A Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy

NCT04663204 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: 07082018-002012-27257450
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

To determine the nephroprotective potential of treatment with sparsentan in 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.

Conditions

Immunoglobulin A Nephropathy; Kidney Diseases; Glomerulonephritis, IGA; Glomerulonephritis; Autoimmune Diseases; Immune System Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• eGFR over a 52-week period

  Week 58

• eGFR over a 104-week period

  Week 110

• Change from baseline in proteinuria

  Up to Week 114

• Abnormalities in clinical laboratory assessments and vital signs

  Up to Week 114

• Incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation, AEs leading to death

  Up to Week 114

Study Arms (1)

Sparsentan

EXPERIMENTAL

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

Interventions

Sparsentan DRUG

Target dose of 400 mg daily

Also known as: RE-021

Sparsentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Leicester: lead
• Travere Therapeutics, Inc.: collaborator

Study Sites (5)

Cambridge University Hospitals NHS Trust

Cambridge, England, United Kingdom

Location

Northern Care Alliance NHS Foundation Trust - Salford Royal

Salford, England, United Kingdom

Location

Royal Infirmary of Edinburgh & Western General Hospital

Edinburgh, Scotland, United Kingdom

Location

University Hospital of wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Leicester General Hospital, University Hospitals of Leicester NHS Trust

Leicester, LE5 4PW, United Kingdom

Location

MeSH Terms

Conditions

Glomerulonephritis, IGA; Kidney Diseases; Glomerulonephritis; Autoimmune Diseases; Immune System Diseases

Interventions

sparsentan

Condition Hierarchy (Ancestors)

Nephritis; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Chee Kay Cheung, MBChB PhD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 10, 2020
• Study Start: December 10, 2020
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)