Treatment of Respiratory Complications Associated With COVID-19 Using Umbilical Cord Mesenchymal Stromal Cells

Study Overview
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Brief Summary
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This is a randomized phase II placebo controlled clinical trial. Active arm: Allogeneic Wharton's jelly derived MSCs (WJ-MSCs). Both groups will receive standard of care treatment for COVID (e.g. dexamethasone)

Detailed Description
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Allogeneic Wharton's jelly-MSCs (WJ-MSC) will be provided by NextCell Pharma under the commercial name of ProTrans®. ProTrans® will be administered at a fixed dose of 100 million cells per patient in a single infusion at bedside. Placebo: Sodium chloride buffer supplemented with 5% HSA and 10% DMSO same volume and mode of administration as treatment group (NextCell Pharma).

Official Title
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Treatment of Respiratory Complications Associated With COVID-19 Infection Using Wharton's Jelly (WJ)-Umbilical Cord (UC) Mesenchymal Stromal Cells (ProTrans®): a Randomized Phase II Controlled Clinical Trial

Conditions
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Covid19

Intervention / Treatment
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* Biological: Allogeneic Wharton's jelly-MSCs (WJ-MSC)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 years-old or older Laboratory-confirmed SARS-CoV-2 infection determined by reverse-transcription polymerase chain reaction (RT-PCR) prior to randomization Hospitalized patients Severe COVID-19 pneumonia defined as patients who cannot saturate > 96% on 4 L/min but are NOT on non-invasive ventilation nor invasive mechanical ventilation nor Extracorporeal membrane oxygenation (ECMO). Patients on high flow would be eligible if they receive treatment in a non-critical care unit only. Use of contraception or acceptable birth control for the duration of the study in women of childbearing potential Provision of written or verbal informed consent by the patient or designated substitute decision maker Exclusion Criteria: Inability to provide informed consent Patients expected to survive less than 24 hours Advanced directives of patient's wishes to refuse intubation. Patients on mechanical ventilation Pregnant women [pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test] Breastfeeding Weight > 100 kg or < 50 kg Cancer not in remission or active serious illness unrelated to COVID-19. Any of the following laboratory results at screening: Absolute neutrophil count (ANC) ≤ 1.0 x 109/L, Platelets (PLT) < 50 G /L, Alanine transaminase (ALT) or Aspartate transaminase (AST) > 5N, eGFR < 30 mL/min Current documented bacterial infection Known infection with Human immunodeficiency virus, Treponema pallidum, Hepatitis B antigen (serology consistent with previous vaccination and a history of vaccination is acceptable) or Hepatitis C On-going therapy against tuberculosis, or exposed to tuberculosis or have travelled in areas with high risk of tuberculosis or mycosis within the last 3 months Known allergies to a component of the ProTrans® product Pre-existing chronic respiratory diseases requiring long-term oxygen therapy or severe pulmonary hypertension (PAPS >30 mm HG) or pulmonary fibrosis Pre-existing cirrhosis with basal Child and Pugh of C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Wharton's jelly-MSCs (WJ-MSC)<br>Intravenous administration, 1 dose, for 20 minutes | Biological: Allogeneic Wharton's jelly-MSCs (WJ-MSC)<br>* The product is provided cryopreserved by NextCell Pharma. The cells are frozen in cryobags at a concentration of 2 × 107 cells/ml in 5% Human Serum Albumin (HSA) and 10% dimethylsulfoxide (DMSO). One cryobag contains one dose. The bags are frozen in a controlled rate freezer and directly transferred to -190 ºC for storage until the time of infusion. Cryobags are thawed at bedside and diluted in 100 ml of saline prior to administration. Cells will be delivered at a rate of 5 million cells per minute over a total of 20 minutes.<br>* Other names: Protrans;|
| Placebo Comparator: Placebo<br>Intravenous administration, 1 dose, for 20 minutes | Other: Placebo<br>* Sodium chloride buffer supplemented with 5% HSA and 10% DMSO same volume and mode of administration as treatment group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint | rate of use of mechanical ventilation (i.e. need for intubation) or death | at 15 days after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status evaluation assessed by the 9-point ordinal scale | Score 0. No clinical or virological evidence of infection. 1. No limitations of activities. 2. Ambulatory, limitation of activities. 3. Hospitalized, not requiring supplemental oxygen. 4. Hospitalized, requiring supplemental oxygen. 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices. 6. Hospitalized, intubated and on mechanical ventilation. 7. Hospitalized, ventilation + additional organ support - pressors, RRT, ECMO, 8. Death | day 7, 15 and 30 | 
| Survival | Rate of patients alive at Day 7, Day 15 and Day 30 | day 7, 15 and 30 | 
| Time to clinical improvement assessed by the 9-point ordinal scale | Score 0. No clinical or virological evidence of infection. 1. No limitations of activities. 2. Ambulatory, limitation of activities. 3. Hospitalized, not requiring supplemental oxygen. 4. Hospitalized, requiring supplemental oxygen. 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices. 6. Hospitalized, intubated and on mechanical ventilation. 7. Hospitalized, ventilation + additional organ support - pressors, RRT (Renal Replacement Therapy), ECMO, 8. Death | time from randomization to either an improvement of 1 point on the 9-point ordinal scale or discharge from hospital | 
| Duration of hospitalization and ICU stay | Length of hospitalization and ICU stay in days | From enrolment to discharge or ICU transfer or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesenchymal stromal cells, wharton's jelly, respiratory complication, biologics