Samples of blood and urine will be taken for clinical laboratory and urinalysis. “We are pleased with the progress we have made to date in our Phase 3 clinical trial with the potential for Bucillamine to become the first orally administered drug to obtain emergency use access from the FDA and also potentially providing another therapeutic option for healthcare professionals to use in treating mild to moderate COVID-19,” said Michael Frank, CEO of Revive. A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). Efficacy will be assessed by comparing clinical outcomes (death or hospitalization), disease severity using the 8-category NIAID COVID ordinal scale, supplemental oxygen use, and progression of COVID‑19 between patients receiving standard-of-care plus Bucillamine (high dose and/or low dose) and patients receiving standard-of-care plus placebo. STATUS Not Recruiting; participants needed 30; sponsor Revive Therapeutics, Ltd. Save Print Send. Originally, Bucillamine conducted Phase 2 clinical trials for the treatment of gout in 2015. The company conducted a Phase 2 clinical study stage for its application of bucillamine to treat acute gout flares. Choosing to participate in a study is an important personal decision. TORONTO, Dec. 23, 2020 (GLOBE NEWSWIRE) — Revive Therapeutics Ltd. (“Revive” or the “Company”) (CSE: RVV, USA: RVVTF), a specialty life sciences company focused on the research and development of therapeutics for medical needs and rare disorders, is pleased to announce an update on the Company’s U.S. Food & Drug Administration (“FDA”) Phase 3 clinical trial (the “Study”) to evaluate the safety and efficacy of Bucillamine in patients with mild to moderate COVID-19. The use of any of the words “could”, “intend”, “expect”, “believe”, “will”, “projected”, “estimated” and similar expressions and statements relating to matters that are not historical facts are intended to identify forward-looking information and are based on Revive’s current belief or assumptions as to the outcome and timing of such future events. An interim analysis will be performed by an Independent Data and Safety Monitoring Board (“DSMB”) after 210 patients have been treated and followed up for 28 days after randomization. Preclinical and clinical studies have demonstrated that reactive oxygen species contribute to the destruction and programmed cell death of pulmonary epithelial cells.3 N-acetyl-cysteine (NAC) has been shown to significantly attenuate clinical symptoms in respiratory viral infections in animals and humans, primarily via donation of thiols to increase antioxidant activity of cellular glutathione.4-7 In addition, it was found that thiol-based drugs decrease binding of SARS-CoV-2 spike protein to its receptor, decrease the entry efficiency of SARS-CoV-2 spike pseudotyped virus, and inhibit SARS-CoV-2 live virus infection.8 Bucillamine (N-(mercapto-2-methylpropionyl)-l-cysteine) has a well-known safety profile and is prescribed in the treatment of rheumatoid arthritis in Japan and South Korea for over 30 years. Bucillamine Phase 2 Trial in Patients With Cystinuria. D Ungheri et al, Protective effect of n-acetylcysteine in a model of influenza infection in mice., Int J Immunopathol Pharmacol. Reference is made to the risk factors disclosed under the heading “Risk Factors” in the Company’s annual MD&A for the fiscal year ended June 30, 2020, which has been filed on SEDAR and is available under the Company’s profile at www.sedar.com. Bucillamine has a well-known safety profile with over 30 years of use as a treatment for rheumatoid arthritis in Japan and South Korea. Please remove one or more studies before adding more. Bucillamine induces phase II antioxidants and detoxifying enzymes in HEI-OC1 cells treated with cisplatin. Subjects will be encouraged to continue their usual self-selected ad-lib diets, fluid and alkali regimen and keep this regimen consistent throughout the duration of the study. 2014 Sep;22(1):1-8). The independent DSMB will actively monitor interim data for the ongoing safety of patients and will recommend continuation, stopping or changes to the conduct of the study based on the interim analysis reports. The study is unmasked, i.e., is open label. And giving more merit to this study, the Buccalimine research is being advised by reputable doctors who are leading some of the most important studies involving COVID-19 treatments (see hydroxychloroquine). A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded. For general information, Learn About Clinical Studies. 1997 Jul;10(7):1535-41). Scientific Rationale of Bucillamine for COVID-19. The Phase 3 confirmatory clinical trial titled, “A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients with Mild-Moderate COVID-19”, will enroll up to 1,000 patients that will be randomized 1:1:1 to receive Bucillamine 100 mg three times a day (“TID”), Bucillamine 200 mg TID or placebo TID for up to 14 days. Entering the Phase 3 study for the use of Bucillamine. Two, it’s quickly jumping into a potential $100 billion psychedelics market opportunity after announcing the acquisition of Psilocin Pharma Corp. 2000 Sep-Dec;13(3):123-128. Enrolled subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day). Patients will then undergo a 12-lead ECG test. Subjects enrolled into Group A will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 100 mg (1 tab) in the morning; 100 mg (1 tab) at noon and 100 mg (1 tab) at night. To date, there have been no serious safety concerns that required the DSMB to be notified. One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments. Information provided by (Responsible Party): Thiol donor which results in a cysteine-bucillamine complex for removing excess cysteine from the urine. K Khanna, et al, Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies., bioRxiv. The primary objective is to compare the frequency of hospitalization or death in patients with mild-moderate COVID-19 receiving Bucillamine therapy with those receiving placebo. In November 2020, the FDA also issued an EUA to permit the emergency use of bamlanivimab (manufacturer Eli Lilly) and the combination of casirivimab and imdevimab (manufacturer Regeneron) for the treatment of mild to moderate COVID-19. Madison, Wisconsin, United States, 53705, Contact: Stephen Nakada, MD    360-252-2500. Most importantly Buccalimine is a real drug, that has already entered Phase 2 in the past, which is now applying for Phase 3 trials. Currently, the Company is exploring the use of Bucillamine for the potential treatment of infectious diseases, with an initial focus on severe influenza and COVID-19. For one, Revive Therapeutics is quickly nearing Phase 3 trials for Bucillamine for the treatment of infectious diseases and the coronavirus disease (COVID-19) by submitting its Phase 3 IND this month. 1. Subjects must have adequate organ function, evidenced by the following laboratory results within 30 days prior to enrollment: SGOT (aspartate aminotransferase [AST]), SGPT (alanine aminotransferase [ALT]), and alkaline phosphatase (ALP). Read our disclaimer for details. Bucillamine [SA96:N-(2-mercapto-2-methylpropanoyl)-L-cysteine] is a synthetic SH compound and an antirheumatic agent developed from tiopronin. Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. Figure2.2.1: Chemical structure of Bucillamine Figure2.2.2: Chemical structure of Cysteine Figure2.2.3: Chemical structure of Bucillamine metabolite SA 981 which has a structural similarity to D- Penicillamine Figure2.2.4: Chemical structure of Bucillamine metabolite SA672 which has one donatable thiol group Arch Biopartners Arranges Non-Brokered Private Placement, Tonix Pharmaceuticals Plans Commercial Scale Vaccine Manufacturing Facility, Clinerion, Medexprim combine clinical and imaging data for research, Nurix Therapeutics Announces Pricing of Upsized Public Offering of Common Stock, Nanobiotix, PharmaEngine conclude collaboration, Genentech’s Actemra first biologic therapy FDA approved for slowing pulmonary functions decline. Revive Therapeutics Ltd (OTCMKTS:RVVTF) (FRA:31R) announced Wednesday that the company is on pace to meet the enrollment goals for its Phase 3 trial of bucillamine in mild-to-moderate cases of the coronavirus.. The FDA recommended that the company submit its IND for a Phase 3 confirmatory trial. Dosing will occur sequentially from low to high dose: The 600 mg bucillamine dose group (Arm A) will enroll first, then after safety is assured, the 900 mg bucillamine dose group will enroll. 2020 Dec 8. Revive is a life sciences company focused on the research and development of therapeutics for infectious diseases and rare disorders, and it is prioritizing drug development efforts to take advantage of several regulatory incentives awarded by the FDA such as Orphan Drug, Fast Track, Breakthrough Therapy and Rare Pediatric Disease designations. 4. Subjects will stop taking their current CBTDs for 7 days and perform a 24-hour urine collection on Day-7 and report for Day 1 Visit . RH Zhang et al, N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury., Int Immunopharmacol. The company previously ran a successful FDA Phase 2 clinical trial with Bucillamine for the treatment of gout and got approved to run a Phase 2 FDA study for Bucillamine to treat ischemia. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision. M Mata et al, N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV)., Biochem Pharmacol. It is mainly used in Japan and Korea. Revive tested the impact of Bucillamine on gout in 2015 in a Phase 2 FDA study. Volume 219, October 2020, 108544. Known for its powerful anti-inflammatory and anti-oxidant benefits, Bucillamine has been prescribed for decades in countries like Japan and South Korea. Neither the Canadian Securities Exchange nor its Regulation Services Provider have reviewed or accept responsibility for the adequacy or accuracy of this release. After completing informed consent, the enrolled subject will have an initial Screening interview. These statements relate to future events or future performance. Patients will undergo a 12-lead ECG test. The better performing Bucillamine dose at the interim analysis will be selected and patients will then be randomized 2:1 to the selected Bucillamine dose or placebo. Bucillamine, a cysteine derivative with two thiol groups, has been shown to be 16 times more potent as a thiol donor in vivo than NAC.2 The drug is non-toxic with high cellular permeability. Subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day), then proceeding to the 600 mg.day dose group.. Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Bucillamine Phase 2 Trial in Patients With Cystinuria The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Given these risks, uncertainties and assumptions, you should not unduly rely on these forward-looking statements. (Read more…). The results met primary efficacy and safety endpoints for the … Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. With its recent acquisition of Psilocin Pharma Corp., Revive is advancing the development of Psilocybin-based therapeutics in various diseases and disorders. In the event of any serious safety concerns, the DSMB would be notified to determine any risks and provide its recommendations. This press release contains ‘forward-looking information’ within the meaning of applicable Canadian securities legislation. Revive Therapeutics has received approval from the US Food and Drug Administration (FDA) to conduct a Phase III clinical trial of Bucillamine in patients with mild to moderate Covid-19. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial. Instructions for handling this sample will be provided in a separate manual. 2011 Sep;82(5):548-55. Research done in the USA showed positive transplant preservation properties. Forward looking information in this press release includes information with respect to the Offering, including the intended use of proceeds. Furthermore, on Day 7 a 24-hour urine collection will be performed. Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Bucillamine, a cysteine derivative with two thiol groups, has been shown to be 16 times more potent as a thiol donor in vivo than N-acetyl-cysteine. on a hydration, alkali therapy and Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies., bioRxiv. The DSMB is independent from the Company, the investigators of the Study, or anyone involved in the clinical care of the Study subjects and oversees the safety of participating patients by reviewing the Study’s accumulating safety and efficacy data for Bucillamine. The findings uncovered a vulnerability of SARS-CoV-2 to thiol-based drugs and provide rationale to test thiol-based drugs as novel treatments for COVID-19. ... (FDA) has approved Revive Therapeutics Ltd. to proceed with a randomized, double-blind, placebo-controlled confirmatory Phase 3 clinical trial protocol to evaluate the safety and efficacy of Bucillamine … After 7 days on the assigned bucillamine dose, a 24-hour urine sample will be taken and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Bucillamine, a cysteine derivative with two thiol groups, has been shown to be 16 times more potent as a thiol donor in vivo than NAC. Revive tested the impact of Bucillamine on gout in 2015 in a Phase 2 FDA study. Subjects enrolled into Group B, will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 200 mg (2 tabs) in the morning; 200 mg (2 tabs) at noon and 200 mg (2 tabs) at night. For more information, visit www.ReviveThera.com. S Ye et al, Inhibition of Reactive Oxygen Species Production Ameliorates Inflammation Induced by Influenza A Viruses via Upregulation of SOCS1 and SOCS3., American Society for Microbiology. 8. had increase in stone size of pre-existing stones while taking a thiol. The Phase 3 confirmatory clinical trial titled, “A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients with Mild-Moderate COVID-19”, will enroll up to 1,000 patients that will be randomized 1:1:1 to receive Bucillamine 100 mg three times a day (“TID”), Bucillamine 200 mg TID or placebo TID for up to 14 days. 5. Revive in April filed a pre-investigational new drug meeting request with the FDA for Bucillamine for the treatment of Covid-19 to proceed to a Phase 2 clinical study. 2020 Dec 8. Further to the DSMB review and recommendations on the interim analysis periods, the Company aims to file for an Emergency Use Authorization (“EUA”) of Bucillamine for mild to moderate COVID-19 with the FDA. (a) Cells were pretreated with 2 m M bucillamine for 1 h followed by the addition of 20 μ M cisplatin at 12 h. Phase II antioxidant genes (HO-1, SOD1 and SOD2) from total RNA were amplified using specific primer sets. The forward-looking information contained in this press release is made as of the date hereof, and Revive is not obligated to update or revise any forward-looking information, whether as a result of new information, future events or otherwise, except as required by applicable securities laws. Read our, ClinicalTrials.gov Identifier: NCT02942420, Interventional Subjects with history of or active blood dyscrasia such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia.  (Clinical Trial). Bucillamine is an antirheumatic agent developed from tiopronin. The primary endpoint is the proportion of patients meeting a composite endpoint of hospitalization or death from the time of the first dose through Day 28 following randomization. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Speculation as to why i think Bucillamine's phase 3 drug trial results will be positive. Bucillamine, a cysteine derivative with two thiol groups, has been shown to be 16 times more potent as a thiol donor in vivo than NAC. This drug regimen will continue for 7 days. Up to 15 subjects each will be enrolled into either Group A or Group B. Research done in USA showed positive transplant preservation properties. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy) is eligible without requiring the use of a contraceptive methods described in Inclusion #8, Placement of intrauterine device (IUD) or intrauterine system (IUS), Condom with spermicidal foam/gel/film/cream/suppository, Diaphragm or cervical/vault caps with spermicidal foam/gel/film/cream/suppository, Subject has had no menstrual period for 12 consecutive months, Contraception use should continue for the duration of the study treatment and for at least 3 months after the last dose of study treatment Periodic abstinence (e.g., calendar ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, Subjects must be willing and able to give written informed consent, Subjects who are scheduled to undergo a surgical procedure, Subjects on D-penicillamine (see page 35 for explanation), Subjects with acute or chronic infections including HIV, tuberculosis, hepatitis B or hepatitis C, Patients with proteinuria ≥30 mg that is confirmed on repeat laboratory assessment within 24 hours, A history of, hypokalemia and family history of Long QT syndrome, Use of concomitant medications that may prolong QT/QTc interval, Patients with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA), Subjects with serious hepatic disorder (Child-Pugh scores B or C), Subjects with a history of alcohol or substance abuse within the 12 months prior to enrollment. Below is an on bucillamine and the Phase 2 initiation, as well as an introduction to the company's strategy in expanding the pipeline through cannabinoid research. The basis of the clinical study will analyze if Bucillamine has the potential, via increasing glutathione activity and other antioxidant and anti-inflammatory activity, to lessen the destructive consequences of SARS-CoV2 infection in the lungs and attenuate the clinical course of COVID-19. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 2 The drug is non-toxic with high cellular permeability. 7. Study diaries will be kept to assess consistency and drug compliance. The Company’s clinical safety team has actively monitored the ongoing interim data of patients and found there have been no safety concerns and no severe adverse events during the interim analysis enrollment period. After 7 days on the assigned bucillamine dose and after providing the 24-hour urine sample, and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. 2 The drug is non-toxic with high cellular permeability. The FDA has asked Revive to submit the IND based on its Phase 2 study of Bucillamine as an anti-inflammatory treatment for gout. Talk with your doctor and family members or friends about deciding to join a study. Revive Therapeutics' missions statement is to advance novel treatment options for … Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine … 6. Measurement of 24-hr urine cystine capacity, i.e., the capacity of a patient's urine to solubilize or precipitate. 2015 Mar;89(5):2672-2683). Individual Participant Data (IPD) Sharing Statement: Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Days 0, 2, 3, 7, 8 and + 1 wk post study ], Cystine Excretion [ Time Frame: Day 0 and Day 8 ], Cystine Capacity [ Time Frame: Day 0 and Day 8 ], Subjects of any gender and of any race ≥18 and ≤80 years of age. There are currently nine clinical sites participating in the Study with an additional six more clinical sites joining the Study in January to satisfy the overall enrollment goal of up to 1,000 patients. Measurement of 24-hr urine cystine excretion. Up to 15 subjects each will be enrolled into either Group A or Group B. 2. Safety will be assessed by reported pre-treatment adverse events and treatment-emergent adverse events (including serious adverse events and adverse events of special interest), laboratory values (hematology and serum chemistry), vital signs (heart rate, respiratory rate, and temperature), and peripheral oxygen saturation. Subjects with Coagulopathy (regardless if controlled by pharmacotherapy or not), Subjects who have any concomitant illness (including active significant infection) or other finding that, in the opinion of the Investigator, would confound the study data or place the subject at unacceptable risk if the subject were to participate in the study, or that would require frequent adjustments in concomitant medications during the course of the study, Use of any investigational drug within 30 days prior to enrollment, Subjects currently participating in another research study or anticipated to enroll in such during participation in this study, Subjects for whom informed consent cannot be obtained.