Clinical trial NCT04303559: The Hemophilia Inhibitor Prevention Trial
Official title: Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hemophilia A Without Inhibitor
Keywords: hemophilia A
eloctate
Emicizumab
inhibitor
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Health Resources and Services Administration (HRSA)
First posted: 2020-03-11
Enrollment: 1
Sex: MALE
Minimum age (years): 4
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase III open-label, randomized controlled trial comparing two drugs in the prevention of hemophilia inhibitor formation.
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Male children \>= 4 months and up to 4 years of age.
2. Severe hemophilia A (FVIII \< 0.01 U/ml).
3. No evidence of an inhibitor i.e. anti-FVIII \< 0.6 B.U.
4. No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.

Exclusion Criteria:

1. Acquired hemophilia or any bleeding disorder other than hemophilia A.
2. Treatment with clotting factor or emicizumab previously.
3. Use of an experimental drug(s).
4. Surgery anticipated in the next 48 weeks.
5. Life expectancy less than 5 years.
6. 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.
7. Other illness, condition or reason in the opinion of the investigator that would make the patient unsuitable for the trial.

Primary outcomes:
measure: Inhibitor Formation
timeFrame: 48 weeks
Secondary outcomes:
measure: Bleeding Events
timeFrame: 48 weeks
measure: FVIII Trough Level
timeFrame: 48 weeks
measure: Human Leukocyte Antigen (HLA) Haplotype
timeFrame: 48 weeks
measure: FVIII Mutation
timeFrame: 48 weeks
measure: Number of FVIII Exposures
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas Medical Sciences Childrens Hospital
state: Arkansas
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh and Hemophilia Center Western PA
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Margaret V Ragni, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Ebbert 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.
citation: Bertolet 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.