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

18 augusti 2020 uppdaterad av: Fu-Sheng Wang, Beijing 302 Hospital

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

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

100

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Kina
    • Hubei
      • Wuhan, Hubei, Kina, 430000
        • General Hospital of Central Theater Command
      • Wuhan, Hubei, Kina, 430000
        • Maternal and Child Hospital of Hubei Province
      • Wuhan, Hubei, Kina, 430000
        • Wuhan Huoshenshan Hospital

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
Biologisk: UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
Placebo-jämförare: Placebo
Participants will receive standard of care plus 3 does of placebo
Biologisk: Saline containing 1% Human serum albumin（solution without UC-MSCs）
3 does of placebo（intravenously at Day 0, Day 3, Day 6）

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Change in lesion proportion (%) of full lung volume from baseline to day 28.
Tidsram: Day 28
Evaluation of Pneumonia Improvement
Day 28

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
Tidsram: Day 10, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 90
Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Tidsram: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Tidsram: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
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
Tidsram: Day 90
Evaluation of Pneumonia Improvement
Day 90
Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
Tidsram: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.
Tidsram: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Time to clinical improvement in 28 days.
Tidsram: 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.
Day 28
Oxygenation index( PaO2/FiO2)
Tidsram: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
Duration of oxygen therapy(days)
Tidsram: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Blood oxygen saturation
Tidsram: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
6-minute walk test
Tidsram: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Maximum vital capacity (VCmax)
Tidsram: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Diffusing Capacity (DLCO)
Tidsram: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
mMRC (Modified Medical Research Council) dyspnea scale
Tidsram: 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.
Day 28, Day 90
Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
Tidsram: Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
Tidsram: Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Adverse events
Tidsram: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
Serious adverse events
Tidsram: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
All-cause mortality
Tidsram: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Beijing 302 Hospital

Samarbetspartners

Maternal and Child Health Hospital of Hubei Province
Huoshenshan Hospital
VCANBIO Cell & Gene Engineering Corporation, Ltd
The General Hospital of Central Theater Command

Utredare

  • Studiestol: Fu-Sheng Wang, MD, PhD, Beijing 302 Hospital

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

5 mars 2020

Primärt slutförande (Faktisk)

12 maj 2020

Avslutad studie (Faktisk)

9 juli 2020

Studieregistreringsdatum

Först inskickad

24 februari 2020

Först inskickad som uppfyllde QC-kriterierna

25 februari 2020

Första postat (Faktisk)

28 februari 2020

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

19 augusti 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

18 augusti 2020

Senast verifierad

1 augusti 2020

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 2020-013-D

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

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.

Läkemedels- och apparatinformation, studiedokument

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