Safety and Efficacy of STL303 In Patients With Primary Immunoglobulin A (IgA) Nephropathy

Официальное название

A Multicenter, Randomised, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of STL303 In Patients With Primary Immunoglobulin A (IgA) Nephropathy

Обзор

This is a multicenter, randomized, double-blind, placebo controlled Phase IIb study to explore the efficacy and safety of STL303 capsules in IgAN patients. About 15 patients dignosed with primary IgAN will be enrolled and randomized to three cohorts and take different dosage of STL303 or placebo capsules orally according to protocol.

Подробное описание

This is a multicenter, randomized, double-blind, placebo-controlled study in approximately 15 patients with primary IgA nephropathy (IgAN).

Participants receiving background therapy will be randomized in a 1:1:1 ratio to receive STL303 capsules dose 1, dose 2, or placebo, administered orally once daily.

The study aims to evaluate the efficacy and safety of STL303 in patients with primary IgAN and to identify the optimal clinical dose.

Вмешательства

• Препарат STL303
  STL303 arm participants will receive a specific dose of STL303
• Препарат STL303
  STL303 arm participants will receive a specific dose of STL303
• Препарат Placebo capsule
  Placebo arm participants will receive placebo capsules

Первичные конечные точки

• Treatment emergent adverse events (TEAEs), adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Adverse events will be closely monitored, and participants will report to the clinic on Days 7, 14, 30, 45, 60, 90, 135 and at end of treatment on Day 180. On Day 210 an End of study safety follow up will also be conducted.]

Вторичные конечные точки (12)

• Change from baseline urine protein-to-creatinine ratio (UPCR) [Срок оценки: 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180]
• Change in UPCR [Срок оценки: 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60 and 90]
• Change in urine albumin-to-creatinine ratio (UACR) [Срок оценки: 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180]
• Change in blood creatinine level [Срок оценки: Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180]
• Change in eGFR slope [Срок оценки: Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180]
• Maximum Concentration at steady-state (Tmax, ss) of STL303 [Срок оценки: Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing]
• Maximum plasma concentration at steady-state (Cmax, ss) of STL303 [Срок оценки: Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing]
• Trough plasma concentration at steady-state of STL303 [Срок оценки: Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing]
• Area under plasma concentration-time curve for STL303 [Срок оценки: Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing]
• Change urine protein excretion (UPE), [Срок оценки: 24-hour urine collection pre-dose Days 1 (baseline), 30, 60, 90 and 180]
• Alternative Pathway Activity (Wieslab Assay) [Срок оценки: Pre-dose and post-dose on Day 1 and Day 14; pre-dose on Days 7, 60, 90, 135, and 180; intensive time points (pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours post-dose) on Day 30]
• Urinary Complement Biomarker C3a [Срок оценки: Day 1, Day 7 (FMV only), Day 14 (FMV only), Day 30, Day 60, Day 90, Day 135 (FMV only), and Day 180 (all pre-dose)]

Критерии участия

Критерии включения

• Male and female patients aged 18 years and older, with primary IgAN confirmed by renal biopsy:
• eGFR (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) greater than or equal to 30 mL/min/1.73 m2 at screening and after completion of run-in.
• UPCR greater than or equal to 0.75 g/g at screening and after completion of run-in.
• Vaccinated against Neisseria meningitidis and Streptococcus pneumoniae before the first dose.
• Have received stable treatment with RASis (ACEi or ARB) at the maximum recommended dose or MTD for at least 90 days prior to the first dose.
• If the patient has been treated with SGLT2i, diuretics, other antihypertensive treatments, ERA, and/or hydroxychloroquine for IgAN prior to the first dose, the drug should also be used stably for at least 90 days.

Критерии исключения

• Secondary IgAN or unclear exclusion of secondary causes.
• Rapidly progressive IgAN (eGFR decline greater than or equal to 50% in 3 months, or less than 50% but at high risk).
• Other systemic diseases causing proteinuria/CKD or severe urinary obstruction.
• Known or suspected immunodeficiency or hereditary complement deficiency.
• Any organ transplant recipients except corneal.
• Poorly controlled blood pressure (SBP greater than 150 or DBP great than 90).
• Use of immunosuppressive drugs within 90 days or 5 half-lives.
• Prior oral budesonide (Nefecon/Tarpeyo/Kinpeygo) within 6 months.
• Prior complement inhibitors within 30 days, 5 half-lives, or residual effect period.
• Major systemic diseases preventing participation (e.g., NYHA IV, severe pulmonary disease).
• Significantly abnormal liver function (greater than 3× ULN enzymes or greater than 2× ULN bilirubin).
• QTcF greater than 500 ms.
• History of malignancy within 5 years (exceptions apply).
• History of meningococcal, pneumococcal, or Hib infection.
• Chronic/recurrent infections in past year (e.g., liver abscess, pyelonephritis).
• Active systemic infections within 2 weeks or fever greater than 38°C within 7 days.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 3 центра

• Research Site — Woolloongabba
• Research Site — Clayton
• Research Site — Saint Albans

Идентификаторы

NCT: NCT07606352 · STL303-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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