Efficacy and Safety of SCM-CGH in Patients With Steroid-Refractory or Dependent Chronic Graft-Versus-Host Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy of SCM-CGH in participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).

Official Title
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A Multicenter, Randomized, Parallel Group, Double-blind, Phase 2 Trial to Evaluate Efficacy and Safety of SCM-CGH in Patients With Steroid-Refractory or Dependent Chronic Graft-Versus-Host Disease

Conditions
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Chronic Graft-versus-host-disease

Intervention / Treatment
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* Biological: SCM-CGH
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are males or females aged >= 19 years, 40kg to 80kg in weight Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as the National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): Refractory disease, defined as, 1) when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at >=1 mg/kg/day for at least 2 weeks) or 2), 3) Persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks Dependent disease, defined as, 4), 5) when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. Participants must be receiving less than 3 systemic glucocorticoid therapies or other immunosuppressive therapies in addition to glucocorticoids for cGVHD for at least 4 weeks before Screening visit. The dose of steroids or Immunosuppressant must be stable for 14 days(2 weeks) prior to starting SCM-CGH or Placebo. Laboratory test sufficiency as follows; Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Serum creatinine < 2 x upper limit of normal (ULN) Exclusion Criteria: Active acute graft versus host disease (GVHD) Active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus (HCV) Uncontrolled underlying disease such as moderate or severe infections and hemorrhage Severe Heart failure (NYHA class III/IV), congestive heart failure or arrhythmia requiring treatment History of allogenic hematopoietic stem cell more than once Positive reaction of a Penicillin test at screening History of relapse of causative diseases (ALL, CML, CLL, AML, NHL, multiple myeloma e.t.c.) with hematopoietic stem cell transplantation or diagnosed with secondary malignant diseases after hematopoietic stem cell transplantation History of Anti-thymocyte globulin(ATG) for 2 weeks before Screening visit History of pulmonary embolism or deep venous thrombosis for 24 weeks before Screening visit

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Multicenter, Randomized, Parallel Group, Double-blind
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCM-CGH<br>Ingredient: Allogeneic human bone marrow-derived mesenchymal stem cells Dose: 1x10^6 cells/Kg | Biological: SCM-CGH<br>* SCM-CGH will be administrated 3 times with 2-week intervals by IV infusion to subjects at Weeks 0, 2 and 4 (Visits 2, 3 and 4).<br>|
| Placebo Comparator: Placebo<br>3 times with 2-week intervals by IV infusion. | Other: Placebo<br>* Placebo will be administrated 3 times with 2-week intervals by IV infusion to subjects at Weeks 0, 2 and 4 (Visits 2, 3 and 4).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR]) | ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR). Response is defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014) and must occur, in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death. CR: Resolution of all manifestations in each organ or site. PR: Improvement in at least 1 organ or site without progression in any other organ or site. cGVHD Progression: Clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR]). | ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR). Response is defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014) and must occur, in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death. CR: Resolution of all manifestations in each organ or site. PR: Improvement in at least 1 organ or site without progression in any other organ or site. cGVHD Progression: Clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. | Week 0, 2, 4, 6, 8, 16, 20, 24 and 48 | 
| Organ-specific Assessments | Percentage of participants with organ-specific assessments is defined as rate of NIH defined CR or PR. | Week 0, 2, 4, 6, 8, 16, 20, 24 and 48 | 
| Patient-Reported Outcomes | Patient-reported Chronic GVHD-specific Measures are defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). | Week 0, 2, 4, 6, 8, 16, 20, 24 and 48 | 
| Clinician-Assessed Global Rating/Scale | Global Rating(0 3)/Scale(0 10) of clinician-assessed chronic GVHD-specific measures are defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). | Week 0, 2, 4, 6, 8, 16, 20, 24 and 48 | 
| Failure-free Survival | Failure-free survival, defined as absence of relapse, death and addition of new treatment, survival free of impairment, or reduction in steroid dosing that do not rely on direct assessment of organ responses. | Week 24 and 48 |