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Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)

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ClinicalTrials.gov Identifier: NCT04288102
Recruitment Status : Completed
First Posted : February 28, 2020
Last Update Posted : August 19, 2020
Sponsor:
Collaborators:
Huoshenshan Hospital
Maternal and Child Health Hospital of Hubei Province
General Hospital of Central Theater Command, Wuhan, China
VCANBIO CELL & GENE ENGINEERING CORP.,LTD, China
Information provided by (Responsible Party):
Fu-Sheng Wang, Beijing 302 Hospital

Brief Summary:
COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.

Condition or disease Intervention/treatment Phase
Corona Virus Disease 2019(COVID-19) Biological: UC-MSCs Biological: Saline containing 1% Human serum albumin(solution without UC-MSCs) Phase 2

Detailed Description:

The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has unprecedentedly spread in the worldwide and been declared as a pandemic by the world health organization. COVID-19 is characterized by sustained cytokines production and hyper-inflammation, can cause clusters of severe respiratory illness with a fatality rate around 2-5%. There are currently no prophylactic vaccine and no specific antiviral treatment agents available recommended for COVID-19. Therefore, it is urgent to find a safe and effective therapeutic approach to COVID-19.

During the last decade, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. These findings seem to highlight that the beneficial effect of MSC-based treatment could be principally due by the immunomodulation and regenerative potential of these cells. MSCs could significantly reduce the pathological changes of lung and inhibit the cell-mediated immune inflammatory response induced by influenza virus in animal model . MSCs has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. Our phase I preliminary data of parallel assignment study(NCT04252118) showed that three doses of MSCs was safe in patients with COVID-19. Randomized control trial is needed to assess efficacy and safety.

The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 90 severe COVID-19 patients will be recruited in China. 60 patients will receive i.v. transfusion 3 times of MSCs (4.0*10E7 cells per time) and the standard of care as the treated group. In addition, the 30 patients will receive placebo and standard of care as control group.

Change in lesion proportion (%) of full lung volume from baseline to day 10, day28 and 90, change in consolidation/ ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90, time to clinical improvement in 28 days, mMRC (Modified Medical Research Council) dyspnea scale, 6-minute walk test, maximum vital capacity (VCmax), Diffusing Capacity (DLCO), oxygen saturation, oxygenation index, duration of oxygen therapy, side effects, immunological characteristics (immune cells, inflammatory factors, etc.) will be evaluated during the 90 days follow up.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blind, placebo-controlled study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients
Actual Study Start Date : March 5, 2020
Actual Primary Completion Date : May 12, 2020
Actual Study Completion Date : July 9, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
Biological: UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.

Placebo Comparator: Placebo
Participants will receive standard of care plus 3 does of placebo
Biological: Saline containing 1% Human serum albumin(solution without UC-MSCs)
3 does of placebo(intravenously at Day 0, Day 3, Day 6)




Primary Outcome Measures :
  1. Change in lesion proportion (%) of full lung volume from baseline to day 28. [ Time Frame: Day 28 ]
    Evaluation of Pneumonia Improvement


Secondary Outcome Measures :
  1. Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90 [ Time Frame: Day 10, Day 90 ]
    Evaluation of Pneumonia Improvement

  2. Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90. [ Time Frame: Day 10, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  3. Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90. [ Time Frame: Day 10, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  4. Pulmonary fibrosis - related morphological features in CT scan at day 90 a. cord-like shadow b. honeycomb-like shadows c. interlobular septal thickening d. intralobular interstitial thickening e. pleural thickening [ Time Frame: Day 90 ]
    Evaluation of Pneumonia Improvement

  5. Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel) [ Time Frame: Day 10, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  6. Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90. [ Time Frame: Day 10, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  7. Time to clinical improvement in 28 days. [ Time Frame: Day 28 ]

    Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale:

    1. Not hospitalized;
    2. Hospitalized, not requiring supplemental oxygen;
    3. Hospitalized, requiring supplemental oxygen;
    4. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    5. Hospitalized, on invasive mechanical ventilation or ECMO;
    6. Death.

  8. Oxygenation index( PaO2/FiO2) [ Time Frame: Day 6, Day 10, Day 28 ]
    Evaluation of Pneumonia Improvement

  9. Duration of oxygen therapy(days) [ Time Frame: Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  10. Blood oxygen saturation [ Time Frame: Day 6, Day 10, Day 28 ]
    Evaluation of Pneumonia Improvement

  11. 6-minute walk test [ Time Frame: Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  12. Maximum vital capacity (VCmax) [ Time Frame: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  13. Diffusing Capacity (DLCO) [ Time Frame: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90 ]
    Evaluation of Pneumonia Improvement

  14. mMRC (Modified Medical Research Council) dyspnea scale [ Time Frame: Day 28, Day 90 ]

    Evaluation of Pneumonia Improvement

    No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.


  15. Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90. [ Time Frame: Day 6, Day 10, Day 28, Day 90 ]
    Marker of Immunological function

  16. Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90. [ Time Frame: Day 6, Day 10, Day 28, Day 90 ]
    Marker of Immunological function

  17. Adverse events [ Time Frame: Day 0 through Day 90 ]
    Safety endpoints

  18. Serious adverse events [ Time Frame: Day 0 through Day 90 ]
    Safety endpoints

  19. All-cause mortality [ Time Frame: Day 0 through Day 90 ]
    Safety endpoints



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged at 18 years (including) -75 years old
  2. Hospitalized
  3. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source
  4. Pneumonia that is judged by computed tomography
  5. In accordance with any one of the following : 1)dyspnea (RR ≥ 30 times / min), 2)finger oxygen saturation ≤ 93% in resting state, 3)arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG, 4)pulmonary imaging shows that the focus progress > 50% in 24-48 hours
  6. Interstitial lung damage is judged by computed tomography.

Exclusion Criteria:

  1. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;
  2. Patients with malignant tumor, other serious systemic diseases and psychosis;
  3. Patients who are participating in other clinical trials;
  4. Inability to provide informed consent or to comply with test requirements.
  5. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
  6. Invasive ventilation
  7. Shock
  8. Combined with other organ failure( need organ support)
  9. Interstitial lung damage caused by other reasons ( in 2 weeks)
  10. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04288102


Locations
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China, Hubei
General Hospital of Central Theater Command
Wuhan, Hubei, China, 430000
Maternal and Child Hospital of Hubei Province
Wuhan, Hubei, China, 430000
Wuhan Huoshenshan Hospital
Wuhan, Hubei, China, 430000
Sponsors and Collaborators
Beijing 302 Hospital
Huoshenshan Hospital
Maternal and Child Health Hospital of Hubei Province
General Hospital of Central Theater Command, Wuhan, China
VCANBIO CELL & GENE ENGINEERING CORP.,LTD, China
Investigators
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Study Chair: Fu-Sheng Wang, MD, PhD The fifth medical center of PLA general hospital
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Responsible Party: Fu-Sheng Wang, Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor, Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT04288102    
Other Study ID Numbers: 2020-013-D
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections