| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| For all patients participating in the trial:Male subjects with severe or moderately severe hemophilia A (FVIII:C ≤ 2%) previously treated with ≥ 150 exposure days to any Factor VIII product.For patients participating in the Pharmacokinetic period of the trial:Male subjects as described immediately above except they must have a Factor VIII:C of ≤ 1% |
|
| 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 |
Safety: To determine the incidence rate of Factor VIII inhibitors in the study patient population
Efficacy: To establish the bioequivalence of ReFacto AF with a full-length recombinant Factor VIII (Advate) using the one stage factor VIII activity assay. |
|
| E.2.2 | Secondary objectives of the trial |
| To characterize the efficacy of ReFacto AF in preventing and treating bleeding episodes during prophylaxis treatment;To characterize the pharmacokinetics of ReFacto AF in comparison to Advate and over time;To characterize the efficacy response of both prophylactic and on- demand infusions of ReFacto AF;To characterize the adverse events;To characterize the rate of “Less than Expected Therapeutic Effect” responses of ReFacto AF when used either prophylactically or for treatment of a bleeding episode (“on-demand”) or in the instance of low recovery;To characterize the consumption of ReFacto AF (international units/kg) over time;To characterize the incidence of allergic reactionsTo characterize patient compliance with prescribed regimen(s) |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| For all patients participating in the trial:- Male subjects with severe or moderately severe hemophilia A (FVIII:C ≤ 2%) previously treated with ≥ 150 exposure days to any Factor VIII product. - Age ≥ 12 years- 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 >400 µL- PT ≤1.25 x ULN or INR ≤ 1.5- Patients receiving therapy for HIV or Hepatitis infection, must be on a stable regimen at the time of study entry- The patient is able to comply with the mandatory 72-hour washout period preceding each FVIII:C and FVIII inhibitor assessment during Visit 1, 4, 5, 7 and 10- The patient must sign and date informed consent and/or assent form, approved by the IRB.The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to inclusion criteriaFor patients participating in the pharmacokinetic period of the trial:- Male subjects as described immediately above except they must have a Factor VIII:C of ≤ 1% confrimed by the central laboratory screening test- The patient’s site has the facilities, in the opinion of the Sponsor, adequate to conduct the Pharmacokinetic analysis- The patient should be able to comply with the mandatory 72 hour washout period preceding each PK period of the study during Visit 2, 3 and 10. |
|
| 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 - Elective surgery planned to occur within an 8 to 9 month period following study entry (i.e., during the course of the study)- 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) |
| Determination of the number of Factor VIII inhibitors in the patient populationDetermination of the safety and efficacy of ReFacto AF in the prevention and treatment of bleeding |
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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 | Yes |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Yes |
| 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) | Yes |
| 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 |
|
| 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
| |
| 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 |
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