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

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

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)

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).

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