The Hemophilia Inhibitor Prevention Trial

Phase 3

Terminated

• Conditions: Hemophilia A Without Inhibitor
• Interventions: Drug: Emicizumab Injection [Hemlibra]; Drug: Eloctate Injectable Product

• Registration Number: NCT04303559
• Lead Sponsor: Margaret Ragni

Brief Summary

This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.

Detailed Description

This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which consecutive hemostatic agents will be compared using adaptive design to prevent inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. The INHIBIT Clinical Trials Platform includes two linked trials, the Inhibitor Prevention Trial (Prevention Trial) and the Inhibitor Eradication Trial (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) with severe hemophilia A will be enrolled. Subjects will include children from 4 months of age up to 4 years of age who have not been previously treated with clotting factor. Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria will be randomized to preemptive weekly Eloctate (rFVIIIFc) vs. weekly Emicizumab (Hemlibra) to prevent inhibitor formation, defined as anti-FVIII \>= 0.6 BU. 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 Inhibitor Prevention Trial is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained. (NB: The Inhibitor Prevention Trial (PRO19040140) is linked to the Inhibitor Eradication Trial (PRO19070080), as part of the INHIBIT Clinical Trials Platform, with both trials will be conducted efficiently in the same hemophilia treatment centers (HTCs), with the same MDs, coordinators, visit frequency, blood sampling, and assays.

Study Timeline

• Study First Submitted: 2020-03-02
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-11
• Study Start: 2021-10-11
• Primary Completion: 2022-04-06
• Study Completion: 2022-06-16
• Results First Submitted: 2023-01-17
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-17
• Last Update Submitted: 2023-03-17
• Results First Posted: 2023-04-11
• Last Update Posted: 2023-04-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 1

Inclusion Criteria

1. Male children >= 4 months and up to 4 years of age.
2. Severe hemophilia A (FVIII < 0.01 U/ml).
3. No evidence of an inhibitor i.e. anti-FVIII < 0.6 B.U.
4. No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.

Exclusion Criteria

1. Acquired hemophilia or any bleeding disorder other than hemophilia A.
2. Treatment with clotting factor or emicizumab previously.
3. Use of an experimental drug(s).
4. Surgery anticipated in the next 48 weeks.
5. Life expectancy less than 5 years.
6. Parent/caretaker unable or unwilling to keep a personal diary of bleeding frequency and study drug treatment, make monthly visits and blood draws at weeks 4, 12, 24, 36, and 48.
7. Other illness, condition or reason in the opinion of the investigator that would make the patient unsuitable for the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Emicizumab	Emicizumab Injection [Hemlibra]	Arm B: Emicizumab 1.5 mg/kg will be administered weekly by subcutaneous injection (following 3 mg/kg/wk x4 induction) in previously untreated children with severe hemophilia A beginning before the first bleed and continue up to 48 weeks.
Eloctate	Eloctate Injectable Product	Arm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks.

Primary Outcome Measures

Name	Time	Method
Inhibitor Formation	48 weeks	The proportion developing anti-FVIII inhibitors.

Secondary Outcome Measures

Name	Time	Method
FVIII Mutation	48 weeks	The number of FVIII mutation variants.
Bleeding Events	48 weeks	The number of bleeding events:hematoma, joint, central nervous system, other bleeds.
FVIII Trough Level	48 weeks	The FVIII trough activity by chromogenic assay
Human Leukocyte Antigen (HLA) Haplotype	48 weeks	The number of HLA haplotype variants.
Number of FVIII Exposures	48 weeks	Number of FVIII exposures,

Trial Locations

Locations (3)

Hemophilia Center of Western PA; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh and Hemophilia Center Western PA; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Arkansas Medical Sciences Childrens Hospital; 🇺🇸 Little Rock, Arkansas, United States