Bucillamine in Treatment of Patients With COVID-19

• Sponsor: Revive Therapeutics, Ltd. (Industry)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT04504734
• Collaborator: (none)
• Enrollment: 1,000
• Locations: 47
• Arms: 3
• Anticipated Duration (Months): 19.1
• Patients Per Site: 21.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: Bucillamine; Drug: Placebo; Drug: Bucillamine	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind, placebo controlled
• Primary Purpose: Treatment
• Official Title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19
• Actual Study Start Date: Nov 27, 2020
• Anticipated Primary Completion Date: Jun 30, 2022
• Anticipated Study Completion Date: Jun 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Efficacy: Frequency of hospitalization or death [From time of first dose through Day 28 following randomization]

   Proportion of patients meeting a composite endpoint of hospitalization or death

Secondary Outcome Measures

1. Safety: Changes in adverse events from baseline to end of study [From time of first dose through Day 28 following randomization]

   Number of adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cullman Clinical Trials	Cullman	Alabama	United States	35055
2	Avant Research Associates, LLC	Huntsville	Alabama	United States	35802
3	West Valley Research Clinic	Phoenix	Arizona	United States	85031
4	HealthStar Research LLC	Hot Springs	Arkansas	United States	71913
5	ASCADA Research	Huntington Beach	California	United States	92648
6	Samuel Ross MD Inc.	Los Angeles	California	United States	90035
7	Amicis Research Center	Northridge	California	United States	91324
8	Optimus Medical Group	San Francisco	California	United States	94102
9	C & R Research Services USA	Coral Gables	Florida	United States	33134
10	Sweet Hope Research Specialty Inc	Hialeah	Florida	United States	33016
11	Encore Medical Research	Hollywood	Florida	United States	33021
12	Entrust Clinical Research	Kendall	Florida	United States	33156
13	Columbus Clinical Services	Miami	Florida	United States	33125
14	Verus Clinical Research	Miami	Florida	United States	33125
15	Nuren Medical & Research Center	Miami	Florida	United States	33144
16	Advance Medical Research Services Corp	Miami	Florida	United States	33165
17	Amavita Clinical Research	North Miami Beach	Florida	United States	33169
18	C & R Research Services USA	Tampa	Florida	United States	33614
19	Encore Medical Research of Weston LLC	Weston	Florida	United States	33321
20	Clinical Site Partners LLC	Winter Park	Florida	United States	32789
21	American Clinical Trials LLC	Acworth	Georgia	United States	30101
22	Quad Clinical Research LLC	Chicago	Illinois	United States	60643
23	Koch Family Medicine	Morton	Illinois	United States	61550
24	Revive Research Institute Inc.	Farmington Hills	Michigan	United States	48334
25	SRI International	Plymouth	Michigan	United States	48170
26	Great Lakes Research Institute	Southfield	Michigan	United States	48075
27	Revival Research Institute LLC	Sterling	Michigan	United States	48312
28	Machuca Family Medicine	Las Vegas	Nevada	United States	89104
29	Prime Global Research	Bronx	New York	United States	10456
30	OnSite Clinical Solutions	Charlotte	North Carolina	United States	28208
31	OnSite Clinical Solutions, LLC	Charlotte	North Carolina	United States	28277
32	Monroe Biomedical Research	Monroe	North Carolina	United States	28112
33	Superior Clinical Research	Smithfield	North Carolina	United States	27577
34	Superior Clinical Research	Yanceyville	North Carolina	United States	27379
35	Dayton Clinical Research	Dayton	Ohio	United States	45406
36	Pharmacorp Clinical Trials Inc.	Charleston	South Carolina	United States	29412
37	Novaceut Clinical Research	Clarksville	Tennessee	United States	37043
38	Physicians Quality Care	Jackson	Tennessee	United States	38305
39	Inquest Clinical Research	Baytown	Texas	United States	77521
40	C & R Research Services USA	Houston	Texas	United States	77022
41	Encore Imaging and Medical Research	Houston	Texas	United States	77065
42	R & H Clinical Research Inc.	Katy	Texas	United States	77494
43	FMC Science	Lampasas	Texas	United States	76550
44	Family Practice Center	McAllen	Texas	United States	78501
45	R & H Clinical Research Inc.	Stafford	Texas	United States	77477
46	Renovatio Clinical	The Woodlands	Texas	United States	77380
47	Dr. Orvil Martínez-Rivera	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Revive Therapeutics, Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Revive Therapeutics, Ltd.
• ClinicalTrials.gov Identifier: NCT04504734
• Other Study ID Numbers: RT-003
• First Posted: Aug 7, 2020
• Last Update Posted: Apr 22, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Bucillamine

Study Results

No Results Posted as of Apr 22, 2022