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

• ClinicalTrials.gov Identifier: NCT04362189
• Recruitment Status: Terminated
• First Posted: April 24, 2020
• Last Update Posted: February 7, 2022
• Sponsor: Hope Biosciences Stem Cell Research Foundation
• Collaborators: Advanced Diagnostics Healthcare; Hope Biosciences; United Memorial Medical Center
• Information provided by (Responsible Party): Hope Biosciences ( Hope Biosciences Stem Cell Research Foundation )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: HB-adMSC; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19
• Actual Study Start Date: June 30, 2020
• Actual Primary Completion Date: September 30, 2021
• Actual Study Completion Date: September 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HB-adMSCs; 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; Hope Biosciences allogeneic adipose-derived mesenchymal stem cells
Placebo Comparator: 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.	Other: Placebo; Saline

Outcome Measures

Primary Outcome Measures :

1. Interleukin-6 [ Time Frame: screening, day 0, 7, 10 ]
   change from baseline in interleukin-6
2. C Reactive protein [ Time Frame: screening, day 0, 7, 10 ]
   Change from baseline in C Reactive protein
3. Oxygenation [ Time Frame: screening, day 0, 7, 10 ]
   change from baseline oxygenation (%)
4. TNF alpha [ Time Frame: screening, day 0, 7, 10 ]
   change from baseline in TNF alpha
5. IL-10 [ Time Frame: screening, day 0, 7. 10 ]
   change from baseline level of IL-10 in the blood (pg/mL)
6. Return to room air (RTRA) [ Time Frame: Day 0, 3, 7, 10, 28 ]
   Time to return to room air

Secondary Outcome Measures :

1. EKG qt interval [ Time Frame: screening, day 0, 3, 7, 10 ]
   Monitoring for changes in qt interval
2. Leukocyte differential [ Time Frame: screening, day 0, 7, 10 ]
   change from baseline in leukocyte differential
3. Glucose [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of glucose in the blood (mg/dL)
4. Calcium [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of calcium in the blood (mg/dL)
5. Albumin [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of albumin in the blood (g/dL)
6. Total protein [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of total protein in the blood (g/dL)
7. Sodium [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of sodium in the blood (mol/L)
8. Total carbon dioxide [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)
9. Potassium [ Time Frame: screening, day 0, 7, 10 ]
   clinical lab evaluation of level of potassium in the blood (mmol/L)
10. Chloride [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of chloride in the blood (mmol/L)
11. BUN [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of BUN in the blood (mg/dL)
12. Creatinine [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of creatinine in the blood (mg/dL)
13. Alkaline phosphatase [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)
14. Alanine aminotransferase [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)
15. Total bilirubin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of total bilirubin in the blood (mg/dL)
16. White blood cells [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)
17. Red blood cells [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)
18. Hemoglobin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of hemoglobin in the blood (g/dL)
19. Hematocrit [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of hematocrit in the blood (%)
20. Mean corpuscular volume [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of mean corpuscular volume in the blood (fL)
21. Mean corpuscular hemoglobin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)
22. Mean corpuscular hemoglobin concentration [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)
23. Red cell distribution width [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of red cell distribution width in the blood (%)
24. Neutrophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of neutrophils in the blood (%)
25. Lymphs [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of lymphocytes in the blood (%)
26. Monocytes [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of monocytes in the blood (%)
27. Eosinophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of eosinophils in the blood (%)
28. Basophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of basophils in the blood (%)
29. Absolute neutrophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)
30. Absolute lymphs [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)
31. Absolute monocytes [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)
32. Absolute eosinophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)
33. Absolute basophils [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)
34. Immature granulocytes [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)
35. Platelets [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of platelets in the blood (x10^3/uL)
36. Prothrombin time [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of time for blood to coagulate (seconds)
37. INR [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of international normalized ratio of blood coagulation (no unit)
38. NK cell surface antigen (CD3-CD54+) [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of percentage of cells CD3- and CD54+ (%)
39. CD4+/CD8+ ratio [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)
40. Myoglobin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of myoglobin in the blood (ng/mL)
41. Troponin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of myoglobin in the blood (ng/mL)
42. Creatinine kinase MB [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of creatinine kinase in the blood (U/L)
43. Serum ferritin [ Time Frame: screening, day 0, 7, 10 ]
    clinical lab evaluation of level of serum ferritin in the blood (ng/mL)
44. Adverse events [ Time Frame: screening through day 28 ]
    incidence of adverse events
45. 7-point ordinal scale [ Time Frame: screening, day 0, 3, 7, 10, 28 ]
    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.
46. D-dimer [ Time Frame: screening, day 0, 7, 10 ]
    change from baseline in D-dimer
47. Chest X-ray [ Time Frame: Day 0, Day 28 ]
    change from baseline chest x-ray result
48. CT scan [ Time Frame: Day 0, Day 28 ]
    change from baseline CT scan result
49. PCR test for SARS-CoV-2 [ Time Frame: day 0, 3, 7, 10 ]
    time to achieve negative PCR test results

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men, and women, over 18 years of age inclusively
• Patient is hospitalized due to suspected COVID-19 infection
• Agrees to the collection of venous blood per protocol

Exclusion Criteria:

• Pregnancy, lactation and 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.
• Acute intercurrent infections such as Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Syphilis.
• 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.
• Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study.

Contacts and Locations

Locations

United States, Texas

River Oaks Hospital and Clinics

Houston, Texas, United States, 77027

United Memorial Medical Center

Houston, Texas, United States, 77091

Sponsors and Collaborators

Hope Biosciences Stem Cell Research Foundation

Advanced Diagnostics Healthcare

Hope Biosciences

United Memorial Medical Center

Investigators

• Principal Investigator: Rajiv Thakur, MD; Advanced Diagnostics Healthcare

More Information

• Responsible Party: Hope Biosciences Stem Cell Research Foundation
• ClinicalTrials.gov Identifier: NCT04362189
• Other Study ID Numbers: HBCOV03
• First Posted: April 24, 2020
• Last Update Posted: February 7, 2022
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hope Biosciences ( Hope Biosciences Stem Cell Research Foundation ):

Coronavirus; Stem cells; Mesenchymal stem cells; Adipose-derived mesenchymal stem cells

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases