A Phase 4 interventional study of Optivate 500IU in Haemophilia A, sponsored by Bio Products Laboratory. Terminated at 4 sites in 3 countries. Per ClinicalTrials.gov, last updated 2021-07-22.
Sponsored by Bio Products Laboratory · Phase 4, Interventional, and Treatment
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
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.
HIV negative or a viral load \< 200 particles / µl.
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®.
Optivate 500IU
Biological: Optivate 500IU
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).
Time frame: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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).
Time frame: Over a period of 12 months
Seven patients were enrolled. One patient in Germany; 4 patients in Colombia and 2 patients in Poland.
| Milestone | Optivate 500IU |
|---|---|
| Started | 7 |
| Completed | 5 |
| Not completed | 2 |
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).
| Participants | Optivate 500IU |
|---|---|
| Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU) | 5 |
Recovery with prior FVIII concentrate (Screening Visit) versus recovery with first dose with Optivate® (Visit 1) for the protocol population.
| IU/dL per IU/kg | Optivate 500IU |
|---|---|
| Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population. | -0.91 (-1.87 to 0.04) |
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.
| IU/dL per IU/kg | Optivate 500IU |
|---|---|
| Optivate® Recovery Across Visits 1 to 4 for the Protocol Population. | -0.01 (-1.72 to 1.70) |
Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months.
| Bleeds per subject per year | Optivate 500IU |
|---|---|
| Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population. | 3.99 ± 2.961 |
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.
| Days | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population. | 116.2 ± 18.12 |
Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months.
| IU/kg | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use. | 3639.97 ± 993.464 |
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.
| IU/kg | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population. | 97.72 ± 117.086 |
Overall consumption of Optivate®: Total number of infusions for prophylactic use per subject in the protocol population.
| Infusions | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population. | 116.8 ± 17.66 |
Total number of infusions to treat a bleed per subject in the protocol population.
| Infusions | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population. | 2.4 ± 3.21 |
Overall consumption of Optivate®: Overall mean dose in IU/kg of Optivate® per subject/year for prophylactic use in the protocol population.
| IU/kg | Optivate 500IU |
|---|---|
| Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population. | 3890.02 ± 1033.993 |
Treatment emergent adverse events (non-serious) in the safety population.
| treatment emergent events | Optivate 500IU |
|---|---|
| Treatment Emergent Adverse Events (Non-serious) in the Safety Population | 5 |
Treatment emergent adverse events (serious) in safety population over a period of 12 months
| treatment emergent events | Optivate 500IU |
|---|---|
| Treatment Emergent Adverse Events (Serious) in Safety Population | 1 |
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).
| Participants | Optivate 500IU |
|---|---|
| Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units) | 0 |
Collected over Over a period of 12 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Optivate 500IU | 1/7 (14.3%) | 2/7 (28.6%) | 3/7 (42.9%) |
| Event | Optivate 500IU |
|---|---|
| Fatal road traffic accidentInjury, poisoning and procedural complications | 1/7 |
| Asthmatic crisisRespiratory, thoracic and mediastinal disorders | 1/7 |
| Event | Optivate 500IU |
|---|---|
| COMMON COLDInfections and infestations | 1/7 |
| ANKLE TRAUMAInjury, poisoning and procedural complications | 1/7 |
| BRONCHOSPASMRespiratory, thoracic and mediastinal disorders | 1/7 |
| SOFT TISSUE TRAUMA LEFT HANDInjury, poisoning and procedural complications | 1/7 |
| ANEMIABlood and lymphatic system disorders | 1/7 |
| HEMARTHROSIS OF RIGHT ELBOWMusculoskeletal and connective tissue disorders | 1/7 |
| GENERAL PAINGeneral disorders | 1/7 |
| JOINT PAINMusculoskeletal and connective tissue disorders | 1/7 |
| HEMARTHROSIS OF RIGHT KNEEMusculoskeletal and connective tissue disorders | 1/7 |
| Age, Categorical(Participants) | Optivate 500IU |
|---|---|
| <=18 years | 2 |
| Between 18 and 65 years | 5 |
| >=65 years | 0 |
| Age, Continuous(Years) | Optivate 500IU |
|---|---|
| Mean | 23.6 ± 7.37 |
| Sex: Female, Male(Participants) | Optivate 500IU |
|---|---|
| Female | 0 |
| Male | 7 |
| Ethnicity (NIH/OMB)(Participants) | Optivate 500IU |
|---|---|
| Hispanic or Latino | 5 |
| Not Hispanic or Latino | 2 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Optivate 500IU |
|---|---|
| Colombia | 4 |
| Poland | 2 |
| Germany | 1 |
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Bio Products Laboratory