Zofin to Treat COVID-19 Long Haulers

This is a phase I/II randomized, double blinded and placebo control. COVID-19 Long Haulers

In double blinded and placebo control trial, neither the patients nor the researchers know who is getting a placebo and who is getting the treatment. The ratio between groups is 1:1 for total 30 subjects. Each subject will be randomized to receive either treatment or placebo.

A total of 30 subjects will be enrolled and randomized.

Group 1 (15 subjects) Fifteen subjects will receive 1 mL of Zofin diluted with 100ml of sterile saline on day 0, day 4 and day 8, containing 2-5 x 10^11 particles/ml intravenously.

Group 2 (15 subjects) Fifteen subjects will receive 1mL of placebo diluted with 100ml of sterile saline on day 0, day 4 and day 8, containing sterile saline intravenously.

Inclusion criteria

• Subjects age > 18 years at the time of signing the informed consent form.
• Male or female.
• COVID-19 survivor and had documented SARS-CoV-2 positive (FDA EUA approved RT-PCR or equivalent tests such as FDA EUA approved Rapid Antigen Test which is performed at CLIA certified lab or the readout of the test reviewed and documented by a doctor).
• Subject experiencing fatigue for over 6 weeks after their positive test result while currently being negative.
• Subject has not fully recovered from COVID-19 for at least over 6 weeks despite a negative SARS-COV-02 test.
• Subjects tested positive for anti-SARS-CoV-2 antibodies using FDA EUA approved test.
• Subject is experiencing the following three symptoms for at least over 6 weeks either continually or intermittently with relapses not experienced pre-illness, that interferes with normal daily activities. Symptoms must be new symptoms i.e., subject didn't have symptoms, and had not sought medical treatment for the symptoms prior to COVID-19:

• Extreme fatigue - feeling overtired with low energy and a strong desire to sleep but unable to have good sleep.
• Body aches - muscle soreness or generalized achiness throughout the body.
• Joint pain - pain in the joints due to inflammation not experienced before illness.
• Chalder Fatigue Scale Bimodal Score ≥ 4 at the time of Screening.
• Fatigue Severity Scale (FSS) ≥ 4 at the time of Screening.
• Fatigue Assessment Scale Score (FAS) ≥ 10.5 at the time of Screening.
• Beck Depression Inventory (BDI) score <15 at the time of Screening (score of 15 is an exclusion).
• Investigator(s) has access to medical documentation of previous COVID-19 treatments.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Subjects must be reasonably able to return for multiple follow-up visits.
• Adequate venous access.
• For Subjects of Child-Bearing Potential only, willingness to use FDA recommended birth control until 6 months post-treatment. The FDA approved and cleared methods for birth control are listed below:

• Permanent sterilization
• Long-acting reversible contraceptives (LARC)
• Contraceptive injection
• Short-acting hormonal methods
• Barrier methods
• Emergency contraception https://www.fda.gov/consumers/free-publications-women/birthcontrol
• Any male subject must agree to use contraceptives and not donate sperm during the study.

Exclusion criteria

• Tested positive for SARS-CoV-2 infection at the time of screening (acute infection) which will involve a nasal swab sample or another FDA-approved test.
• Subjects with a BDI ≥ 15 are excluded.
• Subjects with homicidal or suicidal ideation are excluded.
• Subjects with a diagnosis of depression upon entry into the study must have had at least 2-months of treatment (psychotherapy, antidepressive medication, or both) prior to enrollment, be stable on their current treatment regimen, and be followed by a medical provider who is actively treating and managing their depression throughout the study period.
• Subjects who had recovered fully from COVID-19 and have a new onset of extreme fatigue, body aches, or joint pain that were due to other etiologies, not COVID-19 are excluded.
• Subjects with serious co-morbidities are excluded. For example:

• Liver enzymes are >2X ULN;
• eGFR is <60 ml/min by the CKD- EPI equation;
• Hb is <11 mg/dL;
• Platelet count is <100K;
• Uncontrolled arrhythmias;
• BP systolic <90 mmHg or >160 mmHg;
• Pulse is <60 or >100;
• Respiratory rate is <12 or >25;
• Abnormal ECG or any signs of active ischemic heart disease;
• Heart failure of any degree (including NYHA classification Class 1- 4).
• History of migraines prior to COVID-19 infection.
• History of neuropathy prior to COVID-19 infection.
• History of inflammatory and irritable bowel disease prior to COVID-19 infection.
• History of depression and anxiety disorders prior to COVID-19 infection.
• History of chronic fatigue syndrome, fibromyalgia, and arthritic disorders prior to COVID-19 infection.
• Exhibiting signs of moderate or severe chronic respiratory disease (such as COPD, asthma, or pulmonary fibrosis) and history of these illnesses prior to COVID-19 infection.
• Patient with rheumatologic disorders.
• History of chronic liver disease or patient showing signs of clinical jaundice at the time of screening.
• History of severe chronic kidney disease or requiring dialysis.
• Showing signs of severe pneumonia, acute respiratory distress syndrome (ARDS), or respiratory failure needing mechanical ventilation.
• Subjects with a history of bleeding disorders or currently on anticoagulation therapy that cannot be stopped prior to infusion which is not related to previous COVID-19 infection.
• Oxygen-dependent on nasal canula greater than 2-L per minute.
• Patient with pulse oxygen saturation (SpO2) of <94% on room air.
• Active or recently treated malignancies.
• Any unstable condition of clinical significance, e.g., uncontrolled hypertension, unstable angina pectoris, worsening asthma.
• Hydroxychloroquine, oral or parenteral corticosteroids, immunosuppressants, or immunomodulating agents within 7 days prior to the screening visit.
• Albuterol as nebulizer for the off-label treatment of COVID-19 within 7 days prior to the screening visit.
• Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening which will be within 72 hours of the IP infusion.
• Subject has a body mass index (BMI) greater than 42 kg/m2
• Subject has or had an active infection requiring systemic antibiotics within 12 weeks of enrollment in the study.
• Inability to perform any of the assessments required for endpoint analysis.
• Active listing (or expected future listing) for transplant of any organ.
• Be a solid organ transplant recipient. This does not include prior cell based therapy (>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting.
• Have a history of organ or cell transplant rejection.
• History of drug abuse (illegal "street" drugs except marijuana, if it is legal to use in states where patient resides), or prescription medications not being used appropriately for a pre-existing medical condition or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months.
• Patients with untreated HIV infection. However, patients can be enrolled if have been treated for HIV and the test negative for HIV viral load but still test positive for antibodies.