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

Marie Hudson, MD

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Mesenchymal Stem Cells; Sclerosis, Systemic

Treatments: Other: Placebo; Biological: UCMSC

Study type: Interventional

Funder types: Other

Identifiers

NCT04356287

MP-05-2020-2251

Details and patient eligibility

About

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).

Full 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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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18 participants in 3 patient groups, including a placebo group

One infusion of UCMSC

Experimental group

Description:

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.

Treatment:

Biological: UCMSC

Two infusions of UCMSC

Experimental group

Description:

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.

Treatment:

Biological: UCMSC

Placebo infusions

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo