Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens

Severe Haemophilia A Clinical Trial

— PERSONAL  

Official title:

Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02314325
• Other study ID #: 2013-003240-23
• Status: Recruiting
• Phase: Phase 4
• First received: September 3, 2014
• Last updated: December 10, 2014
• Start date: April 2014
• Est. completion date: October 2016

Study information

• Verified date: December 2014
• Source: St. James's Hospital, Ireland
• Contact: Michelle M Lavin, FRCPath
• Phone: +35314162142
• Email: mlavin[@]stjames.ie
• Is FDA regulated: No
• Health authority: Ireland: Irish Medicines Board
• Study type: Interventional

Clinical Trial Summary

This trial is designed to assess if there is evidence of subclinical joint bleeding on MRI/X-Ray in adults with severe Haemophilia A while on standard and/or pharmacokinetically tailored prophylaxis regimens. Participants with severe Haemophilia A will have longitudinal MRI and XRay imaging of their elbows, ankles and knees at 0, 6 and 18 months while on standard ( 0-6 months) and then pharmacokinetically tailored (7-18 months) recombinant Factor VIII prophylaxis.

Description:

Subclinical joint bleeding (SJB) in Haemophilia may cause early and progressive joint damage. Clinical haemarthrosis is a traditional outcome measure in Haemophilia trials but may not always correlate with the degree of arthropathy. Even in the absence of haemarthrosis, abnormalities may be detected on MRI. MRI offers greater sensitivity than physical examination for early joint damage and use of the International Prophylaxis Study Group (IPSG) score allows standardisation across clinical trials. Early awareness of haemophiliac arthropathy can prompt intervention with physiotherapy, specific exercise programmes, optimization of prophylaxis and orthotics to improve overall joint outcomes.

The time spent with Factor VIII (FVIII) levels <0.01 IU/mL is a known risk for bleeding. Conventional prophylaxis schedules follow a weight based regimen and are titrated according to clinical bleeds. FVIII pharmacokinetics (PK) may be used to optimise FVIII prophylactic regimens, maintaining adequate FVIII trough levels. This offers the possibility to not only tailor individual regimens but also may potentially reduce the rate of clinical and subclinical joint bleeding.

This is a national, investigator led clinical trial investigating the feasibility of PK tailored prophylaxis in adults with severe Haemophilia A. This trial will prospectively and longitudinally assess SJB and joint health in Irish adults with severe Haemophilia A.

SJB will be compared while on standard (weight based, 20-40 IU/kg) and PK tailored prophylaxis(maintaining trough FVIII > 0.015 IU/mL). This is a crossover study will participants spending months 0-6 on standard prophylaxis and then changing over to PK tailored dosing for months 7-18. A comprehensive joint assessment involving bleed history, clinical examination, physical activity, specialist physiotherapy review, X-rays and MRI scanning of bilateral ankles, knees and elbow will be performed at months 0,6 and 18. Haemophilia Joint Health Score (HJHS), International Physical Activity (IPAQ) and EuroQoL 5-Dimensions (EQ5D) Questionnaires will also be performed at these three timepoints.

Clinical bleeds and FVIII usage will be recorded throughout the trial using the investigators Home Scan system, a smart phone application that allows patients to log factor VIII usage.

Results will be compared between both arms and between participants on primary and secondary prophylaxis. Information on those with naïve joints versus established arthropathy will be compared.

Due to the relative rarity of severe Haemophilia A the investigators plan to recruit 20 patients in total. All patients will act as their own control, crossing over from standard to PK tailored prophylaxis with joint assessments prior to crossover to allow comparison of the two regimes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male patients with severe Haemophilia A (baseline Factor VIII level of <0.01 IU/mL)

• Age 18 years and above

• Patients taking any regular prophylactic regimen (defined as regular factor VIII infusions, at least 5 times a fortnight, with the aim of minimising haemarthroses and other clinically significant bleeds).

• Low titre inhibitors, past history of an inhibitor, abnormal liver function, drugs that interfere with haemostasis and low Cluster of Differentiation 4 (CD4) counts are allowed.

Exclusion Criteria:

• Presence of a target joint on prophylaxis (defined as 3 bleeds into one joint, during a 6 month period, during the last year).

• The occurrence of more than 3 haemarthroses in the last year that required more than 2 infusions to resolve.

• Patients with a learning disability or dementia

• Prisoners

• Adults who are unconscious/unable to give informed consent

• Participants with a pacemaker or implanted medical devices which are unsuitable to have a MRI will be excluded from the MRI scans during the trial but may proceed with other components.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Hemarthrosis
• Hemophilia A
• Severe Haemophilia A

Intervention

Drug:
• ADVATE [Antihemophilic Factor (Recombinant)]
In Arm 1 prior patients will be dosed as per body weight 20-40 IU/kg 5-7 infusions per fortnight
• ADVATE [Antihemophilic Factor (Recombinant)]
In Arm 2 patients who have completed arm 1 will cross over onto an individualised PK tailored alternate day dosing regimen

Locations

Country	Name	City	State
Ireland	St. James's Hospital	Dublin

Sponsors (2)

Lead Sponsor	Collaborator
St. James's Hospital, Ireland	Baxter BioScience

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subclinical haemarthroses	The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints	18 months	Yes
Secondary	EQ5D QoL score	Comparison of score on EQ5D Quality of life questionnaire on standard versus PK tailored dosing	18 months	No
Secondary	Percentage of prescribed doses of prophylaxis taken	The number of missed doses of prophylaxis on the standard and PK tailored dosing regimens	18 months	No
Secondary	IPAQ score	Comparison of IPAQ activity scores (numeric) on standard versus PK tailored dosing	18 months	No
Secondary	Haemophilia joint health score (HJHS)	Comparison of HJHS numeric score on standard versus PK tailored dosing	18 months	No
Secondary	Amount of FVIII usage (units)	Comparison of FVIII usage in units on standard versus PK tailored dosing	18 months	No
Secondary	MRI joint score	Comparison of joint score (numeric) determined on MRI by the International prophylaxis study group (IPSG) score	18 months	No
Secondary	Petterson joint score	Comparison of Petterson joint score (numeric) on plain films for patients on standard versus PK tailored dosing	18 months	No
Secondary	Number of clinical haemarthroses	Number of patient reported haemarthroses on standard prophylaxis versus PK tailored prophylaxis	18 months	Yes