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Organicell Flow for Patients With COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04384445
Recruitment Status : Not yet recruiting
First Posted : May 12, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Organicell Regenerative Medicine

Tracking Information
First Submitted Date  ICMJE May 9, 2020
First Posted Date  ICMJE May 12, 2020
Last Update Posted Date July 1, 2020
Estimated Study Start Date  ICMJE July 2020
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • Incidence of any infusion associated adverse events [ Time Frame: 60 Days ]
    Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
  • Incidence of Severe Adverse Events [ Time Frame: 60 Days ]
    Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2020)
To demonstrate the safety of OrganicellTM Flow administered intravenously in patients with severe acute respiratory syndrome (SARS) related to COVID-19 infection. [ Time Frame: Day 60 ]
The primary objective of the proposed clinical trial is to demonstrate the safety of OrganicellTM Flow when administered via intravenous infusion as a therapeutic for patients suffering with COVID-19 infection induced severe acute respiratory syndrome (SARS).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • All Cause Mortality [ Time Frame: 60 Days ]
    Measured at day 60 or at hospital discharge, whichever comes first.
  • Survival Rate [ Time Frame: 60 Days ]
    Number of participants that are alive at 60 days post first infusion follow up
  • Cytokine Levels [ Time Frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28 ]
    Measure IL-6, IL-2, TNF-alpha from serum of blood samples
  • D-dimer Levels [ Time Frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28 ]
    D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
  • C-reactive protein Levels [ Time Frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28 ]
    CRP from serum of blood samples
  • Quantification of the COVID-19 [ Time Frame: Day 0, Day 4, Day 8 ]
    Viral load by real time RT methodology using blood samples or nose / throat swab
  • Improved Organ Failure [ Time Frame: Day 30 ]
    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 [ Time Frame: Day o, Day 30 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2020)
  • All Cause Mortality [ Time Frame: Day 60 ]
    Measured at day 60 or at hospital discharge, whichever comes first.
  • Survival Rate [ Time Frame: Day 60 ]
    Number of participants that are alive at 60 days post first infusion follow up
  • Systemic Inflammation [ Time Frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28 ]
    Measure IL-6, IL-2, TNF-alpha, D-dimer, CRP from serum of blood samples
  • Quantification of the COVID-19 [ Time Frame: Day 0, Day 4, Day 8 ]
    Viral load by real time RT-or equivalent methodology using blood samples or nose / throat swab
  • Improved Organ Failure [ Time Frame: Day 30 ]
    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 [ Time Frame: Day 30 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Organicell Flow for Patients With COVID-19
Official Title  ICMJE A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Organicell Flow for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo
Brief Summary The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow 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.

Organicell 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 Organicell Flow 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Double (Participant, Investigator)
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.
Primary Purpose: Treatment
Condition  ICMJE
  • Corona Virus Infection
  • COVID-19
  • SARS
  • Acute Respiratory Distress Syndrome
Intervention  ICMJE
  • Biological: Organicell Flow
    Biological: Organicell Flow. Organicell Flow will be administered intravenously with 1ml, containing 2-5 x 10^11 particles/mL in addition to the Standard Care. The Organicell Flow dose will be diluted in 100 mL of sterile saline at subject's bedside.
  • 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.
Study Arms  ICMJE
  • Experimental: Organicell Flow Plus Standard Care
    Participants in this group will receive standard of care plus Organicell Flow on day 0, day 4 and day 8.
    Intervention: Biological: Organicell Flow
  • 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.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Maria Ines Mitrani, MD, PhD 1-888-963-7881 clinicaltrials@organicell.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04384445
Other Study ID Numbers  ICMJE 19881
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Organicell Regenerative Medicine
Study Sponsor  ICMJE Organicell Regenerative Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
Principal Investigator: William Kapp, MD, FAAOS Co-Investigator
PRS Account Organicell Regenerative Medicine
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP