E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male subjects with hemophilia A (FVIII:C ≤2% confirmed at screening), previously treated with ≥ 150 exposure days to any Factor VIII product, undergoing elective major surgery that is anticipated to require FVIII infusions over a period of at least 6 days following surgery |
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MedDRA Classification |
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 |
Demonstration of the safety and efficacy of ReFacto AF administered by bolus injection or continuous infusion during the perioperative management of patients with hemophilia A undergoing major surgery |
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E.2.2 | Secondary objectives of the trial |
- Characterize and compare the total and daily dose of ReFacto AF for both bolus injection and continuous infusion - Characterize the pharmacokinetics of ReFacto AF in the patient population - Characterize the pharmacokinetic measurements required for surgical prophylaxis - Characterize the predicted and estimated actual blood loss and transfusion requirements in the study patient population - Characterize the variety of regimens used in those patients treated by continuous infusion - Characterize patient compliance with prescribed regimens in the outpatient setting |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Male subjects with hemophilia A- FVIII:C ≤ 2% - Age ≥ 12 years - A negative FVIII inhibitor at both the local laboratory and central laboratory at screening - A negative past medical history of a FVIII inhibitor - Previously treated with ≥ 150 exposure days to any Factor VIII product - The subject will be undergoing elective major surgery that is anticipated to require FVIII infusions and daily FVIII activity monitoring over a period of at least 6 days following surgery - ALT (SGOT) and AST (SGPT) ≤5.0 x ULN, and bilirubin ≤2mg/dL (33 µmol/L) - Serum albumin ≥ LLN- Serum creatinine ≤1.25 x ULN- Platelet count ≥ 100,000 /µL - Absolute CD4 count >200 µL - PT ≤1.25 x ULN or INR ≤ 1.5 - Patients receiving therapy for HIV or Hepatitis infection, must be on a stable antiviral regimen at the time of study entry - The patient should be able to comply with the required inpatient length of stay including at least 2 days for BI subjects and at least 6 days for all CI subjects. The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to inclusion criteria. |
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E.4 | Principal exclusion criteria |
- A history of FVIII inhibitor (clinical or laboratory based assessment, as defined in the protocol definitions), such as recurrent low titer values. Any measured Bethesda inhibitor titer greater than or equal to 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay - Presence of a bleeding disorder in addition to hemophilia A - Treatment with any investigational drug or device within the past 30 days, except for subjects entering from other studies of ReFacto AF - prior participation in this study (except for screen failures) - Regular (e.g. daily, QOD) use of antifibrinolytic agents or medications known to influence platelet function such as aspirin or certain NSAIDs - Concomitant therapy with immunosuppressive drugs (e.g., IVIG, routine systemic corticosteroids) - Known hypersensitivity to hamster protein - Unwilling or unable to follow the terms of the protocol The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Assessment of hemostatic efficacy at the end of surgery as determined by the investigator and/or the surgeon using the 4 point ordinal scale below: a) Excellent – Achieved hemostasis comparable to that expected after similar surgery in a non-hemophilic subject b) Good – Prolonged time to hemostasis, with somewhat increased bleeding compared to that expected after similar surgery in a non-hemophilic subject c) Moderate – Obviously delayed hemostasis, but manageable with additional infusions of FVIII d) None – No hemostatic response Safety: evaluations will include routine physical and laboratory examinations, including assessment for FVIII inhibitor development, thrombosis and allergic reactions. All adverse events will be recorded |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |