The Hemophilia Inhibitor Eradication Trial

Phase 3

Terminated

• Conditions: Hemophilia A With Inhibitor
• Interventions: Drug: Eloctate ITI; Drug: Emicizumab

• Registration Number: NCT04303572
• Lead Sponsor: Margaret Ragni

Brief Summary

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 severe hemophilia A.

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 Timeline

• Study First Submitted: 2019-10-31
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-11
• Study Start: 2021-11-01
• Primary Completion: 2022-06-27
• Study Completion: 2022-06-27
• Status Verified: 2023-01
• Results First Submitted: 2023-01-25
• Results First Submitted QC: 2023-01-25
• Last Update Submitted: 2023-01-25
• Results First Posted: 2023-02-21
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

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

Inclusion Criteria

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

Exclusion Criteria

1. Acquired hemophilia or any bleeding disorder other than hemophilia A.
2. Current use of Emicizumab, or if used, > 8 weeks since last treatment.
3. Use of an experimental drug(s).
4. Surgery anticipated in the next 48 weeks.
5. Life expectancy less than 5 years.
6. 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.
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
Eloctate ITI	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.
Eloctate ITI plus Emicizumab	Eloctate ITI	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.
Eloctate ITI plus Emicizumab	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.

Primary Outcome Measures

Name	Time	Method
Inhibitor Eradication	48 weeks	The proportion eradicating anti-FVIII inhibitors

Secondary Outcome Measures

Name	Time	Method
Number of 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.

Trial Locations

Locations (2)

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

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