The Hemophilia Inhibitor Eradication Trial

Sponsor

Margaret Ragni (Other)

Overall Status

Terminated

CT.gov ID

NCT04303572

Collaborator

Health Resources and Services Administration (HRSA) (U.S. Fed)

Enrollment

Locations

Arms

7.8

Actual Duration (Months)

0.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A With Inhibitor	Drug: Eloctate ITI Drug: Emicizumab	Phase 3

Detailed Description

This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in patients with severe hemophilia A This adaptive design is necessary as randomized trials in rare diseases are often 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 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 > 0.6 B.U.), will be enrolled. Subjects will include individuals with severe hemophilia A who develop inhibitors during the linked Inhibitor Prevention Trial and adults or children at the same HTCs refractory to or never undergoing immune tolerance induction (ITI). Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria, will be randomized to weekly Eloctate ITI plus weekly Emicizumab vs. weekly 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 Inhibitor Eradication 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 Eradication Trial (PRO19070080) is linked to the Inhibitor Prevention Trial (PRO19040140), as part of the INHIBIT Clinical Trials Platform, and 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 Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a phase III open-label, randomized controlled trial comparing immune tolerance induction with one drug, with or without a second drug in the eradication of hemophilia inhibitors.This is a phase III open-label, randomized controlled trial comparing immune tolerance induction with one drug, with or without a second drug in the eradication of hemophilia inhibitors.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Multi-Center, Randomized, Controlled Inhibitor Eradication Trial, Comparing Eloctate Immune Tolerance Induction (ITI) Plus Emicizumab vs. Eloctate ITI Alone to Eradicate Inhibitor Formation in Severe Hemophilia A

Actual Study Start Date :

Nov 1, 2021

Actual Primary Completion Date :

Jun 27, 2022

Actual Study Completion Date :

Jun 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eloctate ITI plus Emicizumab Arm A: Eloctate 100 IU/kg every other day by intravenous infusion plus Emicizumab 1.5 mg/kg subcutaneously (following 3 mg/kg/wk x 4 induction) in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks.	Drug: Eloctate ITI This is a factor VIII-Fc infusion protein. Other Names: rFVIIIFc Drug: Emicizumab This is a bispecific monoclonal antibody FVIII mimic. Other Names: Hemlibra
Active Comparator: Eloctate ITI Arm B: Eloctate 100 IU/kg every other day by intravenous infusion in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks.	Drug: Eloctate ITI This is a factor VIII-Fc infusion protein. Other Names: rFVIIIFc

Arm

Intervention/Treatment

Experimental: Eloctate ITI plus Emicizumab

Arm A: Eloctate 100 IU/kg every other day by intravenous infusion plus Emicizumab 1.5 mg/kg subcutaneously (following 3 mg/kg/wk x 4 induction) in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks.

Drug: Eloctate ITI

This is a factor VIII-Fc infusion protein.

Other Names:

rFVIIIFc

Drug: Emicizumab

This is a bispecific monoclonal antibody FVIII mimic.

Other Names:

Hemlibra

Active Comparator: Eloctate ITI

Arm B: Eloctate 100 IU/kg every other day by intravenous infusion in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks.

Drug: Eloctate ITI

This is a factor VIII-Fc infusion protein.

Other Names:

rFVIIIFc

Outcome Measures

Primary Outcome Measures

Inhibitor eradication [48 weeks]
The proportion eradicating anti-FVIII inhibitors

Secondary Outcome Measures

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.
FVIII mutation [48 weeks]
The number of FVIII mutation variants.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male adults or children > 4 months of age.
Severe hemophilia A (FVIII < 0.01 U/ml).
Current or past high-responding inhibitor, anti-FVIII >= 5.0 B.U., ITI-refractory or ITI-naive.

Exclusion Criteria:

Acquired hemophilia or 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.
Patient/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, 8, 12, 24, 36, and 48.
Other illness, condition, or reason in the opinion of the investigator that would make the patient unsuitable for the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hemophilia Center of Western PA	Pittsburgh	Pennsylvania	United States	15213
2	University of Pittsburgh and Hemophilia Center Western PA	Pittsburgh	Pennsylvania	United States	15213