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).

Study Overview

• Status: Terminated
• Conditions: GVHD,Acute
• Intervention / Treatment: Drug: Prednisone; Drug: Itacitinib; Drug: Methylprednisolone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Suzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Itacitinib+corticosteroids; Itacitinib administered in combination with corticosteroids

Drug: Prednisone; 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.; Drug: Itacitinib; at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.; Other Names: IBI377; Drug: Methylprednisolone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate based on Center for International Bloe index	Defined as the percentage of participants demonstrating a complete response (CR), very good partial responseod and Marrow Transplant Research (CIBMTR) respons (VGPR), or partial response (PR).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nonrelapse mortality	Defined as the percentage of participants who died due to causes other than malignancy relapse	Month 6
Duration of response	Defined as the interval from first response until GVHD progression or death.	Baseline through 30-35 days after end of treatment, expected to average approximately 6 months
Cmax of itacitinib when administered in combination with corticosteroids	Defined as maximum observed plasma concentration.	Protocol-defined timepoints up to Day 28
Cmin of itacitinib when administered in combination with corticosteroids	Defined as minimum observed plasma concentration	Protocol-defined timepoints up to Day 28
Tmax of itacitinib when administered in combination with corticosteroids	Defined as time to maximum plasma concentration	Protocol-defined timepoints up to Day 28
AUC(area under curve) of itacitinib when administered in combination with corticosteroids	Protocol-defined timepoints up to Day 28	Protocol-defined timepoints up to Day 28
CL/F(clearance) of itacitinib when administered in combination with corticosteroids	Defined as oral dose clearance	Protocol-defined timepoints up to Day 28

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): October 10, 2020
• Study Completion (Actual): October 10, 2020

Study Registration Dates

• First Submitted: January 4, 2020
• First Submitted That Met QC Criteria: January 4, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 29, 2020
• Last Update Submitted That Met QC Criteria: October 27, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone
• Other Study ID Numbers: CIBI377A201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No