Randomized Double-Blind Phase 2 Study of Allogeneic HB-adMSCs for the Treatment of Chronic Post-COVID-19 Syndrome

Exclusion Criteria

• •A study participant will not be eligible for inclusion in this clinical trial if any of the following criteria apply:
• •1. The subject is unable to provide informed consent or to comply with study requirements.
• •2. A study participant has currently been diagnosed with active COVID-19 disease, defined as ongoing symptoms related to acute infection (such as fever or chills, cough, shortness of breath, or difficulty breathing, among other symptoms), and evidence of a positive RT-PCR SARS- CoV-2.
• •3. The subject is unwilling to agree to the use of acceptable methods of contraception \* throughout the study and for six months after the last dose of the investigational product.
• •4. Pregnancy, lactation. Women of childbearing age who are not pregnant but do not take adequate contraceptive measures. \*
• •5. The study participant has a history of addiction or dependency, or he or she is currently abusing or using substances.
• •6. Study participant has any active malignancy, including but not limited to evidence of cutaneous basal, squamous cell carcinoma, or melanoma.
• •7. The study participant has one or more significant concurrent medical conditions (verified by medical records), including the following:
• •* Diabetes Mellitus (DM) Poorly controlled diabetes mellitus (PCDM), defined as a history of deficient standard of care treatment or pre-prandial glucose \>130mg/dl during screening visit or post-prandial glucose \>200mg/dl.
• •* Chronic kidney disease (CKD): Medical History of Chronic kidney disease (CKD) diagnosis or screening results of eGFR \< 59mL/min/1.73m2. Subjects with any form of kidney dialysis will be excluded from participation in this clinical trial.
• •* Heart Failure Presence of New York Heart Association (NYHA) Class III/IV heart failure during the screening visit.
• •* Myocardial Infarction: Medical history of myocardial infarction in any of the different types, such as ST-elevation myocardial infarction (STEMI) or non-ST-elevated myocardial infarction (NSTEMI), coronary spasm, or unstable angina.
• •* High Blood Pressure: Medical history of uncontrolled high blood pressure is defined as a deficient standard of care treatment or blood pressure \> 140/90 mm/Hg during the screening visit in a patient taking anti-hypertensive treatment. At screening visit, all patients must have a blood pressure \<140/90 mmHg.
• •* Other diseases: Medical history of inherited thrombophilias, cancer of the lung, brain, lymphatic, gynecologic system (ovary or uterus), or gastrointestinal tract (like pancreas or stomach).
• •* Other conditions: Lower extremity paralysis due to spinal cord injury, fracture of the pelvis, hips or femur or recent major general surgery (within 12 months before the Screening).
• •8. Study participant has received any stem cell treatment within 12 months before the first dose of the investigational product other than stem cells produced by Hope Biosciences.
• •9. The study participant has received an experimental drug within 12 months before the first dose of the investigational product. (Except for COVID-19 vaccinations)
• •10. Study participant has a laboratory abnormality during screening, including the following:
• •* White blood cell count WBC \< 3.0 K/UL and \> 12.0 K/UL
• •* Platelet count \< 80 K/UL and or \> 450 K/UL
• •* Absolute neutrophil count \< 1.50 K/UL and or \> 7.50 K/UL
• •* Alanine aminotransferase (ALT) of \> 75 U/L
• •* Aspartate aminotransferase (AST) of \> 75 U/L
• •* Hemoglobin (Hgb) \<11 G/DL or \>18 G/DL
• •* Hematocrit (HCT) \<33% or \>54 %
• •* Mean corpuscular volume (MCV) \< 75 FL or \>100 FL
• •* Mean corpuscular hemoglobin (MCH) \<23 PG or \>36 PG
• •* Mean corpuscular hemoglobin concentration (MCHC) \<30 G/DL or \> 37gG/DL
• •* Red cell distribution width (RDW) \< 10% or \>14%
• •* Abnormal laboratory results considered clinically significant by the principal investigator will exclude patients from participation in this investigation.
• •11. The study participant has any known ongoing infection, including TB, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV, syphilis infections, hepatitis B surface antigen-positive, or hepatitis C PCR positivity.
• •12. The study participant is unlikely to complete the study or adhere to the study procedures.
• •13. The study participant has a previously diagnosed psychiatric condition that may affect self-assessments in the investigator's opinion.
• •14. Study participants with any systemic infection requiring treatment with antibiotics, antivirals, or antifungals within 30 days before the first dose of the investigational product.
• •15. Male study participants expect to donate sperm during the trial or within six months after the last dose. Female patients intend to donate eggs or have IVF treatment during the trial or within six months after the last dose.
• •16. Study participants who the Investigator determines to be unsuitable for study enrollment for other reasons, such as, but not limited to deep vein thrombosis (DVT), pulmonary embolus, those who have a prothrombotic condition, or who require persistent oxygen supplementation.
• •17. The subject has recently been diagnosed with an unstable Chronic obstructive pulmonary disease (COPD) as defined by patients who experience frequent or severe exacerbations and a faster decline in pulmonary function.
• •18. Subjects who have fatigue due to chronic kidney disease, iron deficiency anemia, B12 deficiency and other anemias will be excluded.
• •19. Any participant who has suicidal ideation at the screening visit will be excluded from this clinical trial.
• •20. Subjects with the following diseases must be excluded from participation in the trial.
• •* chronic liver disease
• •* pneumonia
• •* history of chronic fatigue syndrome
• •* subjects with fatigue symptoms due to fibromyalgia, arthritic disorders, inflammatory and rheumatological disorders
• •* respiratory failure
• •* emphysema
• •* uncontrolled asthma
• •* any subject requiring supplemental oxygen for any cause.
• •* Acceptable reversible and permanent methods of birth control include:
• •1\. True sexual abstinence (abstaining from sexual activity during the entire period of risk).
• •2\. Surgery (occlusion bilateral tubal ligation, vasectomized partner). 3. Hormonal contraceptives associated with ovulation inhibition (oral, injectable, implantable patch, or intravaginal). 4. Intrauterine device (IUD), or intrauterine hormone-releasing system (IUS). 5. Condoms.