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The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause (MEND)

Primary Purpose

Covid19, Acute Respiratory Distress Syndrome

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
CYP-001
Sponsored by
Cynata Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring Mesenchymal stem cells, MSC, Induced pluripotent stem cells, iPSC, Cellular therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female, 18 years of age or older

  • Respiratory failure with the following signs and symptoms:

    1. P/F ratio <300 mmHg
    2. Onset within one week of a known insult or new or worsening respiratory symptoms.
    3. Chest imaging shows bilateral opacities, which are not fully explained by effusions, lobar/lung collapse, or nodules.
  • Respiratory failure which is not fully explained by cardiac failure or fluid overload.
  • Onset of respiratory failure within the past 48 hours (as defined in inclusion criterion 2

Exclusion Criteria:

  • <18 years of age
  • Patient is known to be pregnant
  • Known active malignancy that required treatment in the last year
  • WHO Class III or IV pulmonary hypertension
  • Venous thromboembolism currently receiving anti-coagulation or within the past 3 months
  • Currently receiving extracorporeal life support
  • Severe chronic liver disease (Child-Pugh score >12)
  • "Do Not Attempt Resuscitation" order in place
  • Treatment withdrawal imminent within 24 hours
  • BMI > 45 kg/m2.
  • Received any investigational research agent within 60 days or within five half-lives of the last treatment (if the half-life of the investigational agent is known to be longer than 12 days) prior to the planned administration of study treatment.
  • Known positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus, Hepatitis C virus or any other infection which the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study.
  • Known sensitivity to dimethylsulfoxide (DMSO) or any other component of the study treatment.

Sites / Locations

  • Nepean Hospital
  • St George Hospital
  • Westmead Hospital
  • Footscray Hospital
  • Sunshine Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

CYP-001

Standard of care

Arm Description

The investigational medicinal product used in this study is known as CYP-001. The active agent in CYP-001 is Cymerus™ MSCs. CYP-001 is supplied as 100 million Cymerus MSCs formulated in 20 mL cryoprotectant medium. On D1 and D3, each participant randomised to receive CYP-001 will receive an IV infusion of 2 million Cymerus MSCs/kg of body weight (up to a maximum of 200 million cells per infusion).

Control participants will be randomised to received standard of care treatment.

Outcomes

Primary Outcome Measures

Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups
Assessment of respiratory dysfunction

Secondary Outcome Measures

Incidence and severity of treatment-emergent adverse events
Assessment of safety
Change in C-reactive protein (CRP) levels
Circulating biomarker of inflammation
Proportional differences between groups on the Clinical Improvement Scale
Not hospitalised, with resumption of normal activities = 1; Not hospitalised, but unable to resume normal activities = 2; Hospitalised, not requiring supplemental oxygen = 3; Hospitalised, requiring supplemental oxygen = 4; Hospitalised, requiring humidified nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both = 5; Hospitalised, requiring invasive mechanical ventilation, extracorporeal membrane oxygenation or both = 6; Death = 7
Changes in P/F ratio
Assessment of respiratory dysfunction
Changes in respiratory rate
Assessment of respiratory dysfunction
Changes in oxygenation index
Assessment of respiratory dysfunction
Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient)
Assessment of respiratory dysfunction
Changes in positive end-expiratory pressure
Assessment of respiratory dysfunction
Ventilator-free days
Number of days from the time of initiating unassisted breathing to D28, assuming survival for at least 48 hours after initiating unassisted breathing and continued unassisted breathing to D28
Proportional differences between groups on the SF-36
Quality of life assessment
Proportional differences between groups on the mini mental state examination
Disability assessment

Full Information

First Posted
August 25, 2020
Last Updated
August 30, 2023
Sponsor
Cynata Therapeutics Limited
Collaborators
Cerebral Palsy Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT04537351
Brief Title
The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause
Acronym
MEND
Official Title
A Pilot, Open-label, Randomised Controlled Clinical Trial to Investigate Early Efficacy of CYP-001 in Adults Admitted to Intensive Care With Respiratory Failure
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 24, 2020 (Actual)
Primary Completion Date
April 27, 2022 (Actual)
Study Completion Date
May 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cynata Therapeutics Limited
Collaborators
Cerebral Palsy Alliance

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a pilot, multi-centre, open-label randomised controlled study to assess the early efficacy of intravenous (IV) administration of CYP-001 in adults admitted to an intensive care unit (ICU) with respiratory failure
Detailed Description
After enrolment upon meeting eligibility criteria (D0), participants baseline data will be collected and participants will be randomised to receive either standard of care treatment only, or standard of care plus CYP-001. On D1 and D3, each participant randomised to receive CYP-001 will receive an IV infusion of 2 million Cymerus mesenchymal stem cells (MSCs)/kg of body weight (up to a maximum of 200 million cells). Participants will have further data collection throughout their ICU and hospital stay and follow up to 28 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Acute Respiratory Distress Syndrome
Keywords
Mesenchymal stem cells, MSC, Induced pluripotent stem cells, iPSC, Cellular therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYP-001
Arm Type
Experimental
Arm Description
The investigational medicinal product used in this study is known as CYP-001. The active agent in CYP-001 is Cymerus™ MSCs. CYP-001 is supplied as 100 million Cymerus MSCs formulated in 20 mL cryoprotectant medium. On D1 and D3, each participant randomised to receive CYP-001 will receive an IV infusion of 2 million Cymerus MSCs/kg of body weight (up to a maximum of 200 million cells per infusion).
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
Control participants will be randomised to received standard of care treatment.
Intervention Type
Biological
Intervention Name(s)
CYP-001
Other Intervention Name(s)
Cymerus MSCs
Intervention Description
The active agent in CYP-001 is Cymerus mesenchymal stem cells (MSCs), which are derived through a proprietary induced pluripotent stem cell (iPSC) and mesenchymoangioblast (MCA)-derived production process.
Primary Outcome Measure Information:
Title
Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups
Description
Assessment of respiratory dysfunction
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events
Description
Assessment of safety
Time Frame
28 days
Title
Change in C-reactive protein (CRP) levels
Description
Circulating biomarker of inflammation
Time Frame
7 days
Title
Proportional differences between groups on the Clinical Improvement Scale
Description
Not hospitalised, with resumption of normal activities = 1; Not hospitalised, but unable to resume normal activities = 2; Hospitalised, not requiring supplemental oxygen = 3; Hospitalised, requiring supplemental oxygen = 4; Hospitalised, requiring humidified nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both = 5; Hospitalised, requiring invasive mechanical ventilation, extracorporeal membrane oxygenation or both = 6; Death = 7
Time Frame
28 days
Title
Changes in P/F ratio
Description
Assessment of respiratory dysfunction
Time Frame
28 days
Title
Changes in respiratory rate
Description
Assessment of respiratory dysfunction
Time Frame
28 days
Title
Changes in oxygenation index
Description
Assessment of respiratory dysfunction
Time Frame
28 days
Title
Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient)
Description
Assessment of respiratory dysfunction
Time Frame
28 days
Title
Changes in positive end-expiratory pressure
Description
Assessment of respiratory dysfunction
Time Frame
28 days
Title
Ventilator-free days
Description
Number of days from the time of initiating unassisted breathing to D28, assuming survival for at least 48 hours after initiating unassisted breathing and continued unassisted breathing to D28
Time Frame
28 days
Title
Proportional differences between groups on the SF-36
Description
Quality of life assessment
Time Frame
28 days
Title
Proportional differences between groups on the mini mental state examination
Description
Disability assessment
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18 years of age or older Respiratory failure with the following signs and symptoms: P/F ratio <300 mmHg Onset within one week of a known insult or new or worsening respiratory symptoms. Chest imaging shows bilateral opacities, which are not fully explained by effusions, lobar/lung collapse, or nodules. Respiratory failure which is not fully explained by cardiac failure or fluid overload. Onset of respiratory failure within the past 48 hours (as defined in inclusion criterion 2 Exclusion Criteria: <18 years of age Patient is known to be pregnant Known active malignancy that required treatment in the last year WHO Class III or IV pulmonary hypertension Venous thromboembolism currently receiving anti-coagulation or within the past 3 months Currently receiving extracorporeal life support Severe chronic liver disease (Child-Pugh score >12) "Do Not Attempt Resuscitation" order in place Treatment withdrawal imminent within 24 hours BMI > 45 kg/m2. Received any investigational research agent within 60 days or within five half-lives of the last treatment (if the half-life of the investigational agent is known to be longer than 12 days) prior to the planned administration of study treatment. Known positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus, Hepatitis C virus or any other infection which the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study. Known sensitivity to dimethylsulfoxide (DMSO) or any other component of the study treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jolanta Airey, MD
Organizational Affiliation
Cynata Therapeutics Limited
Official's Role
Study Director
Facility Information:
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Footscray Hospital
City
Footscray
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Sunshine Hospital
City
Saint Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD relating to efficacy of MSCs in COVID-19 may be shared, subject to permission from Sponsor and ethics approval if required. All de-identified data collected during this study may be shared confidentially to contribute to meta-analysis of mesenchymal stem cell treatments for COVID-19. Request for IPD from this trial for other purposes will be considered by the Sponsor.
IPD Sharing Time Frame
Data requests will be considered after the completion of the study. There is no specified end date.
IPD Sharing Access Criteria
All reasonable requests for raw and analysed data that are not included in primary publications from this study may be available upon request and discretion from the Sponsor from the beginning to the trial. Data may be made available to active collaborators in the COVID-19 Stem Cell Treatment (CSCT) Group, subject to permission from the Sponsor and ethics approval if required. All other reasonable requests for raw and analysed data will be considered by the Sponsor. Data may be obtained upon permission from the Sponsor.

Learn more about this trial

The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause

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