Sparsentan for proteinuria after kidney transplant due to IgA nephropathy or FSGS

A Multicenter, Open-label Single Arm Study to Evaluate the Safety and Efficacy of Sparsentan in Posttransplant Immunoglobulin A Nephropathy (IgAN) or Focal Segmental Glomerulosclerosis (FSGS) (SPARX)

This study will try daily sparsentan pills for up to 36 weeks in adults who have proteinuria after a kidney transplant caused by IgA nephropathy or FSGS.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Travere Therapeutics, Inc. (Industry-sponsored)
• Locations: 9 sites (Birmingham, Alabama and 8 other locations)
• Trial ID: NCT07219121 on ClinicalTrials.gov

What this trial studies

This 46-week, open-label, single-group Phase 4 study gives sparsentan once daily for 36 weeks followed by a 4-week off-drug follow-up in adults with biopsy-proven IgAN or FSGS in the transplanted kidney and proteinuria ≥0.5 g/g. Participants remain on standard immunosuppression, stop RAAS inhibitors before starting sparsentan, and have scheduled visits through Week 36 plus a telephone follow-up at Week 40. Dosing differs by diagnosis: posttransplant IgAN starts 200 mg daily for 2 weeks then 400 mg daily, while FSGS-pattern grafts start 400 mg then escalate to 800 mg daily for maintenance. The trial will monitor safety and changes in proteinuria and kidney function (eGFR) over the treatment period.

Who should consider this trial

Good fit: Adults at least 12 months after kidney transplant with biopsy-proven IgAN or FSGS in the graft, UPCR ≥0.5 g/g, and eGFR ≥30 mL/min/1.73 m2 who can stop RAAS inhibitors and remain on stable immunosuppression.

Not a fit: People with multiorgan transplants, uncontrolled blood pressure, eGFR below 30, or other contraindications to sparsentan are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, sparsentan could reduce proteinuria and help preserve graft function in transplant recipients with IgAN or FSGS.

How similar studies have performed: Previous trials of sparsentan in native-kidney FSGS and IgAN have shown meaningful proteinuria reductions, but its use in the post-transplant setting has been little studied.

Eligibility criteria

Inclusion Criteria:

* Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
* Male and female aged ≥18 years
* Participants with a kidney transplant with biopsy-proven IgAN or FSGS histological pattern in the graft.
* A period of ≥12 months since kidney transplantation.
* UPCR ≥0.5 g/g and eGFR (CKD-EPI creatinine-based formula ≥30 mL/min/1.73 m2.
* Participants who can become pregnant, must agree to the use of 1 highly reliable method of contraception from 7 days prior to the first dose of study intervention until 30 days after the last dose of study intervention.
* Systolic BP ≤160 mmHg and ≥100 mmHg, and diastolic BP ≤100 mmHg and ≥60 mmHg at screening.
* For participants on an ACEI and/or ARB, and/or sodium glucose cotransporter-2 (SGLT2) inhibitor, the dosing regimen(s) is stable for ≥6 weeks prior to screening.

Exclusion Criteria:

* Participant has multiorgan transplants (with the exception of pancreas and corneal transplants).
* Immunosuppressive therapy (IST) regimen for kidney transplant or other systemic chronic ISTs including enteric budesonide that is not stable for \>6 weeks prior to Day 1. Exceptions include routine changes in the dose of CNIs to meet target level.
* \<3 months after antirejection treatment and active rejection.
* Active bacterial, fungal or viral infection and/or active treatment of infection including BK virus (BKV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B and C \<3 months prior to and during the screening period.
* Current treatment for surgical complications.
* 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.
* 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 ERA.
* Participant requires any of the prohibited concomitant medications.
* Treatment with sparsentan \<12 weeks prior to screening.
* Participant has participated in a study of another investigational product \<28 days prior to screening or plans to participate in such a study during the course of this study.
* Hematocrit \<27%, hemoglobin \<90 g/L (9 g/dL), or potassium \>5.5 mmol/L (5.5 mEq/L).
* The participant 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 IMP whole.
* The participant, 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.

Where this trial is running

Birmingham, Alabama and 8 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
• Cornell Medical Center — New York, New York, United States (Recruiting)
• University of North Carolina Chapel Hill — Morrisville, North Carolina, United States (Recruiting)
• Ohio State University — Columbus, Ohio, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Dallas Nephrology Associates — Dallas, Texas, United States (Recruiting)
• University of Texas — Galveston, Texas, United States (Recruiting)
• University of Washington — Seattle, Washington, United States (Recruiting)
• University of Wisconsin — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: Travere Call Center

Conditions Proteinuria; Immunoglobulin A Nephropathy; Focal Segmental Glomerulosclerosis; Kidney Transplant; IgAN; FSGS; kidney transplant; proteinuria