Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform

NCT02196207 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: PRO14020038
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate if Eloctate is superior to Emicizumab in reducing inhibitors in children with severe hemophilia when given before the first bleed (preemptive) and continued weekly to prevent bleeds (prophylaxis); and whether Eloctate immune tolerance induction (ITI) plus emicizumab is superior to Eloctate ITI alone in eradicating inhibitor formation in children and adults with severe hemophilia A.

Conditions

Severe Hemophilia A

Keywords

Severe Hemophilia A; Hemophilia Inhibitor Formation; Eloctate; Emicizumab; Inhibitor Prevention; Inhibitor Eradication

Outcome Measures

Primary Outcomes (2)

• Prevention Trial: Time to inhibitor formation

  Inhibitor formation is defined as anti-FVIII \> / = 5.0 B.U. by chromogenic Nijmegen-modified Bethesda assay, performed on plasma, repeated for confirmation.

  Up to 48 weeks

• Eradication Trial: Time to inhibitor eradication

  Inhibitor eradication is defined as anti-FVIII \< 0.6 B.U. by chromogenic Nijmegen Bethesda assay, performed on plasma, repeated for confirmation.

  Up to 48 weeks

Secondary Outcomes (3)

• Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other

  Up to 48 weeks

• Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay

  Up to 48 weeks

• Prevention & Eradication Trials: HLA type and factor VIII genotype

  Up to 48 weeks

Other Outcomes (1)

• Prevention & Eradication Trials: T Cell Elispot Assay

  Up to 48 weeks

Study Arms (4)

Eloctate Prophylaxis

EXPERIMENTAL

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

Drug: Eloctate Prophylaxis

Emicizumab Prophylaxis

EXPERIMENTAL

Prevention Trial, Arm B: Emicizumab 1.5 mg/kg weekly (following 4-wk induction at 3 mg/kg weekly) will be administered by subcutaneous injection in previously untreated children with severe hemophilia A beginning before the first bleed and continued for up to 48 weeks.

Drug: Emicizumab Prophylaxis

Eloctate ITI plus Emicizumab

EXPERIMENTAL

Eradication Trial, Arm A: Eloctate 100 IU/kg every other day will be administered by intravenous infusion as immune tolerance plus Emicizumab 1.5 mg/kg weekly by subcutaneous injection in previously treated children and adults with severe hemophilia A and high-titer inhibitors and continued for up to 48 weeks.

Drug: Eloctate ITI plus Emicizumab

Eloctate ITI Alone

ACTIVE COMPARATOR

Eradication Trial, Arm B: Eloctate 100 IU/kg every other day will be administered by intravenous infusion as immune tolerance alone in previously treated children and adults with severe hemophilia A and high-titer inhibitors and continued for up to 48 weeks.

Drug: Eloctate ITI

Interventions

Eloctate Prophylaxis DRUG

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

Also known as: rFVIIIFc Prophylaxis

Eloctate Prophylaxis

Emicizumab Prophylaxis DRUG

Prevention Trial, Arm B: Emicizumab (1.5 mg/kg) will be administered weekly by subcutaneous injection for up to 48 weeks in previously untreated children with severe hemophilia A.

Also known as: Hemlibra Prophylaxis

Emicizumab Prophylaxis

Eloctate ITI plus Emicizumab DRUG

Eradication Trial, Arm A: Eloctate (100 IU/kg) ITI every other day by intravenous infusion plus Emicizumab (1.5 mg/kg) weekly by subcutaneous injection will be administered for up to 48 weeks as immune tolerance in children and adults with severe hemophilia A and high-titer inhibitors.

Also known as: rFVIIIFc ITI plus Hemlibra

Eloctate ITI plus Emicizumab

Eloctate ITI DRUG

Eradication Trial, Arm A: Eloctate (100 IU/kg) ITI every other day by intravenous infusion will be administered for up to 48 weeks as immune tolerance in children and adults with severe hemophilia A and high-titer inhibitors.

Also known as: rFVIIIFc ITI

Eloctate ITI Alone

Eligibility Criteria

• Age: 4 Months - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male children \>/= 4 months of age.
• Severe hemophilia A (FVIII \< 0.01 U/ml)
• No previous bleed or surgery requiring treatment (except circumcision)
• No previous factor VIII product (except for circumcision)
• Willingness to comply with weekly prophylaxis for 48 weeks
• Willingness of parent/caregiver to keep a personal diary of bleeding frequency and factor treatment.
• Willingness to make monthly visits and coagulation testing at weeks 4, 12, 24, 36, and 48 (end of study)

You may not qualify if:

• Acquired hemophilia.
• Any bleeding disorder other than hemophilia A.
• Treatment with clotting factor previously, other than circumcision.
• Presence of an inhibitor to factor VIII.
• Use of an experimental drug(s).
• Surgery anticipated in the next 48 weeks.
• Life expectancy less than 5 years.
• Inability to comply with study requirements.
• Male adults or children with no age limitation.
• Severe hemophilia A (FVIII \<0.01 U/ml).
• Presence of an inhibitor to FVIII (anti-FVIII \> 5.0 B.U.)
• Willingness to comply with study drugs for up to 48 weeks.
• Willingness to keep a personal diary of bleed frequency and drug treatment.
• Willingness to make monthly visits and coagulation testing at weeks 4, 12, 24, 36, and 48 (end of study).
• Acquired hemophilia.

Sponsors & Collaborators

• Margaret Ragni: lead

Study Sites (1)

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Ragni MV. The effect of emicizumab regimen on haemophilia outcomes. Lancet Haematol. 2019 Jun;6(6):e286-e287. doi: 10.1016/S2352-3026(19)30070-5. Epub 2019 Apr 16. No abstract available.

  PMID: 31003964 DERIVED

MeSH Terms

Conditions

Hemophilia A

Interventions

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

Study Officials

• Margaret V Ragni, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

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

Model Details: Two phase III randomized trials, each with two arms, including one inhibitor prevention trial and one inhibitor eradication trial.

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 21, 2014
• Study Start: August 1, 2020
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 20, 2019

Record last verified: 2019-08

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 NHLBI.

Locations

US (1)