GRAVITAS-301: A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease

Purpose

The purpose of this study is to evaluate itacitinib or placebo in combination with corticosteroids as first-line treatment of participants with Grade II to IV acute graft-versus-host disease (aGVHD).

Condition

  • Graft-versus-host Disease (GVHD)

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible. - Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. - Evidence of myeloid engraftment. Use of growth factor supplementation is allowed. - Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min measured or calculated by Cockroft Gault equation. - Willing to avoid pregnancy or fathering children. - Able to give written informed consent and comply with all study visits and procedures. - Able to swallow and retain oral medication.

Exclusion Criteria

  • Has received more than 1 allo-HSCT. - Has received more than 2 days of systemic corticosteroids for aGVHD. - Presence of GVHD overlap syndrome. - Presence of an active uncontrolled infection. - Known human immunodeficiency virus infection. - Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. - Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed. - Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization. - Severe organ dysfunction unrelated to underlying GVHD, including: - Cholestatic disorders or unresolved veno-occlusive disease of the liver. - Clinically significant or uncontrolled cardiac disease. - Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen. - Currently breast feeding. - Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted. - Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment. - Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. - Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Double Blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Itacitinib 		Itacitinib plus corticosteroids
  • Drug: Itacitinib
    Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.
    Other names:
    • INCB039110
  • Drug: Prednisone
    Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.
    Other names:
    • Deltasone
    • Prednicot
    • predniSONE Intensol
    • Rayos
    • Sterapred
    • Sterapred DS
  • Drug: Methylprednisolone
    Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.
    Other names:
    • Medrol
    • Medrol Dosepak
    • Solu-Medrol
Placebo Comparator
Placebo 		Matching placebo plus corticosteroids
  • Drug: Placebo
    Matching placebo tablets administered orally once daily (QD) plus corticosteroids.
  • Drug: Prednisone
    Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.
    Other names:
    • Deltasone
    • Prednicot
    • predniSONE Intensol
    • Rayos
    • Sterapred
    • Sterapred DS
  • Drug: Methylprednisolone
    Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.
    Other names:
    • Medrol
    • Medrol Dosepak
    • Solu-Medrol

More Details

Status
Completed
Sponsor
Incyte Corporation

Study Contact