A Phase 3b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of TRC101 in Delaying Chronic Kidney Disease Progression in Subjects With Metabolic Acidosis

The purpose of this study is to evaluate the effect of TRC101 on the progression of chronic kidney disease (CKD) and to evaluate the safety profile of TRC101 in CKD patients with metabolic acidosis.

开始日期2018-11-20

申办/合作机构

Tricida, Inc.

NCT03390842

/ Completed临床3期

A Blinded, Placebo-Controlled Extension to Study TRCA-301 to Evaluate the Long-term Safety and Durability of Effect of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

This study is a 40-week, blinded, placebo-controlled extension of Study TRCA-301 (NCT03317444). Eligible subjects who complete the 12-week treatment period in Study TRCA-301 have the option to participate in this extension study evaluating the long-term safety and durability of effect of TRC101 in subjects with non-dialysis dependent chronic kidney disease and metabolic acidosis. Eligible subjects will be treated with TRC101 or placebo once daily (QD) on an out-patient basis for the subsequent 40 weeks. Subjects will continue to receive the same blinded treatment (TRC101 or placebo) that they received in Study TRCA-301.

开始日期2017-12-20

申办/合作机构

Tricida, Inc.

NCT03317444

/ Completed临床3期

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

This is a multicenter, double-blind, placebo-controlled, parallel-design study. The study will enroll approximately 210 adult male and female subjects with stage 3 or 4 chronic kidney disease and metabolic acidosis. The study dosing (TRC101 or placebo) will continue for 12 weeks once daily.
The maximum study duration is anticipated to be up to 16 weeks.

开始日期2017-09-26

申办/合作机构

Tricida, Inc.

100 项与 Veverimer 相关的临床结果

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100 项与 Veverimer 相关的转化医学

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100 项与 Veverimer 相关的专利（医药）

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项与 Veverimer 相关的文献（医药）

2025-05-01·Kidney360

Veverimer, a Nonabsorbed Gastrointestinal Tract HCl Binder, Decreases Renal Ammoniagenesis and Mitigates Nephrotoxic Serum Nephritis

Article

作者: Johnson, Ali C.M. ; Zager, Richard A.

Key Points:

Veverimer, a nonabsorbed gastrointestinal tract HCl binder, increases bicarbonate generation, causes bicarbonaturia, and thus decreases renal ammoniagenesis.Decreases in ammoniagenesis can suppress kidney disease–induced alternative complement pathway activation.As a result of the above changes, decreases in renal injury, as induced by nephrotoxic serum injection, can occur.

Background:

Increased tubular ammoniagenesis is an adaptive response to progressive kidney disease, facilitating net acid excretion. However, excess ammonia production can also exacerbate kidney disease progression, in part, by activating the alternative complement cascade. Oral Na bicarbonate therapy can decrease the systemic H+ burden, limiting ammonia production. However, poor compliance limits bicarbonate's efficacy. Veverimer is an oral, Na+-free, nonabsorbed polymer that binds H+ within the gastrointestinal (GI) tract. This stimulates GI carbonic anhydrase-mediated bicarbonate production and systemic bicarbonate uptake. Hence, the goals of this study were to test whether GI HCl binding decreases renal tubular ammoniagenesis, to assess whether complement activation decreases, and to determine whether these changes can mitigate nephrotoxic serum (NTS) nephritis, in which complement activation may play a role.

Methods:

A normal diet± veverimer (4.5% w/w) was fed to normal mice for approximately 1 week. Veverimer's effect on plasma bicarbonate; blood/urinary pH; urinary ammonia excretion; and tubular H+ transporter, NHE3, density was assessed. Additional mice were fed the normal or veverimer diet after NTS injection. Urine protein, albumin, ammonia, C5b-9 excretion, and plasma C3a levels were measured 1 week and/or 2 weeks after NTS injection. Renal histologic changes (hematoxylin and eosin stain; C5b-9, CD45 immunohistochemistry), and selected injury mediators/biomarkers (NGAL, IL-6, MCP-1, TGFβ1, and endothelin-1 mRNAs) were also assessed.

Results:

Veverimer increased plasma bicarbonate/urinary pH, reduced urinary ammonia, and decreased NHE3 in normal mice. Veverimer also reduced NTS-induced proteinuria/albuminuria, urinary ammonia, and C5b-9 excretion (by approximately 60%, 75%, and 50%, respectively). Significant reductions in NTS-induced glomerular/tubulointerstitial injury, inflammatory/profibrotic gene expression, renal C5b-9 deposition, and suppressed plasma C3a levels were observed. Oral bicarbonate also conferred protection, implicating bicarbonate's role in veverimer's beneficial effect.

Conclusions:

Veverimer-mediated bicarbonate generation can suppress renal ammoniagenesis and complement activation. These findings suggest a potential benefit of veverimer/bicarbonate therapy in selected complement-mediated kidney diseases.

2024-05-01·Current opinion in nephrology and hypertension

A basic solution for a complex problem: does treatment of metabolic acidosis slow CKD progression?

Review

作者: Arora, Nayan ; Freidin, Natalie ; Bodker, Kevin

Purpose of this review:

Metabolic acidosis is frequently encountered in patients with chronic kidney disease (CKD), with increasing prevalence as kidney function worsens. Treating electrolyte disturbances is the sine qua non of Nephrologists, and alkali therapy to normalize serum bicarbonate levels and slow progression of kidney disease has been embedded in clinical practice guidelines for decades on the basis of animal models and controversial clinical trials. This review will critically appraise the literature base for this recommendation and determine whether the available evidence supports this common practice, which is a timely endeavor considering the impending demotion of metabolic acidosis treatment from recommendation to practice point in forthcoming KDIGO guidelines.

Recent findings:

Earlier, open-label, studies supporting the utility of sodium bicarbonate therapy to slow progression of chronic kidney disease have been challenged by more recent, blinded, studies failing to show benefit on CKD progression. This was further demonstrated in the absence of concomitant sodium administration with the hydrochloric acid binder veverimer, which failed to demonstrate benefit on renal death, end stage kidney disease or 40% reduction in estimated glomerular filtration rate in a large multicenter trial.

Summary:

The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice.

2024-03-01·Journal of the American Society of Nephrology : JASN

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis

Article

作者: Perkovic, Vlado ; Wheeler, David C ; Wesson, Donald E ; Bushinsky, David A ; Stasiv, Yuri ; Parsell, Dawn ; Li, Elizabeth ; Mathur, Vandana S ; Tangri, Navdeep ; Inker, Lesley A ; Walker, Michael ; Klaerner, Gerrit

Significance Statement:

Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated.

Background:

Metabolic acidosis is common in CKD, but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate.

Methods:

In a phase 3, double-blind, placebo-controlled trial, patients with CKD (eGFR of 20–40 ml/min per 1.73 m2) and metabolic acidosis (serum bicarbonate of 12–20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite end point of CKD progression, defined as the development of ESKD (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of ≥40% from baseline, or death due to kidney failure.

Results:

The mean (±SD) baseline eGFR was 29.2±6.3 ml/min per 1.73 m2, and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4±2.0 mEq/L after the active treatment run-in. After randomized withdrawal, the mean serum bicarbonate was 22.0±3.0 mEq/L and 20.9±3.3 mEq/L in the veverimer and placebo groups at month 3, and this approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 0.8 to 1.2; P = 0.90). Serious and overall adverse event incidence did not differ between the groups.

Conclusions:

Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis.

Clinical Trial registry name and registration number:

VALOR-CKD, NCT03710291.

项与 Veverimer 相关的新闻（医药）

2025-04-25

·PRNewswire

Renibus Therapeutics Announces Poster Presentation on RBT-1 at the 47th Annual Meeting of the Society of Cardiovascular Anesthesiologists (SCA)

- Renibus recently completed enrollment in a Phase 3 pivotal trial PROTECT to reduce the risk of post-operative complications and improve outcomes following cardiac surgery - SOUTHLAKE, Texas, April 25, 2025 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardiac, renal, and metabolic diseases, today announced that a poster presentation will be delivered on RBT-1 at the 47th Annual Meeting of the Society of Cardiovascular Anesthesiologists (SCA), taking place April 26-29, 2025 in Montreal. RBT-1 is a single-dose, first-in-class, preconditioning agent that is administered intravenously 24-48 hours prior to patients undergoing non-emergent cardiac and/or valve surgery. Renibus previously completed a Phase 2 study of RBT-1 (NCT04564833) in February 2023, announced positive final results from this study in May 2023, and has recently completed enrollment in its Phase 3 PROTECT study. RBT-1 has received Breakthrough and Fast Track Designations from the US FDA. "We are excited to build on our recent momentum of achieving full enrollment in our Phase 3 PROTECT study with a poster presentation at SCA 2025 that we can share with the global anesthesiologist community," stated Jeffrey Keyser, RPh, JD, PhD, President and CEO of Renibus. "Our poster highlights the complicated economic impact of post-operative complications and increasing costs for CABG and value surgery to the healthcare system, which directly affects anesthesiologists. With the use of RBT-1 in our Phase 2 study, we reduced the complication rates from cardiovascular surgery, and in turn, the overall healthcare costs. We look forward to continuing to demonstrate these encouraging results in Phase 3." Frans van Wagenberg, MD, Huntsville Heart Center, Huntsville, Alabama, commented, "I am pleased to present results of a cost-analysis based on a Phase 2 trial which suggest that RBT-1 has a protective effect, leading to lower complication rates and reduced average expected costs overall. Additional data from an ongoing Phase 3 trial, which includes a 1-year post-discharge follow-up, will further evaluate the impact of RBT-1 on clinical, economic, and qualitative outcomes compared to standard care." Details of the poster presentation at SCA 2025: Title: "Clinical and Economic Impact of RBT-1 on Post-operative Complications and Costs for CABG and Valve Surgery" Date and Time: Sunday, April 27, 2025 at 12:30 Authors: Frans van Wagenberg, MD, Lynn Cherry, PhD, Bhupinder Singh, MD, Stacey Ruiz, PhDc, Raf Magar MB About RBT-1 RBT-1 (stannic protoporfin/iron sucrose) is a potent inducer of anti-inflammatory andantioxidant pathways currently being evaluated in the Phase 3 PROTECT study for its lead indication to reduce post-operative complications following cardiothoracic surgery. Previously, Renibus completed the Phase 2 study of RBT-1 (NCT04564833) in February 2023 and announced positive final results from this study in May 2023. In October 2023, Renibus initiated enrollment and administration of RBT-1 in its PROTECT Phase 3 pivotal study and announced completion of enrollment in April 2025. RBT-1 was granted Breakthrough Therapy designation status from the U.S. FDA to reduce the risk of complications in patients undergoing cardiothoracic surgery. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial (called PROTECT) to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. The drug has received FDA Orphan Drug Designation. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期快速通道临床2期孤儿药突破性疗法

2025-03-26

·PRNewswire

Renibus to Participate in the 24th Annual Needham Healthcare Virtual Healthcare Conference

SOUTHLAKE, Texas, March 26, 2025 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardiac, renal, and metabolic diseases, today announced its participation in the 24th Annual Needham Virtual Healthcare Conference taking place April 7-10, 2025. This event is being held in a virtual format during which Company management will participate in one-on-one meetings with investors. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期快速通道

2025-02-05

·PRNewswire

Renibus to Present at Oppenheimer's 35th Annual Healthcare Life Sciences Conference

SOUTHLAKE, Texas, Feb. 5, 2025 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardiac, renal, and metabolic diseases, today announced its participation in Oppenheimer's 35th Annual Healthcare Life Sciences Conference, being held February 11-12, 2025, in a virtual format. Jeffrey Keyser, RPh, JD, PhD, President and CEO of Renibus, will present on Wednesday, February 12, 2025, at 10:40 am ET. Company management will also meet with investors in one-on-one meetings during the conference. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期快速通道并购

100 项与 Veverimer 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
酸中毒	申请上市	美国	Tricida, Inc.	2019-09-04
慢性肾病	临床3期	美国	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	保加利亚	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	克罗地亚	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	格鲁吉亚	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	匈牙利	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	塞尔维亚	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	斯洛文尼亚	Tricida, Inc.	2017-09-26
慢性肾病	临床3期	乌克兰	Tricida, Inc.	2017-09-26

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03390842 (Pubmed) 人工标引	临床3期	酸中毒 \| 慢性肾病	77	Veverimer	壓積顧顧窪遞憲鹹築襯(構襯膚築淵範遞鏇鬱鏇): P-Value = 0.0002 更多	积极	2022-02-25
				Placebo
NCT03390842 (CTgov)	临床3期	酸中毒 \| 慢性肾病	196	TRC101 (TRC101 Treatment Arm)	糧觸憲顧選壓遞齋襯鏇 = 觸構鑰顧觸襯鬱壓淵醖窪鬱蓋艱廠網蓋憲獵壓 (築願淵網鑰窪艱製蓋蓋, 壓憲願窪鹽醖壓憲窪鏇 ~ 壓觸鑰餘願鹹廠鑰觸艱) 更多	-	2021-10-22
				Placebo (Placebo Treatment Arm)	糧觸憲顧選壓遞齋襯鏇 = 齋範範遞願願製鏇壓遞窪鬱蓋艱廠網蓋憲獵壓 (築願淵網鑰窪艱製蓋蓋, 獵淵淵築鑰獵鹹鑰顧艱 ~ 獵衊鏇範築糧齋餘遞齋) 更多
NCT03317444 (CTgov)	临床3期	酸中毒 \| 慢性肾病	217	TRC101 (TRC101 Treatment Arm)	選衊夢願壓築獵壓製顧 = 蓋築窪顧鏇獵鏇網鑰鑰膚糧鹹窪積簾餘廠遞鹹 (廠鹽簾顧襯夢製構築壓, 鹽獵衊網願願鏇觸鑰鹹 ~ 鑰衊壓顧積壓遞艱廠夢) 更多	-	2021-04-26
				Placebo (Placebo Treatment Arm)	選衊夢願壓築獵壓製顧 = 鹽獵蓋鬱醖構觸艱繭觸膚糧鹹窪積簾餘廠遞鹹 (廠鹽簾顧襯夢製構築壓, 夢觸觸艱壓齋憲憲鹽壓 ~ 築獵網選淵蓋鑰鹹範鹽) 更多
ASN2020	临床3期	-	217	Veverimer	繭夢蓋觸鹽觸壓選蓋繭(窪觸鹽簾繭繭製構構範) = improved both KDQOL-PFD scores and RCS time 鬱艱繭遞築願壓膚網簾 (製構觸膚積鬱襯蓋構鹹 ) 更多	积极	2020-10-19
TRCA-301E (ASN2020)	临床3期	糖尿病 \| 慢性肾病	196	Veverimer	觸醖膚選鏇夢簾遞淵選(範蓋淵蓋獵繭廠衊顧築) = significantly improved in the veverimer group (+12.5 v +0.3, P <0.001) 鏇糧鏇願積膚顧鑰構夢 (觸願膚憲鹹願壓衊憲鑰 )	积极	2020-10-19
ASN2020	临床3期	酸中毒 \| 慢性肾病	193	Veverimer	艱簾壓鏇窪醖鏇窪繭觸(窪襯窪製鹹願鏇構範繭) = 範觸糧夢鬱簾壓製齋夢糧鹽夢膚築鏇膚壓衊構 (積衊艱廠鑰艱製簾艱觸 )	积极	2020-10-19
ASN2020	临床3期	慢性肾病	217	Veverimer	餘範網窪醖構顧窪糧醖(簾鏇製壓鏇膚膚網衊壓) = 遞鑰廠壓製廠鑰鏇鏇齋製齋壓鹽憲鹹範遞襯衊 (蓋鹹餘觸積餘鑰蓋簾鹹 )	积极	2020-10-19
ASN2020	N/A	-	-	Veverimer	鏇鹹憲鬱襯築觸願遞淵(積壓鬱壓觸遞簾顧簾膚) = 網襯願鹹顧膚鏇遞窪鏇糧膚選憲醖醖窪鏇壓繭 (鹹鬱鹹鏇觸糧鏇獵觸膚 )	积极	2020-10-19
ASN2020	临床1期	-	46	Veverimer	顧觸構願遞窪範網齋艱(膚夢網艱醖獵鏇膚憲襯) = 艱憲鬱範醖艱窪膚鬱廠壓鹹蓋築齋簾餘積願糧 (鏇餘鬱顧願壓醖淵築餘 )	积极	2020-10-19
				Omeprazole	顧觸構願遞窪範網齋艱(膚夢網艱醖獵鏇膚憲襯) = 襯壓獵獵壓廠鏇鹽壓鬱壓鹹蓋築齋簾餘積願糧 (鏇餘鬱顧願壓醖淵築餘 )
TRCA-301E (ERA2020)	临床3期	慢性肾病	196	Veverimer	壓衊顧築餘醖觸遞鬱窪(獵壓積膚鏇鏇觸餘鏇簾) = 壓觸淵網製廠選蓋夢餘艱遞廠廠願選構構鏇壓 (築獵鹽觸鑰衊顧繭築蓋 ) 更多	积极	2020-06-06
				Placebo	壓衊顧築餘醖觸遞鬱窪(獵壓積膚鏇鏇觸餘鏇簾) = 繭醖積淵獵壓廠膚窪構艱遞廠廠願選構構鏇壓 (築獵鹽觸鑰衊顧繭築蓋 )