Study Evaluating the Safety and Efficacy of Autologous Non-Hematopoietic Peripheral Blood Stem Cells in COVID-19

Study Overview
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Brief Summary
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SENTAD-COVID Study is an adaptive, prospective, multicentric, open-label, and randomized controlled clinical trial involving hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19) infection during the outbreak in Abu Dhabi, 2020. The patients were randomly allocated in a parallel assignment involving two groups of participants: Group A (Experimental arm): autologous non-hematopoietic peripheral blood stem cells (NHPBSC) therapy as add-on COVID-19 standard care, or Group B (No investigational intervention arm): COVID-19 standard care. Standard care is defined as per the UAE National Guidelines for Clinical Management and Treatment of COVID-19. SENTAD-COVID Study was conducted in the Sheikh Khalifa Medical City (SKMC) of Abu Dhabi, as Primary Care Clinical Trial Unit, while the cell processing and investigational product formulation were completed by Abu Dhabi Stem Cells Center (ADSCC), according to Good Laboratory Practices (GLPs) and Good Manufacturing Practices (GMPs).

Detailed Description
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Group A patients received autologous NHPBSC therapy through jet nebulization, in addition to the standard care, while Group B (No investigational intervention arm) received only the UAE approved standard care. The primary endpoints were the safety and efficacy assessment, measured as Adverse Reactions (ARs) incidence [according to World Health Organization - Uppsala Monitoring Centre (WHO-UMC) causality assessment system], rate of mortality within 28-days, and the time to clinical improvement of 2 points on a seven-category ordinal scale or discharge from the Hospital, whichever came first. Immune response profile, acute-phase serum markers, and coagulation testing profile were evaluated as well, before treatment (baseline - Day 0), at Day 14, and Day 21 (in patients with early response, defined as 2 points of difference in the clinical critical treatment index within 7 days of treatment, the assessment will be performed at Day 7). The trial was approved by the institutional ADSCC Research Ethics Committees (REC), and the Emirates Institutional Review Board (IRB) for COVID-19 Research and the written informed consent was obtained from all patients or from the patient's legal representative if the patient was too unwell to provide consent. SENTAD-COVID Study was conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice (GCP) Guidelines of the International Conference on Harmonization (ICH). The authors were responsible for designing the trial and for compiling and analyzing the data.

Official Title
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Adaptive Open-label Study Evaluating the Safety and Efficacy of Autologous Non- Hematopoietic Peripheral Blood Stem Cells Therapy in COVID-19 Outbreak in Abu Dhabi, 2020 (SENTAD-COVID Study)

Conditions
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Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
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* Biological: Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC)
* Drug: COVID-19 standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RT-PCR Laboratory confirmation of COVID-19. Male or female aged ≥ 18 years. Interstitial lung change ≥ 3 judged by Lungs Lobar based scoring according to computed tomography (CT) scans. Hospitalized and symptomatic patients, referring one or more of the following symptoms (fever, cough, or shortness of breath), in association with (at least one): tiredness, runny nose, headache, sore throat, chills, muscle pain, or new loss of taste or smell). Ability to comply with test requirements and peripheral blood stem cells collection. The patient or legal representative agrees to participate in the study, and signs the SENTAD-COVID Study informed consent form. Exclusion Criteria: Pediatric patients (aged < 18 years). Diagnosis of any kind of shock. Organ transplants in the past 3 months. Patients receiving immunosuppressive therapy. Diagnostic of Hepatitis B Virus (HBV) infection. Diagnostic of Human Immunodeficiency Virus (HIV) infection or Acquired Immunodeficiency Syndrome (AIDS). Current diagnosis of cancer. History of malignancies in the past 5 years. Pregnant or lactating women. Have participated in other clinical trials in the past 3 months. Inability to comply with test requirements and peripheral blood stem cells collection. Inability to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment involving two groups of participants: Group A (Experimental arm): Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC) therapy as add-on COVID-19 standard care. Group B (No investigational intervention arm): COVID-19 standard care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC) therapy as add-on COVID-19 standard care. | Biological: Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC)<br>* SENTAD-COVID Study intervention consists of Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC) therapy through jet nebulization in addition to standard care. The NHPBSC were characterized as CD90+, CD133+, Oct-4+ (pluripotent markers), and CD45-, CD71-, based on multiparameter flow cytometry.<br>* Other names: UAECell19;|
| Active Comparator: Group B<br>COVID-19 Standard care. | Drug: COVID-19 standard care<br>* UAE National Guidelines for Clinical Management and Treatment of COVID-19.<br>* Other names: Current COVID-19 standard care in the UAE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions incidence. | Proportion of participants with treatment-related Adverse Event as assessed by CTCAE v5.0. | Day 0 - 28 | 
| Rate of mortality within 28-days. | Incidence of deaths within 28-days in enrolled patients. | Day 0 - 28 | 
| Time to clinical improvement on a seven-category ordinal scale. | Days from administration of the Investigational Product to improvement of seven-category ordinal scale by at least 2 points. | Day 0 - 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the immune response profile. | Immune response profile characterized according the biomarkers: CD3, CD4, CD8, CD11c, CD14, CD16, CD19, CD20, CD25, CD27, CD28, CD38, CD45, CD45RA, CD45RO, CD56, CD57, CD66b, CD123, CD127, CD161, CD294, CCR4, CCR6, CCR7, CXCR3, CXCR5, HLA-DR, IgD, and TCRγδ, for the identification of immune cells and subsets analysis; and the humoral Immune profile: IgG, IgA, IgM levels. | Days 0, 14, and 28 | 
| Assessment of acute-phase serum markers. | Complete Blood Counts (CBC), Acute phase proteins and Inflammatory markers: CRP, ESR, LDH, Procalcitonin (PCT), Ceruloplasmin, Haptoglobin, alpha 1 antitrypsin, IL-6, ferritin C3, PT, fibrinogen and D-dimer. | Days 0, 14, and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Non-Hematopoietic Peripheral Blood Stem Cells