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

Incyte

Status and phase: Completed; Phase 3

Conditions: Graft-versus-host Disease (GVHD)

Treatments: Drug: Placebo; Drug: Methylprednisolone; Drug: Itacitinib; Drug: Prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03139604

2017-000538-78 (EudraCT Number)

INCB 39110-301

Details and patient eligibility

About

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).

Enrollment: 439 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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439 participants in 2 patient groups, including a placebo group

Itacitinib

Experimental group

Description:

Itacitinib plus corticosteroids

Treatment:

Drug: Prednisone

Drug: Itacitinib

Drug: Methylprednisolone

Placebo

Placebo Comparator group

Description:

Matching placebo plus corticosteroids

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Drug: Placebo