Expanded Access to ZofinTM (OrganicellTM Flow) for Patients With COVID-19
Expanded Access to ZofinTM (OrganicellTM Flow) for Patients With COVID-19
This expanded access protocol will provide access to the investigational product ZofinTM
 (OrganicellTM Flow) for patients in outpatient facilities infected with SARS-CoV-2 who have
 mild to moderate COVID-19, or who are judged by a healthcare provider to be at high risk of
 progression to moderate disease.
A human coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak
 worldwide. Common symptoms of COVID-19 include fever, cough, and shortness of breath. The
 majority of cases result in mild symptoms, but some can progress into pneumonia and
 multi-organ failure. According to the severity it is divided into mild, normal, severe and
 critically ill, which is associated with ICU admission and mortality. At present, the
 standard treatment of COVD-19 patients is oxygen therapy, mechanical ventilation, and
 medications to maintain blood pressure. As of today, no specific antiviral therapy is
 available for patients with COVID-19. Immune activation in some patients, and the appearance
 of cytokine storm syndrome (CSS) is one of the important causes of severe damage to lungs and
 other organs, which may lead to death. There is an urgent need to develop new interventions
 to suppress the excessive immune response in a timely manner during the course of disease,
 protect alveolar function, and reduce lung and systemic organ damage.

 ZofinTM (OrganicellTM Flow) is an acellular, minimally manipulated product, derived from
 human amniotic fluid (HAF). This product contains over 300 growth factors, cytokines, and
 chemokines as well as other extracellular vesicles/nanoparticles derived from amniotic stem
 and epithelial cells. The product contains a mean concentration of 5.24x10^11 particles/mL
 with a mean mode size of 125.2nm. Surface marker analysis confirmed the presence of exosome
 associated proteins CD63, CD81, and CD9 in addition to high expression of CD133. The
 completed sequencing revealed 102 commonly expressed miRNA (with a 100-copy expression
 minimum). Bioinformatics analysis linked 63 miRNAs to 1216 RNA targets. Major players in the
 proinflammatory cytokine cascade found to be targeted by miRNA were discovered in
 Organicell's product include TNF, IL-6, and IL-8. Additionally, a broader array of
 pro-inflammatory cytokines is also targeted by the collection of miRNA such as FGF2, IFNB1,
 IGF1, IL36a, IL37, TGF-B2, VEGFA, CCL8, and CXCL12. It has been suggested in published
 research that inhibition or suppression of this pro-inflammatory cytokine cascade may reduce
 the severity of symptoms associated with elevated immune response. Furthermore, the miRNA was
 found to target 148 genes associated with immune response.

 The property of ZofinTM (OrganicellTM Flow) demonstrates the therapeutic potential as a
 suppressor of cytokine activation for the reduction of COVID-19 infection severity. This is
 an open label expanded access protocol to treat subjects using ZofinTM (OrganicellTM Flow)
 for treatment of mild to moderate COVID-19 due to SARS-Cov-2.
Inclusion Criteria:

 1. Provide written informed consent

 2. Subjects age > 18 years at the time of signing the Informed Consent Form.

 3. Male or Female

 4. Must have a clinical diagnosis of COVID-19 by the qualitative reverse-transcription
 polymerase chain reaction (RT-PCR), with at least one of mild or moderate COVID-19
 clinical symptoms which are defined below in #5

 5. Individuals with mild to moderately COVID-19 symptoms for outpatient and inpatient
 population.

 The main symptoms of mild illness are:

 -  low grade fever <38°C (37.5 to 37.9)

 -  a dry cough

 -  tiredness

 -  feeling slightly breathless

 -  muscle pain

 -  headache

 -  sore throat

 -  diarrhea

 The main symptoms of moderate illness are:

 In addition to the symptoms patients may get with a mild illness, they may also
 experience:

 -  fever ≥38°

 -  a dry and more persistent cough several times an hour

 -  tiredness and a need to stay in bed

 -  feeling breathless when doing moderate exercise (such as walking upstairs)

 -  muscle pain and aches and need to stay in bed

 -  headache particularly if you are feeling hot

 -  sore throat, soreness from coughing, but no pain

 -  diarrhea

 -  a dry mouth

 6. Adequate venous access

 7. For Women of Child-Bearing Potential (WOCBP) 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/birth-control

 8. Any male subject must agree to use contraceptives and not donate sperm during the
 study.

 9. Must agree to comply with all protocol requirements and be willing to complete all
 study visits

 Exclusion Criteria:

 1. Patients who have moderate to severe respiratory distress syndrome due to COVID-19

 2. 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.

 3. Inability to perform any of the assessments required.

 4. Active listing (or expected future listing) for transplant of any organ.

 5. 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.

 6. History of drug abuse (illegal "street" drugs except marijuana (If it is legal 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

 7. 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.