Clinical trial NCT04362189: Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19
Official title: A Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus
Stem cells
Mesenchymal stem cells
Adipose-derived mesenchymal stem cells
MSCs
COVID
SARS-CoV-2
Coronavirus disease
Lead sponsor: Hope Biosciences
Sponsor class: INDUSTRY
Collaborators: name: River Oaks Hospital and Clinics
name: Hope Biosciences
name: United Memorial Medical Center
First posted: 2020-04-24
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

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.

Primary outcomes:
measure: Tumor Necrosis Factor-Alpha (TNF-alpha)
timeFrame: Day 0, 3, 7, and 10
measure: Interleukin-10 (IL-10)
timeFrame: Day 0, 3, 7, and 10
measure: Interleukin-6 (IL-6)
timeFrame: Day 0, 3, 7, and 10
measure: C-Reactive Protein (CRP)
timeFrame: Day 0, 3, 7, and 10
measure: Oxygenation
timeFrame: Day 0, 3, 7, and 10
measure: Return To Room Air (RTRA)
timeFrame: Day 0, 3, 7, and 10
Secondary outcomes:
measure: D-dimer
timeFrame: Day 0, 3, 7, and Day 10
measure: Myoglobin
timeFrame: Day 0, 3 7, and 10
measure: Troponin
timeFrame: Day 0, 3, 7, and 10
measure: Creatinine Kinase MB (CK-MB)
timeFrame: Day 0, 3, 7, and 10
measure: Serum Ferritin
timeFrame: Day 0, 3, 7, and 10
measure: NK Cell Surface Antigen (CD3-CD56+)
timeFrame: Day 0, 3, 7, and 10
measure: CD4+/CD8+ Ratio
timeFrame: Day 0, 3, 7, and 10
measure: 7-Point Ordinal Scale
timeFrame: Day 0, 3, 7, 10, and 28 (End of Study)
measure: Computed Tomography (CT) Score
timeFrame: Day 0 and Day 28
measure: Chest X-Ray Score
timeFrame: Day 0, Day 28
measure: Glucose
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Blood Urea Nitrogen (BUN)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Estimated Glomerular Filtration Rate (eGFR) if Non-African American
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Estimated Glomerular Filtration Rate (eGFR) if African American
timeFrame: Screening, Day 0, 3, 7, and 10
measure: BUN/Creatinine Ratio
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Sodium
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Potassium
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Chloride
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Carbon Dioxide Total
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Calcium
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Protein Total
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Albumin
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Globulin Total
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Albumin/Globulin (A/G) Ratio
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Bilirubin Total
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Alkaline Phosphatase
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Aspartate Aminotransferase (SGOT)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Alanine Aminotransferase (SGPT)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: White Blood Count (WBC)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Red Blood Cell (RBC) Count
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Hemoglobin
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Hematocrit
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Mean Corpuscular Volume (MCV)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Mean Corpuscular Hemoglobin (MCH)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Mean Corpuscular Hemoglobin Concentration (MCHC)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Red Cell Distribution Width (RDW)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Platelets
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Neutrophils
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Lymphocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Monocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Eosinophils
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Basophils
timeFrame: Screening, Day 0, 3, 7 and 10
measure: Absolute Neutrophils
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Absolute Lymphocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Absolute Monocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Absolute Eosinophils
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Absolute Basophils
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Immature Granulocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Absolute Immature Granulocytes
timeFrame: Screening, Day 0, 3, 7, and 10
measure: International Normalized Ratio (INR)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Prothrombin Time (PT)
timeFrame: Screening, Day 0, 3, 7, and 10
measure: Partial Thromboplastin Time (PTT)
timeFrame: Screening, Day 0, 3, 7, and 10
Other outcomes:
Locations:
city: Houston
country: United States
facility: River Oaks Hospital and Clinics
state: Texas
city: Houston
country: United States
facility: United Memorial Medical Center
state: Texas
Study officials:
affiliation: River Oaks Hospital and Clinics
name: Rajiv Thakur, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: United Memorial Medical Center
name: Joseph Gathe, MD
role: PRINCIPAL_INVESTIGATOR
References: