The Hemophilia Inhibitor Prevention Trial

Phase 3TerminatedNCT04303559

Margaret Ragni1 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Hemophilia A Without Inhibitor

Interventions

Eloctate Injectable ProductDRUG

This is a factor VIII-Fc fusion protein.

Emicizumab Injection [Hemlibra]DRUG

This is a bispecific monoclonal antibody FVIII mimic.

Eligibility

Sex: MALEMin age: 4 MonthsMax age: 4 Years

Medical Language ↔ Plain English

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.

Locations (3)

University of Arkansas Medical Sciences Childrens Hospital

Little Rock, Arkansas, United States

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, United States

University of Pittsburgh and Hemophilia Center Western PA

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

Inhibitor Formation

The proportion developing anti-FVIII inhibitors.

Time frame: 48 weeks

Secondary Outcomes

Bleeding Events

The number of bleeding events:hematoma, joint, central nervous system, other bleeds.

Time frame: 48 weeks

FVIII Trough Level

The FVIII trough activity by chromogenic assay

Time frame: 48 weeks

Human Leukocyte Antigen (HLA) Haplotype

The number of HLA haplotype variants.

Time frame: 48 weeks

FVIII Mutation

The number of FVIII mutation variants.

Time frame: 48 weeks

Number of FVIII Exposures

Number of FVIII exposures,

Time frame: 48 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.