Severe Hemophilia APhase 3INHIBITNCT02196207
Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform
A Phase 3 study testing Eloctate Prophylaxis, Emicizumab Prophylaxis and Eloctate ITI plus Emicizumab in people with Severe Hemophilia A, run by Margaret Ragni at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 4 months to 99 years, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- Eloctate Prophylaxis, Emicizumab Prophylaxis and Eloctate ITI plus Emicizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2020to Jul 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 99 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213
About this study
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
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.
Read the 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
- Being tested
- Eloctate Prophylaxis, Emicizumab Prophylaxis, Eloctate ITI plus Emicizumab, Eloctate ITI
- Keywords
- Severe Hemophilia A, Hemophilia Inhibitor Formation, Eloctate, Emicizumab, Inhibitor Prevention, Inhibitor Eradication
- 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 ProphylaxisDrug
Also called rFVIIIFc 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 ProphylaxisDrug
Also called Hemlibra 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 EmicizumabDrug
Also called rFVIIIFc ITI plus Hemlibra
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 ITIDrug
Also called rFVIIIFc 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.
| Study group | Role | What they receive |
|---|---|---|
| Eloctate Prophylaxis | Experimental | 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. Receives: Drug: Eloctate Prophylaxis |
| Emicizumab Prophylaxis | Experimental | 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. Receives: Drug: Emicizumab Prophylaxis |
| Eloctate ITI plus Emicizumab | Experimental | 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. Receives: Drug: Eloctate ITI plus Emicizumab |
| Eloctate ITI Alone | Active comparator | 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. Receives: Drug: Eloctate ITI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 weeks
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.
Measured: Up to 48 weeks
Secondary outcomes (3)
Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other
Number of bleeding events
Measured: Up to 48 weeks
Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay
FVIII activity
Measured: Up to 48 weeks
Prevention & Eradication Trials: HLA type and factor VIII genotype
HLA haplotype and FVIII mutation
Measured: Up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study startAug 2020 (estimated)
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Why it stopped: The trial was revised to be two protocols, one Prevention, one Eradication Trials.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Hemophilia AStudies 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
- Two phase III randomized trials, each with two arms, including one inhibitor prevention trial and one inhibitor eradication trial.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Margaret Ragni
- Sponsor type
- University, hospital or other
- 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
- NCT02196207
- Sponsor's protocol ID
- PRO14020038
- Acronym
- INHIBIT
- Status last verified
- Aug 2019
- First submitted
- 17 Jul 2014
- Last updated
- 20 Aug 2019
- Results posted
- No
- 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, 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.
Publications
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.
PubMed 31003964
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02196207
- Acronym / sponsor ID
- INHIBIT / PRO14020038
- Conditions
- Severe Hemophilia A
- Keywords
- Severe Hemophilia A, Hemophilia Inhibitor Formation, Eloctate, Emicizumab, Inhibitor Prevention, Inhibitor Eradication
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The trial was revised to be two protocols, one Prevention, one Eradication Trials.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Margaret RagniUniversity, hospital or other
- Study start
- Aug 2020 (estimated)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 21 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Two phase III randomized trials, each with two arms, including one inhibitor prevention trial and one inhibitor eradication trial.
| Arm | Type | Receives |
|---|---|---|
| Eloctate Prophylaxis | Experimental | Drug: Eloctate ProphylaxisPrevention 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. |
| Emicizumab Prophylaxis | Experimental | Drug: Emicizumab ProphylaxisPrevention 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. |
| Eloctate ITI plus Emicizumab | Experimental | Drug: Eloctate ITI plus EmicizumabEradication 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. |
| Eloctate ITI Alone | Active comparator | Drug: Eloctate ITIEradication 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. |
Who may qualify
- Ages
- 4 months to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 ProphylaxisAlso: rFVIIIFc ProphylaxisPrevention 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. | Drug | Eloctate Prophylaxis |
| Emicizumab ProphylaxisAlso: Hemlibra ProphylaxisPrevention 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. | Drug | Emicizumab Prophylaxis |
| Eloctate ITI plus EmicizumabAlso: rFVIIIFc ITI plus HemlibraEradication 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. | Drug | Eloctate ITI plus Emicizumab |
| Eloctate ITIAlso: rFVIIIFc ITIEradication 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. | Drug | Eloctate ITI Alone |
Primary outcome
Prevention Trial: Time to inhibitor formation
Time frame: Up to 48 weeks
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
Time frame: Up to 48 weeks
Inhibitor eradication is defined as anti-FVIII < 0.6 B.U. by chromogenic Nijmegen Bethesda assay, performed on plasma, repeated for confirmation.
3 secondary outcomes
Prevention & Eradication Trials: Bleeding events including hematoma, joint, central nervous system, other
Time frame: Up to 48 weeks
Prevention & Eradication Trials: Factor VIII trough activity by chromogenic assay
Time frame: Up to 48 weeks
Prevention & Eradication Trials: HLA type and factor VIII genotype
Time frame: Up to 48 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Derived from this study: PubMed 31003964Ragni 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.
- Individual participant dataSharing planned: Yes. 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.
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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
1 site 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 Prophylaxis, Emicizumab Prophylaxis and Eloctate ITI plus Emicizumab in people with Severe Hemophilia A, run by Margaret Ragni at 1 site 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?
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: withdrawn, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Prevention Trial: Time to inhibitor formation (time frame: Up to 48 weeks). The study lists 2 primary outcomes in all. 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 NCT02196207, which also lists 1 linked publication.
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 20 Aug 2019.