Previfenon® as Chemoprophylaxis of COVID-19 in Health Workers

NCT ID: NCT04446065

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 524 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2021-10-30

Brief Summary

The purpose of this clinical trial is to determine the efficacy of Previfenon® (EGCG) to prevent COVID-19, enhance systemic immunity, and decrease the frequency and intensity of selected symptoms when used as pre-exposure chemoprophylaxis to SARS-CoV-2.

Detailed Description

Background. Experimental studies have revealed that epigallocatechin-3-galeate (EGCG), a biologically active polyphenol extracted and purified from Camellia Sinensis, may prevent infection by various kinds of viruses, including coronaviruses. Recent double blind, placebo controlled clinical trials, reported up to 75% reduction in the risk of respiratory infection by healthcare workers during an outbreak of H1N1 influenza, simultaneously enhancing systemic immunity by increasing proliferation of ϒδ T cells (28%) and production of IFN-γ (26%). In molecular docking studies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the causal agent of coronavirus disease 2019 outbreak also known as COVID-19) EGCG was identified as a candidate with very high potential for antiviral chemoprophylaxis of COVID-19.

Primary objective: To determine whether Previfenon®, a proprietary formulation of EGCG ≥ 98% purity stabilized with selected excipients, may clinically prevent COVID-19, enhance systemic immunity, decrease the rate for acute respiratory disease, and reduce the frequency and intensity of selected symptoms of COVID-19.

Secondary objective: To determine safety and tolerability of Previfenon® in terms of liver toxicity and frequency of adverse events.

Design. Multicenter randomized double-blind placebo-controlled trial of healthcare workers in treatment by 40 consecutive days as minimum, or a maximum variable time between 60 to 70 days during a SARS-CoV-2 outbreak in Latin American hospitals exposed to clinical care, contact, or circulation of patients with suspected respiratory acute disease caused by SARS-CoV-2 also known as COVID -19.

Sample size: A minimum effect size of 25% (OR = 0.75) is considered; 5% alpha error; 90% power; R = 0.25 for confounders and 20% for loss to follow up. If a conservative event rate of 7.5% in the untreated group is considered, the trial will require 524 participants (262 each group); if the event rate reaches 13.5%, the trial will require 298 participants (149 each group). It is expected to recruit between 100 to 240 subjects per site.

Intervention. The treatment group will receive 3 capsules of Previfenon® daily containing 250 mg of EGCG one every 8 hours. The control group will receive 3 placebo capsules (starch 250 mg) under the same frequency.

Outcomes. The primary outcome will be the rate of clinically defined COVID-19 confirmed with rt-PCR for SARS-CoV-2 viral RNA. Secondary outcomes will be (1) rate of positive cases for IgM or IgG anti-SARS-CoV-2 as measured by a rapid immuno-chromatographic test; (2) rate of positive cases for rtPCR for SARS-Cov-2 viral RNA (3) rate of hospitalization for acute respiratory disease; (4) total rate of lower or upper acute respiratory disease. Exploratory outcomes will be the frequency and intensity of selected symptoms for COVID-19. Safety outcomes will be the number of events of major hepatic toxicity accounted by an increment in liver enzymes and frequency of adverse events during the treatment.

Analysis. Comparison of frequencies, means, and proportions for all relevant variables between treated group and placebo will be performed. An interim analysis will be conducted with the first 366 subjects with at least 20 days of treatment during the outbreak. It will be utilized logistic regression to explore the ongoing effect size in a fixed-effect model. Disease-free person-days curves over the total follow up period will be analyzed using Kaplan-Meier and the total effect size will be computed by Cox proportional hazards multiple regression.

Leading hypothesis: The use of Previfenon® will have a high efficacy in the chemoprophylaxis of COVID-19 through multiple complementary mechanisms, which ultimately prevent an efficient incubation of the SARS-CoV-2 in the host cells, and simultaneously, enhances systemic immunity against the pathogen.

Conditions

COVID-19; SARS-CoV2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Previfenon®

Participants will receive coded non-transparent bottles of Previfenon®, each containing 90 EGCG capsules (250 mg per capsule plus excipients) The total EGCG dose per patient will be 750 mg/day (3 capsules) for 40 consecutive days as minimum or a maximum variable time between 60 to 70 days. It will be divided into three daily intakes of one capsule of Previfenon® every 8 hours.

Group Type: EXPERIMENTAL

Previfenon®

Intervention Type: DRUG

Every capsule of Previfenon® (patent pending) provides 250 mg EGCG ≥ 98% purity with a carefully selected set of excipients to improve flowability, stabilize EGCG against early auto-oxidation, and increase its hepatoprotective activity with prolonged use.

Placebo

Participants will receive coded non-transparent bottles of placebo, each containing 90 starch capsules (250 mg plus excipients) under the same dosage, frequency and duration that Previfenon@ arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive placebo starch capsules (250 mg plus excipients) identical in appearance and taste to Previfenon® capsules in a double-blind manner.

Interventions

Previfenon®

Every capsule of Previfenon® (patent pending) provides 250 mg EGCG ≥ 98% purity with a carefully selected set of excipients to improve flowability, stabilize EGCG against early auto-oxidation, and increase its hepatoprotective activity with prolonged use.

Intervention Type: DRUG

Placebo

Participants will receive placebo starch capsules (250 mg plus excipients) identical in appearance and taste to Previfenon® capsules in a double-blind manner.

Intervention Type: DRUG

Other Intervention Names

Epigallocatechin-3-Gallate, EGCG; Starch

Eligibility Criteria

Inclusion Criteria

• Volunteer healthcare worker with any valid credential of the center
• 25 years old and over
• Not having been diagnosed with COVID-19
• A healthy individual as per investigator's judgment or stating stable non-transmissible chronic disease without hospitalization in the last year, without change of medications or addition of medications to treat chronic illnesses in the last 3 months.
• No pregnancy or breastfeeding
• Female subjects of childbearing potential using an effective family planning method or surgical sterilization or not sexually active during the study
• Do not drink more than 300 ml of tea a day
• Do not take supplements or products containing EGCG during the study
• Being able to set aside time each day to complete the study questionnaires
• Being able to read and understand the informed consent form before the study

Exclusion Criteria

• Healthcare worker who does not have a valid credential from the center
• Under 25 years of age
• Having been diagnosed with a positive rtPCR for COVID-19
• History of febrile acute respiratory disease within the previous 12 weeks
• Volunteer with significant alteration from laboratory tests (standard biochemical profile and hemogram) at screening. A significant abnormality will be defined according investigator's medical judgment.
• Women during pregnancy or breastfeeding
• Female subjects of childbearing age who are sexually active during the study who do not use an effective method of family planning or do not have surgical sterilization
• Known allergy to green tea or EGCG
• Known starch allergy
• User of any medication or supplement containing EGCG
• Volunteer using immunosuppressive drugs
• Autoimmune disease (Lupus, Sjögren or another), liver disease
• Anemia requiring treatment
• Having a chronic infectious disease under treatment

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universidad Austral

UNKNOWN

Sponsor Role: collaborator

MELISA Institute Genomics & Proteomics Research SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Elard Koch, PhD

Head of Reserach

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elard S Koch, PhD

Role: STUDY_DIRECTOR

MELISA Institute Genomics & Proteomics Research SpA

Central Contacts

Cristian Vargas, MD

Role: CONTACT

cvargas@melisainstitute.org

+56412467242

Miguel A Bravo, MPH

Role: CONTACT

mbravo@melisainstitute.org

+56412467242

Related Links

http://www.melisainstitute.org

MELISA Institute

Other Identifiers

MEL109042020

Identifier Type: -

Identifier Source: org_study_id