Hemophilia A Without InhibitorPhase 3NCT04303559
The Hemophilia Inhibitor Prevention Trial
A Phase 3 study testing Eloctate Injectable Product and Emicizumab Injection [Hemlibra] in people with Hemophilia A Without Inhibitor, run by Margaret Ragni at 3 sites in United States.
Trial summary
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A. Read more about this study
- Who is it for?
- Ages 4 months to 4 years, men only
- Conditions the study is for
- Hemophilia A Without Inhibitor
- What is being tested?
- Eloctate Injectable Product and Emicizumab Injection [Hemlibra]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 Oct 2021to 16 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 4 months to 4 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male children >= 4 months and up to 4 years of age.
- Severe hemophilia A (FVIII < 0.01 U/ml).
- No evidence of an inhibitor i.e. anti-FVIII < 0.6 B.U.
- No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.
Who cannot join
- Acquired hemophilia or any bleeding disorder other than hemophilia A.
- Treatment with clotting factor or emicizumab previously.
- Use of an experimental drug(s).
- Surgery anticipated in the next 48 weeks.
- Life expectancy less than 5 years.
- 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, 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
3 sites in 1 country.
United States3 sites
University of Arkansas Medical Sciences Childrens Hospital
Little Rock, Arkansas, 72202
Hemophilia Center of Western PA
Pittsburgh, Pennsylvania, 15213
University of Pittsburgh and Hemophilia Center Western PA
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia A
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.
Read the detailed description
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which consecutive hemostatic agents will be compared using adaptive design to prevent inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. This adaptive design is necessary as randomized trials in rare diseases are otherwise 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 Prevention Trial is a 48-week randomized phase III trial, in which 66 previously untreated patients (PUPs) with severe hemophilia A will be enrolled. Subjects will include children from 4 months of age up to 4 years of age who have not been previously treated with clotting factor. Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria will be randomized to preemptive weekly Eloctate (rFVIIIFc) vs. weekly Emicizumab (Hemlibra) to prevent inhibitor formation, defined as anti-FVIII >= 0.6 BU. 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 Prevention 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 Prevention Trial (PRO19040140) is linked to the Inhibitor Eradication Trial (PRO19070080), as part of the INHIBIT Clinical Trials Platform, with 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 Without Inhibitor
- Being tested
- Eloctate Injectable Product, Emicizumab Injection [Hemlibra]
- Keywords
- hemophilia A, eloctate, Emicizumab, inhibitor
- 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 Injectable ProductDrug
Also called rFVIIIFc
This is a factor VIII-Fc fusion protein.
Emicizumab Injection [Hemlibra]Drug
Also called Hemlibra
This is a bispecific monoclonal antibody FVIII mimic.
| Study group | Role | What they receive |
|---|---|---|
| Eloctate | Active comparator | Arm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks. Receives: Drug: Eloctate Injectable Product |
| Emicizumab | Experimental | Arm B: Emicizumab 1.5 mg/kg will be administered weekly by subcutaneous injection (following 3 mg/kg/wk x4 induction) in previously untreated children with severe hemophilia A beginning before the first bleed and continue up to 48 weeks. Receives: Drug: Emicizumab Injection [Hemlibra] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inhibitor Formation
The proportion developing anti-FVIII inhibitors.
Measured: 48 weeks
Secondary outcomes (5)
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
Number of FVIII Exposures
Number of FVIII exposures,
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 start11 Oct 2021
- Primary completion6 Apr 2022
- Study completion16 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 Without 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a phase III open-label, randomized controlled trial comparing two drugs in the prevention of hemophilia inhibitor formation.
- 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
- NCT04303559
- Sponsor's protocol ID
- PRO19040140
- Other IDs
- H30MC24050
- Status last verified
- Mar 2023
- First submitted
- 2 Mar 2020
- Last updated
- 11 Apr 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 11 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT04303559
- Acronym / sponsor ID
- PRO19040140
- Conditions
- Hemophilia A Without Inhibitor
- Keywords
- hemophilia A, eloctate, Emicizumab, inhibitor
- 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
- 11 Oct 2021 (actual)
- Primary completion
- 6 Apr 2022 (actual)
- Study completion
- 16 Jun 2022 (actual)
- First posted
- 11 Mar 2020 (actual)
- Results
- Posted 11 Apr 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 Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.
Detailed description
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which consecutive hemostatic agents will be compared using adaptive design to prevent inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. This adaptive design is necessary as randomized trials in rare diseases are otherwise 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 Prevention Trial is a 48-week randomized phase III trial, in which 66 previously untreated patients (PUPs) with severe hemophilia A will be enrolled. Subjects will include children from 4 months of age up to 4 years of age who have not been previously treated with clotting factor. Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria will be randomized to preemptive weekly Eloctate (rFVIIIFc) vs. weekly Emicizumab (Hemlibra) to prevent inhibitor formation, defined as anti-FVIII >= 0.6 BU. 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 Prevention 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 Prevention Trial (PRO19040140) is linked to the Inhibitor Eradication Trial (PRO19070080), as part of the INHIBIT Clinical Trials Platform, with 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
- Prevention
- 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 two drugs in the prevention of hemophilia inhibitor formation.
| Arm | Type | Receives |
|---|---|---|
| Eloctate | Active comparator | Drug: Eloctate Injectable ProductArm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks. |
| Emicizumab | Experimental | Drug: Emicizumab Injection [Hemlibra]Arm B: Emicizumab 1.5 mg/kg will be administered weekly by subcutaneous injection (following 3 mg/kg/wk x4 induction) in previously untreated children with severe hemophilia A beginning before the first bleed and continue up to 48 weeks. |
Who may qualify
- Ages
- 4 months to 4 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Male children >= 4 months and up to 4 years of age.
- Severe hemophilia A (FVIII < 0.01 U/ml).
- No evidence of an inhibitor i.e. anti-FVIII < 0.6 B.U.
- No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.
Key exclusion criteria (7 listed)
- Acquired hemophilia or any bleeding disorder other than hemophilia A.
- Treatment with clotting factor or emicizumab previously.
- 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 Injectable ProductAlso: rFVIIIFcThis is a factor VIII-Fc fusion protein. | Drug | Eloctate |
| Emicizumab Injection [Hemlibra]Also: HemlibraThis is a bispecific monoclonal antibody FVIII mimic. | Drug | Emicizumab |
Primary outcome
Inhibitor Formation
Time frame: 48 weeks
The proportion developing anti-FVIII inhibitors.
5 secondary outcomes
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
Number of FVIII Exposures
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 11 Apr 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
3 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 Injectable Product and Emicizumab Injection [Hemlibra] in people with Hemophilia A Without Inhibitor, run by Margaret Ragni at 3 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 4 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 11 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 11 Apr 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 Formation (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 NCT04303559, 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 11 Apr 2023.