Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform

Severe Hemophilia A Clinical Trial

— INHIBIT  

Official title:

Phase III INHIBIT Platform: Prevention Trial, Eloctate vs Emicizumab to Prevent Inhibitors; Eradication Trial: Eloctate Immune Tolerance (ITI) Plus Emicizumab vs vs Eloctate ITI Alone to Eradicate Inhibitors in Severe Hemophilia A

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02196207
• Other study ID #: PRO14020038
• Status: Withdrawn
• Phase: Phase 3
• Start date: August 2020
• Est. completion date: July 2027

Study information

• Verified date: August 2019
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Months to 99 Years

Eligibility

Prevention Trial, 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)

Prevention Trial, 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.

Eradication Trial, Inclusion Criteria:

• 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).

Eradication Trial, Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Margaret Ragni

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prevention & Eradication Trials: T Cell Elispot Assay	T cell reactivity to FVIII	Up to 48 weeks
Primary	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
Primary	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	Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other	Number of bleeding events	Up to 48 weeks
Secondary	Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay	FVIII activity	Up to 48 weeks
Secondary	Prevention & Eradication Trials: HLA type and factor VIII genotype	HLA haplotype and FVIII mutation	Up to 48 weeks