Clinical trial NCT04473170: Study Evaluating the Safety and Efficacy of Autologous Non-Hematopoietic Peripheral Blood Stem Cells in COVID-19
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Coronavirus Disease 2019 (COVID-19)
Keywords: COVID-19
Non-Hematopoietic Peripheral Blood Stem Cells
Lead sponsor: Abu Dhabi Stem Cells Center
Sponsor class: OTHER_GOV
First posted: 2020-07-16
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse reactions incidence.
timeFrame: Day 0 - 28
measure: Rate of mortality within 28-days.
timeFrame: Day 0 - 28
measure: Time to clinical improvement on a seven-category ordinal scale.
timeFrame: Day 0 - 28
Secondary outcomes:
measure: Assessment of the immune response profile.
timeFrame: Days 0, 14, and 28
measure: Assessment of acute-phase serum markers.
timeFrame: Days 0, 14, and 28
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: Abu Dhabi Stem Cells Center
Study officials:
affiliation: Abu Dhabi Stem Cells Center (ADSCC)
name: Yendry Ventura Carmenate, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Castillo Aleman YM, Villegas Valverde CA, Ventura Carmenate Y, Abdel Hadi L, Rivero Jimenez RA, Rezgui R, Alagha SH, Shamat S, Bencomo Hernandez AA. Viability assessment of human peripheral blood-derived stem cells after three methods of nebulization. Am J Stem Cells. 2021 Oct 15;10(4):68-78. eCollection 2021.
citation: Ventura-Carmenate Y, Alkaabi FM, Castillo-Aleman YM, Villegas-Valverde CA, Ahmed YM, Sanna P, Almarzooqi AA, Abdelrazik A, Torres-Zambrano GM, Wade-Mateo M, Quesada-Saliba D, Abdel Hadi L, Bencomo-Hernandez AA, Rivero-Jimenez RA. Safety and efficacy of autologous non-hematopoietic enriched stem cell nebulization in COVID-19 patients: a randomized clinical trial, Abu Dhabi 2020. Transl Med Commun. 2021;6(1):25. doi: 10.1186/s41231-021-00101-5. Epub 2021 Nov 3.