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

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

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]).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Biological: SCM-CGH; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bawi Kim; Phone Number: +82-2-6001-3542; Email: bwkim@scmlifescience.com

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 49267
    • Kosin University Gospel Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Seoul
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCM-CGH; Ingredient: Allogeneic human bone marrow-derived mesenchymal stem cells; Dose: 1x10^6 cells/Kg	Biological: SCM-CGH; 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).
Placebo Comparator: Placebo; 3 times with 2-week intervals by IV infusion.	Other: Placebo; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: SCM Lifescience Co., LTD.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2016
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: SCM-CGH2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No