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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Covid19, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Biological: CYP-001


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYP-001<br>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<br>* 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.<br>* Other names: Cymerus MSCs;|
| No Intervention: Standard of care<br>Control participants will be randomised to received standard of care treatment. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells, MSC, Induced pluripotent stem cells, iPSC, Cellular therapy