Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A

Study Overview
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Brief Summary
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Primary objective: To assess post-marketing immunogenicity of Optivate® by monitoring plasma inhibitor levels for at least 100 Exposure Days (EDs) for each subject. Secondary objectives: To assess efficacy and tolerability by monitoring FVIII recovery and adverse events

Detailed Description
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The primary efficacy endpoint is to assess immunogenicity of Optivate® by monitoring plasma inhibitor level for at least 100 EDs for each subject. FVIII inhibitor evaluation FVIII inhibitor screen data will be listed. FVIII quantitative inhibitor results will be listed. Shift tables will present the number of subjects with positive (≥ 0.6 BU) and negative (< 0.6 BU) results and those for whom the results change during the study. The number of exposure days until development of inhibitors will be summarised. For the secondary endpoints: Descriptive statistics will be presented on the number of recoveries at each timepoint and for each subject. These will be presented for each visit and for each subject and then for each batch of FVIII/ Optivate® used. All the AE data (from CRF and study diary) will be pooled together and reported in terms of the type, duration, treatment and/or severity.

Official Title
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Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A

Conditions
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Haemophilia A

Intervention / Treatment
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* Biological: Optivate 500IU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent or, if less than 18 years of age written assent (where possible) and their parent/guardian's written informed consent. Severe haemophilia A (< 1%# FVIII:C). Previously Treated Patients (PTPs) with > 150 exposure days on prior Factor VIII therapy (of which at least the last 50 EDs or 2 years treatment can be confirmed by way of subject records). Immunocompetent with CD4 count > 200 / µl. HIV negative or a viral load < 200 particles / µl. subjects suffering from severe haemophilia A (<2%) may be enrolled, but only after approval by BPL. Subjects with a Factor VIII of <2% may not constitute more than 50% of the total patient population. A separate statistical evaluation will be conducted for the <1% and <2% populations. Exclusion Criteria: • History of inhibitor development to FVIII or a positive result on the Nijmegen Bethesda at screening (quantitative result of > 0.6 BU) prior to the administration of Optivate®. Known or suspected hypersensitivity to the investigational medicinal product or its excipients. Clinically significant liver disease, renal disease, or coagulopathy other than haemophilia A. History of unreliability or non cooperation (including not being able to complete the study diary). Participating in, or have taken part in another trial within the last 30 days.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optivate 500IU<br>Optivate 500IU | Biological: Optivate 500IU<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU) | FVIII inhibitor status at any of the study visits was measured by a Nijmegen Bethesda assay and inhibitor screens. A result of ≥ 0.6 BU confirmed that the subject had developed inhibitors to FVIII. If this occurred, the test was repeated on a separate sample; if both tests were confirmed to be ≥ 0.6 BU, this was to be reported by the Investigator as a serious adverse event (SAE). | At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population. | Recovery with prior FVIII concentrate (Screening Visit) versus recovery with first dose with Optivate® (Visit 1) for the protocol population. | Screening and Visit 1 (up to 4 weeks) | 
| Optivate® Recovery Across Visits 1 to 4 for the Protocol Population. | A recovery assessment was conducted at each study visit. Recovery assessments were only conducted after a 3-day washout period and when the subject was not actively bleeding. At the Screening Visit, subjects who had completed a 3-day washout period and were not actively bleeding were dosed with 30 IU/kg of their prior FVIII concentrate. The dose was measured to the nearest 0.1 mL. Blood samples for the recovery assessment were to be collected at the following time points: Predose 15 minutes postinfusion (±5 minutes). 30 minutes postinfusion (±5 minutes). 1 hour postinfusion (±10 minutes). Actual times of sample collection were to be recorded in the CRF At visits 1, 2, 3 and 4 subjects were dosed with 30 IU/kg of Optivate and blood samples for recovery assessments were taken at the same timepoints as specified above. An ANOVA model (analysis of variance) was used to calculate the adjusted mean for recovery across visits 1 to 4. | Visits 1 to 4 (Up to 100 Optivate exposure days) | 
| Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population. | Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population. | Overall consumption of Optivate®: Number of exposure days for each subject per year/subject in the per protocol population over a period of 12 months. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use. | Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population. | Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject to treat a bleed in the protocol population over a period of 12 months. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population. | Overall consumption of Optivate®: Total number of infusions for prophylactic use per subject in the protocol population. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population. | Total number of infusions to treat a bleed per subject in the protocol population. | Over a period of 12 months | 
| Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population. | Overall consumption of Optivate®: Overall mean dose in IU/kg of Optivate® per subject/year for prophylactic use in the protocol population. | Over a period of 12 months | 
| Treatment Emergent Adverse Events (Non-serious) in the Safety Population | Treatment emergent adverse events (non-serious) in the safety population. | Over a period of 12 months | 
| Treatment Emergent Adverse Events (Serious) in Safety Population | Treatment emergent adverse events (serious) in safety population over a period of 12 months | Over a period of 12 months | 
| Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units) | Inhibitor Development: Positive FVIII inhibitor status in safety population measured by ≥0.6 Bethesda units (this was a safety measurement but was assessed as a primary efficacy endpoint). | Over a period of 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemophilia A