Treatment of Coronavirus COVID-19 Pneumonia (Pathogen SARS-CoV-2) With Cryopreserved Allogeneic P_MMSCs and UC-MMSCs

Phase 1

• Conditions: COVID-19 Pneumonia
• Interventions: Drug: Antibiotics; Procedure: Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells; Drug: Hormones; Drug: Anticoagulant Therapy; Device: Оxygen therapy

• Registration Number: NCT04461925
• Lead Sponsor: Institute of Cell Therapy

Brief Summary

Assessment of the clinical effects of infusions of cryopreserved allogeneic multipotent mesenchymal stem cells of the placenta and umbilical cord for COVID-19 patients with acute respiratory distress syndrome.

Detailed Description

Currently, cell-based therapy and especially stem cell therapy has become a promising therapeutic field, in which many see opportunities to cure incurable diseases. Severe respiratory consequences of the COVID-19, the disease caused by the novel SARS-CoV-2 coronavirus, have prompted urgent need for novel therapies.

Cell-based approaches, primarily using mesenchymal stem cells (MSCs), have demonstrated safety and efficacy in patients with the acute respiratory distress syndrome (ARDS) - common manifestation of cytokine storms, and the cause of death in many COVID-19 patients.

Mesenchymal stem cells are a powerful immunomodulator, they secrete many anti-inflammatory biologically active substances (cytokines) that reduce the inflammatory process in the lungs. Also mesenchymal stem cells secrete numerous growth factors that contribute to the recovery of not only the affected lung tissue but also other organs.

Study Timeline

• Study Start: 2020-05-02
• Status Verified: 2020-06
• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-07
• Last Update Submitted: 2020-07-07
• Study First Posted: 2020-07-08
• Last Update Posted: 2020-07-08
• Primary Completion: 2021-05-02
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Male or female, aged at 18 years (including) - 75 years old.
• Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source.
• Pneumonia that is judged by X-ray imaging.

In accordance with any one of the following:

• dyspnea (RR ≥ 30 times / min);
• finger oxygen saturation ≤ 93% in resting state;
• arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG (if possible);
• invasive ventilation< 48 h.

Exclusion Criteria

• Male or female, aged at <18 years and > 75 years old.
• Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures.
• Patients with malignant tumor, other serious systemic diseases and psychosis.
• Patients who are participating in other clinical trials.
• Inability to provide informed consent or to comply with test requirements.
• Co-Infection of HIV, syphilis.
• Invasive ventilation > 48 h.
• Combined with other organ failure (need organ support).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Hormones	On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".
Experimental group	Anticoagulant Therapy	On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".
Experimental group	Оxygen therapy	On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".
Control Group	Antibiotics	Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies
Control Group	Hormones	Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies
Control Group	Anticoagulant Therapy	Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies
Control Group	Оxygen therapy	Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies
Experimental group	Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells	On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".
Experimental group	Antibiotics	On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".

Primary Outcome Measures

Name	Time	Method
Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio.	up to 28 days	Improvement of pulmonary function. Arterial oxygen tension PaO2 (in mmHg)/fractional inspired oxygen FiO2 (expressed as a fraction, not a percentage), most conveniently the P/F ratio. The normal P/F ratio is \~ 400-500 mmHg (\~55-65 kPa). P/F ratio \<300mmHg - sign of Acute Respiratory Distress Syndrome (ARDS)
Changes in length of hospital stay	up to 28 days	Length of Hospital Stay
Changes in mortality rate	up to 28 days	Marker for efficacy of treatment

Secondary Outcome Measures

Name	Time	Method
Evaluation of Pneumonia Improvement	At baseline, Day 1, Week 1, Week 2, Week 4, Week 8	CT assessment of pulmonary lesions and lung tissue changes
Peripheral blood count recovery time	At baseline, Day 1, Week 1, Week 2, Week 4, Week 8	Degree of infection
Duration of respiratory symptoms (difficulty breathing, dry cough, fever, etc.)	At baseline, Day 1, Week 1, Week 2, Week 4, Week 8	Indirect response to lung function
Changes of С-reactive protein (CRP, mg/L)	At baseline, Day 1, Week 1, Week 2, Week 4, Week 8	Infection biomarker. Serum CRP levels can be used for early diagnosis of pneumonia, patients with severe pneumonia had high CRP levels.

Trial Locations

Locations (1)

Institute of Cell Therapy; 🇺🇦 Kyiv, Ukraine