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

A Pilot, Open-label, Randomised Controlled Clinical Trial to Investigate Early Efficacy of CYP-001 in Adults Admitted to Intensive Care With Respiratory Failure

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

Study Overview

• Status: Completed
• Conditions: Covid19; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Biological: CYP-001

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital
    • Saint Albans, Victoria, Australia, 3021
      • Sunshine Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYP-001; 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).	Biological: CYP-001; 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.; Other Names: Cymerus MSCs
No Intervention: Standard of care; Control participants will be randomised to received standard of care treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups	Assessment of respiratory dysfunction	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent adverse events	Assessment of safety	28 days
Change in C-reactive protein (CRP) levels	Circulating biomarker of inflammation	7 days
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	28 days
Changes in P/F ratio	Assessment of respiratory dysfunction	28 days
Changes in respiratory rate	Assessment of respiratory dysfunction	28 days
Changes in oxygenation index	Assessment of respiratory dysfunction	28 days
Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient)	Assessment of respiratory dysfunction	28 days
Changes in positive end-expiratory pressure	Assessment of respiratory dysfunction	28 days
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	28 days
Proportional differences between groups on the SF-36	Quality of life assessment	28 days
Proportional differences between groups on the mini mental state examination	Disability assessment	28 days

Collaborators and Investigators

• Sponsor: Cynata Therapeutics Limited
• Collaborators: Cerebral Palsy Alliance
• Investigators: Study Director: Jolanta Airey, MD, Cynata Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): April 27, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Mesenchymal stem cells; MSC; Cellular therapy; Induced pluripotent stem cells; iPSC
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CYP-COVID-19-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• 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