Severe Haemophilia APhase 4PERSONALNCT02314325
Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens
A Phase 4 study testing ADVATE [Antihemophilic Factor (Recombinant)] in people with Severe Haemophilia A, run by St. James's Hospital, Ireland at 1 site in Ireland.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Severe Haemophilia A
- What is being tested?
- ADVATE [Antihemophilic Factor (Recombinant)]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIreland
- Study dates
- Apr 2014to Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Niamh M O'Connell, FRCPath contact
Ireland1 site, 1 recruiting
- Recruiting
St. James's Hospital
Dublin, Dublin, D8
Niamh M O'Connell, FRCPath,PhD
About this study
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.
Read the detailed 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.
- Conditions
- Severe Haemophilia A
- Being tested
- ADVATE [Antihemophilic Factor (Recombinant)]
- Keywords
- Factor VIII deficiency, Arthropathy, MRI, XRay, Joint, HJHS
- Medical subject headings
- Hemophilia A, Joint Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADVATE [Antihemophilic Factor (Recombinant)]Drug
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)]Drug
In Arm 2 patients who have completed arm 1 will cross over onto an individualised PK tailored alternate day dosing regimen
| Study group | Role | What they receive |
|---|---|---|
| Standard prophylaxis | Active comparator | Advate [Antihemophilic Factor(Recombinant)] 20-40 IU/kg 5-7 infusions per 14days Receives: Drug: ADVATE [Antihemophilic Factor (Recombinant)] |
| Pharmacokinetic tailored prophylaxis | Experimental | Advate [Antihemophilic Factor(Recombinant)] dose determined by individual patient pharmacokinetics and infusions administerd on alternate days Receives: Drug: ADVATE [Antihemophilic Factor (Recombinant)] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subclinical haemarthroses
The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints
Measured: 18 months
Secondary outcomes (8)
EQ5D QoL score
Comparison of score on EQ5D Quality of life questionnaire on standard versus PK tailored dosing
Measured: 18 months
Percentage of prescribed doses of prophylaxis taken
The number of missed doses of prophylaxis on the standard and PK tailored dosing regimens
Measured: 18 months
IPAQ score
Comparison of IPAQ activity scores (numeric) on standard versus PK tailored dosing
Measured: 18 months
Haemophilia joint health score (HJHS)
Comparison of HJHS numeric score on standard versus PK tailored dosing
Measured: 18 months
Amount of FVIII usage (units)
Comparison of FVIII usage in units on standard versus PK tailored dosing
Measured: 18 months
MRI joint score
Comparison of joint score (numeric) determined on MRI by the International prophylaxis study group (IPSG) score
Measured: 18 months
Petterson joint score
Comparison of Petterson joint score (numeric) on plain films for patients on standard versus PK tailored dosing
Measured: 18 months
Number of clinical haemarthroses
Number of patient reported haemarthroses on standard prophylaxis versus PK tailored prophylaxis
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study startApr 2014
- Primary completionMay 2016 (estimated)
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Haemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. James's Hospital, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter BioScience
- Responsible party
- Principal investigator, Dr. Niamh O'Connell, St. James's Hospital, Ireland
- Investigators
- Niamh M O'Connell, PhD, FRCPath, Principal investigator, St. James's Hospital, IrelandJames O'Donnell, PhD, FRCPath, Principal investigator, St. James's Hospital, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02314325
- Sponsor's protocol ID
- 2013-003240-23
- Acronym
- PERSONAL
- Status last verified
- Dec 2014
- First submitted
- 3 Sep 2014
- Last updated
- 11 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subclinical Joint Bleeding in Irish Adults With Severe Haemophilia A on Personalised Prophylaxis Regimens
- ClinicalTrials.gov ID
- NCT02314325
- Acronym / sponsor ID
- PERSONAL / 2013-003240-23
- Conditions
- Severe Haemophilia A
- Keywords
- Factor VIII deficiency, Arthropathy, MRI, XRay, Joint, HJHS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- St. James's Hospital, IrelandUniversity, hospital or other
- Collaborators
- Baxter BioScience
- Study start
- Apr 2014
- Primary completion
- May 2016 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard prophylaxis | Active comparator | Drug: ADVATE [Antihemophilic Factor (Recombinant)]Advate [Antihemophilic Factor(Recombinant)] 20-40 IU/kg 5-7 infusions per 14days |
| Pharmacokinetic tailored prophylaxis | Experimental | Drug: ADVATE [Antihemophilic Factor (Recombinant)]Advate [Antihemophilic Factor(Recombinant)] dose determined by individual patient pharmacokinetics and infusions administerd on alternate days |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | Standard prophylaxis |
| 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 | Drug | Pharmacokinetic tailored prophylaxis |
Primary outcome
Number of subclinical haemarthroses
Time frame: 18 months
The number of subclinical haemarthroses identifed on serial MRI scans of elbow, knee and ankle joints
8 secondary outcomes
EQ5D QoL score
Time frame: 18 months
Percentage of prescribed doses of prophylaxis taken
Time frame: 18 months
IPAQ score
Time frame: 18 months
Haemophilia joint health score (HJHS)
Time frame: 18 months
Amount of FVIII usage (units)
Time frame: 18 months
MRI joint score
Time frame: 18 months
Petterson joint score
Time frame: 18 months
Number of clinical haemarthroses
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niamh M O'Connell, FRCPath contact
Niamh M O'Connell, PhD, FRCPath principal investigator
St. James's Hospital, Ireland
James O'Donnell, PhD, FRCPath principal investigator
St. James's Hospital, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ADVATE [Antihemophilic Factor (Recombinant)] in people with Severe Haemophilia A, run by St. James's Hospital, Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michelle M Lavin, FRCPath (+35314162142, mlavin@stjames.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subclinical haemarthroses (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2014.