other bleeding disorder in addition to hemophilia A. 4. Documented Human Immunodeficiency Virus (HIV). 5. Subjects anticipating elective surgery or other invasive procedure within 1 month following study entry. 6. Treatment with immunomodulatory therapy within 30 days or 5 half-lives whichever is longer, prior to study entry or planned use for the duration of study participation. 7. Subjects with known hypersensitivity to the active substance or to any of the excipients of Xyntha. 8. Subjects with a known hypersensitivity to Chinese Hamster Ovary cell (CHO cell) proteins. 9. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: significant hepatic or renal impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN, or total bilirubin >2 x ULN or serum creatinine >2 x ULN), prothrombin time >1.5 x ULN, platelet count <80,000 L. Subjects with Gilbert’s disease may be enrolled. 10. Any condition which may compromise the subject’s ability to comply with and/or perform study-related activities or that poses a clinical contraindication to study participation, in the opinion of the investigator or sponsor. 11. A positive urine drug screen. 12. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine, 12 ounces (360 mL) of beer, or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening. 13. Treatment with an investigational drug within 30 days or 5 half-lives preceding Day 1, whichever is longer. 14. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject’s eligibility. 15. Screening supine 12-lead ECG demonstrating QTcF >450 or a QRS interval >120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject’s eligibility. 16. Blood donation (excluding plasma donations) of approximately 500 mL or more within 56 days prior to dosing. 17. History of sensitivity to heparin or heparin-induced thrombocytopenia. 18. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol. 19. Subjects who are 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. 20. 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. 21. Subjects with history of infection within 1 week prior to study entry. 22. Male subjects with partners currently pregnant and male subjects 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic Endpoints: FVIII Cmax, AUClast, AUCinf, tmax, CL, Vss, kel, t½, MRT, and incremental recovery after administration of a single dose of Xyntha. Safety Endpoints: Adverse events, laboratory abnormalities, vital signs and inhibitor development.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples will be collected predose (within 2 hours before administration) and at 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 and 72 hours after the start of the infusion. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
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 | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial months | 1 |