Brief Title
Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform
Official Title
Phase III INHIBIT Platform: Prevention Trial, Eloctate vs Emicizumab to Prevent Inhibitors; Eradication Trial: Eloctate Immune Tolerance (ITI) Plus Emicizumab vs vs Eloctate ITI Alone to Eradicate Inhibitors in Severe Hemophilia A
Brief Summary
This study will evaluate if Eloctate is superior to Emicizumab in reducing inhibitors in
children with severe hemophilia when given before the first bleed (preemptive) and continued
weekly to prevent bleeds (prophylaxis); and whether Eloctate immune tolerance induction (ITI)
plus emicizumab is superior to Eloctate ITI alone in eradicating inhibitor formation in
children and adults with severe hemophilia A.
Detailed Description
This is a multi-center, randomized Phase III Clinical Trials Platform (INHIBIT) in which
hemostatic agents will be compared using adaptive design to prevent and eradicate inhibitors
in patients with severe hemophilia A. This adaptive design is necessary as randomized trials
in rare diseases are otherwise not possible. The INHIBIT Trial Platform includes one
Inhibitor Prevention Trial and one Inhibitor Eradication Trial that will be conducted at up
to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. The Inhibitor
Prevention Trial is a 48-week randomized phase III trial in which 66 previously untreated
patients (PUPs) (children < 6 yr) with severe hemophilia A will be enrolled and randomized to
preemptive weekly Eloctate vs. Emicizumab to prevent inhibitor formation, defined as
anti-FVIII > 5.0 BU. The Inhibitor Eradication Trial is a 48-week randomized phase III trial
in which 90 previously-treated patients (PTPs) with severe hemophilia A and high-responding
inhibitors (anti-VIII >5.0 B.U.), including subjects developing inhibitors during the
Prevention Trials and adults or children of any age at the same HTCs refractory to or never
previously tolerated, will be enrolled and randomized to Eloctate ITI god plus weekly
Emicizumab vs. Eloctate ITI alone to eradicate inhibitor formation, defined as anti-FVIII<0.6
B.U. Blood draws will be minimized to 6 timepoints, pre, 4, 12, 24, 36, and 48 weeks, and
validated for small volumes, 3.8 cc (¾ tsp) each. The Inhibit Trials Platform is considered
greater than minimal risk as study drug is given before the first bleed and special inhibitor
studies are obtained.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Prevention Trial: Time to inhibitor formation
Secondary Outcome
Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other
Condition
Severe Hemophilia A
Intervention
Eloctate Prophylaxis
Study Arms / Comparison Groups
Eloctate Prophylaxis
Description: Prevention Trial, Arm A: rFVIIIFc (Eloctate) 65 IU/kg weekly will be administered by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued for up to 48 weeks.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
0
Start Date
August 2020
Completion Date
July 2027
Primary Completion Date
July 2027
Eligibility Criteria
Prevention Trial, Inclusion Criteria:
- Male children >/= 4 months of age.
- Severe hemophilia A (FVIII < 0.01 U/ml)
- No previous bleed or surgery requiring treatment (except circumcision)
- No previous factor VIII product (except for circumcision)
- Willingness to comply with weekly prophylaxis for 48 weeks
- Willingness of parent/caregiver to keep a personal diary of bleeding frequency and
factor treatment.
- Willingness to make monthly visits and coagulation testing at weeks 4, 12, 24, 36, and
48 (end of study)
Prevention Trial, Exclusion Criteria:
- Acquired hemophilia.
- Any bleeding disorder other than hemophilia A.
- Treatment with clotting factor previously, other than circumcision.
- Presence of an inhibitor to factor VIII.
- Use of an experimental drug(s).
- Surgery anticipated in the next 48 weeks.
- Life expectancy less than 5 years.
- Inability to comply with study requirements.
Eradication Trial, Inclusion Criteria:
- Male adults or children with no age limitation.
- Severe hemophilia A (FVIII <0.01 U/ml).
- Presence of an inhibitor to FVIII (anti-FVIII > 5.0 B.U.)
- Willingness to comply with study drugs for up to 48 weeks.
- Willingness to keep a personal diary of bleed frequency and drug treatment.
- Willingness to make monthly visits and coagulation testing at weeks 4, 12, 24, 36, and
48 (end of study).
Eradication Trial, Exclusion Criteria:
- Acquired hemophilia.
- Any bleeding disorder other than hemophilia A.
- Current use of Emicizumab, or if used, > 8 weeks since last treatment.
- Use of an experimental drug(s).
- Surgery anticipated in the next 48 weeks.
- Life expectancy less than 5 years.
- Inability to copy with study requirements.
Gender
Male
Ages
4 Months - 99 Years
Accepts Healthy Volunteers
No
Contacts
Margaret V Ragni, MD, MPH, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02196207
Organization ID
PRO14020038
Responsible Party
Sponsor-Investigator
Study Sponsor
Margaret Ragni
Study Sponsor
Margaret V Ragni, MD, MPH, Principal Investigator, University of Pittsburgh
Verification Date
August 2019