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Completed

NCT Number: NCT04400032

Cellular Immuno-Therapy for COVID-19 Acute Respiratory Distress Syndrome

The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). ARDS often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world's first clinical trial using MSC therapy for patients with severe infections (sepsis) which is often associated with ARDS (NCT02421484). This trial demonstrated tolerability, and potential signs of efficacy. In addition, the investigators have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in three different clinical studies.

This protocol consists of 2 sequential trials using the same trial infrastructure, noted as the Phase 1 trial 'CIRCA-1901' and the Phase 2a trial 'CIRCA-1902'. CIRCA-1901 is an open-label, dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose of repeated delivery of Umbilical Cord Mesenchymal Stromal Cells (UC-MSC) intravenously. The investigators will enroll up to 9 patients; each receiving repeated unit doses of UC-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs). If no safety issues are identified, we will continue to the Phase 2a trial.

CIRCA-1902 is a single-arm, open-label extension of the CIRCA-1901 trial to assess early signs of efficacy (major morbidity and mortality). The Phase 2a trial (CIRCA-1902) will enroll 12 patients to assess early signals of benefit on mortality and major morbidity in a high risk, high mortality population.

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Key information

Conditions

Acute Respiratory Distress Syndrome COVID-19 Coronaviridae Infections Coronavirus Infections Covid19 Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age of ≥18 years
  • Laboratory-confirmed SARS-CoV-2 infection during the current admission
  • On invasive, non-invasive mechanical ventilation (NIV) (PEEP≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm)
  • ARDS (onset <96h) as per the international consensus definition (P/F) ratio < 300 on fraction of inspired oxygen (FiO2)≥0.5, with PEEP ≥5cm H2O or on HFNC), not due to cardiac causes.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this trial:

  • No consent/inability to obtain consent
  • Moribund patient not expected to survive 24 hours
  • Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  • Currently receiving extracorporeal life support
  • Pregnant or lactating
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
  • Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
  • Lung transplant patient
  • Documented deep venous thrombosis or pulmonary embolism within the past 3 months
  • Inability/contra-indications to receiving local standard of care thromboprophylaxis
  • Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
  • Known HIV, Hep B/C positive, or active Tuberculosis
  • Multisystem shock (SOFA score of >2 in >2 systems)
  • Patient, surrogate, or physician not committed to full support including intubation (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)

Treatment and study plan

Mesenchymal Stromal Cells

Biological

The Mesenchymal Stromal Cells will be administered intravenously

Primary outcomes

  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

    Time frame: At time of infusion until one year post-infusion

    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 to determine the maximum feasible tolerated dose (MFTD) of UC-MSCs given to patients with COVID-19

Secondary outcomes

  1. Number of Participants alive by Day 28

    Time frame: Day 28

    Number of Participants alive by Day 28

  2. Number of Participants with ventilator-free Days by Day 28

    Time frame: Day 28

    Number of Participants with ventilator-free Days by Day 28

Sponsors and collaborators

Lead sponsor

Ottawa Hospital Research Institute

Other

Collaborators

  • Ontario Research Fund
  • Stem Cell Network

Registry information

Official study title

Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19)

Acronym: CIRCA-19

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
May 22, 2020
Registry last updated
Apr 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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