The Hemophilia Inhibitor Prevention Trial

Margaret Ragni

Status and phase: Terminated; Phase 3

Conditions: Hemophilia A Without Inhibitor

Treatments: Drug: Emicizumab Injection [Hemlibra]; Drug: Eloctate Injectable Product

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04303559

PRO19040140

H30MC24050 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: Male

Ages: 4 months to 4 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1 participants in 2 patient groups

Eloctate

Active Comparator group

Description:

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.

Treatment:

Drug: Eloctate Injectable Product

Emicizumab

Experimental group

Description:

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.

Treatment:

Drug: Emicizumab Injection [Hemlibra]