Clinical trial NCT04869397: Treatment of Respiratory Complications Associated With COVID-19 Using Umbilical Cord Mesenchymal Stromal Cells
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Covid19
Keywords: mesenchymal stromal cells
wharton's jelly
respiratory complication
biologics
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2021-05-03
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Composite endpoint
timeFrame: at 15 days after intervention
Secondary outcomes:
measure: Clinical status evaluation assessed by the 9-point ordinal scale
timeFrame: day 7, 15 and 30
measure: Survival
timeFrame: day 7, 15 and 30
measure: Time to clinical improvement assessed by the 9-point ordinal scale
timeFrame: time from randomization to either an improvement of 1 point on the 9-point ordinal scale or discharge from hospital
measure: Duration of hospitalization and ICU stay
timeFrame: From enrolment to discharge or ICU transfer or death
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: Research Institute of the McGill University Health Centre
name: Ines Colmegna
role: PRINCIPAL_INVESTIGATOR
References: