Back to resultsPost-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
Primary Purpose
Haemophilia A
Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Optivate 500IU
Sponsored by
About this trial
This is an interventional treatment trial for Haemophilia A focused on measuring Haemophilia A
Eligibility Criteria
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.
Sites / Locations
- Fundacion BIOS
- Hospital general de Medellin
- HZRM Haemophilia Centre Rhine Main
- Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Optivate 500IU
Arm Description
Optivate 500IU
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Treatment Emergent Adverse Events (Non-serious) in the Safety Population
Treatment emergent adverse events (non-serious) in the safety population.
Treatment Emergent Adverse Events (Serious) in Safety Population
Treatment emergent adverse events (serious) in safety population 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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01811875
Brief Title
Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
Official Title
Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
Study no longer required as Optivate German license expired in Sep-2017.
Study Start Date
November 21, 2014 (Actual)
Primary Completion Date
August 31, 2017 (Actual)
Study Completion Date
August 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio Products Laboratory
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Haemophilia A
Keywords
Haemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Optivate 500IU
Arm Type
Experimental
Arm Description
Optivate 500IU
Intervention Type
Biological
Intervention Name(s)
Optivate 500IU
Primary Outcome Measure Information:
Title
Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU)
Description
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).
Time Frame
At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
Secondary Outcome Measure Information:
Title
Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population.
Description
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)
Title
Optivate® Recovery Across Visits 1 to 4 for the Protocol Population.
Description
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.
Time Frame
Visits 1 to 4 (Up to 100 Optivate exposure days)
Title
Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population.
Description
Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months.
Time Frame
Over a period of 12 months
Title
Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population.
Description
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.
Time Frame
Over a period of 12 months
Title
Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.
Description
Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months.
Time Frame
Over a period of 12 months
Title
Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population.
Description
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.
Time Frame
Over a period of 12 months
Title
Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population.
Description
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
Title
Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population.
Description
Total number of infusions to treat a bleed per subject in the protocol population.
Time Frame
Over a period of 12 months
Title
Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population.
Description
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
Title
Treatment Emergent Adverse Events (Non-serious) in the Safety Population
Description
Treatment emergent adverse events (non-serious) in the safety population.
Time Frame
Over a period of 12 months
Title
Treatment Emergent Adverse Events (Serious) in Safety Population
Description
Treatment emergent adverse events (serious) in safety population over a period of 12 months
Time Frame
Over a period of 12 months
Title
Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)
Description
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).
Time Frame
Over a period of 12 months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Wolford
Organizational Affiliation
Bio Products Laboratory
Official's Role
Study Director
Facility Information:
Facility Name
Fundacion BIOS
City
Barranquilla
ZIP/Postal Code
80-216
Country
Colombia
Facility Name
Hospital general de Medellin
City
Medellin
ZIP/Postal Code
32-102
Country
Colombia
Facility Name
HZRM Haemophilia Centre Rhine Main
City
Darmstadt
State/Province
Mörfelden-Walldorf
ZIP/Postal Code
64546
Country
Germany
Facility Name
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
City
Lodz
ZIP/Postal Code
93-513
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
We'll reach out to this number within 24 hrs