Intensive Replacement Treatment in Haemophilia Patients With Synovitis

NCT04784988 | Completed Phase 4

• 1 other identifier: IISR-2020-103302
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemophilia A

Keywords

Haemophilia; synovitis; ultrasound

Outcome Measures

Primary Outcomes (1)

• changes in synovitis

  The primary outcome of the present study is to assess if an intensive factor VIII replacement treatment is able at reverting synovitis in persons with haemophilia (PwH).

  from baseline up to 6 months

Study Arms (2)

PROPEL-like arm

EXPERIMENTAL

EHL-FVIII prophylaxis targeting a 12% FVIII through level based on PK assessment with WAPPS-Hemo

Drug: EHL-FVIII

Control arm

ACTIVE COMPARATOR

standard treatment with FVIII concentrate according to current guidelines

Drug: FVIII concentrate

Interventions

EHL-FVIII DRUG

prophylaxis with EHL-FVIII targeting a 12% FVIII through level based on PK assessment with WAPPS-Hemo

PROPEL-like arm

FVIII concentrate DRUG

standard prophylaxis with FVIII concentrate according to current guidelines

Control arm

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Evidence at ultrasound evaluation of synovitis (grade 1-2 according to HEAD-US score)
• Signed and dated informed consent form for data collection prior to enrolment.

You may not qualify if:

• Patients with bleeding disorders other than haemophilia A
• Patients with anti-FVIII inhibitor (any titer).
• Patients receiving on-demand treatment with FVIII
• Patients with liver cirrhosis
• Any condition that compromises the patient's ability to perform study-related activities or that poses a clinical contraindication to study participation.
• Patients unwilling or unable to follow the terms of the protocol.

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

Matteo Di Minno

Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Hemophilia A; Synovitis

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Joint Diseases; Musculoskeletal Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: March 5, 2021
• Study Start: March 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: March 27, 2024

Record last verified: 2024-03

Locations

IT (1)