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Zofin (Organicell Flow) for Patients With COVID-19

Primary Purpose

Corona Virus Infection, COVID-19, SARS

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Zofin

Placebo

About this trial

This is an interventional treatment trial for Corona Virus Infection focused on measuring Human Amniotic Fluid, Exosomes, Human

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provide written informed consent
Subjects age > 18 years at the time of signing the Informed Consent Form.
Male or Female
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.
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
Hospitalized and symptomatic (cough, fevers, SOB, or sputum production)
Adequate venous access
Ability to provide informed consent or an authorized representative can sign the informed consent
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.
Must agree to comply with all study requirements and be willing to complete all study visits
Willingness of study participant to accept this treatment arm, and signed informed consent; Need in- patient admission.

Exclusion Criteria:

Intubated or on a ventilator.
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.
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, 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
Be serum positive for HIV, hepatitis BsAg or hepatitis C.

Sites / Locations

George C. Shapiro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Zofin Plus Standard Care

Placebo Plus Standard Care

Arm Description

Participants in this group will receive standard of care plus Zofin on day 0, day 4 and day 8.

Participants in this group will receive standard of care plus placebo (Saline) on day 0, day 4 and day 8.

Outcomes

Primary Outcome Measures

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

Incidence of Severe Adverse Events

Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Secondary Outcome Measures

All Cause Mortality

Measured at day 60 or at hospital discharge, whichever comes first.

Survival Rate

Number of participants that are alive at 60 days post first infusion follow up

Cytokine Levels

Measure IL-6, TNF-alpha from serum of blood samples

D-dimer Levels

D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

C-reactive protein Levels

CRP from serum of blood samples

Quantification of the COVID-19

Viral load by real time RT methodology using blood samples or nose / throat swab

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.

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.

Full Information

NCT ID

NCT04384445

First Posted

May 9, 2020

Last Updated

September 19, 2022

Sponsor

Organicell Regenerative Medicine

1. Study Identification

Unique Protocol Identification Number

NCT04384445

Brief Title

Zofin (Organicell Flow) for Patients With COVID-19

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 8, 2020 (Actual)

Primary Completion Date

July 31, 2023 (Anticipated)

Study Completion Date

August 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Organicell Regenerative Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Corona Virus Infection, COVID-19, SARS, Acute Respiratory Distress Syndrome

Keywords

Human Amniotic Fluid, Exosomes, Human

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

The trial has two groups, each with 10 subjects (n=20). All eligible study subjects will be randomized, double blinded, to either the treatment group or placebo group.

Masking

ParticipantInvestigator

Masking Description

Double blind: neither subjects nor the investigators who are assessing the patient are award of the treatment assignment until the end of the study.

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Zofin Plus Standard Care

Arm Type

Experimental

Arm Description

Participants in this group will receive standard of care plus Zofin on day 0, day 4 and day 8.

Arm Title

Placebo Plus Standard Care

Arm Type

Placebo Comparator

Arm Description

Participants in this group will receive standard of care plus placebo (Saline) on day 0, day 4 and day 8.

Intervention Type

Biological

Intervention Name(s)

Zofin

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of any infusion associated adverse events

Description

Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician

Time Frame

60 Days

Title

Incidence of Severe Adverse Events

Description

Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Time Frame

60 Days

Secondary Outcome Measure Information:

Title

All Cause Mortality

Description

Measured at day 60 or at hospital discharge, whichever comes first.

Time Frame

60 Days

Title

Survival Rate

Description

Number of participants that are alive at 60 days post first infusion follow up

Time Frame

60 Days

Title

Cytokine Levels

Description

Measure IL-6, TNF-alpha from serum of blood samples

Time Frame

Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Title

D-dimer Levels

Description

D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

Time Frame

Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Title

C-reactive protein Levels

Description

CRP from serum of blood samples

Time Frame

Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Title

Quantification of the COVID-19

Description

Viral load by real time RT methodology using blood samples or nose / throat swab

Time Frame

Day 0, Day 4, Day 8

Title

Improved Organ Failure

Description

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.

Time Frame

Day 30

Title

Chest Imaging Changes

Description

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.

Time Frame

Day o, Day 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provide written informed consent Subjects age > 18 years at the time of signing the Informed Consent Form. Male or Female 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. 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 Hospitalized and symptomatic (cough, fevers, SOB, or sputum production) Adequate venous access Ability to provide informed consent or an authorized representative can sign the informed consent 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. Must agree to comply with all study requirements and be willing to complete all study visits Willingness of study participant to accept this treatment arm, and signed informed consent; Need in- patient admission. Exclusion Criteria: Intubated or on a ventilator. 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. 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, 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 Be serum positive for HIV, hepatitis BsAg or hepatitis C.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George C Shapiro, MD, FACC

Organizational Affiliation

Chief Medical Officer at Organicell Regenerative Medicine, Inc

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Maria Ines Mitrani, MD, PhD

Organizational Affiliation

Chief Science Officer at Organicell Regenerative Medicine, Inc

Official's Role

Principal Investigator

Facility Information:

Facility Name

George C. Shapiro

City

New York

State/Province

New York

ZIP/Postal Code

10604

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Zofin (Organicell Flow) for Patients With COVID-19

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