Intensive Replacement Treatment in Haemophilia Patients With Synovitis

• Status: Not yet recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: Male

Summary

Background: Joint haemorrhage represents the most common type of bleeding episode in persons with hemophilia (PwH). In the absence of an adequate prophylaxis with Factor VIII (for hemophilia A) or FIX (for hemophilia B) concentrates up to 85% of patients with severe hemophilia develop a clinically overt joint disease. Screening of early signs of arthropathy is needed. Synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH.

Aim: To assess if an intensive factor VIII replacement treatment is able at reverting synovitis in PwH.

Methods: The present study is a randomized, open-label, cross-over study. Among patients referred to enrolling Haemophilia Centres, consecutive patients with severe (FVIII < 1%) or severe-moderate (FVIII < 2%) haemophilia A without inhibitors will be enrolled. The present study will be organized in 2 phases.

• Phase 1 (US screening): All patients will undergo an ultrasound examination of elbows, ankles and knees to define joint status and to identify presence/absence of synovitis according to the HEAD-US system.

• Phase 2 (Intervention): Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with my-PK-fit to start a prophylaxis with Adynovi® targeting a 12% FVIII through level (PROPEL-like arm) or to continue ongoing standard treatment (control arm). US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode. After six months the two treatment arm will be switched in the frame of a cross-over approach and all PwH will be followed for other 6 months The primary outcome will be represented by changes in synovial status during the intensive factor VIII replacement treatment vs standard treatment.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Federico II University
• Treatments: BAX 855

Criteria

Inclusion Criteria:

1. Male patients with > 12 years of age, with severe (FVIII < 1%) or severe-moderate (FVIII < 2%) haemophilia A without inhibitors, receiving a prophylactic treatment with FVIII.

2. Evidence at ultrasound evaluation of synovitis (grade 1-2 according to HEAD-US score)

3. Signed and dated informed consent form for data collection prior to enrolment.

Exclusion Criteria:

1. Patients with bleeding disorders other than haemophilia A

2. Patients with anti-FVIII inhibitor (any titer).

3. Patients receiving on-demand treatment with FVIII

4. Patients with liver cirrhosis

5. Any condition that compromises the patient's ability to perform study-related activities or that poses a clinical contraindication to study participation.

6. Patients unwilling or unable to follow the terms of the protocol.