Zofin (Organicell Flow) for Patients With COVID-19

A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo

The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Zofin for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.

Study Overview

• Status: Completed
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; Corona Virus Infection; SARS
• Intervention / Treatment: Biological: Zofin; Other: Placebo

Detailed Description

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.

Zofin 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 Zofin demonstrates the therapeutic potential as a suppressor of cytokine activation for the reduction of COVID-19 infection severity. This study aims to investigate safety and potential efficacy of HAF derived acellular product in subjects suffering form COVID-19 infection with severe acute respiratory syndrome (SARS).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10604
      • George C. Shapiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, with at least one of clinical symptoms (e.g., fever ≥38°C, fatigue, cough) and a positive result by the reverse- transcription polymerase chain reaction (RT-PCR) testing or equivalent.

5. Individuals with moderately to severe COVID-19 symptoms.

   Moderate ARDS according to Berlin Criteria:

   Symptoms include: abnormal chest imaging or any degree of hypoxia requiring supplemental oxygen. Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules. Oxygenation: 100 mm Hg < PaO2/FIO2 </= 200 mm Hg with PEEP >/=5 cm H2O

   Severe ARDS according to Berlin Criteria:

   Symptoms include: abnormal chest imaging or any degree of hypoxia requiring supplemental oxygen. Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules. Oxygenation: PaO2/FIO2 </= 100 mm Hg with PEEP >/= 5 cm H2O

6. Hospitalized and symptomatic (cough, fevers, SOB, or sputum production)
7. Adequate venous access
8. Ability to provide informed consent or an authorized representative can sign the informed consent
9. For female patients only, willingness to use FDA- recommended birth control (http://www.fda.gov/downloads/ForConsumers/ByAu dience/ForWomen/FreePublications/UCM356451.pdf ) until 6 months post treatment.
10. Must agree to comply with all study requirements and be willing to complete all study visits
11. Willingness of study participant to accept this treatment arm, and signed informed consent; Need in- patient admission.

Exclusion Criteria:

1. Intubated or on a ventilator.
2. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.
3. Inability to perform any of the assessments required for endpoint analysis.
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, 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. Be serum positive for HIV, hepatitis BsAg or hepatitis C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zofin Plus Standard Care; Participants in this group will receive standard of care plus Zofin on day 0, day 4 and day 8.	Biological: Zofin; Biological: Zofin will be administered intravenously with 1ml, containing 2-5 x 10^11 particles/mL in addition to the Standard Care. The Zofin dose will be diluted in 100 mL of sterile saline at subject's bedside.
Placebo Comparator: Placebo Plus Standard Care; Participants in this group will receive standard of care plus placebo (Saline) on day 0, day 4 and day 8.	Other: Placebo; Other: Placebo Placebo (saline) will be administered intravenously with 1ml in addition to the Standard Care. The Placebo dose will be diluted in 100 mL of sterile saline at subject's bedside.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any infusion associated adverse events	Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician	60 Days
Incidence of Severe Adverse Events	Safety will be defined by the incidence of severe adverse events as assessed by treating physician	60 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Cause Mortality	Measured at day 60 or at hospital discharge, whichever comes first.	60 Days
Survival Rate	Number of participants that are alive at 60 days post first infusion follow up	60 Days
Cytokine Levels	Measure IL-6, TNF-alpha from serum of blood samples	Day 0, Day 4, Day 8, Day14, Day 21, Day 28
D-dimer Levels	D-dimer from serum of blood samples methodology using blood samples or nose / throat swab	Day 0, Day 4, Day 8, Day14, Day 21, Day 28
C-reactive protein Levels	CRP from serum of blood samples	Day 0, Day 4, Day 8, Day14, Day 21, Day 28
Quantification of the COVID-19	Viral load by real time RT methodology using blood samples or nose / throat swab	Day 0, Day 4, Day 8
Improved Organ Failure	Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.	Day 30
Chest Imaging Changes	Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.	Day o, Day 30

Collaborators and Investigators

• Sponsor: Organicell Regenerative Medicine
• Investigators: Principal Investigator: George C Shapiro, MD, FACC, Chief Medical Officer at Organicell Regenerative Medicine, Inc; Principal Investigator: Maria Ines Mitrani, MD, PhD, Chief Science Officer at Organicell Regenerative Medicine, Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: May 9, 2020
• First Submitted That Met QC Criteria: May 9, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Human; Exosomes; Human Amniotic Fluid
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Coronavirus Infections; Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 19881

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No