NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia (HOPE)

Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

This is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Biological: NestaCell®; Biological: Placebo

Detailed Description

The number of infections of COVID-19 worldwide has killed thousands and is continually rising. The novel coronavirus attacks the human body by attaching to the angiotensin-converting enzyme-2 (ACE2), a protective enzyme against lung damage. In addition, the cellular serine protease TMPRSS2 for HCoV-19 Spike protein priming is also essential for the host cell entry and spread. Coronaviruses can be deadly, in large part because they cause "cytokine storms." These storms result from imbalances between pro-inflammatory and anti-inflammatory proteins called cytokines, which can cause extreme inflammation and respiratory complications. Respiratory distress kills hundreds of thousands of people each year worldwide, and hundreds of clinical trials are testing drugs to treat it.

MSCs have been widely used in cell-based therapy, from basic research to clinical trials Safety and effectiveness have been clearly documented in many clinical trials, especially in the immune-mediated inflammatory diseases.

NestaCell® is a mesenchymal stem cell therapy produced by Cellavita and proved to be safe in previous clinical trials.

The aim of this study is assess the efficacy of NestCell® as an add-on therapy to standard treatment to treat patients with severe COVID-19 pneumonia. .

Patients included will be randomized to receive 2x10^7 cells (20 million cells) on days 1, 3, 5 and 7.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • UNIFESP
  • São Paulo, Brazil
    • Hospital de Barueri
  • São Paulo, Brazil
    • IncCOR
  • São Paulo
    • Campinas, São Paulo, Brazil
      • Hospital Vera Cruz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, aged ≥ 18 years 2. Present a confirmed or pending diagnosis of COVID-19, but with tomographic and clinical signs strongly suggestive of SARS-CoV-2 infection (COVID-19), with pulmonary impairment greater than or equal to 50% and: i. Oxygen saturation <95%; ii. CURB-65 rating ≥ a 4; d) Participants with a score on WHO ordinal scale that measures illness severity over time equal to 5 (Hospitalized with non-invasive ventilation or high-flow oxygen).

Exclusion Criteria:

1. Patients with autoimmune diseases in the past or screening;
2. Those who have serious basic diseases that affect their survival, including: malignant tumor, hematopathy, malignant fluid, active hemorrhage, severe malnutrition, etc. which have not been controlled and can not be removed due to multiple metastasis;
3. Known or self-reported HIV or syphilis infected persons;
4. Have participated in stem cell clinical research;
5. Pregnant or lactating women or those who have fertility plans in the past year;
6. The estimated life cycle is less than 48 hours;
7. Other conditions that the researcher thinks are not suitable for participating in the experiment.
8. Shock
9. Continuous use of immunosuppressive agents or organ transplants in the past 6 months;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NestaCell®; A dose of 2x10^7 cells (20 million cells) will be administered IV on days 1, 3, 5 and 7 in all subjects.	Biological: NestaCell®; A dose of 2x10^7 cells (20 million cells) will be administered IV on days 1, 3, 5 and 7 in all subjects.; Other Names: Mesenchymal Stem Cell
Placebo Comparator: Placebo; Matching placebo will be administered IV on days 1, 3, 5 and 7 in all subjects.	Biological: Placebo; Matching Placebo will be administered IV on days 1, 3, 5 and 7 in all subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Condition	Ordinal scale (WHO ordinal scale that measures illness severity over time)	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of mortality within 10-days	Evaluation of Pneumonia change	10 days
Change of Clinical symptoms - respiratory rate	Evaluation of Pneumonia change	10 days
Hypoxia	oxygen saturation	10 days
PaO2 / FiO2 ratio	oxygen saturation	10 days
CD4+ and CD8+ T cell count	Marker of Immunological function	Days 1, 2, 4, 6 and 8.
Changes of blood oxygen	PaO2 / FiO2 ratio	10 days
Side effects in the treatment group	Number of participants with treatment-related adverse events	10 days
Complete blood count, cardiac, hepatic and renal profiles;	Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine	Days 1, 2, 4, 6 and 8.

Collaborators and Investigators

• Sponsor: Azidus Brasil
• Collaborators: Hospital Vera Cruz; Cellavita Pesquisa Científica Ltda
• Investigators: Principal Investigator: Florentino de Araujo Cardoso Filho, Hospital Vera Cruz

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): February 28, 2021

Study Registration Dates

• First Submitted: March 18, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: HOPE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No