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

Phase 2

Terminated

• Conditions: COVID-19
• Interventions: Biological: HB-adMSC; Other: Placebo

• Registration Number: NCT04362189
• Lead Sponsor: Hope Biosciences Stem Cell Research Foundation

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-04-21
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-24
• Study Start: 2020-06-30
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30
• Results First Submitted: 2023-06-07
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-04
• Last Update Submitted: 2023-07-04
• Results First Posted: 2023-07-25
• Last Update Posted: 2023-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Men, and women, over 18 years of age inclusively.
2. Patient is suspected to have COVID-19 infection.
3. Provides consent or consent is given by their legally authorized representative (LAR).
4. Agrees to the collection of venous blood per protocol.
5. 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).

Read More

Exclusion Criteria

1. 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.

2. 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.

3. Inability to provide informed consent or to comply with study requirements.

4. 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.

5. History or evidence of alcohol abuse.

6. History or evidence of consumption of illicit drugs.

7. Patients requiring mechanical ventilation.

8. Patients who are determined by the Principal Investigator to be unsuitable for study enrollment for other reasons.

9. 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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HB-adMSCs	HB-adMSC	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.
Placebo	Placebo	Subjects assigned to this arm will receive 4 intravenous infusions of placebo (saline solution). Infusions will occur at day 0, 3, 7, and 10.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Sodium	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Sodium in the blood (mmol/L)
Potassium	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Potassium in the blood (mmol/L)
CD4+/CD8+ Ratio	Day 0, 3, 7, and 10	Clinical lab evaluation of Ratio of CD4+/CD8+ Cells in the blood
7-Point Ordinal Scale	Day 0, 3, 7, 10, and 28 (End of Study)	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.
Calcium	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Calcium in the blood (mg/dL)
Red Blood Cell (RBC) Count	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Red Blood Cell (RBC) Count in the blood (cells x 10\^3/uL)
Hemoglobin	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Hemoglobin in the blood (g/dL)
Mean Corpuscular Volume (MCV)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Mean Corpuscular Volume (MCV) in the blood (fL)
Platelets	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Platelets in the blood (cells x10\^3/uL)
Eosinophils	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Eosinophils n the blood (%)
Absolute Neutrophils	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Neutrophils in the blood (cells x10\^3/uL)
Absolute Monocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Monocytes in the blood (cells x10\^3/uL)
Blood Urea Nitrogen (BUN)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Blood Urea Nitrogen (BUN) (mg/dL)
Chloride	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Chloride in the blood (mmol/L)
Protein Total	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of total level of Protein in the blood (g/dL)
Albumin	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Albumin in the blood (g/dL)
Albumin/Globulin (A/G) Ratio	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Albumin/Globulin (A/G) Ratio in the blood
Prothrombin Time (PT)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Prothrombin Time (seconds)
D-dimer	Day 0, 3, 7, and Day 10	Change from baseline in D-dimer in the blood (mg/L)
Myoglobin	Day 0, 3 7, and 10	Clinical lab evaluation of level of Myoglobin in the blood (ng/mL)
Troponin	Day 0, 3, 7, and 10	Clinical lab evaluation of level of Troponin in the blood (ng/mL)
Serum Ferritin	Day 0, 3, 7, and 10	Clinical lab evaluation of level of Serum Ferritin in the blood (ng/mL)
Computed Tomography (CT) Score	Day 0 and Day 28	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.
Glucose	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Glucose in the blood (mg/dL)
Creatinine Kinase MB (CK-MB)	Day 0, 3, 7, and 10	Clinical lab evaluation of level of Creatinine Kinase (CK-MB) in the blood (ng/mL)
NK Cell Surface Antigen (CD3-CD56+)	Day 0, 3, 7, and 10	Clinical lab evaluation of Percentage of Cells CD3-CD56+ in the blood (%)
Chest X-Ray Score	Day 0, Day 28	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.
Estimated Glomerular Filtration Rate (eGFR) if African American	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Estimated glomerular filtration rate (eGFR) If African American in the blood (mL/min/1.73)
BUN/Creatinine Ratio	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of BUN/Creatinine Ratio in the blood
Carbon Dioxide Total	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of total level of Carbon Dioxide in the blood (mmol/L)
Bilirubin Total	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of the total level of Bilirubin in the blood (mg/dL)
Hematocrit	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Hematocrit in the blood (%)
Mean Corpuscular Hemoglobin Concentration (MCHC)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Mean Corpuscular Hemoglobin Concentration (MCHC) in the blood (g/dL)
Red Cell Distribution Width (RDW)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Red Cell Distribution Width (RDW) in the blood (%)
Lymphocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Lymphocytes in the blood (%)
Absolute Basophils	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Basophils in the blood (cells x10\^3/uL)
Estimated Glomerular Filtration Rate (eGFR) if Non-African American	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Estimated glomerular filtration rate (eGFR) if Non-African American in the blood (mL/min/1.73)
Globulin Total	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of the total level of Globulin in the blood (g/dL)
Alkaline Phosphatase	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Alkaline Phosphatase in the blood (IU/L)
Alanine Aminotransferase (SGPT)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Alanine aminotransferase (SGPT) in the blood (IU/L)
White Blood Count (WBC)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of count of White Blood Cells (WBCs) in the blood (x10\^3/uL)
Mean Corpuscular Hemoglobin (MCH)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Mean Corpuscular Hemoglobin (MCH) in the blood (pg)
Neutrophils	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Neutrophils in the blood (%)
Aspartate Aminotransferase (SGOT)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Aspartate aminotransferase (SGOT) in the blood (IU/L)
Monocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Monocytes in the blood (%)
Basophils	Screening, Day 0, 3, 7 and 10	Clinical lab evaluation of level of Basophils in the blood (%)
Absolute Lymphocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Lymphocytes in the blood (cells x10\^3/uL)
Absolute Eosinophils	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Eosinophils in the blood (cells x10\^3/uL)
Immature Granulocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Immature Granulocytes in the blood (%)
Absolute Immature Granulocytes	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of level of Absolute Immature Granulocytes in the blood (cells x10\^3/uL)
International Normalized Ratio (INR)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of International Normalized Ratio (INR)
Partial Thromboplastin Time (PTT)	Screening, Day 0, 3, 7, and 10	Clinical lab evaluation of Partial Thromboplastin Time (PTT) (seconds)

Trial Locations

Locations (2)

River Oaks Hospital and Clinics; 🇺🇸 Houston, Texas, United States

United Memorial Medical Center; 🇺🇸 Houston, Texas, United States