A Clinical Trial to Determine the Safety and Efficacy of HB-adMSCs to Provide Protection Against COVID-19

Study Overview
=================
Brief Summary
-----------------
Hope Biosciences is conducting a research study of an investigational product called autologous adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) to provide immune support against COVID-19. The study purpose is to evaluate the safety and efficacy of five IV infusions of HB-adMSCs in subjects with no signs of COVID-19.

Detailed Description
-----------------
This is a Phase II, Open Label, Single-Center, Clinical Trial to Assess Efficacy of HB-adMSCs to Provide Immune Support Against Coronavirus Disease. 51 patients were enrolled. All patients have previously banked their own mesenchymal stem cells at Hope Biosciences. Eligible participants are either 65 years of age or older, have preexisting conditions, or are at high exposure risk of contracting COVID-19. The primary objective of this study is to provide immune support against COVID-19, measured by the presence or absence of adverse events and serious adverse events related to the study drug. In addition, participants will be monitored for overall clinical status by standard clinical laboratories and inflammatory markers. Participants will complete Short Form Health Survey (SF-36) and depression module (PHQ-9) questionnaires.

Official Title
-----------------
A Phase II, Open Label, Single-Center, Clinical Trial to Assess Safety and Efficacy of HB-adMSCs to Provide Immune Support Against Coronavirus Disease

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: HB-adMSCs


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must meet the criteria for 1,2, OR 3, AND 4-7 to be eligible. Men, and women 65 years of age or older (according to CDC provisions) OR Participant works in healthcare facility or other well characterized high-risk environment OR Has underlying conditions including but not limited to cardiopathies, diabetes mellitus, cancer, COPD, asthma or any other systemic autoimmune disease. Subject must have previously banked their cells at Hope Biosciences No signs or symptoms of infection, including but not limited to, body temperature >100 F and pulse rate > 100 BPM. Subject provides written informed consent prior to initiation of any study procedures. Agrees to the collection of venous blood per protocol. Agrees to conformational testing for SARS-CoV-2 before end of study. Exclusion Criteria: Subjects must not have any of the following criteria to be eligible. Women who are pregnant or lactating, or those who are not pregnant but do not take effective contraceptive measures Patients who are participating in other clinical trials or have intake of investigational drug within the previous 30 days; Inability to provide informed consent or to comply with test requirements; Any medical disease or condition that, in the opinion of the site PI or sub-investigator, precludes study participation. Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. Patients who have received a stem cell treatment within one year. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study. Patient currently or recently symptomatic for COVID-19 or anyone with COVID-19 associated symptoms within the past 30-days
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HB-adMSCs<br>Five IV infusions of autologous, adipose-derived mesenchymal stem cells. Baseline laboratory data will be collected prior to first infusion; follow-up data will be compared against baseline according to the following schedule: safety lab follow ups at weeks 6, 14, 26; inflammatory marker follow ups at weeks 6, 14, 26; SF-36 and PHQ-9 Questionnaires at weeks 2, 6, 10, 14, 18, 22, 26. | Biological: HB-adMSCs<br>* Five IV infusions of autologous adipose-derived mesenchymal stem cells. Baseline laboratory values will be collected prior to first infusion and compared at following visits. Safety labs will be assessed at weeks 6, 14, 26. Inflammatory markers will be assessed at weeks 6, 14, 26. SF-36 and PHQ-9 questionnaires will be assessed at weeks 2, 6, 10, 14, 18, 22, 26.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hospitalization for COVID-19 | Number of subjects that require hospitalization for COVID-19 | Week 0 through Week 26 (End of Study) | 
| Incidence of Symptoms for COVID-19 | Number of subjects that develop symptoms associated with COVID-19, such as fever, shortness of breath/difficulty breathing, cough | Week 0 through Week 26 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of Upper/Lower Respiratory Infection | Absence of upper/lower respiratory infection (with hospitalization criteria) | Week 0 through Week 26 (End of Study) | 
| Change From Baseline in Glucose | Change from baseline in level of glucose in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Calcium | Change from baseline in level of calcium in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Albumin | Change from baseline in level of albumin in the blood (g/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Total Protein | Change from baseline in level of total protein in the blood (g/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Sodium | Change from baseline in level of sodium in the blood (mmol/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Total Carbon Dioxide | Change from baseline in level of carbon dioxide in the blood (mmol/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Potassium | Change from baseline in level of potassium in the blood (mmol/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Chloride | Change from baseline in level of chloride in the blood (mmol/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Blood Urea Nitrogen (BUN) | Change from baseline in level of blood urea nitrogen (BUN) in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Creatinine | Change from baseline in level of creatinine in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Alkaline Phosphatase | Change from baseline in level of alkaline phosphatase in the blood (IU/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Alanine Aminotransferase | Change from baseline in level of alanine aminotransferase in the blood (IU/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Aspartate Aminotransferase | Change from baseline in level of aspartate aminotransferase in the blood (IU/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Total Bilirubin | Change from baseline in level of total bilirubin in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Leukocytes | Change from baseline in level of leukocytes in the blood (x 10^9/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Erythrocytes | Change from baseline in erythrocytes in the blood (10^12/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Hemoglobin | Change from baseline in level of hemoglobin in the blood (g/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Hematocrit | Change from baseline in level of hematocrit in the blood (%) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Mean Corpuscular Volume | Change from baseline in mean corpuscular volume in the blood (fL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Mean Corpuscular Hemoglobin | Change from baseline in mean corpuscular hemoglobin in the blood (pg) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Mean Corpuscular Hemoglobin Concentration | Change from baseline in mean corpuscular hemoglobin in the blood (g/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Erythrocyte Distribution Width | Change from baseline in erythrocyte distribution width in the blood (%) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Neutrophils | Change from baseline in neutrophils in the blood (%) (leukocyte differential) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Lymphocytes | Change from baseline in lymphocytes in the blood (%) (leukocyte differential) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Monocytes | Change from baseline in monocytes in the blood (%) (leukocyte differential) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Eosinophils | Change from baseline in eosinophils in the blood (%) (leukocyte differential) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Basophils | Change from baseline in basophils in the blood (%) (leukocyte differential) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Platelets | Change from baseline in platelets in the blood (x 10^9/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Prothrombin Time | Change from baseline in prothrombin time in the blood (seconds) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in International Normalized Ratio (INR) | Change from baseline in international normalized ratio in the blood (INR) (ratio) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Tumor Necrosis Factor Alpha (TNF-alpha) | Change from baseline in tumor necrosis factor alpha (TNF-alpha) in the blood (ng/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Interleukin-6 | Change from baseline in Interleukin-6 in the blood (ng/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Interleukin-10 | Change from baseline in Interleukin-10 in the blood (ng/L) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in C-Reactive Protein | Change from baseline in C-Reactive Protein in the blood (mg/dL) | Weeks 0, 6, 14, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Physical Functioning | Short-form (36) Health Survey domain Average Physical Functioning; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Role Limitations Due to Physical Health | Short-form (36) Health Survey domain Average Role Limitations due to Physical Health; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Role Limitations Due to Emotional Problems | Short-form (36) Health Survey domain Average Role Limitations due to Emotional Problems; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Energy/Fatigue | Short-form (36) Health Survey domain Average Energy/Fatigue; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Emotional Well-being | Short-form (36) Health Survey domain Average Emotional Well-Being; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Social Functioning | Short-form (36) Health Survey domain Average Social Functioning; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average Pain | Short-form (36) Health Survey domain Average Pain; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Short Form (36) Health Survey (SF-36) Domain Average General Health | Short-form (36) Health Survey domain Average General Health; scored on a scale of 0-100; lower score equals more disability. | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 
| Change From Baseline in Patient Health Questionnaire 9 (PHQ-9) Total Score | Depression module; scores DSM-IV criteria to monitor severity of depression through 9 total questions; minimum score of 0, maximum score of 27, each question ranges from scores 0-3; higher scores mean worse outcome | Weeks 0, 2, 6, 10, 14, 18, 22, 26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronavirus, Prevention, Immune support, stem cells, mesenchymal stem cells, adipose-derived mesenchymal stem cells