E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hemophilia A (< 1% FVIII:C) |
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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 | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
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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 evaluate bone and cartilage damage at different ages using MRI in four index joints of subjects with severe hemophilia A in relation to previous treatment schedule of primary or secondary prophylaxis with start at different ages, comparing to subjects who received only on-demand therapy |
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E.2.2 | Secondary objectives of the trial |
To compare historical bleeding frequency between treatment groups.
Other objectives: evaluating bone and cartilage damage in index joints by subject age, correlating MRI findings with clinical joint function evaluation, comparing subject-reported quality-of-life between the treatment groups, and determining the feasibility of imaging four index joints during a single MRI procedure in subjects of various age groups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Test subjects (for MRI quality assessment) ----------------------------------------------------- • Males aged 18 - 35 years • Severe hemophilia A (< 1% FVIII:C) • Written informed consent by subject
Investigation subjects only (subjects participating in the full investigation) --------------------------------------------------------------------------------------------- • Males aged 12 - 35 years • Severe hemophilia A ( < 1 % FVIII:C) • No history of Factor VIII inhibitory antibody measured using the Bethesda assay (< 0.6 BU/ml) • For prophylaxis groups, having received at least two prophylactic infusions per week for 45 weeks per year for the prevention of bleeding without relevant interruption for a consecutive period beginning at prophylaxis initiation and continuing until the present. Relevant interruption is defined as having received therapy that does not qualify as prophylaxis by the above definition or missing documentation of bleeds and consumption for more than 12 consecutive months. • Complete documentation of joints bleeds and their locations prior to start of primary prophylaxis, documentation of the joint status or the joint bleeds and their location of the previous 6 months before start in case of secondary prophylaxis. • Bleeding history and/or treatments received during the last 5 years documented in the subjects’ medical records. The minimum data required is the number and location of joint bleeds, treatment schedule, and Factor VIII consumption over the last 5 years. • For the on-demand subjects > 12 bleeds/year in the last 5 years. • Written informed consent by subject and parent/legal representative, if < 18 years |
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E.4 | Principal exclusion criteria |
Test subjects (for MRI quality assessment) ----------------------------------------------------- • Individuals for whom high-magnetic exposure is contraindicated • Individuals who, in the opinion of the physician, would not be able to meet the requirements of the MRI technique
Investigation subjects only (subjects participating in the full investigation) --------------------------------------------------------------------------------------------- • Individuals with other coagulopathies (e.g., von Willebrand disease) • HIV seropositive subjects • Individuals for whom the most clinically severe joint is not one of the 4 index joints (ankle, knee) • HCV seropositive individuals who underwent interferon therapy during the last 12 months • Individuals for whom high-magnetic exposure is contraindicated (see section 7.1) • Individuals who, in the opinion of the physician or parent/guardian, would not be able to meet the requirements of the MRI technique • Synovectomy performed within the six months prior to investigation enrollment or orthopedic surgery planned to be performed within the investigation period • Joint replacement • For the on-demand treatment group, any period greater than 8 consecutive months having received ≥ 50 IU per kg per week Factor VIII for the prevention of bleeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Epidemiological, cross-sectional, interventional |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
5 factor VIII treatment/prophylaxis regimen strata (horizontally), 4 age groups (vertically) |
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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 |
retrospective comparison of 5 factor VIII treatment/prophylaxis regimens |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | 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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |