A Study of IBI377 in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease

An Open Label, Multicenter, Phase I/II Study of IBI377 in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease

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

This is an open label, single-arm, multicenter Phase I/II study of IBI377 in combination with corticosteroids as first-line treatment of subjects with Grade II to IV aGVHD. In Phase I, the PK, safety, tolerability and efficacy of IBI377 will be assessed in 12 subjects. In Phase II, the efficacy and safety will be assessed in 48 subjects.

Inclusion Criteria:

• Has undergone 1 allo-HSCT(hematopoietic stem cell transplantation) from any donor (related or unrelated with any degree of HLA(human leukocyte antigen) 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 acute-GVHD.
• 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 (HCV) 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(Janus kinase) 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.