The Hemophilia Inhibitor Prevention Trial

Hemophilia A Without Inhibitor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04303559
• Other study ID #: PRO19040140
• Secondary ID: H30MC24050
• Status: Terminated
• Phase: Phase 3
• Start date: October 11, 2021
• Est. completion date: June 16, 2022

Study information

• Verified date: March 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 Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 16, 2022
• Est. primary completion date: April 6, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Months to 4 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A Without Inhibitor

Intervention

Drug:
• Eloctate Injectable Product
This is a factor VIII-Fc fusion protein.
• Emicizumab Injection [Hemlibra]
This is a bispecific monoclonal antibody FVIII mimic.

Locations

Country	Name	City	State
United States	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

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 Formation	The proportion developing anti-FVIII inhibitors.	48 weeks
Secondary	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
Secondary	Number of FVIII Exposures	Number of FVIII exposures,	48 weeks