Hemophilia Inhibitor Prevention and Eradication Clinical Trials (INHIBIT) Platform
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 6 |
| Updated: | 3/28/2019 |
| Start Date: | April 2020 |
| End Date: | March 2027 |
| Contact: | Margaret V Ragni, MD, MPH |
| Email: | ragni@pitt.edu |
| Phone: | 412-209-7288 |
Phase 3 INHIBIT Platform: Trial-1, rFVIIIFc vs rFVIII to Prevent Inhibitors; Trial-2, "Winner" vs Emicizumab to Prevent Inhibitors; Trial-3, rFVIIIFc Immune Tolerance With vs Without Emicizumab to Eradicate Inhibitors in Severe Hemophilia A
This study will evaluate if rFVIIIFc is superior to rFVIII in reducing inhibitors in children
with severe Hemophilia A before the first bleed (preemptive) and continued weekly to prevent
bleeds (prophylaxis); and whether the "winner" is superior to emicizumab in preventing
inhibitors; and whether immune tolerance with rFVIIIFc plus emicizumab is superior to
rFVIIIFc alone in eradicating inhibitor formation in children and adults with severe
hemophilia A.
with severe Hemophilia A before the first bleed (preemptive) and continued weekly to prevent
bleeds (prophylaxis); and whether the "winner" is superior to emicizumab in preventing
inhibitors; and whether immune tolerance with rFVIIIFc plus emicizumab is superior to
rFVIIIFc alone in eradicating inhibitor formation in children and adults with severe
hemophilia A.
This is a multi-center randomized INHIBIT Phase III Clinical Trials Platform in which
consecutive 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 two Inhibitor Prevention Trials 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 #1 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 rFVIIIFc vs. rFVIII to prevent inhibitor
formation, defined as anti-FVIII > 5.0 BU. The "winner" will be compared with the next
hemostatic agent, Emicizumab (Hemlibra) in the Inhibitor Prevention Trial #2, a 48-week
randomized phase III trial, operationally seamless with Prevention Trial #1, with no break in
enrollment. The Inhibitor Eradication Trial #3 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 at the same HTCs refractory to or never undergoing
immune tolerance induction (ITI), will be enrolled and randomized to weekly rFVIIIFc ITI vs.
rFVIIIFc ITI plus weekly Emicizumab 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.
consecutive 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 two Inhibitor Prevention Trials 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 #1 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 rFVIIIFc vs. rFVIII to prevent inhibitor
formation, defined as anti-FVIII > 5.0 BU. The "winner" will be compared with the next
hemostatic agent, Emicizumab (Hemlibra) in the Inhibitor Prevention Trial #2, a 48-week
randomized phase III trial, operationally seamless with Prevention Trial #1, with no break in
enrollment. The Inhibitor Eradication Trial #3 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 at the same HTCs refractory to or never undergoing
immune tolerance induction (ITI), will be enrolled and randomized to weekly rFVIIIFc ITI vs.
rFVIIIFc ITI plus weekly Emicizumab 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.
Trial #1, 2, 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)
Trial #1, 2, 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.
Trial #3, 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).
Trial #3, 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.
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