search
Back to results

Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform (INHIBIT)

Primary Purpose

Severe Hemophilia A

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Eloctate Prophylaxis
Emicizumab Prophylaxis
Eloctate ITI plus Emicizumab
Eloctate ITI
Sponsored by
Margaret Ragni
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Hemophilia A focused on measuring Severe Hemophilia A, Hemophilia Inhibitor Formation, Eloctate, Emicizumab, Inhibitor Prevention, Inhibitor Eradication

Eligibility Criteria

4 Months - 99 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Hemophilia Center of Western Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Eloctate Prophylaxis

Emicizumab Prophylaxis

Eloctate ITI plus Emicizumab

Eloctate ITI Alone

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other
Number of bleeding events
Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay
FVIII activity
Prevention & Eradication Trials: HLA type and factor VIII genotype
HLA haplotype and FVIII mutation

Full Information

First Posted
July 17, 2014
Last Updated
August 16, 2019
Sponsor
Margaret Ragni
search

1. Study Identification

Unique Protocol Identification Number
NCT02196207
Brief Title
Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Withdrawn
Why Stopped
The trial was revised to be two protocols, one Prevention, one Eradication Trials.
Study Start Date
August 2020 (Anticipated)
Primary Completion Date
July 2027 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Margaret Ragni

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Hemophilia A
Keywords
Severe Hemophilia A, Hemophilia Inhibitor Formation, Eloctate, Emicizumab, Inhibitor Prevention, Inhibitor Eradication

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two phase III randomized trials, each with two arms, including one inhibitor prevention trial and one inhibitor eradication trial.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eloctate Prophylaxis
Arm Type
Experimental
Arm Description
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.
Arm Title
Emicizumab Prophylaxis
Arm Type
Experimental
Arm Description
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.
Arm Title
Eloctate ITI plus Emicizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Eloctate ITI Alone
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Eloctate Prophylaxis
Other Intervention Name(s)
rFVIIIFc Prophylaxis
Intervention Description
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
Intervention Name(s)
Emicizumab Prophylaxis
Other Intervention Name(s)
Hemlibra Prophylaxis
Intervention Description
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
Intervention Name(s)
Eloctate ITI plus Emicizumab
Other Intervention Name(s)
rFVIIIFc ITI plus Hemlibra
Intervention Description
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
Intervention Name(s)
Eloctate ITI
Other Intervention Name(s)
rFVIIIFc ITI
Intervention Description
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.
Primary Outcome Measure Information:
Title
Prevention Trial: Time to inhibitor formation
Description
Inhibitor formation is defined as anti-FVIII > / = 5.0 B.U. by chromogenic Nijmegen-modified Bethesda assay, performed on plasma, repeated for confirmation.
Time Frame
Up to 48 weeks
Title
Eradication Trial: Time to inhibitor eradication
Description
Inhibitor eradication is defined as anti-FVIII < 0.6 B.U. by chromogenic Nijmegen Bethesda assay, performed on plasma, repeated for confirmation.
Time Frame
Up to 48 weeks
Secondary Outcome Measure Information:
Title
Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other
Description
Number of bleeding events
Time Frame
Up to 48 weeks
Title
Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay
Description
FVIII activity
Time Frame
Up to 48 weeks
Title
Prevention & Eradication Trials: HLA type and factor VIII genotype
Description
HLA haplotype and FVIII mutation
Time Frame
Up to 48 weeks
Other Pre-specified Outcome Measures:
Title
Prevention & Eradication Trials: T Cell Elispot Assay
Description
T cell reactivity to FVIII
Time Frame
Up to 48 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
4 Months
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret V Ragni, MD, MPH
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hemophilia Center of Western Pennsylvania
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
A biologic specimen and data repository for this trial will be available, pending NHLBI approval, at BioLINCC https://biolincc.nhlbi.nih.gov, to any research or investigator who makes formal application request and is formally approved by NHLBI.
IPD Sharing Time Frame
Within one year of trial completion.
IPD Sharing Access Criteria
Access will be determined by NHLBI.
Citations:
PubMed Identifier
31003964
Citation
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.
Results Reference
derived

Learn more about this trial

Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform

We'll reach out to this number within 24 hrs