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A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease

Title A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease
Therapeutic Area GVHD
Principal Investigator Kellie Sprague, MD
Min Age 18 Years
Gender All
Contact Delfina Gonzalez
More Information


This is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study of itacitinib or placebo in combination with corticosteroids as first-line treatment of subjects with Grade II to IV aGVHD. Subjects will be randomized 1:1 to itacitinib 200 mg once daily (QD) plus corticosteroids or matching placebo plus corticosteroids. Randomization will be stratified by GVHD risk status (standard risk vs high risk). Subjects will receive randomized study treatment until treatment failure (progression of disease, no response, or requiring additional systemic therapy), unacceptable toxicity, completion of taper, or death. Transfusion support and continued use of anti-infective medications, GVHD prophylaxis medications (including calcineurin inhibitors), and topical steroid therapy is permitted.

GVHD staging and grading will be assessed for efficacy as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria; safety and tolerability will be assessed as per NCI CTCAE v4.03. An independent data monitoring committee will perform an interim analysis for futility once 112 subjects (56 per cohort) have completed the Day 28 visit. If the futility boundary is crossed, the study will be terminated. Otherwise, the primary analysis will be conducted once the last subject completes the Day 28 visit or withdraws from the study. The study will end once 75% of subjects have achieved 2-year transplant-related mortality, have died, or have been lost to follow-up.

Study Details

Inclusion Criteria

  • Clinically suspected Grade II to IV aGVHD
  • Evidence of myeloid engraftment
  • Has undergone 1 allo-HSCT from any donor

Exclusion Criteria

  • Has received more than 1 allo-HSCT.
  • Has received more than 2 days of systemic corticosteroids for aGVHD
  • Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.

Study Requirements

Eligible subjects will begin treatment at 200 mg once daily itacitinib plus corticosteroids or placebo plus corticosteroids. Itacitinib or placebo may be taken without regard to food except on Days 1, 7 and 28 when research blood samples are drawn; on those days, subjects should be instructed to fast and refrain from taking itacitinib or placebo in the morning. Eligible subjects will be instructed when to take itacitinib or placebo by your Study Doctor on these days. Participation in this study will be approximately 12 months during which time subjects may not participate in other research studies to treat GVHD.

The total amount of blood that will be drawn at each visit over the course of this study is approximately 4 ounces (23 teaspoons). Besides blood work, subjects will undergo ECG testings, physical examinations, GVHD symptoms assessment and will be asked to complete quality of life questionnaires.