A Randomized, Double-Blind, Single Center, Efficacy and Safety Study of Allogeneic HB-adMSCs Against COVID-19.

Study Overview
=================
Brief Summary
-----------------
Hope Biosciences is conducting a research study of an investigational product called allogeneic 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, Randomized, Placebo-Controlled, Double-Blinded, Clinical Trial to Assess Efficacy of HB-adMSCs to Provide Immune Support Against Coronavirus Disease. 100 patients will be enrolled. Eligible participants are at high or very high exposure risk of contracting COVID-19. The primary endpoint of this study is to provide immune support against COVID-19, measured by the percentage of subjects that develop symptoms of COVID-19. 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 Randomized, Double-Blind, Placebo-Controlled, Clinical Trial to Assess Efficacy and Safety of Allogeneic HB-adMSCs to Provide Immune Support Against COVID-19.

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men, and women 18 years of age or older Participant works in a capacity that is characterized as high-risk or very high-risk High-Risk Exposure jobs are those with high potential for exposure to known or suspected sources of COVID-19. First responders, health care delivery and support staff (e.g., law enforcement, fire fighters, paramedics, doctors, nurses, and other hospital staff who must enter patients' rooms) exposed to individuals potentially having COVID-19. Mortuary workers involved in preparing (e.g., for burial or cremation) the bodies of people who are known to have, or suspected of having, COVID-19 at the time of their death Very High-Risk Exposure jobs are those with high potential for exposure to known or suspected sources of COVID-19 during specific medical, postmortem or laboratory procedures. Health care workers (e.g., doctors, nurses, dentists, paramedics, emergency medical technicians) performing aerosol-generating procedures (e.g., intubation, cough induction procedures, bronchoscopies, some dental procedures and exams or invasive specimen collection) on known or suspected COVID-19 patients. Health care or laboratory personnel collecting or handling specimens from known or suspected COVID-19 patients (e.g., manipulating cultures from known or suspected COVID-19 patients). Morgue workers performing autopsies, which generally involve aerosol-generating procedures, on the bodies of people who are known to have, or suspected of having, COVID-19 at the time of their death 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: 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.
Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic HB-adMSCs 200MM<br>Subjects assigned to this arm will receive 5 intravenous infusions of HB-adMSCs at 200 million cells/dose. Infusions will occur at weeks 0, 2, 6, 10, and 14. | Biological: HB-adMSCs<br>* Hope Biosciences allogeneic adipose-derived mesenchymal stem cells<br>|
| Experimental: Allogeneic HB-adMSCs 100MM<br>Subjects assigned to this arm will receive 5 intravenous infusions of HB-adMSCs at 100 million cells/dose. Infusions will occur at weeks 0, 2, 6, 10, and 14. | Biological: HB-adMSCs<br>* Hope Biosciences allogeneic adipose-derived mesenchymal stem cells<br>|
| Experimental: Allogeneic HB-adMSCs 50MM<br>Subjects assigned to this arm will receive 5 intravenous infusions of HB-adMSCs at 50 million cells/dose. Infusions will occur at weeks 0, 2, 6, 10, and 14. | Biological: HB-adMSCs<br>* Hope Biosciences allogeneic adipose-derived mesenchymal stem cells<br>|
| Placebo Comparator: Placebo<br>Subjects assigned to this arm will receive 5 intravenous infusions of placebo intervention (saline). Infusions will occur at weeks 0, 2, 6, 10, and 14. | Other: Placebos<br>* Saline<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Were Hospitalized Due to COVID-19 Symptoms | Number of subjects that were hospitalized due to COVID-19 symptoms during the conduct of this study. | Week 0 through Week 26 (End of Study) | 
| Number of Participants That Had Symptoms Associated With COVID-19 | Number of subjects who experience symptoms defined to be associated with COVID-19, such as fever, shortness of breath/difficulty breathing, cough, etc. | Week 0 through Week 26 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukocyte Differential Count | Change from baseline in Leukocyte Differential Count | Week 0 to Week 26 (End of Study) | 
| C Reactive Protein | Change from baseline in C Reactive Protein | Week 0 through Week 26 (End of Study) | 
| Tumor Necrosis Factor - Alpha | Change from baseline in TNF alpha | Week 0 through Week 26 (End of Study) | 
| Interleukin 6 | Change from baseline in IL-6 | Week 0 through Week 26 (End of Study) | 
| Interleukin 10 | Change from baseline in IL-10 | Week 0 through Week 26 (End of Study) | 
| Short Form-36 (SF-36) | The Short Form-36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores (including Energy/Fatigue scores, Social Functioning, role limitations due to Physical Health, General Health, Physical Functioning, Pain, Emotional Well-Being, and Emotional Problems) which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. | Week 0 to Week 26 (End of Study) | 
| Patient Health Questionnaire (PHQ-9) Scores | The study used PHQ-9 as a depression module, which scores each of the nine DSM-IV criteria as 0 (not at all) to 3 (nearly every day) to monitor the severity of depression. | Week 0 to Week 26 (End of Study) | 

 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