Back to resultsTherapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients (DW-MSC)
Primary Purpose
Covid19, Corona Virus Infection, SAR
Status
Completed
Phase
Phase 1
Locations
Indonesia
Study Type
Interventional
Intervention
allogeneic mesenchymal stem cell
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring Infectious Disease, covid-19, allogeneic mesenchymal stem cell
Eligibility Criteria
Inclusion Criteria:
- Age of 19 years or older at the time of screening
- Those who have been confirmed COVID-19 infection through PCR test
- Patients with mild or moderate COVID-19 who meet National EWS (0~6)
- Those who have given written consent and voluntarily decided to participate before the screening procedure after understanding the detailed description of the clinical trial.
- 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:
- Those who have history of hypersensitivity to the components of the investigational product or the reference product
- Those with viral or bacterial pneumonia other than expected indications
- Patients receiving organ transplants within 6 months of screening
- Patients with a history of pulmonary embolism
- Patients who have indications of investigational products as an underlying disease (ex. HIV patients in the clinical study of antiretroviral drugs)
- Patients who are pregnant or lactating
- 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.
- Patients participating in other clinical studies
Sites / Locations
- Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Low-dose group
High-dose group
Control group (placebo)
Arm Description
Low-dose group (5 x 10^7cells): Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 2 vials for low-dose group
High-dose group (1 x 10^8 cells): Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 4 vials for High-dose group
Control group (placebo): No Drug substance: 4 vials for Place group
Outcomes
Primary Outcome Measures
Incidence of TEAE* in Treatment group
Incidence of TEAE* in Treatment group
* TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions.
Secondary Outcome Measures
Survival rate
Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given.
Duration of hospitalization
Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group.
Clinical improvement Ordinal scale
Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28
Clinical improvement National EWS
Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28.
EWS Points, Risk and Interpretation as follows:
0~4: Low clinical risk; interpretation= Ward-based response 3~4 : Low~medium clinical risk; interpretation= Urgent ward-based response 5~6: Medium clinical risk; interpretation= Key threshold for urgent response
Clinical improvement Oxygenation index
Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28)
Clinical improvement Lung involvement change
Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28)
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for WBC
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for Lymphocytes
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for ESR
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for CRP
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for Fibrinogen
Clinical improvement Inflammation markers change
Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28)
Full Information
NCT ID
NCT04535856
First Posted
August 28, 2020
Last Updated
January 25, 2021
Sponsor
Ina-Respond
Collaborators
National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Daewoong Pharmaceutical Co. LTD.
1. Study Identification
Unique Protocol Identification Number
NCT04535856
Brief Title
Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients
Acronym
DW-MSC
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
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
November 14, 2020 (Actual)
Primary Completion Date
January 14, 2021 (Actual)
Study Completion Date
January 14, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ina-Respond
Collaborators
National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Daewoong Pharmaceutical Co. LTD.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Corona Virus Infection, SAR
Keywords
Infectious Disease, covid-19, allogeneic mesenchymal stem cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-blind, and Placebo-controlled Clinical Trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind, To maintain the double-blind of the study, a statistician who do not participate in this study will independently generate randomization code only using the PLAN procedure (Proc Plan procedure) of SAS (ver. 9.4 or higher, SAS Institute, Cary, NC, USA).
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low-dose group
Arm Type
Experimental
Arm Description
Low-dose group (5 x 10^7cells):
Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 2 vials for low-dose group
Arm Title
High-dose group
Arm Type
Experimental
Arm Description
High-dose group (1 x 10^8 cells):
Drug substance and the amount: 2.5 × 107 cells/1 mL/vial, 4 vials for High-dose group
Arm Title
Control group (placebo)
Arm Type
Placebo Comparator
Arm Description
Control group (placebo):
No Drug substance: 4 vials for Place group
Intervention Type
Drug
Intervention Name(s)
allogeneic mesenchymal stem cell
Other Intervention Name(s)
Investigational product
Intervention Description
Assignment of Administration Group allogeneic mesenchymal stem cell:
Low-dose group (5 x 10^7cells)
High-dose group (1 x 10^8 cells)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Control group (placebo)
Primary Outcome Measure Information:
Title
Incidence of TEAE* in Treatment group
Description
Incidence of TEAE* in Treatment group
* TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Survival rate
Description
Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given.
Time Frame
until Day 14 and Day 28
Title
Duration of hospitalization
Description
Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group.
Time Frame
28 days
Title
Clinical improvement Ordinal scale
Description
Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28
Time Frame
from baseline to Day 14 and Day 28
Title
Clinical improvement National EWS
Description
Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28.
EWS Points, Risk and Interpretation as follows:
0~4: Low clinical risk; interpretation= Ward-based response 3~4 : Low~medium clinical risk; interpretation= Urgent ward-based response 5~6: Medium clinical risk; interpretation= Key threshold for urgent response
Time Frame
from baseline to Day 7, 14 and Day 28
Title
Clinical improvement Oxygenation index
Description
Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28)
Time Frame
Day 1, 3, 7, 10, 14, 28
Title
Clinical improvement Lung involvement change
Description
Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28)
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for WBC
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for Lymphocytes
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for ESR
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for CRP
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for Fibrinogen
Time Frame
Day 7, 14, 28
Title
Clinical improvement Inflammation markers change
Description
Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28)
Time Frame
Day 7, 14, 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age of 19 years or older at the time of screening
Those who have been confirmed COVID-19 infection through PCR test
Patients with mild or moderate COVID-19 who meet National EWS (0~6)
Those who have given written consent and voluntarily decided to participate before the screening procedure after understanding the detailed description of the clinical trial.
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:
Those who have history of hypersensitivity to the components of the investigational product or the reference product
Those with viral or bacterial pneumonia other than expected indications
Patients receiving organ transplants within 6 months of screening
Patients with a history of pulmonary embolism
Patients who have indications of investigational products as an underlying disease (ex. HIV patients in the clinical study of antiretroviral drugs)
Patients who are pregnant or lactating
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.
Patients participating in other clinical studies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Muhammad Karyana, MPH
Organizational Affiliation
Center for Research and Development of Health Resources and Services, National Institute of Health Research and Development (NIHRD), Indonesia
Official's Role
Study Chair
Facility Information:
Facility Name
Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
City
Makassar
ZIP/Postal Code
90245
Country
Indonesia
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35365239
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.
Results Reference
derived
Learn more about this trial
Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients
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