INdividualized ITI Based on Fviii(ATE) Protection by VWF
Condition: Hemophilia A With Inhibitor; Hemophilia A
MeSH terms: Hemophilia A
Intervention: Wilate
Intervention description: 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.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1.0
Sex: Male
Healthy volunteers: No
Keywords: inhibitor; Factor VIII inhibitor

Summary:

      The primary goal of the INITIATE trial is to compare the clinical outcome of individualized
      lot selection to random lot selection utilizing one plasma-derived von Willebrand factor
      (VWF)/coagulation factor (FVIII) complex concentrate for immune tolerance induction (ITI) in
      subjects with congenital Hemophilia A, FVIII activity ≤2%, and a historical high-titer
      inhibitor [≥5 Bethesda Unit (BU)].
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of congenital Hemophilia A and baseline FVIII ≤2%.

          2. Weight ≥ 5 kg

          3. History of FVIII inhibitor titer ≥5 BU

          4. Current FVIII inhibitor titer ≥5 BU or ≥0.6 BU and failed ITI defined by FVIII
             recovery <66% normal and half-life <6 hours

          5. Adequate venous access for daily concentrate infusions

          6. 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.

          7. Ability to comply with study related treatments, evaluations, and follow-up.

        Exclusion Criteria:

          1. Acquired hemophilia

          2. Congenital or acquired bleeding disorder in addition to Hemophilia A

          3. 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

          4. HIV positive with viral load ≥200 particles/μL or ≥400,000 copies/mL

          5. Rituximab within the past 3 months

          6. IVIG within the past 1 month

          7. Treatment with other immunosuppressive drugs within the past 1 month (excluding
             intermittent steroid use for asthma)

          8. Concomitant experimental treatment

          9. History of hypersensitivity to plasma-derived VWF- or FVIII-containing concentrates

         10. Elective surgery planned in the next 6 months (excluding vascular access procedure)

         11. Any condition or chronic illness, which in the opinion of the investigator makes
             participation ill-advised

         12. Inability or unwillingness to complete required screening, follow-up, and exit studies