Summary

The sparsentan PROTECT trial is one of the largest IgA nephropathy interventional trials to date^1*

Background

IgA nephropathy is the most common primary glomerulopathy worldwide.^2,3 It is a heterogeneous disease that often progresses to kidney failure.⁴

The standard of care consists of treatment with renin angiotensin-aldosterone system (RAAS) inhibitors (i.e. angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blockers [ARB]), blood pressure control, and lifestyle changes.⁵

RAAS inhibitors have a known nephroprotective effect, and models of kidney disease have demonstrated a therapeutic effect with endothelin type A receptor antagonist.^6,7 Together these treatments can target two key pathways in IgA nephropathy.⁷

Sparsentan is a non-immunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist.^8,9

Aim

The objective of the Phase 3 PROTECT study is to evaluate the long-term efficacy and safety of sparsentan compared with the active comparator irbesartan in IgA nephropathy.¹ This manuscript describes the baseline characteristics.¹

Read more about the efficacy and safety findings from the PROTECT trial.

Approach

PROTECT is a large, international, randomized, double-blind, active-controlled Phase 3 trial in IgA nephropathy of sparsentan 400 mg versus irbesartan 300 mg.¹ Key eligibility criteria included¹:

Baseline characteristics were analyzed, compared between Asian and non-Asian geographic regions, and compared to other IgA nephropathy trials.¹

Findings

Baseline characteristics

Randomized and treated patients (N=404) were primarily White (67.3%, 272/404), non-Hispanic (91.1%, 368/404) adult males (69.8%, 282/404) with a median age of 46 years.¹

Patients were from Europe (53%), Asia Pacific (27%), and North America (20%).¹

Key baseline clinical and laboratory assessments included¹:

eGFR varied with the largest portion of patients (35.1%, 142/404) having eGFR corresponding to stage 3b chronic kidney disease (CKD).¹

Prior to receiving the study treatment, 63.4% (256/404) of patients were receiving the maximum labeled ACEi or ARB dose.¹

Comparing baseline characteristics between Asian and non-Asian geographic areas

Parameters between Asian (74/404) and non-Asian geographic areas (330/404) were comparable in terms of major characteristics such as age, baseline eGFR, and proteinuria with a few key differences.¹

Differences between Asian versus non-Asian areas included¹:

Comparing baseline characteristics across IgA nephropathy studies 

When compared to other IgA nephropathy studies, select baseline characteristics from the sparsentan PROTECT trial varied.¹ However, baseline proteinuria was similar across the IgA nephropathy studies with a mean or median UPCR ranging from 1.0 to 1.3 g/g.¹

Key takeaway

Baseline characteristics were racially diverse and demonstrated varying stages of CKD.¹ The sparsentan PROTECT trial will identify the treatment effect of sparsentan across a heterogeneous high risk IgA nephropathy population.¹

Footnotes

FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression, generally a urine protein-creatinine ratio (UPCR) ≥1.5 g/g.

WARNING: HEPATOTOXICITY and EMBRYO-FETAL TOXICITY

Because of the risks of hepatotoxicity and birth defects, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.1, 5.2, 5.3)].

See full prescribing information for complete boxed warning.

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; IgA, immunoglobulin A; RAAS, renin angiotensin-aldosterone system; UACR, urine albumin-creatinine ratio; UPCR, urine protein-creatinine ratio.

*As of July 2024.

MA-SP-24-0056 | August 2024