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

Phase 1
Completed
Conditions
Covid19
Acute Respiratory Distress Syndrome
Interventions
Biological: CYP-001
Registration Number
NCT04537351
Lead Sponsor
Cynata Therapeutics Limited
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CYP-001CYP-001The 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).
Primary Outcome Measures
NameTimeMethod
Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups7 days

Assessment of respiratory dysfunction

Secondary Outcome Measures
NameTimeMethod
Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient)28 days

Assessment of respiratory dysfunction

Changes in P/F ratio28 days

Assessment of respiratory dysfunction

Changes in oxygenation index28 days

Assessment of respiratory dysfunction

Incidence and severity of treatment-emergent adverse events28 days

Assessment of safety

Proportional differences between groups on the Clinical Improvement Scale28 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

Changes in respiratory rate28 days

Assessment of respiratory dysfunction

Changes in positive end-expiratory pressure28 days

Assessment of respiratory dysfunction

Change in C-reactive protein (CRP) levels7 days

Circulating biomarker of inflammation

Proportional differences between groups on the SF-3628 days

Quality of life assessment

Proportional differences between groups on the mini mental state examination28 days

Disability assessment

Ventilator-free days28 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

Trial Locations

Locations (5)

Nepean Hospital

🇦🇺

Kingswood, New South Wales, Australia

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Footscray Hospital

🇦🇺

Footscray, Victoria, Australia

St George Hospital

🇦🇺

Kogarah, New South Wales, Australia

Sunshine Hospital

🇦🇺

Saint Albans, Victoria, Australia

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