Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 Patients

• ClinicalTrials.gov Identifier: NCT04336254
• Recruitment Status: Unknown
• First Posted: April 7, 2020
• Last Update Posted: March 10, 2021
• Sponsor: Renmin Hospital of Wuhan University
• Collaborators: Beijing SH Bio-Tech Corporation, Beijing (CN); Utooth Biological Technology Co., Ltd. Hubei (CN)
• Information provided by (Responsible Party): Ye Qingsong, Renmin Hospital of Wuhan University

Tracking Information

• First Submitted Date: March 28, 2020
• First Posted Date: April 7, 2020
• Last Update Posted Date: March 10, 2021
• Actual Study Start Date: May 6, 2020
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2020)

TTCI [ Time Frame: 1-28 days ]

Time to Clinical Improvement

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 3, 2020)

• Lung lesion [ Time Frame: 1-28 days ]
  Lung Lesion by CT
• Immune function [ Time Frame: 1-28 days ]
  1. Th1 cytokines: IL-1β, IL- 2, TNF-a, ITN-γ;
  2. Th2 cytokines: IL- 4, IL- 6, IL- 10;
  3. Immunoglobulins: IgA, IgG, IgM, and total IgE;
  4. Lymphocyte counts: CD3+, CD4+, CD8+, CD16+,CD19+, CD56+.
• Time of SARS-CoV-2 clearance [ Time Frame: 1-28 days ]
  Time of SARS-CoV-2 test turns negative
• Blood test [ Time Frame: 1-28 days ]
  Blood cell count and classification
• SPO2 [ Time Frame: 1-28 days ]
  Pulse oximetry
• RR [ Time Frame: 1-28 days ]
  Respiratory rate
• Body temperature [ Time Frame: 1-28 days ]
  Body temperature
• Side effects in the treatment group [ Time Frame: 1-28 days ]
  Number of the included patients with hDPSCs-related adverse events, e.g. liver or kidney function failure
• C-reactive protein (mg/L) [ Time Frame: 1-28 days ]
  C-reactive protein in microgram per litre

• 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 Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 Patients
• Official Title: Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe Pneumonia of COVID-19：a Single-center, Prospective, Randomised Clinical Trial
• Brief Summary: This clinical trial is set out to evaluate the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19; to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

Detailed Description

This clinical trial is set out to evaluate the followings:

1. the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19;
2. to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and
3. to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC)
  Intravenous injection of 3.0x10e7 human dental pulp stem cells solution (30ml) on day 1, day 4 and day 7, based on routine treatment of COVID-19
• Other: Intravenous saline injection (Placebo)
  Intravenous injection of 3ml of 0.9% saline on day 1, day 4 and day 7, based on routine treatment of COVID-19

Study Arms

• Experimental: hDPSCs group
  Routine treatment + Intravenous injection of human dental pulp stem cells
  Intervention: Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC)
• Placebo Comparator: Control group
  Routine treatment + Intravenous saline injection (Placebo)
  Intervention: Other: Intravenous saline injection (Placebo)

• Publications *: Ye Q, Wang H, Xia X, Zhou C, Liu Z, Xia ZE, Zhang Z, Zhao Y, Yehenala J, Wang S, Zhou G, Hu K, Wu B, Wu CT, Wang S, He Y. Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II). Trials. 2020 Jun 12;21(1):520. doi: 10.1186/s13063-020-04380-5.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 3, 2020): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Aged 18-65 years;
2. Voluntarily participate in this clinical trial and sign off "informed consent form";
3. Diagnosed with severe pneumonia of COVID: respiratory distress, RR >30 times / min; resting oxygen saturation of 93% or less; arterial partial pressure of oxygen / oxygen concentration 300mmHg; SARS-CoV-2 nucleic acid test was positive.
4. Chest imaging confirm COVID-19 featured lesions in lung.

Exclusion Criteria:

1. Receive any clinical trial drug treatment for COVID-2019 within 30 days before the screening assessment;
2. Severe liver disease (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);
3. Patients with known severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;
4. Co-infection of HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;
5. Female patients who have no sexual protection in the last 30 days prior to the screening assessment;
6. Pregnant or lactating women or women using estrogen contraception;
7. Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;
8. Other conditions that the researchers consider not suitable for participating in this clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 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: NCT04336254
• Other Study ID Numbers: 2020K-G005; hDPSC-CoVID-2019-02-2020 ( Other Identifier: Renmin Hospital of Wuhan University )
• 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

• Plan to Share IPD: No

• Current Responsible Party: Ye Qingsong, Renmin Hospital of Wuhan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Renmin Hospital of Wuhan University
• Original Study Sponsor: Same as current

Collaborators

• Beijing SH Bio-Tech Corporation, Beijing (CN)
• Utooth Biological Technology Co., Ltd. Hubei (CN)

Investigators

• Study Chair: Prof. Qingsong Ye, PhD,DDS; Center for Regenerative Medicine, Renmin Hospital of Wuhan University

• PRS Account: Renmin Hospital of Wuhan University
• Verification Date: March 2021