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

NCT ID: NCT04356287

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-05
• Study Completion Date: 2025-12-31

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).

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.

Conditions

Sclerosis, Systemic; Mesenchymal Stem Cells

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

UCMSC

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

UCMSC

Intervention Type: BIOLOGICAL

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

Placebo infusions

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Each infusion will consist of 50 mL of PlasmaLyte A.

Interventions

UCMSC

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

Intervention Type: BIOLOGICAL

Placebo

Each infusion will consist of 50 mL of PlasmaLyte A.

Intervention Type: OTHER

Other Intervention Names

umbilical cord derived mesenchymal stromal cells

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: collaborator

Université de Montréal

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

University Paris 7 - Denis Diderot

OTHER

Sponsor Role: collaborator

Marie Hudson, MD

OTHER

Sponsor Role: lead

Responsible Party

Marie Hudson, MD

Rheumatologist, Jewish General Hospital; Physician-scientist, Lady Davis Institute for Medical Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marie Hudson, MD

Role: PRINCIPAL_INVESTIGATOR

Sir Mortimer B. Davis - Jewish General Hospital

Locations

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Marie Hudson, MD

Role: CONTACT

marie.hudson@mcgill.ca

514-340-8222 ext. 23476

Facility Contacts

Marie Hudson, MD MPH

Role: primary

marie.hudson@mcgill.ca

1-514-340-8222 ext. 23476

References

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.

Reference Type: BACKGROUND

PMID: 29478901 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30428931 (View on PubMed)

Related Links

https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

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

Other Identifiers

MP-05-2020-2251

Identifier Type: -

Identifier Source: org_study_id