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Safety and Clinical Activity of Itolizumab in aGVHD

Primary Purpose

Acute Graft Versus Host Disease

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Itolizumab
Methylprednisolone
Sponsored by
Biotech Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Graft Versus Host Disease

Eligibility Criteria

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

Inclusion Criteria: Male or female subject at least 18 years of age. Has received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinical diagnosis of Grade II-IV aGVHD per MAGIC guideline requiring systemic immune suppressive therapy. Initiation of systemic steroids therapy ≤ 72 hours. Negative result of serum HCG within 72 hours before enrollment for female with potential fertility. Have a life expectancy of 10 weeks or more. Able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF). Exclusion Criteria: Has received more than 1 allo-HSCT. Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse. Evidence of graft failure based on cytopenia(s), and as determined by the investigator. Evidence of post-transplant lymphoproliferative disease. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids. aGVHD induced by donor lymphocyte infusion(DLI). Clinically or suspected diagnosed of cGVHD or overlap syndrome. Unresolved toxicity or complications due to allo-HSCT,other than aGVHD. Any clinical or laboratory abnormalities that is likely to negatively affect the reliability of the study safety data, as determined by the investigator. Presence of any uncontrolled active infections, which was defined as hemodynamic instability due to sepsis or worsening of new symptoms, signs, or imaging findings due to infection. Presence of any uncontrolled and active infections. Presence of active and uncontrolled viral infections at screening. History of active tuberculosis within 6 months prior to screening or negative result of interferon-gamma release assay at screening. History of class III or IV congestive heart failure per New York Heart Association, clinically significant or uncontrolled unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening. Severe impaired renal function at screening (serum creatinine > 1.5 ULN or creatinine clearance < 30mL/min). Presence of persistent bilirubin abnormalities induced by hepatic sinusoidal obstruction, hepatic veno-occlusive disease, non-GVHD or progressive organ dysfunction at screening. Serum ALT and AST > 4 ULN at screening. Absolute lymphocyte count < 0.5×109/L at screening. Any major surgical procedures performed within 4 weeks prior to screening, that is likely to negatively affect the evaluation of the study safety data, as determined by the investigator. Any malignant tumor other than the transplanted tumor within 5 years before screening. Suspected allergic to the experimental drug product or any of its excipients. Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.

Sites / Locations

  • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Itolizumab Dose Level 1

Itolizumab Dose Level 2

Itolizumab Dose Level 3

Itolizumab Dose Level 4

Arm Description

Itolizumab of 25 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.

Itolizumab of 50 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.

Itolizumab of 100 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.

Itolizumab of 150 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.

Outcomes

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events
Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0

Secondary Outcome Measures

Time to maximum Itolizumab serum concentration, Tmax
Time to maximum Itolizumab serum concentration
Maximum Itolizumab serum drug concentration, Cmax
Maximum Itolizumab serum drug concentration
Minimum Itolizumab serum drug concentration, Cmin
Minimum Itolizumab serum drug concentration
Total Itolizumab exposure across time, AUC
Total Itolizumab exposure across time, AUC
Half life of Itolizumab, t1/2
Half life of Itolizumab
Volume of distribution of Itolizumab, Vd
Volume of distribution of Itolizumab
Clearance, Cl
Clearance
CD6 receptor expression levels on T cells
CD6 receptor expression levels
T cell subsets
T cell subsets
Inflammatory Markers
Including but not limited to:IL-2, IL-6, IL-8, IL-17, IFN-γ, TNF-α, CRP, TNFR1, ST2, REG3α, Elafin
Overall Response Rate (ORR)
Percentage of subjects demonstrating a CR or PR.
Nonrelapse Mortality(NRM) Rate
Proportion of subjects who died due to causes other than malignancy relapse
cGVHD rate
Percentage of subjects demonstrating of cGVHD
Dose Reduction in Systemic Steroid Use
Change from Baselinein Dose of Systemic Steroid Use
Incidence of ADA
Precentage of subjects presenting anti-drug antibody

Full Information

First Posted
March 16, 2023
Last Updated
May 23, 2023
Sponsor
Biotech Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05823675
Brief Title
Safety and Clinical Activity of Itolizumab in aGVHD
Official Title
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Itolizumab in Subjects With Newly Diagnosed Acute Graft Versus Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotech Pharmaceutical 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
To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects with Newly diagnosed Acute Graft Versus Host Disease(aGVHD).
Detailed Description
The study will enroll approximately 44 subjects in three parts: Part 1 is an open label 3+3 single dose escalation phase and will enroll approximately 30 subjects with aGVHD across 4 cohorts, where subjects will receive Itolizumab administered intravenously for 1 dose. Part 2 is an open label phase and subjects from part 1 will receive Itolizumab administered intravenously every two weeks for a total of 4 doses. Part 3 is a randomized phase and will enroll approximately 14 additional subjects, randomized in a 1:1 ratio to one of the 2 recommended doses provided by Part 1 and Part 2. Subjects will receive Itolizumab administered intravenously every two weeks for a total of 5 doses.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Graft Versus Host Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Itolizumab Dose Level 1
Arm Type
Experimental
Arm Description
Itolizumab of 25 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.
Arm Title
Itolizumab Dose Level 2
Arm Type
Experimental
Arm Description
Itolizumab of 50 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.
Arm Title
Itolizumab Dose Level 3
Arm Type
Experimental
Arm Description
Itolizumab of 100 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.
Arm Title
Itolizumab Dose Level 4
Arm Type
Experimental
Arm Description
Itolizumab of 150 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.
Intervention Type
Drug
Intervention Name(s)
Itolizumab
Other Intervention Name(s)
T1h
Intervention Description
Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Methylprednisolone Sodium Succinate
Intervention Description
Methylprednisolone will be taperred as required
Primary Outcome Measure Information:
Title
Incidence of Treatment Emergent Adverse Events
Description
Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Time Frame
Study Day 85
Secondary Outcome Measure Information:
Title
Time to maximum Itolizumab serum concentration, Tmax
Description
Time to maximum Itolizumab serum concentration
Time Frame
Study Day 85
Title
Maximum Itolizumab serum drug concentration, Cmax
Description
Maximum Itolizumab serum drug concentration
Time Frame
Study Day 85
Title
Minimum Itolizumab serum drug concentration, Cmin
Description
Minimum Itolizumab serum drug concentration
Time Frame
Study Day 85
Title
Total Itolizumab exposure across time, AUC
Description
Total Itolizumab exposure across time, AUC
Time Frame
Study Day 85
Title
Half life of Itolizumab, t1/2
Description
Half life of Itolizumab
Time Frame
Study Day 85
Title
Volume of distribution of Itolizumab, Vd
Description
Volume of distribution of Itolizumab
Time Frame
Study Day 85
Title
Clearance, Cl
Description
Clearance
Time Frame
Study Day 85
Title
CD6 receptor expression levels on T cells
Description
CD6 receptor expression levels
Time Frame
Study Day 85
Title
T cell subsets
Description
T cell subsets
Time Frame
Study Day 85
Title
Inflammatory Markers
Description
Including but not limited to:IL-2, IL-6, IL-8, IL-17, IFN-γ, TNF-α, CRP, TNFR1, ST2, REG3α, Elafin
Time Frame
Study Day 85
Title
Overall Response Rate (ORR)
Description
Percentage of subjects demonstrating a CR or PR.
Time Frame
Study Day 337
Title
Nonrelapse Mortality(NRM) Rate
Description
Proportion of subjects who died due to causes other than malignancy relapse
Time Frame
Study Day 337
Title
cGVHD rate
Description
Percentage of subjects demonstrating of cGVHD
Time Frame
Study Day 337
Title
Dose Reduction in Systemic Steroid Use
Description
Change from Baselinein Dose of Systemic Steroid Use
Time Frame
Study Day 337
Title
Incidence of ADA
Description
Precentage of subjects presenting anti-drug antibody
Time Frame
Study Day 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subject at least 18 years of age. Has received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinical diagnosis of Grade II-IV aGVHD per MAGIC guideline requiring systemic immune suppressive therapy. Initiation of systemic steroids therapy ≤ 72 hours. Negative result of serum HCG within 72 hours before enrollment for female with potential fertility. Have a life expectancy of 10 weeks or more. Able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF). Exclusion Criteria: Has received more than 1 allo-HSCT. Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse. Evidence of graft failure based on cytopenia(s), and as determined by the investigator. Evidence of post-transplant lymphoproliferative disease. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids. aGVHD induced by donor lymphocyte infusion(DLI). Clinically or suspected diagnosed of cGVHD or overlap syndrome. Unresolved toxicity or complications due to allo-HSCT,other than aGVHD. Any clinical or laboratory abnormalities that is likely to negatively affect the reliability of the study safety data, as determined by the investigator. Presence of any uncontrolled active infections, which was defined as hemodynamic instability due to sepsis or worsening of new symptoms, signs, or imaging findings due to infection. Presence of any uncontrolled and active infections. Presence of active and uncontrolled viral infections at screening. History of active tuberculosis within 6 months prior to screening or negative result of interferon-gamma release assay at screening. History of class III or IV congestive heart failure per New York Heart Association, clinically significant or uncontrolled unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening. Severe impaired renal function at screening (serum creatinine > 1.5 ULN or creatinine clearance < 30mL/min). Presence of persistent bilirubin abnormalities induced by hepatic sinusoidal obstruction, hepatic veno-occlusive disease, non-GVHD or progressive organ dysfunction at screening. Serum ALT and AST > 4 ULN at screening. Absolute lymphocyte count < 0.5×109/L at screening. Any major surgical procedures performed within 4 weeks prior to screening, that is likely to negatively affect the evaluation of the study safety data, as determined by the investigator. Any malignant tumor other than the transplanted tumor within 5 years before screening. Suspected allergic to the experimental drug product or any of its excipients. Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xijuan Song
Phone
010-51571020
Email
songxijuan@biotechplc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erlie Jiang
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital,Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
City
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erlie Jiang

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Clinical Activity of Itolizumab in aGVHD

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