Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19

Study Overview
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Brief Summary
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Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.

Detailed Description
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This is a Phase II, Randomized, Placebo-Controlled, Double-Blinded, Clinical Trial to Assess Efficacy of HB-adMSCs to treat COVID-19 patients. 100 patients will be enrolled. Eligible participants are suspected to have COVID-19 and consent to participate. The primary endpoints of this study are to detect change from baseline in inflammatory markers (IL-6, IL-10, TNF-alpha, C Reactive protein), improving oxygenation, and decreasing time to return to room air (RTRA). In addition, participants will be monitored for overall clinical status by standard clinical laboratories, change from baseline in exploratory markers (D-dimer, myoglobin, troponin, creatinine kinase MB, serum ferritin, CD4:CD8 ratio, CD3-CD56+), time to negative PCR results and clinical improvement according to 7-point ordinal scale, as well as incidence of adverse events.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: HB-adMSC
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men, and women, over 18 years of age inclusively. Patient is suspected to have COVID-19 infection. Provides consent or consent is given by their legally authorized representative (LAR). Agrees to the collection of venous blood per protocol. Women of childbearing potential (WOCBP) and men (if their sexual partners are WOCBP) must use at least 1 highly effective form of birth control throughout the study and for 6 months after the last dose of study treatment. Highly effective methods of birth control include true sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk, in line with the preferred and usual lifestyle of the patient), surgery (bilateral tubal ligation or occlusion, vasectomized partner), progestogen-only or estrogen/progestogen hormonal contraceptive associated with inhibition of ovulation (oral, patch, injectable, implantable, or intravaginal), intrauterine device (IUD), or intrauterine hormone-releasing system (IUS). Exclusion Criteria: Pregnancy, lactation and those who are not pregnant but do not take effective contraceptive measures, in women of childbearing age. Absence of pregnancy will be confirmed through urine pregnancy test. Patients who have participated or are participating in a clinical trial of an experimental vaccine for SARS-CoV-2 or coronavirus during the study or within 30 days. Inability to provide informed consent or to comply with study requirements. Patients with the following concomitant or past medical history: Both Hypertension and Diabetes Mellitus. Both Hypertension and Chronic Kidney Disease. Both Diabetes Mellitus and Chronic Kidney Disease. History or evidence of alcohol abuse. History or evidence of consumption of illicit drugs. Patients requiring mechanical ventilation. Patients who are determined by the Principal Investigator to be unsuitable for study enrollment for other reasons. Any medical disease or condition that, in the opinion of the site Principal Investigator 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.
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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HB-adMSCs<br>Subjects assigned to this arm will receive 4 intravenous infusions of HB-adMSCs at 100 million cells/dose. HB-adMSC infusions will occur at day 0, 3, 7, and 10. | Biological: HB-adMSC<br>* Hope Biosciences allogeneic adipose-derived mesenchymal stem cells<br>|
| Placebo Comparator: Placebo<br>Subjects assigned to this arm will receive 4 intravenous infusions of placebo (saline solution). Infusions will occur at day 0, 3, 7, and 10. | Other: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Necrosis Factor-Alpha (TNF-alpha) | Change from baseline in Tumor Necrosis Factor-Alpha (TNF-alpha) in the blood (pg/mL) | Day 0, 3, 7, and 10 | 
| Interleukin-10 (IL-10) | Change from baseline level of Interleukin-10 (IL-10) in the blood (pg/mL) | Day 0, 3, 7, and 10 | 
| Interleukin-6 (IL-6) | Change from baseline in Interleukin-6 (IL-6) in the blood (pg/mL) | Day 0, 3, 7, and 10 | 
| C-Reactive Protein (CRP) | Change from baseline in C-Reactive Protein (CRP) in the blood (mg/L) | Day 0, 3, 7, and 10 | 
| Oxygenation | Change from baseline Oxygenation (%) in the blood | Day 0, 3, 7, and 10 | 
| Return To Room Air (RTRA) | Number of participants who returned to room air | Day 0, 3, 7, and 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| D-dimer | Change from baseline in D-dimer in the blood (mg/L) | Day 0, 3, 7, and Day 10 | 
| Myoglobin | Clinical lab evaluation of level of Myoglobin in the blood (ng/mL) | Day 0, 3 7, and 10 | 
| Troponin | Clinical lab evaluation of level of Troponin in the blood (ng/mL) | Day 0, 3, 7, and 10 | 
| Creatinine Kinase MB (CK-MB) | Clinical lab evaluation of level of Creatinine Kinase (CK-MB) in the blood (ng/mL) | Day 0, 3, 7, and 10 | 
| Serum Ferritin | Clinical lab evaluation of level of Serum Ferritin in the blood (ng/mL) | Day 0, 3, 7, and 10 | 
| NK Cell Surface Antigen (CD3-CD56+) | Clinical lab evaluation of Percentage of Cells CD3-CD56+ in the blood (%) | Day 0, 3, 7, and 10 | 
| CD4+/CD8+ Ratio | Clinical lab evaluation of Ratio of CD4+/CD8+ Cells in the blood | Day 0, 3, 7, and 10 | 
| 7-Point Ordinal Scale | Change from baseline in Ordinal scale score. Scale of 1-7. A score of 1 indicates Death and 7 indicates Subject is not Hospitalized and has no Limitations on activities. | Day 0, 3, 7, 10, and 28 (End of Study) | 
| Computed Tomography (CT) Score | Change from baseline Computed Tomography (CT) Scan Score. A semi-quantitative CT severity scoring was calculated per each of the 5 lobes considering the extent of anatomic involvement: 0, no involvement; 1, < 5% involvement; 2, 5-25% involvement; 3, 26-50% involvement; 4, 51-75% involvement; and 5, > 75% involvement. The resulting global CT score was the sum of each individual lobar score and (0 - no involvement to 25 - maximum involvement). Lower score is better. | Day 0 and Day 28 | 
| Chest X-Ray Score | Change from baseline in Chest X-Ray Score. Scoring was calculated per each of the 5 lobes considering the extent of anatomic involvement: 0, no involvement; 1, < 5% involvement; 2, 5-25% involvement; 3, 26-50% involvement; 4, 51-75% involvement; and 5, > 75% involvement. The resulting score was the sum of each individual lobar score and (0 - no involvement to 25 - maximum involvement). Lower score is better. | Day 0, Day 28 | 
| Glucose | Clinical lab evaluation of level of Glucose in the blood (mg/dL) | Screening, Day 0, 3, 7, and 10 | 
| Blood Urea Nitrogen (BUN) | Clinical lab evaluation of level of Blood Urea Nitrogen (BUN) (mg/dL) | Screening, Day 0, 3, 7, and 10 | 
| Estimated Glomerular Filtration Rate (eGFR) if Non-African American | Clinical lab evaluation of level of Estimated glomerular filtration rate (eGFR) if Non-African American in the blood (mL/min/1.73) | Screening, Day 0, 3, 7, and 10 | 
| Estimated Glomerular Filtration Rate (eGFR) if African American | Clinical lab evaluation of level of Estimated glomerular filtration rate (eGFR) If African American in the blood (mL/min/1.73) | Screening, Day 0, 3, 7, and 10 | 
| BUN/Creatinine Ratio | Clinical lab evaluation of BUN/Creatinine Ratio in the blood | Screening, Day 0, 3, 7, and 10 | 
| Sodium | Clinical lab evaluation of level of Sodium in the blood (mmol/L) | Screening, Day 0, 3, 7, and 10 | 
| Potassium | Clinical lab evaluation of level of Potassium in the blood (mmol/L) | Screening, Day 0, 3, 7, and 10 | 
| Chloride | Clinical lab evaluation of level of Chloride in the blood (mmol/L) | Screening, Day 0, 3, 7, and 10 | 
| Carbon Dioxide Total | Clinical lab evaluation of total level of Carbon Dioxide in the blood (mmol/L) | Screening, Day 0, 3, 7, and 10 | 
| Calcium | Clinical lab evaluation of level of Calcium in the blood (mg/dL) | Screening, Day 0, 3, 7, and 10 | 
| Protein Total | Clinical lab evaluation of total level of Protein in the blood (g/dL) | Screening, Day 0, 3, 7, and 10 | 
| Albumin | Clinical lab evaluation of level of Albumin in the blood (g/dL) | Screening, Day 0, 3, 7, and 10 | 
| Globulin Total | Clinical lab evaluation of the total level of Globulin in the blood (g/dL) | Screening, Day 0, 3, 7, and 10 | 
| Albumin/Globulin (A/G) Ratio | Clinical lab evaluation of Albumin/Globulin (A/G) Ratio in the blood | Screening, Day 0, 3, 7, and 10 | 
| Bilirubin Total | Clinical lab evaluation of the total level of Bilirubin in the blood (mg/dL) | Screening, Day 0, 3, 7, and 10 | 
| Alkaline Phosphatase | Clinical lab evaluation of level of Alkaline Phosphatase in the blood (IU/L) | Screening, Day 0, 3, 7, and 10 | 
| Aspartate Aminotransferase (SGOT) | Clinical lab evaluation of level of Aspartate aminotransferase (SGOT) in the blood (IU/L) | Screening, Day 0, 3, 7, and 10 | 
| Alanine Aminotransferase (SGPT) | Clinical lab evaluation of level of Alanine aminotransferase (SGPT) in the blood (IU/L) | Screening, Day 0, 3, 7, and 10 | 
| White Blood Count (WBC) | Clinical lab evaluation of count of White Blood Cells (WBCs) in the blood (x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Red Blood Cell (RBC) Count | Clinical lab evaluation of Red Blood Cell (RBC) Count in the blood (cells x 10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Hemoglobin | Clinical lab evaluation of level of Hemoglobin in the blood (g/dL) | Screening, Day 0, 3, 7, and 10 | 
| Hematocrit | Clinical lab evaluation of level of Hematocrit in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Mean Corpuscular Volume (MCV) | Clinical lab evaluation of level of Mean Corpuscular Volume (MCV) in the blood (fL) | Screening, Day 0, 3, 7, and 10 | 
| Mean Corpuscular Hemoglobin (MCH) | Clinical lab evaluation of level of Mean Corpuscular Hemoglobin (MCH) in the blood (pg) | Screening, Day 0, 3, 7, and 10 | 
| Mean Corpuscular Hemoglobin Concentration (MCHC) | Clinical lab evaluation of Mean Corpuscular Hemoglobin Concentration (MCHC) in the blood (g/dL) | Screening, Day 0, 3, 7, and 10 | 
| Red Cell Distribution Width (RDW) | Clinical lab evaluation of Red Cell Distribution Width (RDW) in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Platelets | Clinical lab evaluation of level of Platelets in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Neutrophils | Clinical lab evaluation of level of Neutrophils in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Lymphocytes | Clinical lab evaluation of level of Lymphocytes in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Monocytes | Clinical lab evaluation of level of Monocytes in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Eosinophils | Clinical lab evaluation of level of Eosinophils n the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Basophils | Clinical lab evaluation of level of Basophils in the blood (%) | Screening, Day 0, 3, 7 and 10 | 
| Absolute Neutrophils | Clinical lab evaluation of level of Absolute Neutrophils in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Absolute Lymphocytes | Clinical lab evaluation of level of Absolute Lymphocytes in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Absolute Monocytes | Clinical lab evaluation of level of Absolute Monocytes in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Absolute Eosinophils | Clinical lab evaluation of level of Absolute Eosinophils in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Absolute Basophils | Clinical lab evaluation of level of Absolute Basophils in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| Immature Granulocytes | Clinical lab evaluation of level of Immature Granulocytes in the blood (%) | Screening, Day 0, 3, 7, and 10 | 
| Absolute Immature Granulocytes | Clinical lab evaluation of level of Absolute Immature Granulocytes in the blood (cells x10^3/uL) | Screening, Day 0, 3, 7, and 10 | 
| International Normalized Ratio (INR) | Clinical lab evaluation of International Normalized Ratio (INR) | Screening, Day 0, 3, 7, and 10 | 
| Prothrombin Time (PT) | Clinical lab evaluation of Prothrombin Time (seconds) | Screening, Day 0, 3, 7, and 10 | 
| Partial Thromboplastin Time (PTT) | Clinical lab evaluation of Partial Thromboplastin Time (PTT) (seconds) | Screening, Day 0, 3, 7, and 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus, Stem cells, Mesenchymal stem cells, Adipose-derived mesenchymal stem cells, MSCs, COVID, SARS-CoV-2, Coronavirus disease