Ignite Creation Date:
2025-12-25 @ 4:05 AM
Ignite Modification Date:
2026-03-04 @ 10:45 AM
Study NCT ID:
NCT04288102
Status:
COMPLETED
Last Update Posted:
2020-08-19
First Post:
2020-02-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized, double-blind, placebo-controlled study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 100}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-03-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-08', 'completionDateStruct': {'date': '2020-07-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-08-18', 'studyFirstSubmitDate': '2020-02-24', 'studyFirstSubmitQcDate': '2020-02-25', 'lastUpdatePostDateStruct': {'date': '2020-08-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-05-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in lesion proportion (%) of full lung volume from baseline to day 28.', 'timeFrame': 'Day 28', 'description': 'Evaluation of Pneumonia Improvement'}], 'secondaryOutcomes': [{'measure': 'Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90', 'timeFrame': 'Day 10, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.', 'timeFrame': 'Day 10, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.', 'timeFrame': 'Day 10, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': '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', 'timeFrame': 'Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': "Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)", 'timeFrame': 'Day 10, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.', 'timeFrame': 'Day 10, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Time to clinical improvement in 28 days.', 'timeFrame': 'Day 28', 'description': 'Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale:\n\n1. Not hospitalized;\n2. Hospitalized, not requiring supplemental oxygen;\n3. Hospitalized, requiring supplemental oxygen;\n4. Hospitalized, on non-invasive ventilation or high flow oxygen devices;\n5. Hospitalized, on invasive mechanical ventilation or ECMO;\n6. Death.'}, {'measure': 'Oxygenation index( PaO2/FiO2)', 'timeFrame': 'Day 6, Day 10, Day 28', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Duration of oxygen therapy(days)', 'timeFrame': 'Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Blood oxygen saturation', 'timeFrame': 'Day 6, Day 10, Day 28', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': '6-minute walk test', 'timeFrame': 'Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Maximum vital capacity (VCmax)', 'timeFrame': 'Baseline, Day 10, Day 14, Day 21, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'Diffusing Capacity (DLCO)', 'timeFrame': 'Baseline, Day 10, Day 14, Day 21, Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement'}, {'measure': 'mMRC (Modified Medical Research Council) dyspnea scale', 'timeFrame': 'Day 28, Day 90', 'description': 'Evaluation of Pneumonia Improvement\n\nNo 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.'}, {'measure': 'Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.', 'timeFrame': 'Day 6, Day 10, Day 28, Day 90', 'description': 'Marker of Immunological function'}, {'measure': 'Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.', 'timeFrame': 'Day 6, Day 10, Day 28, Day 90', 'description': 'Marker of Immunological function'}, {'measure': 'Adverse events', 'timeFrame': 'Day 0 through Day 90', 'description': 'Safety endpoints'}, {'measure': 'Serious adverse events', 'timeFrame': 'Day 0 through Day 90', 'description': 'Safety endpoints'}, {'measure': 'All-cause mortality', 'timeFrame': 'Day 0 through Day 90', 'description': 'Safety endpoints'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Corona Virus Disease 2019(COVID-19)']}, 'referencesModule': {'references': [{'pmid': '40001244', 'type': 'DERIVED', 'citation': 'Yuan MQ, Song L, Wang ZR, Zhang ZY, Shi M, He J, Mo Q, Zheng N, Yao WQ, Zhang Y, Dong T, Li Y, Zhang C, Song J, Huang L, Xu Z, Yuan X, Fu JL, Zhen C, Cai J, Dong J, Zhang J, Xie WF, Li Y, Zhang B, Shi L, Wang FS. Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a randomized, double-blind, placebo-controlled trial. Stem Cell Res Ther. 2025 Feb 25;16(1):94. doi: 10.1186/s13287-025-04148-1.'}, {'pmid': '37149930', 'type': 'DERIVED', 'citation': 'Li TT, Zhang B, Fang H, Shi M, Yao WQ, Li Y, Zhang C, Song J, Huang L, Xu Z, Yuan X, Fu JL, Zhen C, Zhang Y, Wang ZR, Zhang ZY, Yuan MQ, Dong T, Bai R, Zhao L, Cai J, Dong J, Zhang J, Xie WF, Li Y, Shi L, Wang FS. Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial. EBioMedicine. 2023 Jun;92:104600. doi: 10.1016/j.ebiom.2023.104600. Epub 2023 May 5.'}, {'pmid': '34963099', 'type': 'DERIVED', 'citation': 'Shi L, Yuan X, Yao W, Wang S, Zhang C, Zhang B, Song J, Huang L, Xu Z, Fu JL, Li Y, Xu R, Li TT, Dong J, Cai J, Li G, Xie Y, Shi M, Li Y, Zhang Y, Xie WF, Wang FS. Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial. EBioMedicine. 2022 Jan;75:103789. doi: 10.1016/j.ebiom.2021.103789. Epub 2021 Dec 25.'}, {'pmid': '33568628', 'type': 'DERIVED', 'citation': 'Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, Wang S, Zhang C, Yuan X, Xu Z, Huang L, Fu JL, Li Y, Zhang Y, Yao WQ, Liu T, Song J, Sun L, Yang F, Zhang X, Zhang B, Shi M, Meng F, Song Y, Yu Y, Wen J, Li Q, Mao Q, Maeurer M, Zumla A, Yao C, Xie WF, Wang FS. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021 Feb 10;6(1):58. doi: 10.1038/s41392-021-00488-5.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nDuring 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.\n\nThe 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.\n\nChange 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Male or female, aged at 18 years (including) -75 years old\n2. Hospitalized\n3. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source\n4. Pneumonia that is judged by computed tomography\n5. 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\n6. Interstitial lung damage is judged by computed tomography.\n\nExclusion Criteria:\n\n1. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;\n2. Patients with malignant tumor, other serious systemic diseases and psychosis;\n3. Patients who are participating in other clinical trials;\n4. Inability to provide informed consent or to comply with test requirements.\n5. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.\n6. Invasive ventilation\n7. Shock\n8. Combined with other organ failure( need organ support)\n9. Interstitial lung damage caused by other reasons ( in 2 weeks)\n10. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.'}, 'identificationModule': {'nctId': 'NCT04288102', 'briefTitle': 'Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)', 'organization': {'class': 'OTHER', 'fullName': 'Beijing 302 Hospital'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': '2020-013-D'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)', 'description': 'Participants will receive standard of care plus 3 does of UC-MSCs', 'interventionNames': ['Biological: UC-MSCs']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants will receive standard of care plus 3 does of placebo', 'interventionNames': ['Biological: Saline containing 1% Human serum albumin（solution without UC-MSCs）']}], 'interventions': [{'name': 'UC-MSCs', 'type': 'BIOLOGICAL', 'description': '3 does of UC-MSCs(4.0\\*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.', 'armGroupLabels': ['Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)']}, {'name': 'Saline containing 1% Human serum albumin（solution without UC-MSCs）', 'type': 'BIOLOGICAL', 'description': '3 does of placebo（intravenously at Day 0, Day 3, Day 6）', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '430000', 'city': 'Wuhan', 'state': 'Hubei', 'country': 'China', 'facility': 'General Hospital of Central Theater Command', 'geoPoint': {'lat': 30.58333, 'lon': 114.26667}}, {'zip': '430000', 'city': 'Wuhan', 'state': 'Hubei', 'country': 'China', 'facility': 'Maternal and Child Hospital of Hubei Province', 'geoPoint': {'lat': 30.58333, 'lon': 114.26667}}, {'zip': '430000', 'city': 'Wuhan', 'state': 'Hubei', 'country': 'China', 'facility': 'Wuhan Huoshenshan Hospital', 'geoPoint': {'lat': 30.58333, 'lon': 114.26667}}], 'overallOfficials': [{'name': 'Fu-Sheng Wang, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Beijing 302 Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', '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.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Beijing 302 Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Huoshenshan Hospital', 'class': 'OTHER'}, {'name': 'Maternal and Child Health Hospital of Hubei Province', 'class': 'OTHER'}, {'name': 'The General Hospital of Central Theater Command', 'class': 'OTHER'}, {'name': 'Vcanbio Cell and Gene Engineering Corp., Ltd.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor', 'investigatorFullName': 'Fu-Sheng Wang', 'investigatorAffiliation': 'Beijing 302 Hospital'}}}}