The Hemophilia Inhibitor Prevention Trial

NCT04303559 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: PRO19040140H30MC24050
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Hemophilia A Without Inhibitor

Keywords

hemophilia A; eloctate; Emicizumab; inhibitor

Outcome Measures

Primary Outcomes (1)

• Inhibitor Formation

  The proportion developing anti-FVIII inhibitors.

  48 weeks

Secondary Outcomes (5)

• Bleeding Events

  48 weeks

• FVIII Trough Level

  48 weeks

• Human Leukocyte Antigen (HLA) Haplotype

  48 weeks

• FVIII Mutation

  48 weeks

• Number of FVIII Exposures

  48 weeks

Study Arms (2)

Eloctate

ACTIVE COMPARATOR

Arm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks.

Drug: Eloctate Injectable Product

Emicizumab

EXPERIMENTAL

Arm B: Emicizumab 1.5 mg/kg will be administered weekly by subcutaneous injection (following 3 mg/kg/wk x4 induction) in previously untreated children with severe hemophilia A beginning before the first bleed and continue up to 48 weeks.

Drug: Emicizumab Injection [Hemlibra]

Interventions

Eloctate Injectable Product DRUG

This is a factor VIII-Fc fusion protein.

Also known as: rFVIIIFc

Eloctate

Emicizumab Injection [Hemlibra] DRUG

This is a bispecific monoclonal antibody FVIII mimic.

Also known as: Hemlibra

Emicizumab

Eligibility Criteria

• Age: 4 Months - 4 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male children \>= 4 months and up to 4 years of age.
• Severe hemophilia A (FVIII \< 0.01 U/ml).
• No evidence of an inhibitor i.e. anti-FVIII \< 0.6 B.U.
• No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.

You may not qualify if:

• Acquired hemophilia or any bleeding disorder other than hemophilia A.
• Treatment with clotting factor or emicizumab previously.
• Use of an experimental drug(s).
• Surgery anticipated in the next 48 weeks.
• Life expectancy less than 5 years.
• 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.
• 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 (3)

University of Arkansas Medical Sciences Childrens Hospital

Little Rock, Arkansas, 72202, United States

Location

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: PREVENTION
• 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 two drugs in the prevention of hemophilia inhibitor formation.

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 11, 2020
• Study Start: October 11, 2021
• Primary Completion: April 6, 2022
• Study Completion: June 16, 2022
• Last Updated: April 11, 2023
• Results First Posted: April 11, 2023

Record last verified: 2023-03

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 Study Team.

Locations

US (3)