Treatment With Human Umbilical Cord-derived Mesenchymal Stromal Cells in Systemic Sclerosis

NCT04356287 | Recruiting Phase 1 DMC

• 1 other identifier: MP-05-2020-2251
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Sclerosis, Systemic; Mesenchymal Stem Cells

Keywords

Systemic Sclerosis; Umbilical cord-derived mesenchymal stromal cells; Scleroderma, Systemic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in modified Rodnan skin score (mRss) between Month 0 and Month 12

  Month 0 and Month 12

Other Outcomes (11)

• Safety at the time of infusion, 24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12 (adverse events)

  24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12

• Mortality occurring after randomization and up to study completion

  1 year

• Modified Rodnan skin score

  Month 0, Month 3, Month 6 and Month 9

Study Arms (3)

One infusion of UCMSC

EXPERIMENTAL

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

Two infusions of UCMSC

EXPERIMENTAL

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

Placebo infusions

PLACEBO COMPARATOR

Patients receive intravenous placebo infusions at months 0 and 3. Each placebo infusion will consist of 50 ml of PlasmaLyte A.

Other: Placebo

Interventions

UCMSC BIOLOGICAL

Each infusion will consist of 1 million MSC/kg suspended in 50 mL of PlasmaLyte A.

Also known as: umbilical cord derived mesenchymal stromal cells

One infusion of UCMSC; Two infusions of UCMSC

Placebo OTHER

Each infusion will consist of 50 mL of PlasmaLyte A.

Placebo infusions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SSc according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2103 classification criteria for systemic sclerosis
• 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.
• 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
• Ineligibility or unwillingness to undergo autologous hematopoietic stem cell transplant

You may not qualify if:

• Age \< 18 years
• Pregnancy or unwillingness to use adequate contraception
• 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)
• Liver failure defined as an abnormal transaminase level (aspartate aminotransferase (ASAT), alanine aminotransaminase (ALAT) \> 3 normal) unless related to activity of the disease
• Concurrent neoplasms or myelodysplasia
• Uncontrolled hypertension
• 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
• Significant malnutrition with BMI \< 18 kg/m2
• Severe concomitant psychiatric disorder
• 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)
• History of poor compliance

Sponsors & Collaborators

• Marie Hudson, MD: lead
• Medical University of South Carolina: collaborator
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator
• Université de Montréal: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• University Paris 7 - Denis Diderot: collaborator

Study Sites (1)

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Related Publications (2)

• 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.

  PMID: 29478901 BACKGROUND

• 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.

  PMID: 30428931 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Marie Hudson, MD

  Sir Mortimer B. Davis - Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie Hudson, MD

CONTACT

514-340-8222; marie.hudson@mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study participants, physicians (including the outcome assessors) and research nurses will be blinded to treatment arm. Only the study statistician and the personnel at the manufacturing laboratory at the Medical University of South Carolina will be aware of the subject's treatment allocation. The Medical University of South Carolina will send blinded infusion bag(s) to the Clinical Research Unit of the Jewish General Hospital.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Rheumatologist, Jewish General Hospital; Physician-scientist, Lady Davis Institute for Medical Research

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 22, 2020
• Study Start: January 5, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)