Haemophilia APhase 4NCT01811875
Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
A Phase 4 study testing Optivate 500IU in people with Haemophilia A, run by Bio Products Laboratory at 4 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Haemophilia A
- What is being tested?
- Optivate 500IU
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 21 Nov 2014to 31 Aug 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- • 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.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Colombia2 sites
Fundacion BIOS
Barranquilla, 80-216
Hospital general de Medellin
Medellín, 32-102
Germany1 site
HZRM Haemophilia Centre Rhine Main
Darmstadt, Mörfelden-Walldorf, 64546
About this study
Official title: 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
Read the 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.
- Conditions
- Haemophilia A
- Being tested
- Optivate 500IU
- Keywords
- Haemophilia A
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optivate 500IUBiological
| Study group | Role | What they receive |
|---|---|---|
| Optivate 500IU | Experimental | Optivate 500IU Receives: Biological: Optivate 500IU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: Over a period of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2013 (estimated)
- Study start21 Nov 2014
- Primary completion31 Aug 2017
- Study completion31 Aug 2017
Why it stopped: Study no longer required as Optivate German license expired in Sep-2017.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Haemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio Products Laboratory
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric Wolford, Study director, Bio Products Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01811875
- Sponsor's protocol ID
- 8VWF07
- Status last verified
- Jul 2021
- First submitted
- 13 Mar 2013
- Last updated
- 22 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
- ClinicalTrials.gov ID
- NCT01811875
- Acronym / sponsor ID
- 8VWF07
- Conditions
- Haemophilia A
- Keywords
- Haemophilia A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study no longer required as Optivate German license expired in Sep-2017.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Bio Products LaboratoryUniversity, hospital or other
- Study start
- 21 Nov 2014 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 31 Aug 2017 (actual)
- First posted
- 15 Mar 2013 (estimated)
- Results
- Posted 22 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Optivate 500IU | Experimental | Biological: Optivate 500IUOptivate 500IU |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- • 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®.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Optivate 500IU | Biological | Optivate 500IU |
Primary outcome
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
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).
12 secondary outcomes
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.
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.
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.
Time frame: Over a period of 12 months
Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.
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.
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.
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.
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.
Time frame: Over a period of 12 months
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
Time frame: Over a period of 12 months
Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)
Time frame: Over a period of 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Haemophilia A
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Wolford study director
Bio Products Laboratory
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Optivate 500IU in people with Haemophilia A, run by Bio Products Laboratory at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Colombia, Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2021.