Corona Virus InfectionPhase 1/2NCT04384445
Zofin (Organicell Flow) for Patients With COVID-19
A Phase 1/2 study testing Zofin in people with Corona Virus Infection and COVID-19, run by ZEO ScientifiX, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corona Virus Infection, COVID-19, SARS
- What is being tested?
- Zofin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2020to 1 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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).
- Being tested
- Zofin, Placebo
- Keywords
- Human Amniotic Fluid, Exosomes, Human
- Medical subject headings
- Coronavirus Infections, COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZofinBiological
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.
PlaceboOther
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 group | Role | What they receive |
|---|---|---|
| Zofin Plus Standard Care | Experimental | Participants in this group will receive standard of care plus Zofin on day 0, day 4 and day 8. Receives: Biological: Zofin |
| Placebo Plus Standard Care | Placebo comparator | Participants in this group will receive standard of care plus placebo (Saline) on day 0, day 4 and day 8. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 60 Days
Incidence of Severe Adverse Events
Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measured: 60 Days
Secondary outcomes (8)
All Cause Mortality
Measured at day 60 or at hospital discharge, whichever comes first.
Measured: 60 Days
Survival Rate
Number of participants that are alive at 60 days post first infusion follow up
Measured: 60 Days
Cytokine Levels
Measure IL-6, TNF-alpha from serum of blood samples
Measured: 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
Measured: Day 0, Day 4, Day 8, Day14, Day 21, Day 28
C-reactive protein Levels
CRP from serum of blood samples
Measured: 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
Measured: 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.
Measured: 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.
Measured: Day o, Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start8 Sep 2020
- Primary completion1 Jul 2023
- Study completion1 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Corona Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- ZEO ScientifiX, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- George C Shapiro, MD, FACC, Principal investigator, Chief Medical Officer at Organicell Regenerative Medicine, IncMaria Ines Mitrani, MD, PhD, Principal investigator, Chief Science Officer at Organicell Regenerative Medicine, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04384445
- Sponsor's protocol ID
- 19881
- Status last verified
- Oct 2023
- First submitted
- 9 May 2020
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04384445
- Acronym / sponsor ID
- 19881
- Keywords
- Human Amniotic Fluid, Exosomes, Human
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- ZEO ScientifiX, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Sep 2020 (actual)
- Primary completion
- 1 Jul 2023 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 12 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Zofin Plus Standard Care | Experimental | Biological: ZofinParticipants in this group will receive standard of care plus Zofin on day 0, day 4 and day 8. |
| Placebo Plus Standard Care | Placebo comparator | Other: PlaceboParticipants in this group will receive standard of care plus placebo (Saline) on day 0, day 4 and day 8. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZofinBiological: 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. | Biological | Zofin Plus Standard Care |
| PlaceboOther: 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. | Other | Placebo Plus Standard Care |
Primary outcome
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
8 secondary outcomes
All Cause Mortality
Time frame: 60 Days
Survival Rate
Time frame: 60 Days
Cytokine Levels
Time frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28
D-dimer Levels
Time frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28
C-reactive protein Levels
Time frame: Day 0, Day 4, Day 8, Day14, Day 21, Day 28
Quantification of the COVID-19
Time frame: Day 0, Day 4, Day 8
Improved Organ Failure
Time frame: Day 30
Chest Imaging Changes
Time frame: Day o, Day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George C Shapiro, MD, FACC principal investigator
Chief Medical Officer at Organicell Regenerative Medicine, Inc
Maria Ines Mitrani, MD, PhD principal investigator
Chief Science Officer at Organicell Regenerative Medicine, Inc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zofin in people with Corona Virus Infection and COVID-19, run by ZEO ScientifiX, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of any infusion associated adverse events (time frame: 60 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2023.