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

18 de agosto de 2020 actualizado por: 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

100

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
Biológico: UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
Comparador de placebos: Placebo
Participants will receive standard of care plus 3 does of placebo
Biológico: Saline containing 1% Human serum albumin（solution without UC-MSCs）
3 does of placebo（intravenously at Day 0, Day 3, Day 6）

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in lesion proportion (%) of full lung volume from baseline to day 28.
Periodo de tiempo: Day 28
Evaluation of Pneumonia Improvement
Day 28

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
Periodo de tiempo: 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.
Periodo de tiempo: 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.
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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.
Periodo de tiempo: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Time to clinical improvement in 28 days.
Periodo de tiempo: 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)
Periodo de tiempo: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
Duration of oxygen therapy(days)
Periodo de tiempo: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Blood oxygen saturation
Periodo de tiempo: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
6-minute walk test
Periodo de tiempo: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Maximum vital capacity (VCmax)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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.
Periodo de tiempo: 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.
Periodo de tiempo: Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Adverse events
Periodo de tiempo: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
Serious adverse events
Periodo de tiempo: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
All-cause mortality
Periodo de tiempo: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Beijing 302 Hospital

Colaboradores

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

Investigadores

  • Silla de estudio: Fu-Sheng Wang, MD, PhD, Beijing 302 Hospital

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

5 de marzo de 2020

Finalización primaria (Actual)

12 de mayo de 2020

Finalización del estudio (Actual)

9 de julio de 2020

Fechas de registro del estudio

Enviado por primera vez

24 de febrero de 2020

Primero enviado que cumplió con los criterios de control de calidad

25 de febrero de 2020

Publicado por primera vez (Actual)

28 de febrero de 2020

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

19 de agosto de 2020

Última actualización enviada que cumplió con los criterios de control de calidad

18 de agosto de 2020

Última verificación

1 de agosto de 2020

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 2020-013-D

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

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.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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