Clinical trial NCT01811875: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Haemophilia A
Keywords: Haemophilia A
Lead sponsor: Bio Products Laboratory
Sponsor class: OTHER
First posted: 2013-03-15
Enrollment: 7
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU)
timeFrame: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
Secondary outcomes:
measure: Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population.
timeFrame: Screening and Visit 1 (up to 4 weeks)
measure: Optivate® Recovery Across Visits 1 to 4 for the Protocol Population.
timeFrame: Visits 1 to 4 (Up to 100 Optivate exposure days)
measure: Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population.
timeFrame: Over a period of 12 months
measure: Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population.
timeFrame: Over a period of 12 months
measure: Treatment Emergent Adverse Events (Non-serious) in the Safety Population
timeFrame: Over a period of 12 months
measure: Treatment Emergent Adverse Events (Serious) in Safety Population
timeFrame: Over a period of 12 months
measure: Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)
timeFrame: Over a period of 12 months
Other outcomes:
Locations:
city: Barranquilla
country: Colombia
facility: Fundacion BIOS
city: Medellin
country: Colombia
facility: Hospital general de Medellin
city: Darmstadt
country: Germany
facility: HZRM Haemophilia Centre Rhine Main
state: Mörfelden-Walldorf
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Study officials:
affiliation: Bio Products Laboratory
name: Eric Wolford
role: STUDY_DIRECTOR
References: