Using stem cells from umbilical cords to treat systemic sclerosis

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

This study is testing if using stem cells from umbilical cords can help people with systemic sclerosis feel better and improve their condition.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sir Mortimer B. Davis - Jewish General Hospital (other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT04356287 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC) in patients with systemic sclerosis (SSc). It is a single-center, randomized, double-blind, placebo-controlled study involving 18 patients, who will be divided into three groups: one receiving a placebo, one receiving one infusion of UCMSC, and another receiving two infusions. The trial will monitor for treatment-related severe adverse events (TRSAE) before proceeding with subsequent patient blocks. The goal is to determine if UCMSC can provide therapeutic benefits for individuals suffering from this severe autoimmune condition.

Who should consider this trial

Good fit: Ideal candidates for this study are patients diagnosed with severe systemic sclerosis as per established classification criteria.

Not a fit: Patients with mild systemic sclerosis or those who do not meet the severe disease criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with systemic sclerosis, potentially improving their quality of life.

How similar studies have performed: While the use of UCMSC in systemic sclerosis is a novel approach, other studies involving stem cells for autoimmune diseases have shown promising results.

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

Where this trial is running

Montreal, Quebec

• Sir Mortimer B. Davis Jewish General Hospital — Montreal, Quebec, Canada (RECRUITING)

Study contacts

• Principal investigator: Marie Hudson, MD — Sir Mortimer B. Davis - Jewish General Hospital
• Study coordinator: Marie Hudson, MD

Conditions: Sclerosis, Systemic, Mesenchymal Stem Cells, Systemic Sclerosis, Umbilical cord-derived mesenchymal stromal cells, Scleroderma, Systemic