Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDS

Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.

Study Overview

• Status: Unknown
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; Acute Lung Injury; Virus; Pneumonia
• Intervention / Treatment: Biological: CAStem

Detailed Description

CAStem is an injectable product composed of immunity- and matrix-regulatory cells (IMRCs), also named M cells, differentiated from clinical-grade human embryonic stem cells (hESCs) will be expanded, harvested, and formulated at a concentration of 50 x 10^6 cells/mL. CAStem will be cryopreserved and transported to clinical site using liquid nitrogen vapor shipping vessels (< -150ºC). Prior to injection, CAStem will be thawed to liquefy quickly, and then reconstituted in normal saline.In the present study, the intravenous infusion dose of CAStem will be 3, 5 or 10 million cells/kg.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing, Beijing, China, China, 100000
      • Recruiting
      • Beijing Youan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Chinese patients, aged 18 to 70 years old, males or females;
2. Diagnosis of COVID-19, and confirm by chest CT scan;

3. According to the diagnosis and treatment plan for the novel coronavirus disease (COVID-19) (trial version 5) issued by the National Health Commission (NHC) on the diagnostic criteria for severe or critical ill COVID-19 patients including the patients with acute respiratory distress syndrome (ARDS), the specific diagnostic criteria are:

   Severely ill patients should meet all of the following:

   • 1. Respiratory distress, RR ≥ 30 times/min.
   • 2. In a resting state (without oxygen supplementation), oxygen saturation ≤ 93%.
   • 3. Partial arterial oxygen pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kpa). High altitude (above sea level 1000 m) area should be calibrated for PaO2/FiO2 according to the following method: PaO2/FiO2*[atmospheric pressure (mmHg)/760]. Patients with obvious progress in lung lesions by chest CT within 24-48 hours should be counted as the server cases.

   Critically ill patients should meet one of the following :

   • 1. Respiratory failure, the mechanical ventilation required.
   • 2. Shock.
   • 3. Associated with other organ failure, ICU needed for monitoring and management.
4. Voluntarily participate in the study, agree to comply with the requirements of the clinical trial protocol, and sign the informed consent.

Exclusion criteria:

1. Patients with a history of transplantation of cells or organ(s).
2. Patients with a history of malignancy or pathology indicating severe atypical hyperplasia.
3. Patients without life expectancy of 48 hours.
4. Patients with moderate to severe liver failure (Childs Pugh scores > 12).
5. Patients with cardiogenic pulmonary edema.
6. Patients with a history of deep vein thrombosis or pulmonary embolism within 3 months before the screening.
7. Patients with severe chronic pulmonary diseases, including but not restricted to the patients with WHO grade III or IV pulmonary hypertension or those with chronic pulmonary diseases requiring long-term oxygen therapy.
8. Patients with unstable ventricular tachycardia or ventricular fibrillation.
9. Patients with poor coagulation, severe bleeding tendency or active bleeding at present.
10. Patients with serious dysfunction involved in the major organs or systems (liver, kidney, gastrointestinal, cardiovascular, blood coagulation, central system, etc.) besides the respiratory system are not suitable to participate in the present study.
11. Patients with a history of severe conditions in any organs or systems.
12. Patients who are unable to accept other invasive rescue except cardiopulmonary resuscitation.
13. Patients who are allergic to the main active ingredients or excipients of the investigational drug.
14. Women who are pregnant, breastfeeding or planning to become pregnant during the study period. Woman of childbearing age who is not willing to use appropriate contraceptive methods through the completion of the clinical study.
15. Patients whose participation is considered to bring significant risks to the present clinical study, cause confusion in analysis, or significantly interfere with the clinical research results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAStem; A dose-escalation with 3 cohorts with 3 patients/cohort who receive doses of 3, 5 or 10 million cells/kg. If there is no safety concerns for each cohort, the dose will be escalated from lower dose to next higher dose.	Biological: CAStem; CAStem will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reaction (AE) and severe adverse reaction (SAE)	Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment	Within 28 days after treatment
Changes of lung imaging examinations	Evaluation by chest CT	Within 28 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to SARS-CoV-2 RT-PCR negative	Marker for SARS-CoV-2	Within 28 days after treatment
Duration of fever (Celsius)	The duration of a fever above 37.3 degrees Celsius	Within 28 days after treatment
Changes of blood oxygen (%)	Marker for efficacy	Within 28 days after treatment
Rate of all-cause mortality within 28 days	Marker for efficacy	Within 28 days after treatment
Lymphocyte count (*10^9/L)	Counts of lymphocyte in a litre (L) of blood	Within 28 days after treatment
Alanine aminotransferase (U/L)	Alanine aminotransferase in unit (U)/litre(L)	Within 28 days after treatment
Creatinine (umol/L)	Creatinine in micromole (umol)/litre(L)	Within 28 days after treatment
Creatine kinase (U/L)	Creatine kinase in U/L	Within 28 days after treatment
C-reactive protein (mg/L)	C-reactive in microgram (mg)/litre(L)	Within 28 days after treatment
Procalcitonin (ng/L)	Procalcitonin in nanogram (ng)/litre(L)	Within 28 days after treatment
Lactate (mmol/L)	Lactate in millimole(mmol)/litre(L)	Within 28 days after treatment
IL-1beta (pg/mL)	IL-1beta in picogram(pg)/millilitre(mL)	Within 28 days after treatment
IL-2 (pg/mL)	IL-2 in pg/mL	Within 28 days after treatment
IL-6 (pg/mL)	IL-6 in pg/mL	Within 28 days after treatment
IL-8 (pg/mL)	IL-8 in pg/mL	Within 28 days after treatment

Collaborators and Investigators

• Sponsor: Chinese Academy of Sciences
• Collaborators: Beijing YouAn Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Cell Therapy; Stem Cells; CAStem; IMRCs
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia; Lung Diseases; Wounds and Injuries; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; COVID-19; Syndrome; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: ChineseASZQ-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No