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

• ClinicalTrials.gov Identifier: NCT04537351
• Recruitment Status: Completed
• First Posted: September 3, 2020
• Last Update Posted: September 1, 2023
• Sponsor: Cynata Therapeutics Limited
• Collaborator: Cerebral Palsy Alliance
• Information provided by (Responsible Party): Cynata Therapeutics Limited

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

Condition or disease	Intervention/treatment	Phase
Covid19; Acute Respiratory Distress Syndrome	Biological: CYP-001	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 24, 2020
• Actual Primary Completion Date: April 27, 2022
• Actual Study Completion Date: May 18, 2022

Arms and Interventions

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 Name: Cymerus MSCs
No Intervention: Standard of care; Control participants will be randomised to received standard of care treatment.

Outcome Measures

Primary Outcome Measures :

1. Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups [ Time Frame: 7 days ]
   Assessment of respiratory dysfunction

Secondary Outcome Measures :

1. Incidence and severity of treatment-emergent adverse events [ Time Frame: 28 days ]
   Assessment of safety
2. Change in C-reactive protein (CRP) levels [ Time Frame: 7 days ]
   Circulating biomarker of inflammation
3. Proportional differences between groups on the Clinical Improvement Scale [ Time Frame: 28 days ]
   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
4. Changes in P/F ratio [ Time Frame: 28 days ]
   Assessment of respiratory dysfunction
5. Changes in respiratory rate [ Time Frame: 28 days ]
   Assessment of respiratory dysfunction
6. Changes in oxygenation index [ Time Frame: 28 days ]
   Assessment of respiratory dysfunction
7. Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient) [ Time Frame: 28 days ]
   Assessment of respiratory dysfunction
8. Changes in positive end-expiratory pressure [ Time Frame: 28 days ]
   Assessment of respiratory dysfunction
9. Ventilator-free days [ Time Frame: 28 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
10. Proportional differences between groups on the SF-36 [ Time Frame: 28 days ]
    Quality of life assessment
11. Proportional differences between groups on the mini mental state examination [ Time Frame: 28 days ]
    Disability assessment

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Australia, New South Wales

Nepean Hospital

Kingswood, New South Wales, Australia, 2747

St George Hospital

Kogarah, New South Wales, Australia, 2217

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Victoria

Footscray Hospital

Footscray, Victoria, Australia, 3011

Sunshine Hospital

Saint Albans, Victoria, Australia, 3021

Sponsors and Collaborators

Cynata Therapeutics Limited

Cerebral Palsy Alliance

Investigators

• Study Director: Jolanta Airey, MD; Cynata Therapeutics Limited

More Information

• Responsible Party: Cynata Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT04537351
• Other Study ID Numbers: CYP-COVID-19-01
• First Posted: September 3, 2020
• Last Update Posted: September 1, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Time Frame: Data requests will be considered after the completion of the study. There is no specified end date.
• 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.

• 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

Keywords provided by Cynata Therapeutics Limited:

Mesenchymal stem cells; MSC; Induced pluripotent stem cells; iPSC; Cellular therapy

Additional relevant MeSH terms:

COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Acute Lung Injury; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury