- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01811875
Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
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
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Barranquilla, Colombia, 80-216
- Fundacion BIOS
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Medellin, Colombia, 32-102
- Hospital General de Medellin
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Mörfelden-Walldorf
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Darmstadt, Mörfelden-Walldorf, Germany, 64546
- HZRM Haemophilia Centre Rhine Main
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Lodz, Poland, 93-513
- Wojewodzki Szpital Specjalistyczny im. M. Kopernika
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Optivate 500IU
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU)
Time Frame: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
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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).
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At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population.
Time Frame: Screening and Visit 1 (up to 4 weeks)
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Recovery with prior FVIII concentrate (Screening Visit) versus recovery with first dose with Optivate® (Visit 1) for the protocol population.
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Screening and Visit 1 (up to 4 weeks)
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Optivate® Recovery Across Visits 1 to 4 for the Protocol Population.
Time Frame: Visits 1 to 4 (Up to 100 Optivate exposure days)
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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:
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)
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Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population.
Time Frame: Over a period of 12 months
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Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months.
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Over a period of 12 months
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Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population.
Time Frame: Over a period of 12 months
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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.
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Over a period of 12 months
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Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.
Time Frame: Over a period of 12 months
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Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months.
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Over a period of 12 months
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Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population.
Time Frame: Over a period of 12 months
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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.
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Over a period of 12 months
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Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population.
Time Frame: Over a period of 12 months
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Overall consumption of Optivate®: Total number of infusions for prophylactic use per subject in the protocol population.
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Over a period of 12 months
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Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population.
Time Frame: Over a period of 12 months
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Total number of infusions to treat a bleed per subject in the protocol population.
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Over a period of 12 months
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Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population.
Time Frame: Over a period of 12 months
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Overall consumption of Optivate®: Overall mean dose in IU/kg of Optivate® per subject/year for prophylactic use in the protocol population.
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Over a period of 12 months
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Treatment Emergent Adverse Events (Non-serious) in the Safety Population
Time Frame: Over a period of 12 months
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Treatment emergent adverse events (non-serious) in the safety population.
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Over a period of 12 months
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Treatment Emergent Adverse Events (Serious) in Safety Population
Time Frame: Over a period of 12 months
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Treatment emergent adverse events (serious) in safety population over a period of 12 months
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Over a period of 12 months
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Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)
Time Frame: Over a period of 12 months
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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).
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Over a period of 12 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 8VWF07
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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