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

Phase 2

Terminated

• Conditions: Covid19
• Interventions: Other: Placebo; Biological: Allogeneic Wharton's jelly-MSCs (WJ-MSC)

• Registration Number: NCT04869397
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2021-04-29
• Study First Submitted QC: 2021-04-29
• Study First Posted: 2021-05-03
• Study Start: 2021-06-14
• Primary Completion: 2023-05-26
• Study Completion: 2023-05-26
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-16
• Last Update Posted: 2023-06-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Intravenous administration, 1 dose, for 20 minutes
Allogeneic Wharton's jelly-MSCs (WJ-MSC)	Allogeneic Wharton's jelly-MSCs (WJ-MSC)	Intravenous administration, 1 dose, for 20 minutes

Primary Outcome Measures

Name	Time	Method
Composite endpoint	at 15 days after intervention	rate of use of mechanical ventilation (i.e. need for intubation) or death

Secondary Outcome Measures

Name	Time	Method
Clinical status evaluation assessed by the 9-point ordinal scale	day 7, 15 and 30	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
Survival	day 7, 15 and 30	Rate of patients alive at Day 7, Day 15 and Day 30
Time to clinical improvement assessed by the 9-point ordinal scale	time from randomization to either an improvement of 1 point on the 9-point ordinal scale or discharge from hospital	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
Duration of hospitalization and ICU stay	From enrolment to discharge or ICU transfer or death	Length of hospitalization and ICU stay in days

Trial Locations

Locations (1)

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada