Hemophilia A With InhibitorPhase 3NCT04303572
The Hemophilia Inhibitor Eradication Trial
A Phase 3 study testing Eloctate ITI and Emicizumab in people with Hemophilia A With Inhibitor, run by Margaret Ragni at 2 sites in United States.
Trial summary
This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in severe hemophilia A. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Hemophilia A With Inhibitor
- What is being tested?
- Eloctate ITI and Emicizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Nov 2021to 27 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male adults or children > 4 months of age.
- Severe hemophilia A (FVIII < 0.01 U/ml).
- Current or past high-responding inhibitor, anti-FVIII >= 5.0 B.U., ITI-refractory or ITI-naive.
Who cannot join
- Acquired hemophilia or 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.
- Patient/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, 8, 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hemophilia Center of Western PA
Pittsburgh, Pennsylvania, 15213
University of Pittsburgh and Hemophilia Center Western PA
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase III Multi-Center, Randomized, Controlled Inhibitor Eradication Trial, Comparing Eloctate Immune Tolerance Induction (ITI) Plus Emicizumab vs. Eloctate ITI Alone to Eradicate Inhibitor Formation in Severe Hemophilia A
This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in severe hemophilia A.
Read the detailed description
This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in patients with severe hemophilia A This adaptive design is necessary as randomized trials in rare diseases are often not possible. The INHIBIT Clinical Trials Platform includes two linked trials, the Inhibitor Prevention Trial (Prevention Trial) and the Inhibitor Eradication Trial (Eradication Trial) that will be conducted at up to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. 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 > 0.6 B.U.), will be enrolled. Subjects will include individuals with severe hemophilia A who develop inhibitors during the linked Inhibitor Prevention Trial and adults or children at the same HTCs refractory to or never undergoing immune tolerance induction (ITI). Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria, will be randomized to weekly Eloctate ITI plus weekly Emicizumab vs. weekly 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 Inhibitor Eradication Trial is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained. (NB: The Inhibitor Eradication Trial (PRO19070080) is linked to the Inhibitor Prevention Trial (PRO19040140), as part of the INHIBIT Clinical Trials Platform, and both trials will be conducted efficiently in the same hemophilia treatment centers (HTCs), with the same MDs, coordinators, visit frequency, blood sampling, and assays.
- Conditions
- Hemophilia A With Inhibitor
- Being tested
- Eloctate ITI, Emicizumab
- Keywords
- hemophilia, inhibitor formation, Eloctate, Emicizumab
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eloctate ITIDrug
Also called rFVIIIFc
This is a factor VIII-Fc infusion protein.
EmicizumabDrug
Also called Hemlibra
This is a bispecific monoclonal antibody FVIII mimic.
| Study group | Role | What they receive |
|---|---|---|
| Eloctate ITI plus Emicizumab | Experimental | Arm A: Eloctate 100 IU/kg every other day by intravenous infusion plus Emicizumab 1.5 mg/kg subcutaneously (following 3 mg/kg/wk x 4 induction) in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks. Receives: Drug: Eloctate ITI; Drug: Emicizumab |
| Eloctate ITI | Active comparator | Arm B: Eloctate 100 IU/kg every other day by intravenous infusion in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks. Receives: Drug: Eloctate ITI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inhibitor Eradication
The proportion eradicating anti-FVIII inhibitors
Measured: 48 weeks
Secondary outcomes (4)
Number of Bleeding Events
The number of bleeding events: hematoma, joint, central nervous system, other bleeds.
Measured: 48 weeks
FVIII Trough Level
The FVIII trough activity by chromogenic assay.
Measured: 48 weeks
Human Leukocyte Antigen (HLA) Haplotype
The number of HLA haplotype variants.
Measured: 48 weeks
FVIII Mutation
The number of FVIII mutation variants.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start1 Nov 2021
- Primary completion27 Jun 2022
- Study completion27 Jun 2022
Why it stopped: The INHIBIT Trials IDSMB, in a letter dated 05-18-22, recommended, given the slow enrollment, that the INHIBIT Trials be discontinued due to futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemophilia A With InhibitorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a phase III open-label, randomized controlled trial comparing immune tolerance induction with one drug, with or without a second drug in the eradication of hemophilia inhibitors.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Margaret Ragni
- Sponsor type
- University, hospital or other
- Collaborators
- Health Resources and Services Administration (HRSA)
- Responsible party
- Sponsor-investigator, Margaret Ragni, University of Pittsburgh
- Investigators
- Margaret V Ragni, MD, MPH, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04303572
- Sponsor's protocol ID
- PRO19070080
- Other IDs
- H30MC24050
- Status last verified
- Jan 2023
- First submitted
- 31 Oct 2019
- Last updated
- 21 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A biologic specimen and data repository for this trial will be available at the Graduate School of Public Health (GSPH) Data Center repository for investigators who make formal application request and is formally approved by the Coordinating Center (Pitt) and Data Center (GSPH).
Publications
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.
PubMed 31329364Ebbert 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.
PubMed 32653601Bertolet 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.
PubMed 33156923
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Multi-Center, Randomized, Controlled Inhibitor Eradication Trial, Comparing Eloctate Immune Tolerance Induction (ITI) Plus Emicizumab vs. Eloctate ITI Alone to Eradicate Inhibitor Formation in Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT04303572
- Acronym / sponsor ID
- PRO19070080
- Conditions
- Hemophilia A With Inhibitor
- Keywords
- hemophilia, inhibitor formation, Eloctate, Emicizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The INHIBIT Trials IDSMB, in a letter dated 05-18-22, recommended, given the slow enrollment, that the INHIBIT Trials be discontinued due to futility.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Margaret RagniUniversity, hospital or other
- Collaborators
- Health Resources and Services Administration (HRSA)
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 27 Jun 2022 (actual)
- Study completion
- 27 Jun 2022 (actual)
- First posted
- 11 Mar 2020 (actual)
- Results
- Posted 21 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in severe hemophilia A.
Detailed description
This is a multi-center randomized phase III clinical trial, the Inhibitor Eradication Trial, in which Eloctate ITI plus Emicizumab will be compared with Eloctate ITI alone to eradicate inhibitors in patients with severe hemophilia A This adaptive design is necessary as randomized trials in rare diseases are often not possible. The INHIBIT Clinical Trials Platform includes two linked trials, the Inhibitor Prevention Trial (Prevention Trial) and the Inhibitor Eradication Trial (Eradication Trial) that will be conducted at up to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. 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 > 0.6 B.U.), will be enrolled. Subjects will include individuals with severe hemophilia A who develop inhibitors during the linked Inhibitor Prevention Trial and adults or children at the same HTCs refractory to or never undergoing immune tolerance induction (ITI). Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria, will be randomized to weekly Eloctate ITI plus weekly Emicizumab vs. weekly 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 Inhibitor Eradication Trial is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained. (NB: The Inhibitor Eradication Trial (PRO19070080) is linked to the Inhibitor Prevention Trial (PRO19040140), as part of the INHIBIT Clinical Trials Platform, and both trials will be conducted efficiently in the same hemophilia treatment centers (HTCs), with the same MDs, coordinators, visit frequency, blood sampling, and assays.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a phase III open-label, randomized controlled trial comparing immune tolerance induction with one drug, with or without a second drug in the eradication of hemophilia inhibitors.
| Arm | Type | Receives |
|---|---|---|
| Eloctate ITI plus Emicizumab | Experimental | Drug: Eloctate ITI, Drug: EmicizumabArm A: Eloctate 100 IU/kg every other day by intravenous infusion plus Emicizumab 1.5 mg/kg subcutaneously (following 3 mg/kg/wk x 4 induction) in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks. |
| Eloctate ITI | Active comparator | Drug: Eloctate ITIArm B: Eloctate 100 IU/kg every other day by intravenous infusion in children and adults with severe hemophilia A and anti-FVIII inhibitor, continued up to 48 weeks. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Male adults or children > 4 months of age.
- Severe hemophilia A (FVIII < 0.01 U/ml).
- Current or past high-responding inhibitor, anti-FVIII >= 5.0 B.U., ITI-refractory or ITI-naive.
Key exclusion criteria (7 listed)
- Acquired hemophilia or 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eloctate ITIAlso: rFVIIIFcThis is a factor VIII-Fc infusion protein. | Drug | Eloctate ITI, Eloctate ITI plus Emicizumab |
| EmicizumabAlso: HemlibraThis is a bispecific monoclonal antibody FVIII mimic. | Drug | Eloctate ITI plus Emicizumab |
Primary outcome
Inhibitor Eradication
Time frame: 48 weeks
The proportion eradicating anti-FVIII inhibitors
4 secondary outcomes
Number of Bleeding Events
Time frame: 48 weeks
FVIII Trough Level
Time frame: 48 weeks
Human Leukocyte Antigen (HLA) Haplotype
Time frame: 48 weeks
FVIII Mutation
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31329364Ragni 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.
- Background: PubMed 32653601Ebbert 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.
- Background: PubMed 33156923Bertolet 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.
- Individual participant dataSharing planned: Yes. A biologic specimen and data repository for this trial will be available at the Graduate School of Public Health (GSPH) Data Center repository for investigators who make formal application request and is formally approved by the Coordinating Center (Pitt) and Data Center (GSPH).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret V Ragni, MD, MPH principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eloctate ITI and Emicizumab in people with Hemophilia A With Inhibitor, run by Margaret Ragni at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inhibitor Eradication (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04303572, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.