Clinical trial NCT04535856: Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients
Official title: Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients: Randomized, Double-blind, and Placebo-controlled
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Covid19
Corona Virus Infection
SAR
Keywords: Infectious Disease
covid-19
allogeneic mesenchymal stem cell
Lead sponsor: Ina-Respond
Sponsor class: OTHER
Collaborators: name: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
name: Daewoong Pharmaceutical Co. LTD.
First posted: 2020-09-02
Enrollment: 9
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind, and Placebo-controlled Clinical Trial
Primary purpose: TREATMENT

Brief summary: This is a phase 1 clinical trial to verify the safety and efficacy of DW-MSC in COVID-19 patients. A total of 9 subjects are randomly allocated. Subjects who meet the final inclusion and exclusion criteria are randomized to the test groups (low-dose group and high-dose group) or control group (placebo group) in a ratio of 1:1:1. Subjects assigned to the test groups were administered intravenously once with 5 x 10\^7cells of DW-MSC for the low-dose group or 1 x 10\^8cells for the high-dose group after registration. Subjects assigned to the control group were administered with placebo in the same manner as the test drug (DW-MSC). At this time, all of the existing standard co-treatment are allowed. DW-MSC is adjunct therapy to standard therapy.

This clinical trial is a double-blind trial, in which a randomized method will be used. To maintain the double-blindness of the study, statistician who do not participate in this study independently generate randomization code. Subjects will be randomized to the test groups (low-dose group and high-dose group) or the control group (placebo group) in a 1:1:1 ratio. After the completion of the trial, the randomization code will be disclosed after unlocking the database and unblinding procedures. Follow Up period: observed for 28 days after a single administration

Detailed description: Patients with Covid-19 have a mortality rate of about 35 \~ 50% and currently, severe patients caused by the Coronavirus show respiratory distress. To date, the incidence rate has been more than 3 million each year; however, as the increase and globalization of the environmental pollution has been expanded, the number of patients is expected to increase due to acute diseases such as the Middle East Respiratory virus, SARS, and coronavirus.

Since 2015, Daewoong Pharmaceutical intends to use stem cells for product research on rare and intractable diseases including respiratory distress. Stem cells are also called pluripotent cells or truncal cells that can convert to any organ. It is an embryonic stage undifferentiated cell that has stopped differentiating before forming a specific organ whose differentiation has not been determined and has the ability to differentiate into muscle, bone, and internal conformal body organs. There are three types of stem cells: embryonic stem cells, adult stem cells, and induced pluripotent stem cells. Daewoong Pharmaceutical intends to develop cell therapy products using mesenchymal stem cells (MSC).

Eligibility criteria: Inclusion Criteria:

1. Age of 19 years or older at the time of screening
2. Those who have been confirmed COVID-19 infection through PCR test
3. Patients with mild or moderate COVID-19 who meet National EWS (0\~6)
4. Those who have given written consent and voluntarily decided to participate before the screening procedure after understanding the detailed description of the clinical trial.
5. Those who are suitable as subjects for this clinical study when judged by physical examination, clinical laboratory test, and other medical examination as stated in the flowchart of protocol.

Exclusion Criteria:

1. Those who have history of hypersensitivity to the components of the investigational product or the reference product
2. Those with viral or bacterial pneumonia other than expected indications
3. Patients receiving organ transplants within 6 months of screening
4. Patients with a history of pulmonary embolism
5. Patients who have indications of investigational products as an underlying disease (ex. HIV patients in the clinical study of antiretroviral drugs)
6. Patients who are pregnant or lactating
7. Those who are determined by the investigator to be unsuitable for participation in the clinical trial due to other reasons including the results of the clinical laboratory test.
8. Patients participating in other clinical studies

Primary outcomes:
measure: Incidence of TEAE* in Treatment group
timeFrame: 28 days
Secondary outcomes:
measure: Survival rate
timeFrame: until Day 14 and Day 28
measure: Duration of hospitalization
timeFrame: 28 days
measure: Clinical improvement Ordinal scale
timeFrame: from baseline to Day 14 and Day 28
measure: Clinical improvement National EWS
timeFrame: from baseline to Day 7, 14 and Day 28
measure: Clinical improvement Oxygenation index
timeFrame: Day 1, 3, 7, 10, 14, 28
measure: Clinical improvement Lung involvement change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
measure: Clinical improvement Inflammation markers change
timeFrame: Day 7, 14, 28
Other outcomes:
Locations:
city: Makassar
country: Indonesia
facility: Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
Study officials:
affiliation: Center for Research and Development of Health Resources and Services, National Institute of Health Research and Development (NIHRD), Indonesia
name: Dr. Muhammad Karyana, MPH
role: STUDY_CHAIR
References:
citation: Karyana M, Djaharuddin I, Rif'ati L, Arif M, Choi MK, Angginy N, Yoon A, Han J, Josh F, Arlinda D, Narulita A, Muchtar F, Bakri RA, Irmansyah S. Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial. Stem Cell Res Ther. 2022 Apr 1;13(1):134. doi: 10.1186/s13287-022-02812-4.