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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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ClinicalTrials.gov Identifier: NCT04220632
Recruitment Status : Terminated (Adverse events of the first patient)
First Posted : January 7, 2020
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Innovent Biologics (Suzhou) Co. Ltd.

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).

Condition or disease Intervention/treatment Phase
GVHD,Acute Drug: Itacitinib Drug: Prednisone Drug: Methylprednisolone Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 18, 2020
Actual Primary Completion Date : October 10, 2020
Actual Study Completion Date : October 10, 2020


Arm Intervention/treatment
Experimental: Itacitinib+corticosteroids
Itacitinib administered in combination with corticosteroids
Drug: Itacitinib
at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.
Other Name: IBI377

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: 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.




Primary Outcome Measures :
  1. Overall response rate based on Center for International Bloe index [ Time Frame: 28 days ]
    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 :
  1. Nonrelapse mortality [ Time Frame: Month 6 ]
    Defined as the percentage of participants who died due to causes other than malignancy relapse

  2. Duration of response [ Time Frame: Baseline through 30-35 days after end of treatment, expected to average approximately 6 months ]
    Defined as the interval from first response until GVHD progression or death.

  3. Cmax of itacitinib when administered in combination with corticosteroids [ Time Frame: Protocol-defined timepoints up to Day 28 ]
    Defined as maximum observed plasma concentration.

  4. Cmin of itacitinib when administered in combination with corticosteroids [ Time Frame: Protocol-defined timepoints up to Day 28 ]
    Defined as minimum observed plasma concentration

  5. Tmax of itacitinib when administered in combination with corticosteroids [ Time Frame: Protocol-defined timepoints up to Day 28 ]
    Defined as time to maximum plasma concentration

  6. AUC(area under curve) of itacitinib when administered in combination with corticosteroids [ Time Frame: Protocol-defined timepoints up to Day 28 ]
    Protocol-defined timepoints up to Day 28

  7. CL/F(clearance) of itacitinib when administered in combination with corticosteroids [ Time Frame: Protocol-defined timepoints up to Day 28 ]
    Defined as oral dose clearance



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04220632


Locations
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China, Jiangsu
The First Affiliated Hospital of Suzhou University
Suzhou, Jiangsu, China
Sponsors and Collaborators
Innovent Biologics (Suzhou) Co. Ltd.
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Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier: NCT04220632    
Other Study ID Numbers: CIBI377A201
First Posted: January 7, 2020    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents