Bucillamine in Treatment of Patients With COVID-19

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

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.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Bucillamine; Drug: Bucillamine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 713
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00926
    • Dr. Orvil Martínez-Rivera
• United States
  • Alabama
    • Cullman, Alabama, United States, 35055
      • Cullman Clinical Trials
    • Huntsville, Alabama, United States, 35802
      • Avant Research Associates, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85031
      • West Valley Research Clinic
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research LLC
  • California
    • Huntington Beach, California, United States, 92648
      • Ascada Research
    • Los Angeles, California, United States, 90035
      • Samuel Ross MD Inc.
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
  • Florida
    • Coral Gables, Florida, United States, 33134
      • C & R Research Services USA
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty Inc
    • Hollywood, Florida, United States, 33021
      • Encore Medical Research
    • Kendall, Florida, United States, 33156
      • Entrust Clinical Research
    • Miami, Florida, United States, 33125
      • Columbus Clinical Services
    • Miami, Florida, United States, 33125
      • Verus Clinical Research
    • Miami, Florida, United States, 33144
      • Nuren Medical & Research Center
    • Miami, Florida, United States, 33165
      • Advance Medical Research Services Corp
    • North Miami Beach, Florida, United States, 33169
      • Amavita Clinical Research
    • Tampa, Florida, United States, 33614
      • C & R Research Services USA
    • Weston, Florida, United States, 33321
      • Encore Medical Research of Weston LLC
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners LLC
  • Georgia
    • Acworth, Georgia, United States, 30101
      • American Clinical Trials LLC
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Quad Clinical Research LLC
    • Morton, Illinois, United States, 61550
      • Koch Family Medicine
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Revive Research Institute Inc.
    • Plymouth, Michigan, United States, 48170
      • SRI International
    • Southfield, Michigan, United States, 48075
      • Great Lakes Research Institute
    • Sterling, Michigan, United States, 48312
      • Revival Research Institute LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Machuca Family Medicine
  • New York
    • Bronx, New York, United States, 10456
      • Prime Global Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28208
      • OnSite Clinical Solutions
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
    • Smithfield, North Carolina, United States, 27577
      • Superior Clinical Research
    • Yanceyville, North Carolina, United States, 27379
      • Superior Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45406
      • Dayton Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Pharmacorp Clinical Trials Inc.
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
      • Novaceut Clinical Research
    • Jackson, Tennessee, United States, 38305
      • Physicians Quality Care
  • Texas
    • Baytown, Texas, United States, 77521
      • Inquest Clinical Research
    • Houston, Texas, United States, 77022
      • C & R Research Services USA
    • Houston, Texas, United States, 77065
      • Encore Imaging and Medical Research
    • Katy, Texas, United States, 77494
      • R & H Clinical Research Inc.
    • Lampasas, Texas, United States, 76550
      • FMC Science
    • McAllen, Texas, United States, 78501
      • Family Practice Center
    • Stafford, Texas, United States, 77477
      • R & H Clinical Research Inc.
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bucillamine low dose; Bucillamine 100 mg 3 times a day (TID)	Drug: Bucillamine; 100mg tablets; Drug: Bucillamine; 200mg tablets
Active Comparator: Bucillamine high dose; Bucillamine 200 mg 3 times a day (TID)	Drug: Bucillamine; 100mg tablets; Drug: Bucillamine; 200mg tablets
Placebo Comparator: Placebo; Placebo, 3 times a day (TID)	Drug: Placebo; 100mg tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Revive Therapeutics, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2020
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): June 12, 2023

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Protective Agents; Antioxidants; Bucillamine
• Other Study ID Numbers: RT-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No