- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03204539
INdividualized ITI Based on Fviii(ATE) Protection by VWF (INITIATE)
INdividualized ITI Based on Fviii(ATE) Protection by VWF (INITIATE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Participants will be randomized on a one-to-one basis between one of two study arms, individualized lot selection (alternative treatment arm) and random lot selection (standard treatment arm, current US clinical practice in ITI). Study sites, participants, and investigators will be blinded to the treatment status assigned.
Alternative treatment arm:
Half of the participants will be randomized to blinded individualized lot selection for ITI. The target initial dose of FVIII for ITI is ~200 IU/kg/day intravenously. The suggested maximum dose is 20,000 IU/day. Investigators may adjust the dose to a minimum dose of 150 units/kg if infusion volume is not feasible in patients without central venous access or in patients with von Willebrand factor levels >250%. Splitting dose into two infusions per day must be approved by the Steering Committee, and if approved, will be considered a protocol deviation. Wilate® will be the VWF/FVIII complex concentrate (Octapharma USA, Inc., U.S. License No. 1646) prescribed for ITI.
Individualized lot selection will be performed according to a modified Oxford method in a central laboratory, by testing subject's plasma against 4-6 lots of Wilate® and selecting the one with the highest residual FVIII (lowest Oxford titer) activity remaining after incubation. The same lot will be used throughout the entire ITI course for each subject. If the selected lot is depleted prior to the completion of ITI, a second individualized lot selection will be performed using the original plasma sample provided at baseline.
Each Wilate® batch includes 1.6-1.8 million IU and is expected to last for about 3-57 months depending on the weight of the subject and prescribed dose.
Standard treatment arm:
The other half of the participants will receive random lot selection for ITI. The dose and concentrate used will be the same. Concentrate will be randomly selected from available Wilate® lots. The same lot will be used throughout the entire ITI course for each subject. If the random lot is depleted prior to the completion of ITI, a second lot will be randomly selected. In both cases the random lot will be tested against subject's plasma to measure the residual FVIII activity left after incubation but this result will not affect lot selection.
The primary hypothesis is that the time to negative inhibitor (<0.6 BU) will be shorter with individualized lot selection compared to random lot selection and that this will impact monthly break-through bleeding and reduce costs.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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-
California
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Sacramento, California, United States, 95817
- University of California, Davis
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San Diego, California, United States, 92123
- Rady Children's Hospital San Diego
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Louisiana
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New Orleans, Louisiana, United States, 70112
- Tulane University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of congenital Hemophilia A and baseline FVIII ≤2%.
- Weight ≥ 5 kg
- History of FVIII inhibitor titer ≥5 BU
- Current FVIII inhibitor titer ≥5 BU or ≥0.6 BU and failed ITI defined by FVIII recovery <66% normal and half-life <6 hours
- Adequate venous access for daily concentrate infusions
- For participants <18 years, a parent or guardian willing and able to provide informed consent with verbal or written assent from the child if require by the local institution. For participants ≥18 years, a willingness and ability to provide informed consent from the subject.
- Ability to comply with study related treatments, evaluations, and follow-up.
Exclusion Criteria:
- Acquired hemophilia
- Congenital or acquired bleeding disorder in addition to Hemophilia A
- ITI factor replacement regimen within the past one month unless there is clear evidence of ITI failure with no reduction in inhibitor titer over the past two months
- HIV positive with viral load ≥200 particles/μL or ≥400,000 copies/mL
- Rituximab within the past 3 months
- IVIG within the past 1 month
- Treatment with other immunosuppressive drugs within the past 1 month (excluding intermittent steroid use for asthma)
- Concomitant experimental treatment
- History of hypersensitivity to plasma-derived VWF- or FVIII-containing concentrates
- Elective surgery planned in the next 6 months (excluding vascular access procedure)
- Any condition or chronic illness, which in the opinion of the investigator makes participation ill-advised
- Inability or unwillingness to complete required screening, follow-up, and exit studies
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Alternative Treatment
Half of the participants will be randomized to blinded individualized lot selection for ITI.
|
Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
|
Other: Standard Treatment
The other half of the participants will receive random lot selection for ITI.
|
Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Negative Inhibitor
Time Frame: completion of immune tolerance induction, up to 18 months
|
This endpoint was chosen because a shorter time to negative inhibitor should decrease monthly break-through bleeding frequency in the early phase of ITI
|
completion of immune tolerance induction, up to 18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Achieve Partial and Complete Success
Time Frame: completion of immune tolerance induction, up to 18 months
|
Secondary endpoints include time to achieve partial and complete success as defined according to the following criteria:
Complete Success (CS) of ITI: All three criteria above met. Partial Success (PS) of ITI: The first two of the three criteria above met. Partial Response (PR) of ITI: One of the three criteria above met. Partial Failure (PF) of ITI: Inhibitor still present, but titer is decreased to <5 BU in contrast to ≥5 BU before start. Complete Failure (CF) of ITI: None of the above mentioned criteria met, and the inhibitor titer is still ≥5 BU. |
completion of immune tolerance induction, up to 18 months
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Absence of Relapse, up to 12 Months After Achievement of Complete or Partial ITI Success
Time Frame: one year after completion of immune tolerance induction, up to 30 months
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one year after completion of immune tolerance induction, up to 30 months
|
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The Number of Break-through Bleeding Events During the Course of ITI-treatment·
Time Frame: completion of immune tolerance induction, up to 18 months
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completion of immune tolerance induction, up to 18 months
|
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Cost of ITI - Including Bleeding Control Using Bypassing Agents Prior to Start and During ITI
Time Frame: completion of immune tolerance induction, up to 18 months
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completion of immune tolerance induction, up to 18 months
|
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Subject Quality of Life
Time Frame: completion of immune tolerance induction, up to 18 months
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measured with the Haemo-QOL questionnaire
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completion of immune tolerance induction, up to 18 months
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Subject Compliance With ITI Treatment Regimen
Time Frame: completion of immune tolerance induction, up to 18 months
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We will be looking at drug accountability reports/ logs which will reflect each subject's usage of Wilate
|
completion of immune tolerance induction, up to 18 months
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The Impact of Inhibitor Titer at Start of ITI and During the Course of ITI, Including the Peak Titer of the Inhibitor
Time Frame: completion of immune tolerance induction, up to 18 months
|
completion of immune tolerance induction, up to 18 months
|
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Understand Other Factors Related to ITI Success Using Additional Biologic Assays
Time Frame: screening/baseline
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If subject consents, the following assays will be performed: epitope mapping immunogenotyping/HLA genotyping FVIII genetic testing |
screening/baseline
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 988465
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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