Randomized Double-Blind Phase 2 Study of Allogeneic HB-adMSCs for the Treatment of Chronic Post-COVID-19 Syndrome (HBPCOVID02)

• ClinicalTrials.gov Identifier: NCT05126563
• Recruitment Status: Recruiting
• First Posted: November 19, 2021
• Last Update Posted: February 3, 2022
• Sponsor: Hope Biosciences Stem Cell Research Foundation
• Information provided by (Responsible Party): Hope Biosciences ( Hope Biosciences Stem Cell Research Foundation )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Post COVID-19 Syndrome	Biological: HB-adMSCs (allogeneic); Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Double-Blind
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Amber bags will be used to 'blind' the participant and investigator to which group the subject belongs in.
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: January 6, 2022
• Estimated Primary Completion Date: December 20, 2023
• Estimated Study Completion Date: December 20, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment; HB-ad MSC's allogeneic	Biological: HB-adMSCs (allogeneic); HB-adMSCs allogenic; Other Name: Hope Biosciences adipose derived mesenchymal stem cells
Placebo Comparator: Placebo; Sterile Normal Saline	Other: Placebo; Placebo comarator; Other Name: Sterile Normal Saline

Outcome Measures

Primary Outcome Measures :

1. Changes in Visual Analog Scale of Neurological Symptoms. - Extreme fatigue [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Extreme fatigue
2. Changes in Visual Analog Scale of Neurological Symptoms. - Brain fog [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Brain fog
3. Changes in Visual Analog Scale of Neurological Symptoms. - Headache [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Headache
4. Changes in Visual Analog Scale of Neurological Symptoms. - Sleep disturbances [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Sleep disturbances
5. Changes in Visual Analog Scale of Neurological Symptoms. - Loss of taste [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Loss of taste
6. Changes in Visual Analog Scale of Neurological Symptoms. - Loss of smell [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Visual Analog Scale - Loss of smell
7. Incidence of treatment-emergent Adverse Event (TEAEs). [ Time Frame: Baseline to Weeks 26 ]
   Treatment-emergent Adverse Event.
8. Incidence of treatment-emergent Serious Adverse Events (SAEs). [ Time Frame: Baseline to Weeks 26 ]
   SSAEs
9. AEs of special interest (serious or non-serious) - thromboembolic events. [ Time Frame: Baseline to Weeks 26 ]
   Incidence of thromboembolic events.
10. AEs of special interest (serious or non-serious) - thromboembolism of the extremities. [ Time Frame: Baseline to Weeks 26 ]
    Incidence and risk of AEs of special interest (serious or non-serious), including peripheral events defined as, thromboembolism of the extremities.
11. AEs of special interest (serious or non-serious) - infections. [ Time Frame: Baseline to Weeks 26 ]
    Incidence and risk of AEs of special interest (serious or non-serious), including infections.
12. AEs of special interest (serious or non-serious) - hypersensitivities. [ Time Frame: Baseline to Weeks 26 ]
    Incidence and risk of AEs of special interest (serious or non-serious), including hypersensitivities.
13. Changes in Laboratory values. - CBC. [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in CBC values.
14. Changes in Laboratory values. - CMP. [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in CMP values.
15. Changes in Laboratory values. - Coagulation Panel. [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Coagulation Panel values.
16. Changes in Vital Signs. - Respiratory Rate (breaths per minute) [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Respiratory Rate.
17. Changes in Vital Signs. - Heart Rate (beats per minute) [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Heart Rate.
18. Changes in Vital Signs. - Body Temperature (Fahrenheit ) [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Body Temperature.
19. Changes in Vital Signs. - Blood Pressure (mmHg) [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Blood Pressure.
20. Changes in Weight in lb. [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Weight.
21. Changes in Physical examination results. - General [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in general physical examination results.
22. Changes in Physical examination results. - Body Systems [ Time Frame: Baseline to Weeks 26 ]
    Clinically significant changes in Body Systems physical examination results.

Secondary Outcome Measures :

1. Changes in Subject's energy - Fatigue Assessment form. [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Fatigue Assessment form.
2. Changes in Visual Analog Scale of non -Neurological Symptoms. - Dyspnea a rest [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Dyspnea a rest
3. Changes in Visual Analog Scale of non -Neurological Symptoms. - Dyspnea with activity [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Dyspnea with activity
4. Changes in Visual Analog Scale of non -Neurological Symptoms. - Cough [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Cough
5. Changes in Visual Analog Scale of non -Neurological Symptoms. - Body aches [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Body aches
6. Changes in Visual Analog Scale of non -Neurological Symptoms. - Joint pain [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Joint pain
7. Changes in Subject's quality of life - Short Form 36 Health Survey Questionnaire [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in Short Form 36 Health Survey Questionnaire pain
8. Changes in Subject's level of depression - PHQ 9 scale. [ Time Frame: Baseline to Weeks 26 ]
   Clinically significant changes in PHQ 9 scale. pain

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

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.

Contacts and Locations

Contacts

Contact: Sherry Diers, RN; 3469000340 ext 101; Sherry@hopebio.org

Contact: David Gonzalez, RN; 3469000340 ext 101; David@hopebio.org

Locations

United States, Texas

Hope Biosciences Stem Cell Research Foundation; Recruiting

Sugar Land, Texas, United States, 77478

Contact: Sherry Diers, RN 346-900-0340 ext 101 Sherry@hopebio.org

Contact: David Gonzalez, RN 3469000340 ext 101 David@hopebio.org

Principal Investigator: Thanh C Cheng, MD

Sub-Investigator: Djamchid Lotfi, MD

Sponsors and Collaborators

Hope Biosciences Stem Cell Research Foundation

More Information

• Responsible Party: Hope Biosciences Stem Cell Research Foundation
• ClinicalTrials.gov Identifier: NCT05126563
• Other Study ID Numbers: HBPCOVID02
• First Posted: November 19, 2021
• Last Update Posted: February 3, 2022
• Last Verified: February 2022

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

Additional relevant MeSH terms:

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