Clinical trial NCT04504734: Bucillamine in Treatment of Patients With COVID-19
Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Covid19
Lead sponsor: Revive Therapeutics, Ltd.
Sponsor class: INDUSTRY
First posted: 2020-08-07
Enrollment: 713
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: Frequency of hospitalization or death
timeFrame: From time of first dose through Day 28 following randomization
Secondary outcomes:
measure: Safety: Changes in adverse events from baseline to end of study
timeFrame: From time of first dose through Day 28 following randomization
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Cullman Clinical Trials
state: Alabama
city: Huntsville
country: United States
facility: Avant Research Associates, LLC
state: Alabama
city: Phoenix
country: United States
facility: West Valley Research Clinic
state: Arizona
city: Hot Springs
country: United States
facility: HealthStar Research LLC
state: Arkansas
city: Huntington Beach
country: United States
facility: ASCADA Research
state: California
city: Los Angeles
country: United States
facility: Samuel Ross MD Inc.
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: San Francisco
country: United States
facility: Optimus Medical Group
state: California
city: Coral Gables
country: United States
facility: C & R Research Services USA
state: Florida
city: Hialeah
country: United States
facility: Sweet Hope Research Specialty Inc
state: Florida
city: Hollywood
country: United States
facility: Encore Medical Research
state: Florida
city: Kendall
country: United States
facility: Entrust Clinical Research
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services
state: Florida
city: Miami
country: United States
facility: Verus Clinical Research
state: Florida
city: Miami
country: United States
facility: Nuren Medical & Research Center
state: Florida
city: Miami
country: United States
facility: Advance Medical Research Services Corp
state: Florida
city: North Miami Beach
country: United States
facility: Amavita Clinical Research
state: Florida
city: Tampa
country: United States
facility: C & R Research Services USA
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston LLC
state: Florida
city: Winter Park
country: United States
facility: Clinical Site Partners LLC
state: Florida
city: Acworth
country: United States
facility: American Clinical Trials LLC
state: Georgia
city: Chicago
country: United States
facility: Quad Clinical Research LLC
state: Illinois
city: Morton
country: United States
facility: Koch Family Medicine
state: Illinois
city: Farmington Hills
country: United States
facility: Revive Research Institute Inc.
state: Michigan
city: Plymouth
country: United States
facility: SRI International
state: Michigan
city: Southfield
country: United States
facility: Great Lakes Research Institute
state: Michigan
city: Sterling
country: United States
facility: Revival Research Institute LLC
state: Michigan
city: Las Vegas
country: United States
facility: Machuca Family Medicine
state: Nevada
city: Bronx
country: United States
facility: Prime Global Research
state: New York
city: Charlotte
country: United States
facility: OnSite Clinical Solutions
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Smithfield
country: United States
facility: Superior Clinical Research
state: North Carolina
city: Yanceyville
country: United States
facility: Superior Clinical Research
state: North Carolina
city: Dayton
country: United States
facility: Dayton Clinical Research
state: Ohio
city: Charleston
country: United States
facility: Pharmacorp Clinical Trials Inc.
state: South Carolina
city: Clarksville
country: United States
facility: Novaceut Clinical Research
state: Tennessee
city: Jackson
country: United States
facility: Physicians Quality Care
state: Tennessee
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Houston
country: United States
facility: C & R Research Services USA
state: Texas
city: Houston
country: United States
facility: Encore Imaging and Medical Research
state: Texas
city: Katy
country: United States
facility: R & H Clinical Research Inc.
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: McAllen
country: United States
facility: Family Practice Center
state: Texas
city: Stafford
country: United States
facility: R & H Clinical Research Inc.
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: San Juan
country: Puerto Rico
facility: Dr. Orvil Martínez-Rivera
Study officials:
References: