Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform

NCT ID: NCT02196207

Last Updated: 2019-08-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2027-07-31

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.

Detailed Description

This is a multi-center, randomized Phase III Clinical Trials Platform (INHIBIT) in which hemostatic agents will be compared using adaptive design to prevent and eradicate inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. The INHIBIT Trial Platform includes one Inhibitor Prevention Trial and one Inhibitor 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) (children < 6 yr) with severe hemophilia A will be enrolled and randomized to preemptive weekly Eloctate vs. Emicizumab to prevent inhibitor formation, defined as anti-FVIII > 5.0 BU. 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 >5.0 B.U.), including subjects developing inhibitors during the Prevention Trials and adults or children of any age at the same HTCs refractory to or never previously tolerated, will be enrolled and randomized to Eloctate ITI god plus weekly Emicizumab vs. 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 Inhibit Trials Platform is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained.

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eloctate Prophylaxis

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.

Group Type: EXPERIMENTAL

Eloctate Prophylaxis

Intervention Type: 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.

Emicizumab Prophylaxis

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.

Group Type: EXPERIMENTAL

Emicizumab Prophylaxis

Intervention Type: 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.

Eloctate ITI plus Emicizumab

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.

Group Type: EXPERIMENTAL

Eloctate ITI plus Emicizumab

Intervention Type: 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.

Eloctate ITI Alone

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.

Group Type: ACTIVE_COMPARATOR

Eloctate ITI

Intervention Type: 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.

Interventions

Eloctate Prophylaxis

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.

Intervention Type: DRUG

Emicizumab Prophylaxis

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.

Intervention Type: DRUG

Eloctate ITI plus Emicizumab

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.

Intervention Type: DRUG

Eloctate ITI

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.

Intervention Type: DRUG

Other Intervention Names

rFVIIIFc Prophylaxis; Hemlibra Prophylaxis; rFVIIIFc ITI plus Hemlibra; rFVIIIFc ITI

Eligibility Criteria

Inclusion Criteria

• 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)

• 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).

Exclusion Criteria

• 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.

• Acquired hemophilia.
• 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.
• Inability to copy with study requirements.

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Margaret Ragni

OTHER

Sponsor Role: lead

Responsible Party

Margaret Ragni

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Margaret V Ragni, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31003964 (View on PubMed)

Other Identifiers

PRO14020038

Identifier Type: -

Identifier Source: org_study_id