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

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.