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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-002078-29 | EudraCT Number |
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| Name | Class |
|---|---|
| Karolinska Trial Alliance | INDUSTRY |
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To investigate the safety and tolerance of a single infusion of ProTrans® in subjects with "severe" respiratory complications associated with pneumonia caused by COVID-19, Influenza A, Metapneumovirus or RSV infection.
The investigators hypothesize that the systemic delivery of WJ-MSCs exerts an anti-inflammatory action and anti-apoptotic effect in the lung of COVID-19, Influenza A, Metapneumovirus or RSV patients. The nature of these cells to immunomodulate both tissue resident and bloodborne immune cells towards a more anti-inflammatory and tolerogenic profile, results in a reduction of tissue-based inflammation within the lung and triggering of repair responses. This clinically culminates in a beneficial action on patients with "severe" respiratory complications associated with pneumonia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Wharton's Jelly (WJ)-Umbilical Cord (UC) Mesenchymal Stromal Cells (ProTrans®).Study patients 1-3 will receive a single dose of 25 million cells, patients 4-6 will receive 100 million cells and patients 7-9 will receive 200 million cells. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ProTrans® | Biological | Allogeneic Wharton's jelly (WJ) Mesenchymal Stromal Cells |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerance of a single infusion of ProTrans® | Grade 3 or 4 adverse event but not usual in natural course of the disease. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 7 | Effect of ProTrans® -MSC on patient clinical status as assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death. |
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Inclusion Criteria:
Male or female, aged ≥18 years old
Has laboratory-confirmed SARS-CoV-2, Influenza A, Metapneumovirus or RSV infection as determined by reverse-transcription polymerase chain reaction (RT-PCR) in any specimen prior to inclusion.
Hospitalized patients.
Patients classified as severe pneumonia, as defined by the need for continuous supplemental oxygen 5 L/min 02 OR high flow oxygen, 35% FiO2 > 30l/min and cannot saturate > 96% NOT under "non-invasive" ventilation NOR invasive mechanical ventilation NOR ECMO.
Women of childbearing potential must agree to use contraception or acceptable birth control for the duration of the study. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1:
oral
intravaginal
transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation 1:
oral
injectable
implantable 2; intrauterine device (IUD) 2, intrauterine hormone-releasing system (IUS) 2, bilateral tubal occlusion 2, vasectomised partner 2,3, sexual abstinence 4
Provision of a written informed consent
Exclusion Criteria:
Clinical sign of a congestive heart failure refractory; Left ventricular ejection fraction <35% at myocardial scintigraphy or echocardiography; Pulmonary arterial hypertension with systolic pulmonary artery pressure (PAP) at echography > 40 mmHg Chronic atrial fibrillation requiring oral anticoagulant therapy; Uncontrolled ventricular arrhythmia; Pericardial effusion with hemodynamic compromise assessed by echocardiography.
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| Name | Affiliation | Role |
|---|---|---|
| Mathias Svahn, PhD | NextCell Pharma | Study Chair |
| Josefine Sundh, MD | Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital | Örebro | 701 85 | Sweden |
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This is an open, dose escalating Phase IB Clinical Trial
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| 7 days |
| Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 15 | Effect of ProTrans® -MSC on patient clinical status as assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death. | 15 days |
| Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 30 | Effect of ProTrans® -MSC on patient clinical status as assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death. | 30 days |
| Time to clinical improvement after ProTrans® - MSC infusion | Time to clinical improvement of one category from admission on the 7-point ordinal scale after ProTrans® - MSC infusion | 30 days |
| Effect of of ProTrans® -MSC on lung damage | Lung damage examination using imaging techniques (Chest X ray/CT scan /or on doppler ultrasound) when assessed for clinical need up to hospital discharge X ray/CT scan /or on doppler ultrasound) when assessed for clinical need | Up to 60 days |
| Duration of hospitalization and Intensive Care Unit (ICU) stay | Duration of hospitalization and ICU stay | Up to 60 days |
| Kinetics of COVID-19, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) viral load after ProTrans® -MSC infusion | Quantitative PCR for SARS-CoV, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) virus in throat swabs (time frame: before MSC infusion on Day 0 and after MSC infusion on day 30) | Up to 30 days |
| Evolution of biological markers of liver, myocardium and inflammation | Evaluation of different biomarker after ProTrans® -MSC infusion | Up to 24 months |
| Tolerance of allogeneic Wharton's jelly (WJ) Mesenchymal Stromal Cells (ProTrans®) for severe COVID-19, Influenza A, Metapneumovirus or RSV respiratory conditions | Investigation of tolerance of Wharton's jelly (WJ) Mesenchymal Stromal Cells (ProTrans®) for treatment of viral respiratory tract infections | Up to 24 months |