Treatment With Human Umbilical Cord-derived Mesenchymal Stromal Cells in Systemic Sclerosis (CARE-SSc)

Phase I/II Randomized Controlled Trial of Umbilical Cord-derived mesenChymAl stRomal cElls in Systemic Sclerosis

The purpose of this study is to test the safety and efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC) for the treatment of Systemic Sclerosis (SSc).

Study Overview

• Status: Recruiting
• Conditions: Mesenchymal Stem Cells; Sclerosis, Systemic
• Intervention / Treatment: Biological: UCMSC; Other: Placebo

Detailed Description

A single-center, three-arm, randomized, double-blind, placebo-controlled trial is proposed. A total of 18 SSc patients will be enrolled in 3 successive blocks of 6 patients each. After being informed about the study and potential risks, all patients giving written informed consent will be randomized to one of two treatment arms or a placebo arm (total of 6 patients per arm). Within each block, the 6 patients will be randomized in a 2:2:2 ratio in one of the following arms: placebo, 1 infusion of UCMSC (M0), or 2 infusions of UCMSC (M0, M3). Second infusions of UCMSC will be performed only in the absence of Treatment Related Severe Adverse Events (TRSAE). Randomization into blocks 2 and 3 will be staggered, to allow the detection of TRSAE prior to inclusion of patients in a subsequent block, i.e. the second block will be randomized only in the absence of TRSAE one month after the first infusion of all 6 patients in block one, and similarly for the third block.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Marie Hudson, MD; Phone Number: 23476 514-340-8222; Email: marie.hudson@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Sir Mortimer B. Davis Jewish General Hospital
      • Contact: Marie Hudson, MD MPH; Phone Number: 23476 1-514-340-8222; Email: marie.hudson@mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. SSc according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2103 classification criteria for systemic sclerosis

2. Severe disease defined as:

   i) disease duration of 2 years or less with an mRss of > 20 and (ESR > 25 mm and/or hemoglobin < 11 g/dL, not explained by other causes than SSc), or ii) mRss >15 without any restriction as to disease duration plus at least one major organ involvement as defined by: a) respiratory involvement consisting of lung diffusion capacity for carbon monoxide (DLCO) and/or forced vital capacity (FVC) < 80% predicted and evidence of interstitial lung disease (chest X-ray and/or high resolution computed tomography (HRCT) scan); b) renal involvement consisting of past renal crisis and/or stage 2 or 3 chronic kidney disease (glomerular filtration rate between 30-89 mL/min) not explained by other causes than SSc; c) cardiac involvement consisting of reversible congestive heart failure, atrial or ventricular rhythm disturbances such as recurrent episodes of atrial fibrillation or flutter, recurrent atrial paroxysmal tachycardia, conduction abnormalities (2nd or 3rd degree atrioventricular block), and/or mild to moderate pericardial effusion. All causes of organ involvement should be attributed to SSc.

3. Inadequate response (determined by patient and physician judgement) or adverse events necessitating discontinuation of standard therapy (usually consisting of methotrexate 25 mg subcutaneous (or as tolerated) per week and/or mycophenolate mofetil 2-3 gm/d (or as tolerated) for at least 3 months
4. Ineligibility or unwillingness to undergo autologous hematopoietic stem cell transplant

Exclusion Criteria:

1. Age < 18 years
2. Pregnancy or unwillingness to use adequate contraception

3. Life-threatening end-organ damage defined as:

   • FVC < 45% and/or DLCO (corrected for hemoglobin) < 30% predicted;
   • Left ventricular ejection fraction < 40% by cardiac echocardiography;
   • Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 25 mmHg (and pulmonary wedge pressure < 15 mmHg) on right heart catheterization;
   • stage 4 or more chronic kidney disease (glomerular filtration rate < 30 ml/min)
4. Liver failure defined as an abnormal transaminase level (aspartate aminotransferase (ASAT), alanine aminotransaminase (ALAT) > 3 normal) unless related to activity of the disease
5. Concurrent neoplasms or myelodysplasia
6. Uncontrolled hypertension
7. Uncontrolled acute or chronic infection (HIV, HTLV-1/2 (Human T-lymphotropic virus), hepatitis B surface Ag positive, hepatitis C positive) or high risk thereof
8. Significant malnutrition with BMI < 18 kg/m2
9. Severe concomitant psychiatric disorder
10. Bone marrow insufficiency defined as neutropenia < 0.5 x 109 cell/L, thrombocytopenia < 30 x 109 cell/L, anemia < 8g/dL, CD4+ T lymphopenia < 200 x 106 cell/L due to other diseases than SSc (CD4 - cluster of differentiation 4)
11. History of poor compliance
12. Concurrent enrolment in any other protocol using an investigational drug
13. Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: One infusion of UCMSC; Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of placebo at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A. Each placebo infusion will consist of a similar volume of PlasmaLyte A.	Biological: UCMSC; Each infusion will consist of 1 million MSC/kg suspended in 50 mL of PlasmaLyte A.; Other Names: umbilical cord derived mesenchymal stromal cells
Experimental: Two infusions of UCMSC; Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of UCMSC at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A.	Biological: UCMSC; Each infusion will consist of 1 million MSC/kg suspended in 50 mL of PlasmaLyte A.; Other Names: umbilical cord derived mesenchymal stromal cells
Placebo Comparator: Placebo infusions; Patients receive intravenous placebo infusions at months 0 and 3. Each placebo infusion will consist of 50 ml of PlasmaLyte A.	Other: Placebo; Each infusion will consist of 50 mL of PlasmaLyte A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of safety one month after first infusion	Treatment related severe adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification [https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm]	Month 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified Rodnan skin score (mRss) between Month 0 and Month 12	A measure of skin thickness; difference between Month 12 and Month 0 on the mRss [Khanna et al., 2017]	Month 0 and Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety at the time of infusion, 24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12 (adverse events)	Measure of safety of UCMSC in severe SSc using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification [https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm]	24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12
Mortality occurring after randomization and up to study completion	Causes of death and their relation to SSc versus the study intervention will be evaluated by the Data and Safety Monitoring Committee (DSMC).	1 year
Modified Rodnan skin score	A measure of skin thickness [Khanna et al., 2017]	Month 0, Month 3, Month 6 and Month 9
World Health Organization (WHO) performance status	WHO performance status [Oken et al., 1982] describes a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.).	Month 0, Month 3, Month 6, Month 9 and Month 12
Scleroderma-Health Assessment Questionnaire	Disease status as measured by the Scleroderma-Health Assessment Questionnaire [Steen & Medsger, 1997]	Month 0, Month 3, Month 6, Month 9 and Month 12
36-Item Short Form Survey version 2 for health-related quality of life (SF-36v2)	Health-related quality of life as measured by the SF-36v2 [Ware et al., 2007]	Month 0, Month 3, Month 6, Month 9 and Month 12
EuroQoL health status measure (EQ-5D-5L)	Health related quality of life in cost effectiveness analysis as measured by the EQ-5D-5L [Herdman et al., 2011] using five levels of severity in five dimensions.	Month 0, Month 3, Month 6, Month 9 and Month 12
Response to treatment	Defined as decrease in mRss > 25%, increase in FVC > 10% predicted (forced vital capacity) and/or increase in DLCO >15% predicted (diffusing capacity of the lungs for carbon monoxide), without need for further immunosuppression except low dose steroids	Month 0, Month 12
Progression-free survival	Progression defined as any one of the following: decrease in FVC > 10% predicted; decrease in DLCO > 15% predicted; decrease in left ventricular ejection fraction on cardiac echocardiography > 15%; decrease in weight > 15%; decrease in creatinine clearance > 30%; increase in mRss > 25%; and/or increase in Scleroderma-Health Assessment Questionnaire > 0.5	Month 0, Month 12
Global Rank Composite Score	A composite score consisting of a hierarchy of ordered outcomes: death, event-free survival (survival without respiratory, renal, or cardiac failure), FVC, score on the Disability Index of the Health Assessment Questionnaire (HAQ-DI; range, 0 to 3, with higher scores indicating more disability), and the modified Rodnan skin score. [Sullivan et al., 2018]	Month 0, Month 12
ACR Provisional Composite Response Index	ACR Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis (CRISS) [Khanna et al., 2016], a composite measure of treatment response in SSc	Month 0, Month 12

Collaborators and Investigators

• Sponsor: Marie Hudson, MD
• Collaborators: Assistance Publique - Hôpitaux de Paris; Medical University of South Carolina; Centre hospitalier de l'Université de Montréal (CHUM); McGill University Health Centre/Research Institute of the McGill University Health Centre; Université de Montréal; University Paris 7 - Denis Diderot
• Investigators: Principal Investigator: Marie Hudson, MD, Sir Mortimer B. Davis - Jewish General Hospital

Publications and helpful links

General Publications

• Liang J, Zhang H, Kong W, Deng W, Wang D, Feng X, Zhao C, Hua B, Wang H, Sun L. Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study. Stem Cell Res Ther. 2018 Nov 14;9(1):312. doi: 10.1186/s13287-018-1053-4.
• Wang D, Zhang H, Liang J, Wang H, Hua B, Feng X, Gilkeson GS, Farge D, Shi S, Sun L. A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus. Stem Cell Reports. 2018 Mar 13;10(3):933-941. doi: 10.1016/j.stemcr.2018.01.029. Epub 2018 Mar 1.

Helpful Links

• US Department of Health and Human Services. National Cancer Institute Common Terminology Criteria For Adverse Events (CTCAE), Version 5.0. 2017

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Scleroderma, Systemic; Umbilical cord-derived mesenchymal stromal cells
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic
• Other Study ID Numbers: MP-05-2020-2251

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