Not provided
Not provided
Not provided
Not provided
Not provided
Study no longer required as Optivate German license expired in Sep-2017.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Optivate 500IU | Experimental | Optivate 500IU |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Optivate 500IU | Biological |
|
| 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 |
| 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) |
Not provided
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.
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®.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Eric Wolford | Bio Products Laboratory | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fundacion BIOS | Barranquilla | 80-216 | Colombia | |||
| Hospital general de Medellin |
Not provided
Seven patients were enrolled. One patient in Germany; 4 patients in Colombia and 2 patients in Poland.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Optivate 500IU | Optivate 500IU Optivate 500IU |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Optivate 500IU | Optivate 500IU Optivate 500IU |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Patients who completed at least 100 exposure days to Optivate. | Posted | Count of Participants | Participants | At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months |
|
Over a period of 12 months
Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Optivate 500IU | Optivate 500IU Optivate 500IU | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatal road traffic accident | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COMMON COLD | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| European Medical Affairs Lead | Bio Products Laboratory Ltd | +44 20 8957 2200 | medinfo@bpl.co.uk |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 30, 2015 | Nov 12, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 21, 2013 | Nov 12, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C568131 | optivate |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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:
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 |
| Medellín |
| 32-102 |
| Colombia |
| HZRM Haemophilia Centre Rhine Main | Darmstadt | Mörfelden-Walldorf | 64546 | Germany |
| Wojewodzki Szpital Specjalistyczny im. M. Kopernika | Lodz | 93-513 | Poland |
| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | 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. | Recovery with prior FVIII concentrate (Screening Visit) versus first dose with Optivate® (Visit 1) for the protocol population. | Posted | Mean | 95% Confidence Interval | IU/dL per IU/kg | Screening and Visit 1 (up to 4 weeks) |
|
|
|
| Secondary | 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:
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. | Posted | Mean | 95% Confidence Interval | IU/dL per IU/kg | Visits 1 to 4 (Up to 100 Optivate exposure days) |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Bleeds per subject per year | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Days | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | IU/kg | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | IU/kg | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Infusions | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Infusions | Over a period of 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | IU/kg | Over a period of 12 months |
|
|
|
| Secondary | Treatment Emergent Adverse Events (Non-serious) in the Safety Population | Treatment emergent adverse events (non-serious) in the safety population. | A total of 3 patients experienced treatment emergent adverse events. | Posted | Number | treatment emergent events | Over a period of 12 months |
|
|
|
| Secondary | Treatment Emergent Adverse Events (Serious) in Safety Population | Treatment emergent adverse events (serious) in safety population over a period of 12 months | One patient experienced a treatment emergent adverse event (serious). | Posted | Number | treatment emergent events | Over a period of 12 months |
|
|
|
| Secondary | 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). | Posted | Count of Participants | Participants | Over a period of 12 months |
|
|
|
| 7 |
| 2 |
| 7 |
| 3 |
| 7 |
| Asthmatic crisis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| ANKLE TRAUMA | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| BRONCHOSPASM | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| SOFT TISSUE TRAUMA LEFT HAND | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| ANEMIA | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
|
| HEMARTHROSIS OF RIGHT ELBOW | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| GENERAL PAIN | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| JOINT PAIN | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| HEMARTHROSIS OF RIGHT KNEE | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
Not provided
Not provided
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |