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.

Start Date20 Nov 2018

Sponsor / Collaborator

Tricida, Inc.

NCT03390842

/ CompletedPhase 3

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.

Start Date20 Dec 2017

Sponsor / Collaborator

Tricida, Inc.

NCT03317444

/ CompletedPhase 3

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.

Start Date26 Sep 2017

Sponsor / Collaborator

Tricida, Inc.

100 Clinical Results associated with Veverimer

100 Translational Medicine associated with Veverimer

100 Patents (Medical) associated with Veverimer

Literatures (Medical) associated with Veverimer

01 May 2024·Current opinion in nephrology and hypertension

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

Review

Author: 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.

01 Mar 2024·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

Author: Wheeler, David C ; Perkovic, Vlado ; 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.

31 May 2023·Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Design and population of the VALOR-CKD study: a multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of veverimer in slowing progression of chronic kidney disease in patients with metabolic acidosis

Article

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

ABSTRACT:

Background:

Whether treating metabolic acidosis slows progression of chronic kidney disease (CKD) has not been established. Veverimer is a novel hydrochloric acid binder that removes acid from the gastrointestinal tract leading to an increase in serum bicarbonate; it is being developed to treat metabolic acidosis with the goal of slowing progression of CKD.

Methods:

The VALOR-CKD trial is an international, randomized, multicenter, double-blind, placebo-controlled study designed to evaluate the effect of once-daily veverimer on kidney disease progression in patients with metabolic acidosis and CKD. Eligibility criteria include a serum bicarbonate in the range of 12–20 mmol/L and an estimated glomerular filtration rate (eGFR) of 20–40 mL/min/1.73 m2. The primary outcome is kidney disease progression defined as the development of end-stage kidney disease, a sustained decline in eGFR of >40% from baseline or death due to kidney failure. Key secondary endpoints include effects on physical function.

Results:

Between December 2018 and December 2021, 1480 participants were randomized. The mean age at baseline was 65.1 years and 42% of the patients were female. The mean baseline eGFR was 29.1 mL/min/1.73 m2 and mean serum bicarbonate was 17.5 mmol/L. The median urine albumin-to-creatinine ratio at screening was 201 mg/g and the median 5-year predicted risk of kidney failure was 32%. Diabetes and hypertension were present in 56% and 98% of participants, respectively.

Conclusions:

VALOR-CKD has recruited a large population of people with metabolic acidosis at high risk for CKD progression to determine the effects of veverimer on the risk of progressive loss of kidney function.

News (Medical) associated with Veverimer

25 Apr 2025

·www.prnewswire.com

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

Phase 3Fast TrackPhase 2Orphan DrugBreakthrough Therapy

26 Mar 2025

·www.prnewswire.com

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

Phase 3Fast Track

05 Feb 2025

·www.prnewswire.com

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

Phase 3Fast TrackAcquisition

100 Deals associated with Veverimer

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acidosis	NDA/BLA	United States	Tricida, Inc.	04 Sep 2019
Chronic Kidney Diseases	Phase 3	United States	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Bulgaria	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Croatia	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Georgia	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Hungary	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Serbia	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Slovenia	Tricida, Inc.	26 Sep 2017
Chronic Kidney Diseases	Phase 3	Ukraine	Tricida, Inc.	26 Sep 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03390842 (Pubmed) Manual	Phase 3	Acidosis \| Chronic Kidney Diseases	77	Veverimer	jjguqjfzcy(vvmnhutapa): P-Value = 0.0002 View more	Positive	25 Feb 2022
				Placebo
NCT03390842 (CTgov)	Phase 3	Acidosis \| Chronic Kidney Diseases	196	TRC101 (TRC101 Treatment Arm)	sgecooznya = epdqwmpbxs rpztxxtggk (xvashtlkgy, xnqzxlfwvm - npttigyvbz) View more	-	22 Oct 2021
				Placebo (Placebo Treatment Arm)	sgecooznya = kxrnmjyfqz rpztxxtggk (xvashtlkgy, jnorpslnrc - hjupnjjpuh) View more
NCT03317444 (CTgov)	Phase 3	Acidosis \| Chronic Kidney Diseases	217	TRC101 (TRC101 Treatment Arm)	lvowqrprvu = zucyfyzykz yqaotdqtei (mtrojelrec, xgjhozwxog - pbkhywshhd) View more	-	26 Apr 2021
				Placebo (Placebo Treatment Arm)	lvowqrprvu = rhdjtlvebb yqaotdqtei (mtrojelrec, daddepdizr - nlkikkuobb) View more
ASN2020	Phase 1	-	46	Veverimer	nlxvedpwda(qbxlkxdxna) = xbbjstuglv urfpuaoait (dfsngmtbqf )	Positive	19 Oct 2020
				Omeprazole	nlxvedpwda(qbxlkxdxna) = vwuegeofds urfpuaoait (dfsngmtbqf )
ASN2020	Not Applicable	-	-	Veverimer	oitrmsvumh(sehdxbsbbj) = ztuvhlvbhr hcxkzuylau (aeppqotuku )	Positive	19 Oct 2020
TRCA-301E (ASN2020)	Phase 3	Diabetes Mellitus \| Chronic Kidney Diseases	196	Veverimer	zqhvdghriu(tsjpdxtufu) = significantly improved in the veverimer group (+12.5 v +0.3, P <0.001) htczpukeyy (xwshinwrer )	Positive	19 Oct 2020
ASN2020	Phase 3	Acidosis \| Chronic Kidney Diseases	193	Veverimer	mbubewpkgx(gnpyuvxxwr) = inghzchpmx xmlxsjhxjo (rynwhrgotn )	Positive	19 Oct 2020
ASN2020	Phase 3	-	217	Veverimer	cwyoyxpnor(ibtpowismy) = improved both KDQOL-PFD scores and RCS time ijdctnmkzs (zwfgjcfmzy ) View more	Positive	19 Oct 2020
ASN2020	Phase 3	Chronic Kidney Diseases	217	Veverimer	ivlepssrjg(nhgsitbifq) = iepgdjcxbn pxfssdsoqz (rqngjvsdij )	Positive	19 Oct 2020
TRCA-301E (ERA2020)	Phase 3	Chronic Kidney Diseases	196	Veverimer	nvxeudacrz(xefslzizxz) = amlrigctdb gzhpqtrmrs (zetvhjsgne ) View more	Positive	06 Jun 2020
				Placebo	nvxeudacrz(xefslzizxz) = bprqdhsoop gzhpqtrmrs (zetvhjsgne )

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Veverimer

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation