A Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in Participants With IgAN (SPARTACUS)

A Multicentered, Single-group Phase 2, Exploratory, Open-label Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in the Treatment of Adult Participants With Immunoglobulin A Nephropathy (IgAN)

This was a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with IgAN who are at risk of disease progression to kidney failure despite being on both stable RAASi and SGLT2 inhibitor treatment for at least 12 weeks prior to study entry

Study Overview

• Status: Completed
• Conditions: Immunoglobulin A Nephropathy
• Intervention / Treatment: Drug: Sparsentan

Detailed Description

This was a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with Immunoglobulin A Nephropathy (IgAN) who are at risk of disease progression to kidney failure (KF) despite being on both stable renin angiotensin aldosterone system inhibitor (RAASi) and sodium glucose cotransporter-2 (SGLT2) inhibitor treatment for at least 12 weeks prior to study entry.

Participants who provided written informed consent were assessed for eligibility and underwent baseline evaluations including clinical laboratory tests. Per the eligibility criteria, all participants were required to be on a stable dose(s) of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) and on a stable dose of a SGLT2 inhibitor at screening and continued their stable treatments through the screening period. Eligible participants discontinued ACEI and/or ARB therapy the day before the Day 1 visit and remained on stable SGLT2 inhibitor dosing for the duration of the study.

Study intervention was administered daily for a treatment period of 24 weeks with study visits conducted at weeks 2-, 4-, 12-, and 24- following Day 1. Following the 24-week treatment period, study intervention was discontinued for 4 weeks and standard of care RAASi treatment resumed, with a safety visit at Week 28.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Travere Investigational Site
  • Kowloon, Hong Kong
    • Travere Investigational Site
  • Shatin, Hong Kong
    • Travere Investigational Site
  • Sheung Wan, Hong Kong
    • Travere Investigational Site
  • Tsuen Wan, Hong Kong
    • Travere Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Travere Investigational Site
  • California
    • Chula Vista, California, United States, 91910
      • Travere Investigational Site
    • Garden Grove, California, United States, 92844
      • Travere Investigational Site
    • Glendale, California, United States, 91206
      • Travere Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Travere Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83706
      • Travere Investigational Site
    • Chubbuck, Idaho, United States, 83202
      • Travere Investigational Site
    • Idaho Falls, Idaho, United States, 83404
      • Travere Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Travere Investigational Site
    • Evergreen Park, Illinois, United States, 60805
      • Travere Investigational Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Travere Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Travere Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Travere Investigational Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Travere Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Travere Investigational Site
  • New York
    • Clifton Park, New York, United States, 12065
      • Travere Investigation Site
    • Fresh Meadows, New York, United States, 11365
      • Travere Investigational Site
    • New York, New York, United States, 10013
      • Travere Investigational Site
  • North Carolina
    • Jacksonville, North Carolina, United States, 28546
      • Travere Investigational Site
    • New Bern, North Carolina, United States, 28562
      • Travere Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Travere Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Travere Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Travere Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Travere Investigational Site
    • Dallas, Texas, United States, 75230
      • Travere Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years at the time of signing the informed consent.
• Biopsy-proven IgAN. The biopsy may have been performed at any time in the past.
• UA/C ≥0.3 g/g at screening
• An eGFR value of ≥25 mL/min/1.73m^2 at screening.
• On a stable dose of an SGLT2 inhibitor for at least 12 weeks prior to screening.

• On a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening that is:

  • The participant's maximum tolerated dose (MTD), and
  • at least one half of the maximum labeled dose (MLD)
• Systolic BP must be ≤160 mmHg, and diastolic BP must be ≤110 mmHg at screening.
• For participants receiving chronic low dose systemic corticosteroids (defined as ≤10 mg/day prednisone or equivalent), or an enteric formulation of budesonide and/or a mineralocorticoid receptor antagonist (MRA), the dosage must be stable for ≥12 weeks prior to screening.

Exclusion Criteria:

• IgAN secondary to another condition or immunoglobulin A (IgA) vasculitis.
• Undergone any organ transplant, with the exception of corneal transplants.
• Documented history of heart failure.
• Taking high dose (defined as >10 mg/day prednisone) or other any systemic immunosuppressive medications within 12 weeks of prior to screening.
• Has clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 3 months prior to screening.
• Has jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or ALT and/or AST >2 times the ULN range at screening.
• Has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
• Has a history of serious side effect or allergic response to any AngII antagonist, ERA or sparsentan, or has a hypersensitivity to any of the excipients in the study intervention.
• Requires any of the prohibited concomitant medications.
• Treatment with sparsentan within 12 weeks prior to screening
• Has participated in a study of another investigational product within 28 days prior to screening or plans to participate in such a study during the course of this study.
• Has a screening hematocrit value <27% (0.27 Volume/Volume) or hemoglobin value <9 g/dL (90 g/L).
• Has a screening potassium value of >5.5 mEq/L (5.5 mmol/L).
• Is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
• The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the study intervention capsules whole.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sparsentan; Sparsentan will be administered daily as a 200-mg oral tablet. The goal is to titrate from the initial dose of 200 mg (Day 1) to the target dose of 400 mg at Week 2.	Drug: Sparsentan; Target dose of 400 mg daily; Other Names: RE-021; Filspari

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urine Albumin-creatinine Ratio (UA/C) at Week 24	The change from baseline in UA/C at Week 24 based on first morning void (FMV) samples	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UA/C <0.2 g/g at Week 24	Achievement of UA/C of <0.2 g/g at Week 24 based on FMV samples	Week 24
30% Reduction From Baseline in UA/C at Week 24	Achievement of 30% reduction from baseline in UA/C at Week 24 based on FMV samples	Week 24
50% Reduction From Baseline in UA/C at Week 24	Achievement of 50% reduction from baseline in UA/C at Week 24 based on FMV samples	Week 24
Change in Urine Protein-to-creatinine Ratio (UP/C) at Week 24	The change from baseline in UP/C at Week 24 based on FMV samples	Week 24
Estimated Glomerular Filtration Rate (eGFR)	Change from baseline estimated glomerular filtration rate at 24 weeks	Week 24
Systolic Blood Pressure (BP) at Week 24	The change from baseline in systolic BP at Week 24	Week 24
Change in Diastolic Blood Pressure (BP)	The change from baseline in diastolic BP at Week 24	Week 24

Collaborators and Investigators

• Sponsor: Travere Therapeutics, Inc.
• Investigators: Study Director: Radko Komers, MD, PhD, Travere Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Actual): October 14, 2024
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: IgAN
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA; sparsentan
• Other Study ID Numbers: TVTX-RE021-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
• IPD Sharing Time Frame: Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication
• IPD Sharing Access Criteria: Requires submission and approval of intended use and a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No