A Study of the Safety and Activity of Sparsentan for the Treatment of Patients With Immunoglobulin A Nephropathy (SPARTAN)

A Multi-centre, Open-label, Exploratory Trial of the Safety and Activity of Sparsentan for the Treatment of Incident (Cohort A) and Recurrent (Cohort B) Patients With Immunoglobulin A Nephropathy

To determine the nephroprotective potential of treatment with sparsentan in (1: Cohort A) patients newly-diagnosed with immunoglobulin A nephropathy (IgAN) (ie, incident patients) who have not received prior angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy, and in (2: Cohort B) patients with recurrent IgAN following kidney transplantation.

Study Overview

• Status: Recruiting
• Conditions: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Glomerulonephritis; Immunoglobulin A Nephropathy; Glomerulonephritis, IGA
• Intervention / Treatment: Drug: Sparsentan

Detailed Description

This multi-centre, open-label trial will explore the safety of, and response to sparsentan treatment in adult patients with biopsy-proven immunoglobulin A nephropathy (IgAN).

In Cohort A, incident, renin angiotensin system (RAS) blockade-naïve patients will be included. The starting dose of sparsentan will be 200 mg/day, which will be titrated up to the target dose of 400 mg/day at Week 2. Patients who do not tolerate the target dose will have their dose reduced back to 200 or 100 mg/day; throughout the trial, patients will be maintained on the maximum allowed dose of sparsentan they can tolerate. All patients will be treated with sparsentan for a total of 110 weeks, followed by an off-treatment follow-up period of 4 weeks. Urinary protein excretion, estimated and measured glomerular filtration rate (GFR), Oxford Classification (MEST-C) for renal biopsies, magnetic resonance imaging (MRI) for renal interstitial fibrosis and cardiac function, and bioimpedance spectroscopy for total body water will be assessed. Quality of Life (QOL) will also be assessed. Treatment with additional antihypertensive agents is permitted during the trial, with the exception of angiotensin-converting enzyme inhibitors (ACEIs), aldosterone blockers, aliskiren, or angiotensin receptor blockers (ARBs). Safety will be assessed by adverse events (AEs), clinical laboratory evaluations, and vital signs.

In Cohort B, patients with recurrent IgAN following kidney transplantation receiving stable standard of care (SOC) therapy, including standard immunosuppressive therapy (that includes tacrolimus) to prevent graft rejection, will be randomly assigned in a 1:1 ratio to receive sparsentan in addition to SOC therapy for 48 weeks or to remain on SOC therapy for the first 24 weeks after which sparsentan will be added to SOC therapy for the second 24 weeks of the study. All patients will stop ACEIs, ARBs, aldosterone blockers or aliskiren prior to initiating sparsentan treatment. All patients will complete a 4-week follow-up period, during which time treatment will be at the discretion of the investigator. Urinary protein excretion, estimated GFR (eGFR), Oxford Classification (MEST-C) for renal biopsies will be assessed, as well as measurement of tacrolimus levels during the trial. Safety will be assessed by adverse events (AEs), clinical laboratory evaluations, and vital signs.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Justyna Szklarzewicz; Phone Number: +44 116 258 4351; Email: justyna.szklarzewicz@uhl-tr.nhs.uk

Study Locations

• United Kingdom
  • Leicester, United Kingdom, LE5 4PW
    • Recruiting
    • Leicester General Hospital, University Hospitals of Leicester NHS Trust
    • Contact: Justyna Szklarzewicz; Phone Number: +44 116 258 4351; Email: justyna.szklarzewicz@uhl-tr.nhs.uk
    • Principal Investigator: Chee Kay Cheung, MBChB PhD
  • London, United Kingdom
    • Recruiting
    • King's College Hospital
  • England
    • Cambridge, England, United Kingdom
      • Recruiting
      • Cambridge University Hospitals NHS Trust
    • Salford, England, United Kingdom
      • Recruiting
      • Northern Care Alliance NHS Foundation Trust - Salford Royal
  • Scotland
    • Edinburgh, Scotland, United Kingdom
      • Recruiting
      • Royal Infirmary of Edinburgh & Western General Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Recruiting
      • University Hospital of wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For Cohort A (Patients with Incident IgAN)

Inclusion Criteria:

• The patient is willing and able to provide signed informed consent.
• The patient can understand written and spoken English.
• The patient is male or female, aged ≥18 years.
• The patient has been diagnosed with biopsy-proven IgAN within the last 6 months (calculated from the date of kidney biopsy, upon which the IgAN-positive diagnosis was made, to the signing of the informed consent form).
• The patient has a urine total protein value ≥0.5 g/day at screening.
• The patient has an eGFR value ≥30 mL/min/1.73 m2 at screening.
• The patient has not previously been treated with ACEI and/or ARB therapy for IgAN OR has not received ACEI and/or ARB therapy within the last 12 months.
• The patient has a systolic BP ≤150 mmHg and ≥100 mmHg, and diastolic blood pressure ≤100 mmHg and ≥60 mmHg at screening.
• Women of childbearing potential (WOCBP), beginning at menarche, must agree to the use of one highly reliable (ie, can achieve a failure rate of <1% per year) method of contraception from 7 days prior to the first dose of trial medication until 90 days after the last dose of trial medication. Highly reliable contraception methods include stable oral, implanted, transdermal, or injected contraceptive hormones associated with inhibition of ovulation, or an intrauterine device (IUD) in place for at least 3 months. One additional barrier method must also be used during sexual activity, such as a diaphragm or diaphragm with spermicide (preferred), or male partner's use of male condom or male condom with spermicide), from Day 1 until 90 days after the last dose of trial medication.

WOCBP are defined as those who are fertile, following menarche and until becoming postmenopausal unless permanently sterile; permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as amenorrhoea for more than 24 consecutive months without an alternative medical cause; women on hormone replacement therapy must have a documented plasma follicle-stimulating hormone level ≥40 mIU/mL. All WOCBP must have a negative pregnancy test at Visit 1 (serum test) and Visit 2 (urine, with positive results confirmed by serum).

Exclusion Criteria:

• The patient has IgAN secondary to another condition (eg, systemic lupus erythematosus, liver cirrhosis).
• The patient, in the opinion of the Investigator, has a rapidly progressive glomerulonephritis (rapid decline in GFR and crescents on biopsy).
• The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (haemoglobin A1c [HbA1c] >8%), or nonfasting blood glucose >10 mmol/L (180 mg/dL) at screening.
• The patient has undergone any organ transplantation, with the exception of corneal transplants.
• The patient requires any of the prohibited concomitant medications (see Section 14.4).
• The patient has been taking any systemic immunosuppressive medications for >2 weeks within 6 months prior to screening.
• The patient has a documented history of heart failure (New York Heart Association Class II-IV) and/or previous hospitalisation for heart failure or unexplained dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, ascites, and/or peripheral oedema.
• The patient has clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalisation for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularisation procedure) within 6 months prior to screening.
• The patient has jaundice, hepatitis, or known hepatobiliary disease (including asymptomatic cholelithiasis), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of the normal range at screening.
• The patient has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
• The patient has a screening haematocrit value <27% or haemoglobin value <90 g/L (9 g/dL).
• The patient has a screening potassium value of >5.5 mmol/L (5.5 mEq/L).
• The patient has a history of alcohol or illicit drug use disorder (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition).
• The patient has a history of serious side effects or allergic response to any AngII or ERA, including sparsentan, or has a hypersensitivity to any of the excipients in the IMP.
• The female patient is pregnant, plans to become pregnant during the course of the trial, or is breastfeeding.
• The patient has participated in a trial of any investigational product within 28 days prior to screening, or plans to participate in such a trial during the course of this trial.
• The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the trial, including the ability to swallow the IMP whole.
• The patient, in the opinion of the Investigator, has a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity.
• Patients with a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity will be reviewed before consideration of the patient for enrolment.

For Cohort B (Recurrent IgAN following kidney transplantation)

Inclusion Criteria:

• Male and female aged ≥18 years
• Diagnosis of recurrent IgAN based on histological analysis of a transplanted kidney biopsied within the last 6 months
• A time period of >12 months since kidney transplantation
• UPCR ≥50 mg/mmol (≥0.44 g/g) and eGFR value ≥25 mL/min/1.73 m2
• For patients on an ACEI and/or ARB, and/or SGLT2 inhibitor, the dosing regimen is stable for at least 6 weeks prior to and during the screening period
• Tacrolimus treatment as part of standard of care immunosuppression following kidney transplantation
• Systolic BP ≤150 mmHg and ≥100 mmHg, and diastolic blood pressure ≤100 mmHg and ≥60 mmHg at screening.
• Female patients not of childbearing potential, or of childbearing potential and agreeing to use the contraceptive methods listed in Section 5.1

Exclusion Criteria:

• The patient has recurrent IgAN secondary to another condition or cause (eg, systemic lupus erythematosus, liver cirrhosis).
• Evidence of alternative pathology on the kidney transplant biopsy as the main cause for proteinuria (e.g. diabetic nephropathy, chronic transplant glomerulopathy, mTORi treatment)
• Patient has multiorgan transplants (with the exception of corneal transplants)
• Immunosuppressive therapy (IST) regimen for kidney transplant or other chronic immunosuppressive therapies that is not stable for >6 weeks prior to Day 1. Exceptions include routine protocol tapering and for tacrolimus, changes in dose to meet target level
• Treatment with enteric budesonide (nefecon) within 6 months prior to screening, or planned use of enteric budesonide (nefecon) at any time during the study.
• Current treatment for surgical complications
• <3 months after anti-rejection treatment or active rejection
• Active bacterial, fungal or viral infection and/or active treatment of infection including BKV, CMV, HIV, Hepatitis B and C <3 months prior to and during the screening period
• Current treatment for surgical complications
• Uncontrolled diabetes mellitus (defined by HbA1C >8% (>64 mmol/mol)
• History of heart failure (New York Heart Association (NYHA) Class II-IV)
• Jaundice, hepatitis, or known hepatobiliary disease
• Malignancy within the past 2 years with the exception of adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin, with no evidence or recurrence
• Haematocrit <27%, haemoglobin <90 g/L (9 g/dL), or potassium >5.5 mmol/L (5.5 mEq/L)
• History of alcohol or illicit drug use disorder (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition)
• History of serious side effects or allergic response to any angiotensin II antagonist or endothelin receptor antagonist (ERA) or dual endothelin and angiotensin receptor antagonist (DEARA e.g. sparsentan)
• The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
• The patient has participated in a study of any investigational product within 28 days prior to screening, or plans to participate in such a study during the course of this study.
• The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the IMP whole.
• The patient, in the opinion of the Investigator, has a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity.

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 once daily, starting at a dose of 200 mg (two 100 mg oral capsules) for the first 2 weeks of the study. Patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400 mg (one 400 mg tablet). Patients who do not tolerate the target dose will have their dose reduced back to 200 or 100 mg/day; throughout the study, patients will be maintained on the maximum allowed dose of sparsentan they can tolerate. All patients will be treated with sparsentan for a total of 110 weeks.

Drug: Sparsentan; Target dose of 400 mg daily; Other Names: RE-021

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine protein/creatinine ratio (UP/C) at Week 36	The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR over a 52-week period	Rate of change in eGFR over a 1-year (52 week) period following the initial acute effect of therapy (ie, from 6 weeks post-initiation of investigational medicinal product (IMP) to 58 weeks post-initiation of IMP).	Week 58
eGFR over a 104-week period	Rate of change in eGFR over a 2-year (104 week) period following the initial acute effect of therapy (ie, from 6 weeks post-initiation of investigational medicinal product (IMP) to 110 weeks post-initiation of IMP).	Week 110
Change from baseline in proteinuria	Change from baseline in proteinuria, measured by urinary protein/creatinine ratio [UPCR] and 24-hour protein excretion, up to Week 114	Up to Week 114
Abnormalities in clinical laboratory assessments and vital signs	Proportion of patients with abnormalities in clinical laboratory assessments and vital signs at each visit	Up to Week 114
Incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation, AEs leading to death	AEs, serious AEs, AEs leading to discontinuation, AEs leading to death	Up to Week 114

Collaborators and Investigators

• Sponsor: University of Leicester
• Collaborators: Travere Therapeutics, Inc.
• Investigators: Principal Investigator: Chee Kay Cheung, MBChB PhD, University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Nephritis; Glomerulonephritis; Autoimmune Diseases; Kidney Diseases; Glomerulonephritis, IGA; Immune System Diseases; sparsentan
• Other Study ID Numbers: 0708; 2018-002012-27 (EudraCT Number); 257450 (Other Identifier: Health Research Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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