The Hemophilia Inhibitor Eradication Trial

Hemophilia A With Inhibitor Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04303572
• Other study ID #: PRO19070080
• Secondary ID: H30MC24050
• Status: Terminated
• Phase: Phase 3
• Start date: November 1, 2021
• Est. completion date: June 27, 2022

Study information

• Verified date: January 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 27, 2022
• Est. primary completion date: June 27, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitor

Intervention

Drug:
• Eloctate ITI
This is a factor VIII-Fc infusion protein.
• Emicizumab
This is a bispecific monoclonal antibody FVIII mimic.

Locations

Country	Name	City	State
United States	Hemophilia Center of Western PA	Pittsburgh	Pennsylvania
United States	University of Pittsburgh and Hemophilia Center Western PA	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Margaret Ragni	Health Resources and Services Administration (HRSA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bertolet M, Brooks MM, Ragni MV. The design of a Bayesian platform trial to prevent and eradicate inhibitors in patients with hemophilia. Blood Adv. 2020 Nov 10;4(21):5433-5441. doi: 10.1182/bloodadvances.2020002789. — View Citation

Ebbert PT, Xavier F, Malec LM, Seaman CD, Ragni MV. Observational study of recombinant factor VIII-Fc, rFVIIIFc, in hemophilia A. Thromb Res. 2020 Nov;195:51-54. doi: 10.1016/j.thromres.2020.07.004. Epub 2020 Jul 5. — View Citation

Ragni MV, George LA; Members of Working Group 1, the NHLBI State of the Science Workshop on factor VIII inhibitors: Generating a national blueprint for future research. The national blueprint for future factor VIII inhibitor clinical trials: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors. Haemophilia. 2019 Jul;25(4):581-589. doi: 10.1111/hae.13717. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inhibitor Eradication	The proportion eradicating anti-FVIII inhibitors	48 weeks
Secondary	Number of Bleeding Events	The number of bleeding events: hematoma, joint, central nervous system, other bleeds.	48 weeks
Secondary	FVIII Trough Level	The FVIII trough activity by chromogenic assay.	48 weeks
Secondary	Human Leukocyte Antigen (HLA) Haplotype	The number of HLA haplotype variants.	48 weeks
Secondary	FVIII Mutation	The number of FVIII mutation variants.	48 weeks