The Hemophilia Inhibitor Prevention Trial

Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia A

Sponsors

Lead Sponsor: Margaret Ragni

Collaborator: Health Resources and Services Administration (HRSA)

Source University of Pittsburgh
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.

Overall Status Recruiting
Start Date 2021-10-11
Completion Date 2027-08-01
Primary Completion Date 2027-08-01
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Inhibitor formation 48 weeks
Secondary Outcome
Measure Time Frame
Bleeding events 48 weeks
FVIII trough level 48 weeks
Human leukocyte antigen (HLA) haplotype 48 weeks
FVIII mutation 48 weeks
Enrollment 66
Condition
Intervention

Intervention Type: Drug

Intervention Name: Eloctate Injectable Product

Description: This is a factor VIII-Fc fusion protein.

Arm Group Label: Eloctate

Other Name: rFVIIIFc

Intervention Type: Drug

Intervention Name: Emicizumab Injection [Hemlibra]

Description: This is a bispecific monoclonal antibody FVIII mimic.

Arm Group Label: Emicizumab

Other Name: Hemlibra

Eligibility

Criteria:

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.

Gender:

Male

Minimum Age:

4 Months

Maximum Age:

4 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Margaret V Ragni, MD, MPH Principal Investigator University of Pittsburgh
Overall Contact

Last Name: Margaret V Ragni, MD, MPH

Phone: 412-209-7288

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup:
University of Arkansas Medical Sciences Childrens Hospital | Little Rock, Arkansas, 72202, United States Recruiting Shelley Crary, MD 501-364-1494 [email protected]
Hemophilia Center of Western PA | Pittsburgh, Pennsylvania, 15213, United States Recruiting Margaret V Ragni, MD MPH 412-209-7288 [email protected]
University of Pittsburgh and Hemophilia Center Western PA | Pittsburgh, Pennsylvania, 15213, United States Not yet recruiting Dana Ivanco 412-209-7425 [email protected] Margaret V Ragni, MD, MPH Principal Investigator Craig Seaman, MD, MS Sub-Investigator Frederico Xavier, MD MS Sub-Investigator
Location Countries

United States

Verification Date

2021-10-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: University of Pittsburgh

Investigator Full Name: Margaret Ragni

Investigator Title: Professor of Medicine and Clinical and Translational Research

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Eloctate

Type: Active Comparator

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.

Label: Emicizumab

Type: Experimental

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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: This is a phase III open-label, randomized controlled trial comparing two drugs in the prevention of hemophilia inhibitor formation.

Primary Purpose: Prevention

Masking: None (Open Label)

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