SPARTAN: A Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a single centre, open-label, single-group study to explore the safety of, and response to sparsentan treatment in incident, renin angiotensin system (RAS) blockade-naïve patients with biopsy-proven immunoglobulin A nephropathy (IgAN). The purpose is to explore sparsentan treatment as a potential first-line treatment in patients newly diagnosed with IgAN (ie, incident patients), who have thus not received prior treatment with ACEI or ARB therapy for IgAN. Response to treatment will be assessed as changes from baseline rather than comparison to another treatment, and will be based on established proteinuria endpoints (UPCR and protein excretion), and glomerular filtration rate (GFR); a number of exploratory measures will be assessed as well.
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 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, followed by an off-treatment follow-up period of 4 weeks.
Study Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- Urine protein/creatinine ratio (UP/C) at Week 36 [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.
Secondary Outcome Measures
- eGFR over a 52-week period [Week 58]
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).
- eGFR over a 104-week period [Week 110]
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).
- Change from baseline in proteinuria [Up to Week 114]
Change from baseline in proteinuria, measured by urinary protein/creatinine ratio [UPCR] and 24-hour protein excretion, up to Week 114
- Abnormalities in clinical laboratory assessments and vital signs [Up to Week 114]
Proportion of patients with abnormalities in clinical laboratory assessments and vital signs at each visit
- Incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation, AEs leading to death [Up to Week 114]
AEs, serious AEs, AEs leading to discontinuation, AEs leading to death
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Aged 18 years or older at screening.
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Diagnosed with biopsy-proven IgAN within the last 3 months.
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Proteinuria of ≥0.5 g/day at screening.
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eGFR ≥30 mL/min/1.73 m2 at screening.
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Not previously treated with ACEI and/or ARB therapy for IgAN OR has not received ACEI and/or ARB therapy within the last 12 months.
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Systolic BP ≤150 mmHg and ≥100 mmHg, and diastolic blood pressure ≤100 mmHg and ≥60 mmHg at screening.
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Women of childbearing potential (WOCBP) to agree to contraception
Key Exclusion Criteria:
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IgAN secondary to another condition.
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Rapidly progressive glomerulonephritis (e.g. rapid decline in GFR and crescents on biopsy).
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History of type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (haemoglobin A1c [HbA1c] >8%), or nonfasting blood glucose >10 mmol/L (180 mg/dL) at screening.
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History of organ transplantation, with the exception of corneal transplants.
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Requires any of the prohibited concomitant medications listed in protocol.
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Treatment with any systemic immunosuppressive medications for >2 weeks within 6 months prior to screening.
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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.
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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.
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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.
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History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
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Haematocrit value <27% or haemoglobin value <90 g/L (9 g/dL) at screening.
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Potassium >5.5 mmol/L (5.5 mEq/L) at screening.
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History of alcohol or illicit drug use disorder.
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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.
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For females: Pregnancy, or plans to become pregnant during the course of the study, or is breastfeeding.
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Participation 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.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Leicester General Hospital, University Hospitals of Leicester NHS Trust | Leicester | United Kingdom | LE5 4PW |
Sponsors and Collaborators
- University of Leicester
- Travere Therapeutics, Inc.
Investigators
- Principal Investigator: Chee Kay Cheung, MBChB PhD, University of Leicester
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0708
- 2018-002012-27