Bucillamine in Treatment of Patients With COVID-19

Study Overview
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Brief Summary
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This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 1:1 to the selected bucillamine dose or placebo. This dose has now been chosen as 600 mg. The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 50 centers in the United States will conduct this study. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

Detailed Description
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This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 1:1 to the selected bucillamine dose or placebo. This dose has now been chosen as 600 mg. The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 50 centers in the United States will conduct this study. Patients qualifying for study enrollment will initiate therapy as outpatients, under home quarantine. Patients will receive continued standard care of therapy (per study site written policies or guidelines) together with bucillamine and/ or matching placebo for up to 14 days. Dosing should continue until the treatment course is completed or as medically indicated (e.g., deterioration of clinical status and alternative therapy required). If the patient requires hospitalization during the study period, treatment will be discontinued. Following completion of the treatment course, follow up assessments will be performed by a study nurse 14, 28, 42, and 60 days following the end of treatment. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

Official Title
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Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Bucillamine
* Drug: Placebo
* Drug: Bucillamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is within 72 hours from onset of symptoms consistent with COVID 19 at time of study enrollment Has at least 2 of the following: fever (oral temperature ≥38°C), cough, shortness of breath, chest x ray changes consistent with COVID-19 at time of screening Has peripheral capillary oxygen saturation (SpO2) ≥94 by pulse oximetry at time of screening Has either a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-approved rapid diagnostic (e.g., PCR) assay Has a score of ≤ 2 on the 8-category NIAID ordinal scale at time of screening Agrees to the collection of blood and urine samples, nasopharyngeal (NP) swabs, and non-invasive oxygen monitoring (via pulse oximeter) per protocol Patient (or their legally authorized representative) is willing and able to provide written informed consent prior to performing study procedures Understands and agrees to comply with planned study procedures Women of childbearing potential must agree to either abstinence or use at least 1 primary form of contraception not including hormonal contraception from the time of screening through Day 29 following randomization. All subjects of childbearing potential, including males with partners of childbearing potential, must use highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly. Abstinence is NOT an acceptable method of contraception UNLESS it is the subject's normal practice. Exclusion Criteria: Prior history of, or considered to be at risk for, agranulocytosis, nephropathy, liver disease, or interstitial pneumonia Serious hepatic disorder (Child-Pugh scores B or C) or alanine transaminase (ALT) or aspartate transaminase (AST) > 5 times the upper limit of normal (ULN) at screening Chronic kidney disease (CKD) National Kidney Foundation (NKF) stages 3B - 5 chronic renal dysfunction (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73m2 according to Cockcroft Gault formula) Proteinuria ≥ 1+ or ≥ 30 mg on dipstick urinalysis that is confirmed on repeat assessment within 24 hours Serum BUN ≥ 2 × ULN or Cr ≥ 2 × ULN Leukopenia with absolute granulocyte count < 1500/µL History of positive Human Immunodeficiency virus (HIV) test or organ transplant Receipt of cancer chemotherapy or immunomodulatory drugs including (but not limited to) biologics such as anti-CD20, anti-TNF, anti-IL6; alkylating agents (e.g., cyclophosphamide); antimetabolites (e.g., azathioprine); or chronic corticosteroid use equivalent to prednisone >10 gm/day, during preceding 2 months Confirmed positive for influenza at screening Confirmed positive for respiratory syncytial virus (RSV) at screening Pregnant or breastfeeding Current use of, or known allergy to bucillamine or penicillamine (e.g., for Wilson's disease, rheumatoid arthritis) Current participation in any other clinical trial of an experimental treatment Receipt of any experimental treatment for COVID-19 (herbal/homeopathic, off-label, compassionate use, or trial related) within the 30 days prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Bucillamine low dose<br>Bucillamine 100 mg 3 times a day (TID) | Drug: Bucillamine<br>* 100mg tablets<br>|
| Active Comparator: Bucillamine high dose<br>Bucillamine 200 mg 3 times a day (TID) | Drug: Bucillamine<br>* 200mg tablets<br>|
| Placebo Comparator: Placebo<br>Placebo, 3 times a day (TID) | Drug: Placebo<br>* 100mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Frequency of hospitalization or death | Proportion of patients meeting a composite endpoint of hospitalization or death | From time of first dose through Day 28 following randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Changes in adverse events from baseline to end of study | Number of adverse events | From time of first dose through Day 28 following randomization |