A Prospective, Open Label, Dose-escalation, SAD/MAD, Multicenter, 24weeks, Phase I/IIa Clinical Trial to Evaluate the Safety, Tolerability and Pharmacodynamics of Investigational Product (VM-001) in Patients With Graft-versus-host Disease(GvHD)

Study Overview
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Brief Summary
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The present study is multi center, phase I/IIa clinical trial to evaluate the safety and pharmacodynamics of investigational Product (VM-001) in patients with graft-versus-host disease(GvHD). A total of 12 subjects (Part 1 SAD[3 cohort(2 subjects/cohort)], Part 2 MAD[2 cohort(3subjects/cohort)]) are recruited.

Official Title
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A Prospective, Open Label, Dose-escalation, SAD/MAD, Multicenter, 24weeks, Phase I/IIa Clinical Trial to Evaluate the Safety, Tolerability and Pharmacodynamics of Investigational Product (VM-001) in Patients With Graft-versus-host Disease(GvHD)

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Biological: VM-001 1X10^6 cells/kg
* Biological: VM-001 3X10^6 cells/kg
* Biological: VM-001 5X10^6 cells/kg
* Biological: VM-001 1X10^6 cells/kg two dose
* Biological: VM-001 1X10^6 cells/kg four dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥19 years of age Acute GvHD or chronic GvHD after hematopoietic stem cell transplant Subjects who no longer have available standard treatment. ANC≥1,000cells./mm^3 AST, ALT, total bilirubin less than 3 times the upper limit of normal serum creatinine less than 1.5 times the upper limit of normal Exclusion Criteria: Received an anti-thymocyte globulin(ATG) within 14 days before enrollment FCV or FEV less than 70% Any uncontrolled infection or active infection requiring ongoing systemic treatment Received an investigational agent within 6 months before enrollment. Evidence of bleeding diathesis or coagulopathy. Active hepatitis C virus (HCV) or hepatitis B virus (HBV) Breastfeeding or pregnant.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Single Ascending Dose, Cohort 1<br>Cohort 1 : 1X10^6 cells/kg The safety of 2 subjects is evaluated for 1 week after single dose of IP. If CTCAE grade 3 or higher adverse drug events (ADR) do not occur in the two subjects: Begin enrollment for Cohort 2. | Biological: VM-001 1X10^6 cells/kg<br>* Administration: Inject intravenously single dose<br>|
| Experimental: Part 1 Single Ascending Dose, Cohort 2<br>Cohort 2 : 3X10^6 cells/kg The safety of 2 subjects is evaluated for 1 week after single dose of IP. If CTCAE grade 3 or higher adverse drug events (ADR) do not occur in the two subjects: Begin enrollment for Cohort 3. | Biological: VM-001 3X10^6 cells/kg<br>* Administration: Inject intravenously single dose<br>|
| Experimental: Part 1 Single Ascending Dose, Cohort 3<br>Cohort 3 : 5X10^6 cells/kg The safety of 2 subjects is evaluated for 1 week after single dose of IP. | Biological: VM-001 5X10^6 cells/kg<br>* Administration: Inject intravenously single dose<br>|
| Experimental: Part 2 Multiple Ascending Dose, Cohort 1<br>Cohort 1 : two doses in total, 1X10^6 cells/kg per dose, weekly The safety of 3 subjects is evaluated for 4 week after two dose of IP. If CTCAE grade 3 or higher adverse drug events (ADR) do not occur in the three subjects: Begin enrollment for Cohort 2. | Biological: VM-001 1X10^6 cells/kg two dose<br>* Administration: Inject intravenously 1X10^6 cells/kg per dose, two dose in total, weekly<br>|
| Experimental: Part 2 Multiple Ascending Dose, Cohort 2<br>Cohort 2 : four doses in total, 1X10^6 cells/kg per dose, weekly The safety of 3 subjects is evaluated for 8 week after two dose of IP. | Biological: VM-001 1X10^6 cells/kg four dose<br>* Administration: Inject intravenously 1X10^6 cells/kg per dose, four dose in total, weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of VM-001 [ Time Frame: 1 week ] | First 7-day treatment dose limiting toxicities (DLT) graded according to CTCAE in the MTD-determining population in Phase 1 based on the number of participants with adverse effects as measure of tolerability at various dose levels | 7 day cycle |