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

Primary Purpose

GVHD,Acute

Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Itacitinib
Prednisone
Methylprednisolone
Sponsored by
Innovent Biologics (Suzhou) Co. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GVHD,Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Suzhou University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Itacitinib+corticosteroids

Arm Description

Itacitinib administered in combination with corticosteroids

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Nonrelapse mortality
Defined as the percentage of participants who died due to causes other than malignancy relapse
Duration of response
Defined as the interval from first response until GVHD progression or death.
Cmax of itacitinib when administered in combination with corticosteroids
Defined as maximum observed plasma concentration.
Cmin of itacitinib when administered in combination with corticosteroids
Defined as minimum observed plasma concentration
Tmax of itacitinib when administered in combination with corticosteroids
Defined as time to maximum plasma concentration
AUC(area under curve) of itacitinib when administered in combination with corticosteroids
Protocol-defined timepoints up to Day 28
CL/F(clearance) of itacitinib when administered in combination with corticosteroids
Defined as oral dose clearance

Full Information

First Posted
January 4, 2020
Last Updated
October 27, 2020
Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04220632
Brief Title
A Study of IBI377 in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
Adverse events of the first patient
Study Start Date
June 18, 2020 (Actual)
Primary Completion Date
October 10, 2020 (Actual)
Study Completion Date
October 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innovent Biologics (Suzhou) Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GVHD,Acute

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Itacitinib+corticosteroids
Arm Type
Experimental
Arm Description
Itacitinib administered in combination with corticosteroids
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Other Intervention Name(s)
IBI377
Intervention Description
at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate based on Center for International Bloe index
Description
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).
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Nonrelapse mortality
Description
Defined as the percentage of participants who died due to causes other than malignancy relapse
Time Frame
Month 6
Title
Duration of response
Description
Defined as the interval from first response until GVHD progression or death.
Time Frame
Baseline through 30-35 days after end of treatment, expected to average approximately 6 months
Title
Cmax of itacitinib when administered in combination with corticosteroids
Description
Defined as maximum observed plasma concentration.
Time Frame
Protocol-defined timepoints up to Day 28
Title
Cmin of itacitinib when administered in combination with corticosteroids
Description
Defined as minimum observed plasma concentration
Time Frame
Protocol-defined timepoints up to Day 28
Title
Tmax of itacitinib when administered in combination with corticosteroids
Description
Defined as time to maximum plasma concentration
Time Frame
Protocol-defined timepoints up to Day 28
Title
AUC(area under curve) of itacitinib when administered in combination with corticosteroids
Description
Protocol-defined timepoints up to Day 28
Time Frame
Protocol-defined timepoints up to Day 28
Title
CL/F(clearance) of itacitinib when administered in combination with corticosteroids
Description
Defined as oral dose clearance
Time Frame
Protocol-defined timepoints up to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
The First Affiliated Hospital of Suzhou University
City
Suzhou
State/Province
Jiangsu
Country
China

12. IPD Sharing Statement

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

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