Phase III Single‑Arm Study of Atrasentan (EXV811) in Children 2–<18 Years with Primary IgA Nephropathy: Proteinuria, PK, Safety

The primary objective is to assess the effect of atrasentan on reducing proteinuria from baseline to Week 36 by measuring the urinary protein to creatinine ratio (UPCR) in first‑morning void specimens in the overall pediatric cohort with primary IgA nephropathy. Secondary objectives include:

• Evaluation of proteinuria reduction from baseline to Week 36 using UPCR in participants with ≤30 % decrease in proteinuria during the 60‑day pre‑treatment period.
• Characterization of the pharmacokinetics of atrasentan in children aged 2 to <18 years.
• Assessment of safety and tolerability of atrasentan throughout the 104‑week study duration.

The trial enrolled 23 participants, all aged 2 to < 18 years, including both males and females, who were identified as a vulnerable pediatric population. Eligible individuals had biopsy‑confirmed Primary IgAN performed within three years of screening, with less than 50 % tubulointerstitial fibrosis and fewer than 25 % crescents, and demonstrated persistent proteinuria (urinary protein‑to‑creatinine ratio ≥ 1 g/g) despite at least 120 days of treatment with a stable dose of an ACE inhibitor/ARB. Additional selection criteria required an estimated glomerular filtration rate ≥30 mL/min/1.73 m² calculated by the modified Schwartz formula, a minimum body weight of 10 kg, and ongoing supportive care with all antihypertensive and background medications stabilized for the same 120‑day period. Participants were recruited based on these predefined clinical and laboratory parameters, ensuring a homogeneous cohort reflective of pediatric patients with primary IgAN and preserved renal function.

The study is a single‑arm, multicenter phase III trial evaluating the efficacy, pharmacokinetics, safety and tolerability of atrasentan in pediatric patients aged 2 to < 18 years with primary immunoglobulin A nephropathy; participants must have a baseline urinary protein‑to‑creatinine ratio (UPCR) ≥ 1 g/g confirming significant proteinuria. After an initial screening period (Day −90 to Day −60) to verify inclusion criteria, eligible subjects enter a 120‑day run‑in phase on stable maximal ACE‑inhibitor or ARB therapy before receiving the first dose on Day 1. Study visits are scheduled at baseline, Weeks 4, 12, 24, and 36 (end‑of‑treatment), with an end‑of‑study visit at Week 48 for final safety assessment; each visit includes collection of FMV urine for UPCR, blood sampling for PK parameters, adverse‑event monitoring, and vital‑sign measurements. Participant involvement therefore spans approximately nine months from screening through the final visit. Early termination may occur if safety concerns arise, if the participant withdraws consent, if required background therapy cannot be maintained, or if protocol non‑compliance or significant decline in renal function is observed.

The investigational product administered in this study is identified as EXV811, a film‑coated tablet containing 0.75 mg of atrasentan hydrochloride. The tablet is intended for oral use and is provided to participants in accordance with the dosing schedule defined in the protocol.

As a single‑arm trial, no placebo or active comparator is employed; participants receive only the study medication. Standard supportive care may be continued at the discretion of the treating physician, but no additional investigational agents are administered.

Efficacy will be assessed by quantifying changes in IgA nephropathy–related proteinuria using the urinary protein to creatinine ratio (UPCR) measured from first‑morning void (FMV) urine samples. The primary efficacy endpoint is the change from baseline to Week 36 in the natural‑log transformed UPCR. A secondary efficacy analysis will evaluate the same change in the subset of participants who exhibited ≤30 % reduction in proteinuria during the 60‑day period preceding atrasentan initiation. Urine collections are scheduled at baseline and at Week 36; samples are processed in a central laboratory using validated assays for urinary protein and creatinine, and the ratio is calculated and log‑transformed for statistical analysis.