Treatment of Respiratory Complications Associated With COVID-19 Using Umbilical Cord Mesenchymal Stromal Cells (ProTrans19+)
Primary Purpose
Covid19
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Allogeneic Wharton's jelly-MSCs (WJ-MSC)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring mesenchymal stromal cells, wharton's jelly, respiratory complication, biologics
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
Sites / Locations
- McGill University Health Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Allogeneic Wharton's jelly-MSCs (WJ-MSC)
Placebo
Arm Description
Intravenous administration, 1 dose, for 20 minutes
Intravenous administration, 1 dose, for 20 minutes
Outcomes
Primary Outcome Measures
Composite endpoint
rate of use of mechanical ventilation (i.e. need for intubation) or death
Secondary Outcome Measures
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
Survival
Rate of patients alive at Day 7, Day 15 and Day 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
Duration of hospitalization and ICU stay
Length of hospitalization and ICU stay in days
Full Information
NCT ID
NCT04869397
First Posted
April 29, 2021
Last Updated
June 16, 2023
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
1. Study Identification
Unique Protocol Identification Number
NCT04869397
Brief Title
Treatment of Respiratory Complications Associated With COVID-19 Using Umbilical Cord Mesenchymal Stromal Cells
Acronym
ProTrans19+
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
DSMB recommended to end the study prematurely as recruitment goals were not being met and benefit was not influencial enough.
Study Start Date
June 14, 2021 (Actual)
Primary Completion Date
May 26, 2023 (Actual)
Study Completion Date
May 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
mesenchymal stromal cells, wharton's jelly, respiratory complication, biologics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Allogeneic Wharton's jelly-MSCs (WJ-MSC)
Arm Type
Experimental
Arm Description
Intravenous administration, 1 dose, for 20 minutes
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous administration, 1 dose, for 20 minutes
Intervention Type
Biological
Intervention Name(s)
Allogeneic Wharton's jelly-MSCs (WJ-MSC)
Other Intervention Name(s)
Protrans
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Sodium chloride buffer supplemented with 5% HSA and 10% DMSO same volume and mode of administration as treatment group
Primary Outcome Measure Information:
Title
Composite endpoint
Description
rate of use of mechanical ventilation (i.e. need for intubation) or death
Time Frame
at 15 days after intervention
Secondary Outcome Measure Information:
Title
Clinical status evaluation assessed by the 9-point ordinal scale
Description
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
Time Frame
day 7, 15 and 30
Title
Survival
Description
Rate of patients alive at Day 7, Day 15 and Day 30
Time Frame
day 7, 15 and 30
Title
Time to clinical improvement assessed by the 9-point ordinal scale
Description
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 Frame
time from randomization to either an improvement of 1 point on the 9-point ordinal scale or discharge from hospital
Title
Duration of hospitalization and ICU stay
Description
Length of hospitalization and ICU stay in days
Time Frame
From enrolment to discharge or ICU transfer or death
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ines Colmegna
Organizational Affiliation
Research Institute of the McGill University Health Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Treatment of Respiratory Complications Associated With COVID-19 Using Umbilical Cord Mesenchymal Stromal Cells
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