A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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The study is a phase 2 proof of concept study. The purpose of this study is to assess the efficacy and safety of Prothione™ capsules administered orally twice a day for 30 days in subjects with mild to moderate COVID-19. The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. The issued patents relevant to Prothione™ capsules and the treatment of viral disease include: • Nutritional or Therapeutic Compositions and Methods to Increase Bodily Glutathione Levels: US Patent No. RE 42,645 Japanese Patent No. 5601745 European Patent No. 1556023 Canadian Patent No. 2539567 Australian Patent No. 2010201136 • Protective Metallothionein Analog Compounds, Their Compositions and Use Thereof in the Treatment of Pathogenic Disease: Canadian Patent No. 2963131 Australian Patent No. 2018279015

Detailed Description
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This is a Phase 2, proof of concept, two-arm, randomized, double blind, placebo-controlled study to evaluate the safety and efficacy of Prothione™ capsules in subjects with mild-to-moderate symptoms caused by coronavirus 2019 (COVID-19) infection. Subjects will be randomized to receive three Prothione™ capsules, or placebo orally administered twice daily (BID). The study will have three phases: screening period, treatment period, and follow-up period. Screening period is up to 3 days , the treatment period is 30 days and the follow-up period is 7 days after the last dose.Total study duration is up to 40 days.

Official Title
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A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Conditions
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Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
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* Drug: Placebo
* Drug: Prothione™ (6g)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential subjects are required to meet all of the following criteria for enrollment into the study: Male or female adult ≥ 18 years of age at time of enrollment with mild to moderate symptoms caused by coronavirus 2019 confirmed infection with COVID-19 by PCR and one or more of the following: Mild (uncomplicated) Illness: Diagnosed with COVID-19 by a standardized RT-PCR assay AND Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath AND No signs of a more serious lower airway disease AND RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air Moderate Illness: Diagnosed with COVID-19 by a standardized RT-PCR assay AND In addition to symptoms above, more significant lower respiratory symptoms, including shortness of breath (at rest or with exertion) OR Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 125, oxygen saturation (pulse oximetry) > 93% on room air AND If available, lung infiltrates based on X-ray or CT scan < 50% present Subjects with normal level of Vitamin B2; Note: If the result was below the normal range, based on clinical judgment by physician, appropriate treatment to be added to the subject treatment regimen as per standard of care. A B complex daily supplement will be supplied, if needed. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures; Understands and agrees to comply with planned study procedures; and Negative pregnancy test for female subjects. Women of child-bearing potential (WOCBP) and Women not of child-bearing potential are eligible to participate. Both women of child-bearing potential and women of no child-bearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 30 days after taking the last dose of Prothione™ ). Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or 2 years post-menopausal. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study. In addition, subjects may not donate sperm for the duration of the study and for 30 days after taking study drug. Exclusion Criteria: Potential subjects meeting any of the following criteria will be excluded from enrollment: Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening; Subjects who have history of receiving NAC, Prothione™ Capsules or GSH supplements in the past 30 days before the screening visit; Subjects who have history of receiving corticosteroids (topical corticosteroid is excluded) in the past 30 days; Subjects who are currently receiving Chemotherapy or Immunotherapy for the treatment of cancer; Any uncontrolled active systemic infection requiring admission to an intensive care unit (ICU); Subject with active Hepatitis B and Hepatitis C; Subjects who are participating in other clinical trials; Subjects that have had any Covid19 Vaccination; Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Prothione™ are not eligible; Inability to provide informed consent or to comply with study requirements; and Subjects who are pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Experimental: Prothione ™<br> | Drug: Prothione™ (6g)<br>* Prothione is a pro-Glutathione compound includes free-form amino acids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (days) to successful clinical recovery from positive RT-PCR for SARS-COV2 as indicated by two consecutive negative RT-PCR tests measured with three different measurements within a 24-36 hour period. |  | 24-36 hour period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Day 29 in Serum 8-OHdG levels |  | Baseline to day 29 | 
| Change in RBC intracellular Glutathione levels to Day 29 |  | Baseline to day 29 | 
| Quantitative change from Baseline (Screening Visit) to Day 29 oropharyngeal cell intracellular GSH levels |  | Baseline to day 29 | 
| Time to clinical resolution (TTCR) defined as the time (days) from initiation of study treatment until reach a score of 0 at least in three of the following: o Fever o Myalgia o Dyspnea o Cough | ( Each symptom is graded from 0 to 3. [0=none 1=mild 2=moderate and 3=severe] | Baseline to day 29 | 
| Evaluate Cycle Threshold (Ct) numbers used in qualitative and quantitative RT-PCR for SARS-COV2 tests. |  | Baseline to day 29 | 
| Clinical Improvement as assessed by change in symptom score from baseline (for fever, myalgia, dyspnea and cough). | Note: The score per patient ranges from 0 to 3 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe] | Baseline to day 29 | 
| Mortality at Day 29 |  | Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Prothione