A diagnostic interventional, controlled, cross-sectional evaluation of joint status using MRI in subjects with severe hemophilia A treated with primary prophylaxis, secondary prophylaxis, or on-demand therapy - MRI

• Conditions: Severe hemophilia A (< 1% FVIII:C); MedDRA version: 9.1Level: LLTClassification code 10053753Term: Hemophilia A without inhibitors

• Registration Number: EUCTR2009-010147-14-DE
• Lead Sponsor: Bayer Healthcare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-06
• Last Update Posted: 14 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 250

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
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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;Secondary Objective: To compare historical bleeding frequency between treatment groups.<br><br>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.;Primary end point(s): Maximum ankle MRI score