GRAVITAS-301: A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease
Condition: Graft-versus-host Disease (GVHD)
MeSH terms: Graft vs Host Disease
Intervention: Itacitinib; Placebo; Prednisone; Methylprednisolone
Intervention description: Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.; Matching placebo tablets administered orally once daily (QD) plus corticosteroids.; 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.; Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.
Intervention MeSH terms: Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Double Blind
Enrollment: 439.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute graft-versus-host disease; Janus kinase (JAK) inhibitor; itacitinib; corticosteroids; allogeneic hematopoietic stem cell transplant (allo-HSCT)

Summary:

      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).
    

Eligibility criteria:

        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.