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

Phase 2

Completed

• Conditions: Post COVID-19 Syndrome
• Interventions: Other: Placebo; Biological: HB-adMSCs (allogeneic)

• Registration Number: NCT05126563
• Lead Sponsor: Hope Biosciences Stem Cell Research Foundation

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2021-11-12
• Study First Submitted QC: 2021-11-17
• Study First Posted: 2021-11-19
• Study Start: 2022-02-02
• Primary Completion: 2024-04-02
• Study Completion: 2024-04-02
• Status Verified: 2024-10
• Results First Submitted: 2024-10-04
• Results First Submitted QC: 2024-10-31
• Last Update Submitted: 2024-10-31
• Results First Posted: 2024-11-26
• Last Update Posted: 2024-11-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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.

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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:

21. True sexual abstinence (abstaining from sexual activity during the entire period of risk).

22. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Sterile Normal Saline
Treatment	HB-adMSCs (allogeneic)	HB-ad MSC's allogeneic

Primary Outcome Measures

Name	Time	Method
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Extreme Fatigue (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Extreme fatigue. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure extreme fatigue has one end labeled "no fatigue" and the other end labeled "worst fatigue". The patient then marks a point on the line to indicate their current level of fatigue. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (fatigue).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Loss of Smell (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Loss of smell. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure loss of smell has one end labeled "no loss of smell" and the other end labeled "worst loss of smell". The patient then marks a point on the line to indicate their current level of loss of smell. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (loss of smell).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms - Extreme Fatigue (RMA Model)	Baseline to Week 26	Clinically significant changes in Visual Analog Scale. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure extreme fatigue has one end labeled "no fatigue" and the other end labeled "worst fatigue". The patient then marks a point on the line to indicate their current level of fatigue. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (fatigue).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms.. - Brain Fog (RMA Model)	Baseline to Week 26	Clinically significant changes in Visual Analog Scale - Brain fog. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure brain fog has one end labeled "no brain fog" and the other end labeled "worst brain fog". The patient then marks a point on the line to indicate their current level of brain fog. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (brain fog).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms.. - Brain Fog (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Brain fog. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure brain fog has one end labeled "no brain fog" and the other end labeled "worst brain fog". The patient then marks a point on the line to indicate their current level of brain fog. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (brain fog).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Headache (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Headache. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure Headache has one end labeled "no headache" and the other end labeled "worst headache". The patient then marks a point on the line to indicate their current level of Headache. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (headache).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Sleep Disturbances (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Sleep disturbances. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure sleep disturbance has one end labeled "no sleep disturbance" and the other end labeled "worst sleep disturbance". The patient then marks a point on the line to indicate their current level of sleep disturbance. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (sleep disturbance).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Loss of Taste (ANCOVA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Loss of taste. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure loss of taste has one end labeled "no loss of taste" and the other end labeled "worst loss of taste". The patient then marks a point on the line to indicate their current level of loss of taste. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (loss of taste).
Changes in Laboratory Values. - Coagulation Panel. (Seconds)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in Coagulation Panel values with units of seconds.
Changes in Laboratory Values. - CBC (% of Total Blood Cell Count)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit of % of Total Blood Cell Count.
Changes in Laboratory Values. - CMP (g/dL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values.
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Headache (RMA Model)	Baseline to Week 26	Clinically significant changes in Visual Analog Scale - Headache. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure Headache has one end labeled "no headache" and the other end labeled "worst headache". The patient then marks a point on the line to indicate their current level of Headache. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (headache).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Sleep Disturbances (RMA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Sleep Disturbances. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure sleep disturbance has one end labeled "no sleep disturbance" and the other end labeled "worst sleep disturbance". The patient then marks a point on the line to indicate their current level of sleep disturbance. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (sleep disturbance).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Loss of Taste (RMA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Loss of taste. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure loss of taste has one end labeled "no loss of taste" and the other end labeled "worst loss of taste". The patient then marks a point on the line to indicate their current level of loss of taste. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (loss of taste).
Changes From Baseline in Visual Analog Scale of Neurological Symptoms. - Loss of Smell (RMA Model)	Baseline to Weeks 26	Clinically significant changes in Visual Analog Scale - Loss of smell. A VAS is a straight line with two end points that represent the extremes of a range. This VAS used to measure loss of smell has one end labeled "no loss of smell" and the other end labeled "worst loss of smell". The patient then marks a point on the line to indicate their current level of loss of smell. The minimum score is a 0 and the maximum score is a 10. A higher score indicates a worse outcome (loss of smell).
Changes in Laboratory Values. - CBC. (x10^3 Cells/uL)	Baseline to Weeks 26	Clinically significant changes in CBC values.
Changes in Laboratory Values. - CBC. (% of WBC)	Baseline to Weeks 26	Clinically significant changes in CBC values.
Changes in Laboratory Values. - CBC (pg)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit of pg.
Changes in Laboratory Values. - CBC (g/dL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit of g/dL.
Changes in Laboratory Values. - CBC (fL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit of fL.
Changes in Laboratory Values. - CBC (x10^6 Cells/uL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit of 10\^6 cells/uL.
Changes in Laboratory Values. - CBC (% Difference in Volume and Size of RBC)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CBC laboratory values with unit % Difference in Volume and Size of RBC
Changes in Laboratory Values. - Coagulation Panel. Ratio: Prothrombin Time (Seconds) / Mean Normal Prothrombin Time (Seconds	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in Coagulation Panel values with units of Ratio: Prothrombin time (seconds) / Mean normal prothrombin time (seconds).
Changes From Baseline in Vital Signs. - Respiratory Rate (Breaths Per Minute)	Baseline to Weeks 26	Clinically significant changes in Respiratory Rate (breaths per minute)
Changes From Baseline in Vital Signs. - Heart Rate (Beats Per Minute)	Baseline to Weeks 26	Clinically significant changes in Heart Rate (beats per minute)
Changes From Baseline in Vital Signs. - Body Temperature (Celsius)	Baseline to Week 10, End of Study at Weeks 26	Clinically significant changes in Body Temperature (Celsius)
Changes in Vital Signs. - Blood Pressure (mmHg)	Baseline to Weeks 10, End of Study at Week 26	Clinically significant changes in Blood Pressure.
Changes in Weight in kg.	Baseline to Weeks 10, End of Study at Week 26	Change from baseline in Weight in kg.
Changes in Physical Examination Results. - Abdomen	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Abdomen body system
Changes in Laboratory Values. - CMP (Ratio: Albumin (g/dL) to Calc. Globulin (g/dL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Changes from baseline in CMP laboratory values with units of Ratio: Albumin(g/dL) to Calc. Globulin(g/dL)
Changes in Laboratory Values. - CMP (U/L)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values with units of U/L.
Changes in Laboratory Values. - CMP (mg/dL)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values with units of mg/dL.
Changes in Laboratory Values. - CMP (mEq/L)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values with units of mEq/L.
Changes in Laboratory Values. - CMP (mL/Min/1.73m^2)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values with units of mL/min/1.73m\^2.
Changes in Laboratory Values. - CMP (Calc BUN mg/dL /Creat mg/dL Ratio)	Baseline (Week 0), Week 10, and End of Study (Week 26)	Clinically significant changes in CMP values with units of Calc BUN mg/dL /Creat mg/dL Ratio
Changes in Physical Examination Results. - Cardiovascular	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Cardiovascular body system
Changes in Physical Examination Results. - Head, Eyes, Ears, Nose, and Throat	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Head, Eyes, Ears, Nose, and Throat body system
Changes in Physical Examination Results. - Lymph Node	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Lymph Node
Changes in Physical Examination Results. - Musculoskeletal	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Musculoskeletal
Changes in Physical Examination Results. - Neurological	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Neurological
Changes in Physical Examination Results. - Respiratory	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Respiratory
Changes in Physical Examination Results. - Skin	Baseline to Week 10, Follow-up at Week 14, End of Study at Week 26	Clinically significant changes in physical examination results - Skin. Patients are ranked as normal or abnormal per body system.

Secondary Outcome Measures

Name	Time	Method
Changes From Baseline in Visual Analog Scale of Non-Neurological Symptoms. - Dyspnea at Rest (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Visual Analog Scale - Dyspnea at rest. Score ranges from 0 points (no dyspnea) to 10 points (maximum amount of dyspnea).
Changes From Baseline in Visual Analog Scale of Non-Neurological Symptoms. - Dyspnea During Activity (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Visual Analog Scale - Dyspnea during activity. Score ranges from 0 points (no dyspnea) to 10 points (maximum amount of dyspnea)
Changes From Baseline in Visual Analog Scale of Non-Neurological Symptoms. - Cough (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Visual Analog Scale - Cough. Score ranges from 0 points (no cough) to 10 points (maximum amount of cough).
Changes From Baseline in Visual Analog Scale of Non-Neurological Symptoms. - Body Aches (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Visual Analog Scale - Body aches. Score ranges from 0 points (no body aches) to 10 points (maximum amount of body aches).
Changes From Baseline in Visual Analog Scale of Non-Neurological Symptoms. - Joint Pain (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Visual Analog Scale - Joint Pain. Score ranges from 0 points (no pain) to 10 points (maximum amount of pain).
Changes From Baseline in Subject's Energy - Fatigue Assessment Form (ANCOVA Model)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in Fatigue Assessment form. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest.
Changes in Subject's Quality of Life - Short Form 36 Health Survey Questionnaire (General Health)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Short-form (36) Health Survey domain Average General Health; scored on a scale of 0-100; lower score equals more disability.
Changes in Subject's Level of Depression - PHQ 9 Scale.	Baseline (Infusion 1) to Weeks 26 (End of Study)	Clinically significant changes in PHQ (Patient health questionnaire) 9 scale. The PHQ-9 is a 9 question assessment with a total score ranges from 0 to 27 (scores of 5-9 are classified as mild depression; 10-14 as moderate depression; 15-19 as moderately severe depression; ≥ 20 as severe depression) \[30\].
Changes in Subject's Quality of Life - Short Form 36 Health Survey Questionnaire (Physical Functional Score)	Baseline (Infusion 1) to Weeks 26 (End of Study)	Short-form (36) Health Survey domain Average Physical Functioning; scored on a scale of 0-100; lower score equals more disability.

Trial Locations

Locations (1)

Hope Biosciences Research Foundation; 🇺🇸 Sugar Land, Texas, United States