Safety of Itacitinib in Combination With Corticosteroids for Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects

An Open-Label Single-Arm Phase 1 Study Evaluating Safety of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects

The purpose of this study is to assess the safety and tolerability of itacitinib in combination with corticosteroids in Japanese subjects with Grades II to IV acute graft-versus-host disease (aGVHD).

Inclusion Criteria:

• Japanese; subject was born in Japan and has not lived outside of Japan for a total of > 10 years, and subject can trace maternal and paternal Japanese ancestry.
• Has undergone 1 allo-hematopoietic stem cell transplant (HSCT) from any donor and source (unrelated, sibling, haploidentical donors with any matching) using bone marrow, peripheral blood or cord blood for hematologic malignancies. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
• Clinically suspected Grades II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any anti-GVHD prophylactic medication.
• Evidence of myeloid engraftment (eg, absolute neutrophil count [ANC] ≥ 0.5 × 10^9/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
• Female subjects should agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration if of childbearing potential or must have evidence of non-childbearing potential by fulfilling protocol-defined criteria at screening.

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 (defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection; persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection).

• Known human immunodeficiency virus infection.

• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. For subjects with negative HBsAg and positive total hepatitis B core antibody and for subjects who are positive for HCV antibody, HBV DNA and HCV RNA must be undetectable upon testing.

• Evidence of relapsed primary disease or having been treated for relapse after the allo-HSCT was performed.

• Any corticosteroid therapy (for indication other than GVHD) at doses > 1 mg/kg per day methylprednisolone or equivalent within 7 days of enrollment.

• Severe organ dysfunction unrelated to underlying GVHD, including the following:

  • 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.

• Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation

• Received Janus kinase (JAK) inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.

• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.