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

• ClinicalTrials.gov Identifier: NCT04331613
• Recruitment Status: Unknown
• First Posted: April 2, 2020
• Last Update Posted: April 2, 2020
• Sponsor: Chinese Academy of Sciences
• Collaborator: Beijing YouAn Hospital
• Information provided by (Responsible Party): Qi Zhou, Chinese Academy of Sciences

Tracking Information

• First Submitted Date: February 6, 2020
• First Posted Date: April 2, 2020
• Last Update Posted Date: April 2, 2020
• Actual Study Start Date: January 27, 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2020)

• Adverse reaction (AE) and severe adverse reaction (SAE) [ Time Frame: Within 28 days after treatment ]
  Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment
• Changes of lung imaging examinations [ Time Frame: Within 28 days after treatment ]
  Evaluation by chest CT

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 31, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDS
• Official Title: 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)
• Brief Summary: 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• COVID-19
• Acute Respiratory Distress Syndrome
• Virus; Pneumonia
• Acute Lung Injury

Intervention

Biological: CAStem

CAStem will be administered intravenously.

Study Arms

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.

Intervention: Biological: CAStem

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 31, 2020): 9
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04331613
• Other Study ID Numbers: ChineseASZQ-006
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Qi Zhou, Chinese Academy of Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinese Academy of Sciences
• Original Study Sponsor: Same as current
• Collaborators: Beijing YouAn Hospital

Investigators

• Principal Investigator: Zhou Qi, Doctor; Institute of zoology, Chinese Academy of Sciences

• PRS Account: Chinese Academy of Sciences
• Verification Date: January 2020