The Hemophilia Inhibitor Eradication Trial

NCT04303572 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: PRO19070080H30MC24050
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

Hemophilia A With Inhibitor

Keywords

hemophilia; inhibitor formation; Eloctate; Emicizumab

Outcome Measures

Primary Outcomes (1)

• Inhibitor Eradication

  The proportion eradicating anti-FVIII inhibitors

  48 weeks

Secondary Outcomes (4)

• Number of Bleeding Events

  48 weeks

• FVIII Trough Level

  48 weeks

• Human Leukocyte Antigen (HLA) Haplotype

  48 weeks

• FVIII Mutation

  48 weeks

Study Arms (2)

Eloctate ITI plus Emicizumab

EXPERIMENTAL

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; Drug: Emicizumab

Eloctate ITI

ACTIVE COMPARATOR

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

Interventions

Eloctate ITI DRUG

This is a factor VIII-Fc infusion protein.

Also known as: rFVIIIFc

Eloctate ITI; Eloctate ITI plus Emicizumab

Emicizumab DRUG

This is a bispecific monoclonal antibody FVIII mimic.

Also known as: Hemlibra

Eloctate ITI plus Emicizumab

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Margaret Ragni: lead
• Health Resources and Services Administration (HRSA): collaborator

Study Sites (2)

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh and Hemophilia Center Western PA

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• 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.

  PMID: 31329364 BACKGROUND

• 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.

  PMID: 32653601 BACKGROUND

• 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.

  PMID: 33156923 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Interventions

factor VIII-Fc fusion protein; emicizumab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Margaret Ragni, Principal Investigator
• Organization: University of Pittsburgh

ragni@pitt.edu

412-209-7288

Study Officials

• Margaret V Ragni, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Clinical and Translational Research

Model Details: 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.

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: March 11, 2020
• Study Start: November 1, 2021
• Primary Completion: June 27, 2022
• Study Completion: June 27, 2022
• Last Updated: February 21, 2023
• Results First Posted: February 21, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within one year of trial completion.
• Access Criteria: Access will be determined by the Study Team.

Locations

US (2)