E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A or B and a high titer inhibitor |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056492 |
E.1.2 | Term | Haemophilia A with anti factor VIII |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056494 |
E.1.2 | Term | Haemophilia B with anti factor IX |
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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 demonstrate that the annualized rate of all types of bleeds in subjects on the prophylaxis arm is less than that of the subjects on the on-demand arm. |
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E.2.2 | Secondary objectives of the trial |
Efficacy: - To characterize the bleeding episodes requiring treatment between the 2 treatment regimens. - To determine the efficacy of FEIBA NF for the control of bleeding episodes. Safety: - To evaluate the safety of prophylactic treatment versus on-demand treatment with FEIBA NF. Pharmacoeconomic and Quality of Life Parameters: - To determine differences in HRQoL between prophylactic and on-demand treatment regimens. - To determine pharmacoeconomic differences between prophylactic and on-demand treatment regimens. Exploratory Objective: - Evaluation of Thrombin Generation Assay (TGA) parameters for hemostatic efficacy correlation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed and dated informed consent form by the subject or the subject’s legally authorized representative - The subject is ≥ 4 to ≤ 65 years of age - The subject has Karnofsky performance score of ≥ 60 - Hemophilia A and B of any severity, with documented history of high-titer inhibitor (>5BU) for at least 12 months; or, if inhibitor titer is ≤ 5 BU, and the subject is refractory with increased dosing of either FVIII or FIX, as demonstrated from the subject’s medical history - Currently being treated on an on-demand basis for treatment of bleeding episodes - Adequate venous access, with or without central venous device - >/= 12 bleeding episodes requiring treatment with by-passing agents in the past 12 months, based on medical history - Competent in home treatment and infusion therapy - Currently using bypassing agents (APCCs, or rFVIIa) for treatment of bleeding episodes - HCV-, either by antibody testing or PCR; or HCV+ with stable hepatic disease - HIV-, or HIV+ with stable disease and CD4 count > 200 cells/mm3 at screening
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E.4 | Principal exclusion criteria |
- Currently receiving immune tolerance induction (ITI) - Currently on regular prophylactic therapy to prevent bleeding episodes - Clinically symptomatic liver disease (e.g. diagnosis of cirrhosis, [liver biopsy confirmed], portal vein hypertension, ascites, prothrombin time (PT) 5 seconds above upper limit of normal) - Platelet count < 100,000/ml - Planned elective surgery during participation in this study - Subject is currently participating in another clinical study and has received an investigational product or device within 30 days prior to study entry - Planned use of pegylated and non-pegylated alpha-interferon with or without ribavarin for HCV infected subjects or planned use of a protease inhibitor for HIV infected subjects. Subjects currently taking any of these medications for a 30-day course are eligible - D-dimer levels twice the upper level of normal - Known hypersensitivity to AICCs - Currently treated with a systemic immunomodulating drug - Prior history of thromboembolic event: acute myocardial infarction, deep vein thrombosis, pulmonary embolism - Diagnosis of advanced atherosclerosis, malignancy and/or other diseases that may increase the subject’s risk of thromboembolic complications - Clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
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E.5 End points |
E.5.1 | Primary end point(s) |
A reduction in the annualized bleed rate among subjects receiving prophylactic treatment as compared to those treated on-demand. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Exploratory for hemostatic efficacy- Trombin Generation Assay |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
prophylactic treatment versus on-demand treatment with the same IMP |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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 | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |