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

Study Overview
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Brief Summary
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This study will enroll up to 80 subjects with Chronic Post COVID-19 Syndrome. Subjects will receive four intravenous injections of either allogeneic HB-adMSC's or a placebo over 10 weeks with two follow-up visits and an end of study visit at week 26.

Detailed Description
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Active Product: HB- adMSCs (Hope Biosciences adipose-derived mesenchymal stem cells - allogeneic) Dose: 200 million Route: Intravenous Regimen: Weeks 0, 2, 6, and 10. Placebo: Saline Solution 0.9% Dose: N/A Route: Intravenous Regimen: Weeks 0, 2, 6, and 10.Duration of administration 1 hour Laboratory Samples. Screening, Week 0, 6, and 26. Visits by Weeks Screening Week 0 - Infusion 1 Week 2 - Infusion 2 Week 6 - Infusion 3 Week 10 - Infusion 4 Week 14 - Follow Up 1 Week 20 - Follow Up 2 Week 26 - End of Study

Official Title
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A Randomized, Double-blinded, Single-center, Phase 2 Efficacy, and Safety Study of Allogeneic HB-adMSCs for the Treatment of Patients With Chronic Post-COVID-19 Syndrome.

Conditions
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Post COVID-19 Syndrome

Intervention / Treatment
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* Biological: HB-adMSCs (allogeneic)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A study participant will be eligible for inclusion in this study only if all the following criteria apply: 1 Male and female participants 18 - 70 years of age. 2. Participants in the study have proof of Post COVID-19 Syndrome in their medical records. 3. Study participants must have been diagnosed with Chronic post-COVID-19 syndrome for at least twelve weeks before enrollment in the clinical trial. 4. The study participant is experiencing one or more neurological symptoms for at least 12 weeks, either continually or intermittently, with relapses not experienced pre-illness that interferes with regular daily activities. Symptoms must be new symptoms or dramatic worsening of preexisting symptoms, i.e., the subject didn't have symptoms and had not sought medical treatment for the symptoms before COVID-19, or the symptoms are dramatically worse (in severity and frequency). At least one symptom must have a severity of 5cm on the neurological symptom VAS at screening. See the list of symptoms below: Extreme fatigue: Feeling overtired with low energy and a strong desire to sleep. Brain Fog: A diminished mental capacity marked by the inability to concentrate, think or reason clearly interferes with daily activities. Headache: Sharp or dull reoccurring or intermittent that were not present pre-illness. Sleep Issues: Any sleep disturbances in sleep quality that makes sleep seem inadequate or unrefreshing like insomnia or hypersomnia. Loss of Taste/Smell: A diminished sense of taste or smell. 5. Study participants should be able to read, understand, and provide written consent. 6. Female study participants should not be pregnant or plan to become pregnant during study participation and six months after the last investigational product administration. 7. If their sexual partners can become pregnant, male participants should use a method of contraception during study participation and for six months after the last administration of the experimental drug. * 8. The study participant is able and willing to comply with the requirements of this clinical trial. Exclusion Criteria: A study participant will not be eligible for inclusion in this clinical trial if any of the following criteria apply: The subject is unable to provide informed consent or to comply with study requirements. 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. 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. Pregnancy, lactation. Women of childbearing age who are not pregnant but do not take adequate contraceptive measures. * The study participant has a history of addiction or dependency, or he or she is currently abusing or using substances. Study participant has any active malignancy, including but not limited to evidence of cutaneous basal, squamous cell carcinoma, or melanoma. 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). 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. The study participant has received an experimental drug within 12 months before the first dose of the investigational product. (Except for COVID-19 vaccinations) 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. 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. The study participant is unlikely to complete the study or adhere to the study procedures. The study participant has a previously diagnosed psychiatric condition that may affect self-assessments in the investigator's opinion. Study participants with any systemic infection requiring treatment with antibiotics, antivirals, or antifungals within 30 days before the first dose of the investigational product. 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. 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. 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. Subjects who have fatigue due to chronic kidney disease, iron deficiency anemia, B12 deficiency and other anemias will be excluded. Any participant who has suicidal ideation at the screening visit will be excluded from this clinical trial. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

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
Interventional Model Description: Randomized Double-Blind
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>HB-ad MSC's allogeneic | Biological: HB-adMSCs (allogeneic)<br>* HB-adMSCs allogenic<br>* Other names: Hope Biosciences adipose derived mesenchymal stem cells;|
| Placebo Comparator: Placebo<br>Sterile Normal Saline | Other: Placebo<br>* Placebo comarator<br>* Other names: Sterile Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Visual Analog Scale of Neurological Symptoms. - Extreme fatigue | Clinically significant changes in Visual Analog Scale - Extreme fatigue | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of Neurological Symptoms. - Brain fog | Clinically significant changes in Visual Analog Scale - Brain fog | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of Neurological Symptoms. - Headache | Clinically significant changes in Visual Analog Scale - Headache | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of Neurological Symptoms. - Sleep disturbances | Clinically significant changes in Visual Analog Scale - Sleep disturbances | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of Neurological Symptoms. - Loss of taste | Clinically significant changes in Visual Analog Scale - Loss of taste | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of Neurological Symptoms. - Loss of smell | Clinically significant changes in Visual Analog Scale - Loss of smell | Baseline to Weeks 26 | 
| Incidence of treatment-emergent Adverse Event (TEAEs). | Treatment-emergent Adverse Event. | Baseline to Weeks 26 | 
| Incidence of treatment-emergent Serious Adverse Events (SAEs). | SSAEs | Baseline to Weeks 26 | 
| AEs of special interest (serious or non-serious) - thromboembolic events. | Incidence of thromboembolic events. | Baseline to Weeks 26 | 
| AEs of special interest (serious or non-serious) - thromboembolism of the extremities. | Incidence and risk of AEs of special interest (serious or non-serious), including peripheral events defined as, thromboembolism of the extremities. | Baseline to Weeks 26 | 
| AEs of special interest (serious or non-serious) - infections. | Incidence and risk of AEs of special interest (serious or non-serious), including infections. | Baseline to Weeks 26 | 
| AEs of special interest (serious or non-serious) - hypersensitivities. | Incidence and risk of AEs of special interest (serious or non-serious), including hypersensitivities. | Baseline to Weeks 26 | 
| Changes in Laboratory values. - CBC. | Clinically significant changes in CBC values. | Baseline to Weeks 26 | 
| Changes in Laboratory values. - CMP. | Clinically significant changes in CMP values. | Baseline to Weeks 26 | 
| Changes in Laboratory values. - Coagulation Panel. | Clinically significant changes in Coagulation Panel values. | Baseline to Weeks 26 | 
| Changes in Vital Signs. - Respiratory Rate (breaths per minute) | Clinically significant changes in Respiratory Rate. | Baseline to Weeks 26 | 
| Changes in Vital Signs. - Heart Rate (beats per minute) | Clinically significant changes in Heart Rate. | Baseline to Weeks 26 | 
| Changes in Vital Signs. - Body Temperature (Fahrenheit ) | Clinically significant changes in Body Temperature. | Baseline to Weeks 26 | 
| Changes in Vital Signs. - Blood Pressure (mmHg) | Clinically significant changes in Blood Pressure. | Baseline to Weeks 26 | 
| Changes in Weight in lb. | Clinically significant changes in Weight. | Baseline to Weeks 26 | 
| Changes in Physical examination results. - General | Clinically significant changes in general physical examination results. | Baseline to Weeks 26 | 
| Changes in Physical examination results. - Body Systems | Clinically significant changes in Body Systems physical examination results. | Baseline to Weeks 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Subject's energy - Fatigue Assessment form. | Clinically significant changes in Fatigue Assessment form. | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of non -Neurological Symptoms. - Dyspnea a rest | Clinically significant changes in Dyspnea a rest | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of non -Neurological Symptoms. - Dyspnea with activity | Clinically significant changes in Dyspnea with activity | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of non -Neurological Symptoms. - Cough | Clinically significant changes in Cough | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of non -Neurological Symptoms. - Body aches | Clinically significant changes in Body aches | Baseline to Weeks 26 | 
| Changes in Visual Analog Scale of non -Neurological Symptoms. - Joint pain | Clinically significant changes in Joint pain | Baseline to Weeks 26 | 
| Changes in Subject's quality of life - Short Form 36 Health Survey Questionnaire | Clinically significant changes in Short Form 36 Health Survey Questionnaire pain | Baseline to Weeks 26 | 
| Changes in Subject's level of depression - PHQ 9 scale. | Clinically significant changes in PHQ 9 scale. pain | Baseline to Weeks 26 |