A Phase II, Open Label, Single-Center, Clinical Trial to Assess Safety and Efficacy of HB-adMSCs to Provide Immune Support Against Coronavirus Disease
Phase: PHASE2
Conditions: COVID-19
Sponsor: Hope Biosciences Research Foundation

HB-adMSCs to provide immune support against COVID-19                                                                            
 
 
Protocol Version 1.2  
0  
Version Date: 20-APR-2020  
Clinical Study Protocol  
  
  
Protocol Number: HBCOVID-01  
  
“A Phase II, Open Label, Single-Center, Clinical Trial to Assess Safety 
and Efficacy of HB-adMSCs to Provide Immune Support Against  
Coronavirus Disease”   
  
  
  
IND Number:  
19680  
NCT Number  
  
NCT04349631  
  
Name of Product  
HB-adMSCs  
Hope Biosciences Adipose Derived Mesenchymal Stem  
Cells  
Phase of development   
II  
Indication  
Coronavirus Disease (COVID-19)   
Sponsor Contact  
Katherine Ruppert, PhD  
Director of Research  
Hope Biosciences Stem Cell Foundation 
16700 Creek Bend Dr.   
Sugar Land. TX 77478  
Tel. (832) 975 8840 
Fax: (855) 700 6838 
katie@hope.bio  
Protocol Version  
1.2   
Protocol Version Date  
  
  
  
  
20-APR-2020  
  
-CONFIDENTIAL-  
This document and its contents are the property of and confidential to Hope Biosciences. 
Any unauthorized copying or use of this document is prohibited.  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Ethics and Regulatory Compliance Statement  
  
The procedures set forth in this protocol are designed to ensure that the Hope Biosciences 
StemCell Foundation and principal investigator(s) abide by the International Conference 
onHarmonization (ICH) current Good Clinical Practice (cGCP) guidelines, current 
GoodLaboratory Practice (cGLP) guidelines, the Declaration of Helsinki, and applicable 
local regulatory requirements and laws in the conduct, evaluation, and documentation of 
this study. 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Synopsis   
  
Title of the Study:  
“A Phase II, Open Label, Single-Center, Clinical Trial to Assess 
Safety and Efficacy of HB-adMSCs to Provide Immune Support 
Against Coronavirus Disease”   
Protocol Number:  
HBCOVID-01  
Investigators   
Principal Investigator: Thanh Cheng, MD  
Sub-Investigator: Djamchid Lotfi, MD  
Study Site: Single site:  
Hope Biosciences 
16700 Creek Bend Dr.  
Sugar Land, TX 77478  
Phase of development   
II  
Objectives  
Primary:  
- 
To investigate the efficacy of HB-adMSCs in providing 
immune support against development of COVID-19 by 
decreasing the percentage of subjects that develop 
symptoms of COVID-19 infection.   
  
Secondary:   
- 
To investigate the efficacy of HB-adMSCs in the 
prevention of upper and lower respiratory infections 
requiring hospitalization.  
Study Design:  
This phase II, open label, single-center, safety and efficacy study 
is designed to evaluate HB-adMSCs to support immunity against 
Coronavirus Disease.   
The screening period, up to 14 days long for each patient, will be 
used to assess eligibility. Once eligibility is confirmed, the 
patient will be considered enrolled.   
Upon study completion, the investigators should know whether 
or not HB-adMSCs are effective to use in this population and if it 
does protect against the Coronavirus Disease.    
To ensure that the drug is safe, a Medical Monitor will oversee 
the entire study, review any clinically significant laboratory data, 
including complete blood counts, serum chemistry, adverse 
events.  
Planned Sample Size:   
  
Population: 55 patients.  
The sample size required assumes a 15% drop-out of patients.  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Investigational Therapy:  HB-adMSCs (Hope Biosciences adipose-derived mesenchymal 
stem cells) is provided as a white-yellowish solution in a 30 ml 
syringe. Each 20-mL contains 2x108 of HB-adMSCs to be diluted 
in a volume of 250 mL saline solution. HB-adMSCs is to be 
administered by IV infusion at a rate of 83 gtts/min at Weeks 0, 
2, 6, 10 and 14. Each patient shall receive 5 HB-adMSCs 
infusions.  
Treatment Duration:  
The approximate maximum duration of treatment for each patient 
is 14 weeks (Week 0 through 14), and the approximate duration 
of the study is 26 weeks.   
Criteria for Evaluation:   
  
Safety:   
Safety will be assessed by adverse event (AE) reporting, physical 
examinations, vital signs, and clinical laboratory values. Patient 
safety data will be closely monitored by the clinical team to 
ensure patient safety, as well as the Medical Monitor and DSMB.   
  
Clinical Efficacy:   
Efficacy will be evaluated through the analysis of Complete 
Blood Count with differential.  Exploratory measures will include 
changes from baseline inflammation, SF-36 and PHQ-9.  
Statistical Methods and 
Planned Analyses:   
The statistical analysis plan is defined and enumerated.   
 
Introduction   
 
Study Objectives and Endpoints   
 
Study Objectives  
  
Primary:  
  
- 
To investigate the efficacy of HB-adMSCs in providing immune support against 
development of Coronavirus Disease by incidence of hospitalization for COVID-19, 
incidence of symptoms associated with COVID-19 (ie., fever, shortness of 
breath/difficulty breathing, and/or cough), and severity of COVID-19 associated 
symptoms ((fever 38C or higher, cough, shortness of breath/difficulty breathing).   
  
Secondary:   
  
- 
To investigate the efficacy of HB-adMSCs in the prevention of upper and lower 
respiratory infections in a high-risk population.  
 

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Study Endpoints   
  
Primary endpoints:   
- 
Incidence of hospitalization for COVID-19.   
- 
Incidence of symptoms associated with COVID-19  
  
Secondary endpoints:   
- 
Absence of upper/lower respiratory infections (with hospitalization criteria) up to 3 
months post infusions.  
- 
Change from baseline in leukocyte differential  
- 
Change from baseline in C-Reactive Protein  
- 
Change from baseline in TNF-alpha  
- 
Change from baseline in IL-6  
- 
Change from baseline in IL-10  
- 
Clinically significant changes in laboratory values, vital signs, weight, and physical 
examination results.   
- 
Incidence of AEs (AEs) and serious AEs (SAEs) related to the drug  
 
Investigational Plan  
  
This Phase II, open label, single center, assesses efficacy in a population of patients who 
have already banked their cells to evaluate HB-adMSCs to provide immune support against 
Coronavirus Disease. It is designed to be conducted over 3 periods or phases:  
  
● Phase 1 (Screening): Our screening process starts with a telephone call to provide a 
general overview of the study and discuss eligibility requirements.  The study patient 
will receive the informed consent document by e-mail or in the pre-paid envelope 
provided. If, after reviewing this consent the study patient is still interested in 
participating in the study, he/she will need to sign and return the consent form to 
Hope Biosciences Stem Cell Research Foundation. This process can take up to 14 
days.   
  
● Phase 2 (Treatments): Includes Infusion 1 (Week 0), Infusion 2 (Week 2), Infusion 3 
(Week 6), Infusion 4 (Week 10) and Infusion 5 (Week 14). Subjects will be 
monitored at the clinical site for 1 hour following HB-adMSCs administration.   
  
● Phase 3 (follow-up): Includes Follow Up Week 18, 22 and End of Study at Week 26.   
  
Safety assessments will be ongoing. A follow up phone call will be done a day after every 
infusion. Blood tests will include Complete Blood Count with differential, Comprehensive 
Metabolic Profile and Coagulation Panel screening for hepatotoxicity, cytopenia, renal 
failure or alterations in the coagulation cascade that might entail a safety concern for the 
individual.  Efficacy assessments will include PHQ-9, SF-36, TNF-a, IL-6, IL-10, and CRP.   

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Selection and Withdrawal of Patients   
  
Inclusion Criteria   
 
1. Men and women 65 years of age and older (according to CDC provisions) OR  
2. Participant works in healthcare facility or other well characterized high-risk 
environment  
OR  
3. Has underlying conditions including but not limited to cardiopathies, diabetes 
mellitus, cancer, COPD, asthma or any other systemic autoimmune disease.  
4. Subject has previously banked their cells with Hope Biosciences  
5. No signs or symptoms of infection, including but not limited to, body temperature 
>100 F and pulse rate > 100 BPM.   
6. Subject provides written informed consent prior to initiation of any study procedures.  
7. Agrees to the collection of venous blood per protocol.   
8. Agrees to conformational testing for SARS-CoV-2 before end of study  
  
Exclusion Criteria:  
 
1. Women who are pregnant or lactating, or those who are not pregnant but do not take 
effective contraceptive measures  
2. Patients who are participating in other clinical trials or have intake of investigational 
drug within the previous 30 days;  
3. Inability to provide informed consent or to comply with test requirements;  
4. 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.  
5. Patients who have received a stem cell treatment within one year.  
6. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any 
time prior to or during the study.  
7. Patient currently or recently symptomatic for COVID-19 or anyone with COVID-19 
associated symptoms within the past 30-days  
  
Withdrawal, Removal, and Replacement of Patients  
  
Patients will be considered to have completed the study if they complete treatment and 
assessments through Week 26. A patient’s investigational treatment should be discontinued if 
any of the following situations occurs:  
  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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● The Investigator believes that for safety reasons, it is in the best interest of the patient 
to stop treatment.  
● The patient is non-compliant with the study visit schedule or other protocol 
requirements.  
● The patient develops a severe allergic reaction that occurs following investigational 
product administration.  
  
A patient may voluntarily withdraw or be withdrawn from the study at any time for reasons 
including, but not limited to, the following:  
  
● Patient withdrawal of consent: At any time, a patient's participation in the study may 
terminate at his/her request. The specific reason for patient withdrawal will be noted 
on the case report form (CRF).  
● Lost to follow-up: The patient stops coming for visits, and study personnel is unable 
to contact the patient after repeated attempts (e.g., mail, or email).  
● This study may be terminated at the discretion of the Sponsor or any regulatory 
agency.   
  
If a patient’s infusions are discontinued at any point during the trial and the patient maintains 
consent to contribute additional outcome information, the patient should continue to be 
followed through Week 26 for all safety and efficacy assessments. Investigators will be 
trained about the importance of retention and steps to prevent missing data.   
The date and reason for withdrawal are to be documented in the CRF. The study site must 
immediately notify the medical monitor. The patients who withdraw prematurely must attend 
an early discontinuation visit if possible, at which time they will complete all assessments 
described in Table 2 under the Week 26 visit.   
  
In the event that a patient discontinues prematurely from the study due to an Adverse Event 
(AE) or serious AE, the event will be followed until it resolves (returns to normal or 
baseline values) or stabilizes, or until it is judged by the Investigator to be no longer 
clinically significant.  Once a patient is withdrawn from the study, the patient may not re-
enter the study.   
  
If the subject develops symptoms associated with COVID-19 during the conduct of this 
study, they will be asked to consult their personal physician and be tested for COVID-19, 
and to selfquarantine for at least 14 days. Quarantine must occur while waiting for COVID-
19 test results. Once asymptomatic, subject may resume site visits. If the test results are 
positive, the subject will be asked to quarantine and may continue to receive infusions at the 
quarantine site. If the subject develops severe symptoms (ie., shortness of breath/difficulty 
breathing) they should go to the ER instead of personal physician.  
 
 
 

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Treatments  
 
Details of the investigational product  
  
HB-adMSCs is to be administered as an IV infusion. Each 30-mL syringe contains 2x108 
cells suspended in 20 ml of sterile saline, meant to be diluted in a volume of 250 mL.   
Each syringe of HB-adMSCs is specific for each patient (autologous). Each syringe will be 
provided by Hope Biosciences on the day of the infusion after all quality control essays have 
been performed and the results are within normal range.  
 
Instructions for Administration   
 
The designated study staff will administer the investigational product in the following 
manner:   
  
● Prior to administration, visually inspect the infusion solution for particulates. If 
foreign particles are present, do not use the solution.  
● Emergency equipment, such as epinephrine, antihistamines, and corticosteroids must 
be available in the event of infusion-related reactions.  
● Start IV administration after dilution.   
● Administer the infusion solution over a period of 1h. Observe the patient for at least 1 
hour post-infusion for acute infusion-related reactions, including anaphylaxis. See 
Appendix 1 for guidelines on diagnosing anaphylaxis.  
● Do not store or reuse any unused portion of the infusion solution. Any unused 
product or waste material should be disposed.   
● Volume of study drug infused, start times, and stop times will be recorded. If any 
portion of the infusion (cell solution) is discarded, the reason will be recorded in the 
CRF.  
● The patient will be monitored for a total of 2 hours from drug exposure to discharge.  
a. During the Investigational product administration (1 hour) vital signs will be 
measured at minute 0, 15, 30 and 45.  
b. Post infusion, vital signs will be measured at minute 0, 30, and 60.   
  
Investigational Product Assignment and Infusion Schedule.   
  
Each patient will be allocated a unique subject number at screening and will retain this 
number throughout the study.   
  
The Investigational Product is to be administered to all eligible, enrolled patients by 
intravenous infusion at a dose of 2x108 cells at weeks 0, 2, 6, 10 and 14. Every effort should 
be made to adhere to the dosing schedule. However, a scheduled infusion should not be 
administered if a patient has an ongoing AE that, in the Investigator’s opinion, warrants 
holding the infusion.  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Prior and concomitant conditions  
  
The investigators should document all prior significant medical history. Additional 
conditions present at the time when informed consent is given and up to the time of first 
infusion (Week 0) are to be regarded as concomitant conditions.   
  
Illnesses first occurring or detected during the study and/or worsening of a concomitant 
condition during the study should be documented as AEs in the CRF.   
  
  
Prior and concomitant medications   
  
All medications, including over-the-counter treatments and preventative vaccines taken by 
the patient during the study, including those treatments initiated prior to the start of the study, 
must be recorded in the CRF. The entry must include the dose, regimen, route, indication, 
and dates of use.   
Study Procedures  
  
Table 2 outlines the timing of procedures, and assessments to be performed throughout the 
study. 

HB-adMSCs to provide immune support against COVID-19                                                                             
 
Table 2. Schedule of Assessments  
Visit Number  
1  
2  
3  
4  
5  
6  
7  
8  
9  
Weeks  
N/A  
Week 0  
Week 2  
Week 6  
Week 10  
Week 14  
Week 18  
Week 22  
Week 26  
Visit Name  
Screening  
(Phone call)  
Infusion- 
1  
/Baseline   
Infusion 2  
Infusion 3  
Infusion 4  
Infusion 5  
Follow Up  Follow Up  
EOS  
Window Period  
Up to 14 days  
+3 days  
+3 days  
+3 days  
+3 days  
+3 days  
+3 days  
+3 days  
+3 days  
STUDY PROCEDURES  
 
 
 
 
 
 
 
 
 
Informed Consent   
X  
X  
   
   
   
   
   
   
   
Inclusion and Exclusion Criteria   
X  
X  
   
   
   
   
   
   
   
Pre-infusion assessment  
   
X  
X  
X  
X  
X  
   
   
   
Review of Medical History   
X  
X  
X  
X  
X  
X  
X  
X  
X  
Concomitant Medication Review  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Vital Signs  
   
X  
X  
X  
X  
X  
X  
X  
X  
Weight and Height1   
   
X  
X  
X  
X  
X  
X  
X  
X  
Physical Examination   
   
X  
X  
X  
X  
X  
X  
X  
X  
SF-36 Questionnaire   
   
X  
X  
X  
X  
X  
X  
X  
X  
PHQ-9   
   
X  
X  
X  
X  
X  
X  
X  
X  
Rapid antibody COVID-19  
  
X  
  
  
  
  
  
  
X  
CBC with differential  
   
X  
   
X  
   
X  
   
   
X  
Chemistry  
   
X  
   
X  
   
X  
   
   
X  
Coagulation Panel  
   
X  
   
X  
   
X  
   
   
X  
CRP  
   
X  
   
X  
   
X  
   
   
X  
IL-6  
   
X  
   
X  
   
X  
   
   
X  
IL-10  
   
X  
   
X  
   
X  
   
   
X  
TNFa  
   
X  
   
X  
   
X  
   
   
X  
HB-adMSCs Administration  
   
X  
X  
X  
X  
X  
   
   
   
24-hour telephone encounter  
   
X  
X  
X  
X  
X  
   
   
   
Adverse Event Monitoring   
   
X  
X  
X  
X  
X  
X  
X  
X  
1. Height will only be measured at baseline  

HB-adMSCs to provide immune support against COVID-19                                                                            
 
 
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Informed Consent (ICF)  
  
Prior to commencement of any trial related activity, the investigator or designated staff will 
obtain written informed consent from the patient.   
  
Patient Re-Screening  
  
If a patient is screened and fails to meet any study entry criteria may be re-screened only 
once. Such patient must be fully consented a second time before the second set of screening 
assessments take place and shall be assigned a new subject number. Investigator discretion 
should be exercised in determining who may be re-screened.  
  
If a patient is enrolled after they have been re-screened, such subject shall be assigned a new 
subject ID number, different from the previous attempt to enroll.  
  
Assessments by Week  
  
Assessments will occur as outlined in the following subsections. For visits at Weeks 0 
through 26, there will be a window of ±3 days.   
  
Screening  
  
The Screening visit will last up to 14 days. These are the procedures to be performed during 
this visit:  
  
● Demographic Information will be obtained.  
● Medical History and Current conditions will be obtained,   
● Concomitant Medications will be obtained. Every medication listed should match a 
condition in the medical history.   
● Ascertain patient eligibility by evaluating patient results against the 
inclusion/exclusion criteria.  
  
Upon completion of all Screening procedures, the Principal Investigator must confirm and 
document the patient eligibility in the “Screening Result” CRF and notify the Sponsor via 
Fax or e-mail.   
  
Infusion Visits (Baseline/Week 0, Week 2, Week 6, Week 10, and Week 14)   
  
Generally, these are the procedures to be performed at every infusion visit. For details please 
refer to the schedule of assessments.   
  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Baseline assessments will be taken before the administration of the first infusion.  A second 
assessment of informed consent shall be obtained prior to the first infusion.  
  
● Pre-infusion assessment will be made by telephone call in the morning prior to all 
infusion visits to assess any occurrence of symptoms.  In the event a subject is 
exhibiting symptoms, the subject will be asked to remain home.   
● Weight and height will be measured 
● Vital Signs will be measured.   
● Concomitant medications will be reviewed and updated if necessary.   
● Medical History will be reviewed and updated if necessary. If the patient reported a 
medication which does not match the current medical history, further investigation 
will be required to determine whether it was added due to an Adverse Event, or the 
patient just forgot to mention it before. If it is found to be an AE, it should be 
recorded in the appropriate CRF. If the patient forgot to mention it before, a note to 
file (NTF) should be made to clarify the case.  
● Blood will be collected for laboratory assessments at weeks 0, 6, and 14.    
● Physical examination performed by principal investigator or sub-investigator.   
● Administer investigational product.  
● Monitor for AEs. Observe the patient for at least 1 hours after infusion for symptoms 
of infusion-related reactions and allergic reactions, including anaphylaxis (See 
Appendix 1).   
● Instruct the patient on recognition of delayed serious allergic reactions, including 
anaphylaxis and seeking for medical assistance.   
● Telephone encounter 24 hours after the infusion will be performed to assess the 
occurrence of AEs.   
  
Follow Up Weeks 18, and 22.   
  
● Weight will be measured  
● Vital Signs will be measured.   
● Concomitant medications will be reviewed and updated if necessary.   
● Medical History will be reviewed and updated if necessary. If the patient reported a 
medication which does not match the current medical history, further investigation 
will be required to determine whether it was an Adverse Event, or the patient just 
forgot to mention it before. If it is found to be an AE, it should be recorded in the 
appropriate CRF. If the patient forgot to mention it before, a note to file (NTF) should 
be made to clarify the case.  
● Physical examination performed by principal investigator or sub-investigator.   
  
Weeks 26 (End of the Study or Early Discontinuation Visit)  
  
● Weight will be measured  
● Vital Signs will be measured.   
● Concomitant medications will be reviewed and updated if necessary.   

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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● Medical History will be reviewed and updated if necessary. If the patient reported a 
medication which does not match the current medical history, further investigation 
will be required to determine whether it was an Adverse Event, or the patient just 
forgot to mention it before. If it is found to be an AE, it should be recorded in the 
appropriate CRF. If the patient forgot to mention it before, a note to file (NTF) should 
be made to clarify the case.  
● Blood samples will be collected.  
● Physical examination performed by principal investigator or sub-investigator.   
  
If a patient prematurely withdraws from the study for any reason, the early 
discontinuation visit requirements should be completed. If the early discontinuation visit 
is not done, the reason(s) will be recorded in the CRF.   
  
Unscheduled Visits  
  
The Investigator may at his/her discretion arrange for a patient to have an unscheduled 
assessment, especially in the case of adverse events (AEs) that require follow-up, or an AE 
considered by the Investigator to be possibly related to the use of the investigational product. 
The unscheduled visit page in the CRF must be completed.   
Efficacy Assessments  
  
Complete Blood Count with Differential  
The evaluation of the Complete Blood count with differential will help suspect the presence 
of a bacterial or viral infection with the predominance of either the neutrophils or 
lymphocytes.  
Generally, a healthy person’s blood count would not show out of range values in the 
differential in the absence of a pathological condition.  
  
CRP  
C-reactive protein is considered to be an "acute phase protein," an early indicator of 
infectious or inflammatory conditions. CRP must be interpreted in the clinical context; no 
single value will be used to rule in or rule out a specific diagnosis.  
  
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, 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.   
  
PHQ-9  
The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" 
(not at all) to "3" (nearly every day). It is not a screening tool for depression, but it is used to 

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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monitor the severity of depression. In addition to making criteria-based diagnoses of 
depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity.   
  
TNF-a  
The primary role of TNF is in the regulation of immune cells. TNF, being an endogenous 
pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit 
tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells.  
  
IL-6   
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an 
antiinflammatory cytokine. In humans, it is encoded by the IL6 gene.   
  
IL-10  
IL-10 is a cytokine with multiple effects in immunoregulation and inflammation. It 
downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory 
molecules on macrophages. It also enhances B cell survival, proliferation, and antibody 
production.  
Safety Assessments  
  
Safety assessments (vital signs, weight, physical examinations, AEs, routine clinical 
laboratory tests (CBC, CMP, PT and PTT/INR) will be performed at the visits specified in 
the schedule of assessments in Table 2.  
  
Vital Signs, Height, and Weight   
  
Vital signs (body temperature, pulse, oxygen saturation, systolic and diastolic blood pressure 
measurements) will be evaluated at the visits indicated in the schedule of assessments. It is 
important that all vital signs be measured after the patient has been resting in a sitting 
position for at least 5 minutes. Blood pressure measurements are to be taken in the same arm 
for the duration of the study. Body weight (without coats and shoes) will be recorded 
whenever vital signs are recorded, and height (without shoes) will be recorded at Infusion 1 
(baseline) only.   
  
Vital sign measurements will be repeated if clinically significant or machine/equipment 
errors occur. Out-of-range blood pressure and pulse measurements will be repeated at the 
Investigator’s discretion. Any confirmed, clinically significant vital sign measurements will 
be recorded as AEs and followed up as such.   
  
 
 
 

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Physical Examination   
  
A complete physical examination (head, eyes, ears, nose, throat, heart, lungs, abdomen, skin, 
cervical and axillary lymph nodes, neurological, and musculoskeletal systems) will be 
performed at Infusion 1 (Baseline).   
  
A limited physical examination to verify continued patient eligibility and to follow up any 
change in medical history will be performed at the visits indicated in the schedule of 
assessments. Symptom-driven physical examinations will be performed as clinically 
indicated at any study visit. All changes not present at baseline or described in the past 
medical history and identified as clinically noteworthy will be recorded as AEs.   
  
Clinical Laboratory Parameters   
  
The Investigator must review all laboratory reports and document the review. Any laboratory 
test result or change considered by the Investigator to be clinically significant should be 
considered an AE and recorded in the AE CRF. Clinically significant abnormal values 
occurring during the study will be followed until repeat test results return to normal, 
stabilize, or are no longer clinically significant.   
  
Laboratory tests to be performed during the study:  
  
Complete Blood Count with Differential  
Il-10  
Chemistry  
IL-6  
Coagulation study (PTT/PT/INR)      
Tumor Necrosis Factor alpha  
C Reactive Protein  
Rapid Antibody Test COVID-19  
  
Adverse Events  
  
An AE is any symptom, physical sign or disease that either emerges during the study or, if 
present at screening, worsens during the study, regardless of the suspected cause of the event. 
All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented in the medical history CRF. Changes in these 
conditions and new symptoms, physical signs, or diseases should be noted on the AE CRF 
during the rest of the study.   
  
Clinically significant laboratory abnormalities should also be recorded as AEs. Surgical 
procedures that were planned before the patient enrolled in the study are not considered AEs 
if the conditions were known before study inclusion; the medical condition should be 
reported in the patient’s medical history.   
  

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Serious Adverse Events (SAE)  
  
A serious adverse event (SAE) is any AE that is:   
- 
fatal  
- 
life-threatening  
- 
requires or prolongs hospital stay  
- 
results in persistent or significant disability or incapacity  
- 
Important Medical Events (IME): those events that may not result in death, be 
immediately life threatening, or require hospitalization. They may be considered a 
SAE when, based upon medical judgement, they may jeopardize the subject and may 
require intervention to prevent one of the other serious outcomes noted above.  For 
example, drug overdose or abuse, a seizure that did not result in in-patient 
hospitalization, or intensive treatment of bronchospasm in an emergency department 
would typically be considered serious. (FDA, 21CFR312.32; ICH E2A and ICH E6)  
  
All SAEs must be reported to Hope Biosciences immediately after the Investigator becomes 
aware of the event, along with a determination as to whether it is associated with the study 
drug.  Patients will be instructed to report AEs at each study visit. All AEs are to be followed 
until resolution or until a stable clinical endpoint is reached.   
Each AE is to be documented in the CRF with reference to onset date, duration, frequency, 
severity, relationship to study drug, treatment of event, and outcome. Furthermore, each AE 
is to be classified as being serious or non-serious. Changes in AEs and resolution dates are to 
be documented in the CRF.   
  
For the purposes of this study, the period of observation for collection of AEs extends from 
the time the patient gives informed consent through Week 26 (or early discontinuation visit). 
Follow-up of the AE is required until the event resolves or stabilizes at a level acceptable to 
the Investigator.  
  
Intensity of Adverse Event  
  
The intensity of the AE will be judged based on the following:  
  
Mild   
Awareness of sign(s) or symptom(s) which is/are easily tolerated  
Moderate   
Enough discomfort to cause interference with usual activity  
Severe   
Incapacitating or causing inability to work or to perform usual activities  
  
Infusion Stopping Rules  
  
Infusion will be stopped when:  
  
• 
Allergic reaction is aroused after the product has been administered intravenously.  
• 
Patient verbally decline the treatment at any moment prior, or during the infusion.   

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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• 
Hyperpyrexia develops after infusion administration begins (core body temperature 
greater than or equal to 40°C) [57].  
• 
PI may stop the study at any time, based upon PI’s discretion  
• 
Malignant Hypertension (180/120 mm/Hg)  
• 
Sudden Severe Hypotension (30-40 mm/Hg drop from pre-infusion level)  
  
Study Alteration Rules  
  
If any of the following events listed below occur, administration of the study drug will be 
immediately suspended. The Internal Monitoring Committee (IMC), presided by the Medical 
Monitor will meet to review the incident and its etiology. The committee determine if it is 
likely related to the drug, the infusion or unrelated. If the IMC along with the Medical 
Monitor agree that the SAE is unlikely or unrelated to the drug, the study will be continued. 
If the SAE appears to be definitely drug-related, the study will be stopped. If the SAE is 
probably or possibly linked to the drug, the IMC will determine the risk to future patients and 
decide if the study should proceed or be stopped.   
 
Study Stopping Rules  
  
The stopping rules listed below will trigger cessation of enrollment and potential study 
closure pending a comprehensive DSMB safety review.   
  
1. Any infusion related death, deemed by PI to be associated or possibly associated with 
study drug.   
2. Three or more of the same Grade 3 or higher AEs (judged by the investigator, 
medical monitor or sponsor), including infusion site reactions.  
3. Any event which, in the opinion of the investigator, medical monitor or sponsor, 
contraindicates further dosing of additional subjects.  
4. An infusion related, sustained (over 3 minutes) episode of hypoxia (SaO2 of less than 
80%).  
5. Any Grade 4-5 Adverse Event as defined in the NCI CTCAE v4.0 and determined to 
be  temporally related to the HB-adMSC infusion by the Medical Safety Monitor 
and/or DSMB.   
  
After such review, resumption of dosing may be considered, including consideration 
for any prophylactic interventions (e.g. antihistamines or corticosteroids for injection 
site reactions).   
  
Regarding SARS-CoV-2 infection, participants will be monitored for vital signs and physical 
examination at every visit. If the PI suspects possible COVID-19, it is at the PI’s discretion 
to order testing. In the event the participant test results are positive for COVID-19, they will 
be allowed to complete treatment with quarantine site infusion visits only.   
  
 

HB-adMSCs to provide immune support against COVID-19                                                                                 
 
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Protocol Deviations  
  
An Investigator may not knowingly deviate from the study protocol without prior approval 
by Hope Biosciences and/or the IRB unless the deviations are necessary under emergency 
circumstances to protect the rights, safety, or well-being of human subjects or the scientific 
integrity of the clinical investigation. Deviations must be documented and promptly reported 
to Hope Biosciences and, if applicable, to the IRB providing oversight of the study.