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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04356287
Recruitment Status : Not yet recruiting
First Posted : April 22, 2020
Last Update Posted : April 1, 2022
Sponsor:
Collaborators:
Medical University of South Carolina
McGill University Health Centre/Research Institute of the McGill University Health Centre
Université de Montréal
Assistance Publique - Hôpitaux de Paris
Centre hospitalier de l'Université de Montréal (CHUM)
University Paris 7 - Denis Diderot
Information provided by (Responsible Party):
Marie Hudson, MD, Sir Mortimer B. Davis - Jewish General Hospital

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).

Condition or disease Intervention/treatment Phase
Sclerosis, Systemic Mesenchymal Stem Cells Biological: UCMSC Other: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Controlled Trial of Umbilical Cord-derived mesenChymAl stRomal cElls in Systemic Sclerosis
Estimated Study Start Date : May 2022
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma

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 months 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 Name: 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 Name: 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.




Primary Outcome Measures :
  1. Measure of safety one month after first infusion [ Time Frame: Month 1 ]
    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]


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


Other Outcome Measures:
  1. Safety at the time of infusion, 24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12 (adverse events) [ Time Frame: 24 hours, 10 days +/- 24 hours, Month 6, Month 9 and Month 12 ]
    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]

  2. Mortality occurring after randomization and up to study completion [ Time Frame: 1 year ]
    Causes of death and their relation to SSc versus the study intervention will be evaluated by the Data and Safety Monitoring Committee (DSMC).

  3. Modified Rodnan skin score [ Time Frame: Month 0, Month 3, Month 6 and Month 9 ]
    A measure of skin thickness [Khanna et al., 2017]

  4. World Health Organization (WHO) performance status [ Time Frame: Month 0, Month 3, Month 6, Month 9 and Month 12 ]
    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.).

  5. Scleroderma-Health Assessment Questionnaire [ Time Frame: Month 0, Month 3, Month 6, Month 9 and Month 12 ]
    Disease status as measured by the Scleroderma-Health Assessment Questionnaire [Steen & Medsger, 1997]

  6. 36-Item Short Form Survey version 2 for health-related quality of life (SF-36v2) [ Time Frame: Month 0, Month 3, Month 6, Month 9 and Month 12 ]
    Health-related quality of life as measured by the SF-36v2 [Ware et al., 2007]

  7. EuroQoL health status measure (EQ-5D-5L) [ Time Frame: Month 0, Month 3, Month 6, Month 9 and Month 12 ]
    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.

  8. Response to treatment [ Time Frame: Month 0, Month 12 ]
    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

  9. Progression-free survival [ Time Frame: Month 0, Month 12 ]
    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

  10. Global Rank Composite Score [ Time Frame: Month 0, Month 12 ]
    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]

  11. ACR Provisional Composite Response Index [ Time Frame: Month 0, Month 12 ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04356287


Contacts
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Contact: Marie Hudson, MD 514-340-8222 ext 23476 marie.hudson@mcgill.ca

Sponsors and Collaborators
Marie Hudson, MD
Medical University of South Carolina
McGill University Health Centre/Research Institute of the McGill University Health Centre
Université de Montréal
Assistance Publique - Hôpitaux de Paris
Centre hospitalier de l'Université de Montréal (CHUM)
University Paris 7 - Denis Diderot
Investigators
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Principal Investigator: Marie Hudson, MD Sir Mortimer B. Davis - Jewish General Hospital
Additional Information:
Publications:
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Responsible Party: Marie Hudson, MD, Rheumatologist, Jewish General Hospital; Physician-scientist, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis - Jewish General Hospital
ClinicalTrials.gov Identifier: NCT04356287    
Other Study ID Numbers: MP-05-2020-2251
First Posted: April 22, 2020    Key Record Dates
Last Update Posted: April 1, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Marie Hudson, MD, Sir Mortimer B. Davis - Jewish General Hospital:
Systemic Sclerosis
Umbilical cord-derived mesenchymal stromal cells
Scleroderma, Systemic
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases