A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease

Официальное название

A Parallel-group Treatment, Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Umbrella Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, and Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)

Обзор

This is a parallel, Phase 2a, double-blind, 6-arm study for the treatment of primary focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). The purpose of this study is to measure the change in proteinuria and its impact on the rates of remission of nephrotic syndrome with frexalimab, brivekimig or rilzabrutinib compared with placebo in participants with primary FSGS or MCD aged 16 to 75 years. Study details for each participant include: The study duration will be up to 52 weeks. The treatment duration will be 24 weeks. There will be up to 16 visits.

Вмешательства

• Препарат frexalimab
  frexalimab treatment
• Препарат brivekimig
  brivekimig treatment
• Препарат rilzabrutinib
  rilzabrutinib treatment
• Препарат placebo
  placebo treatment

Первичные конечные точки

• Percent reduction in urine protein to creatinine ratio (UPCR) [Срок оценки: From baseline to Week 12]

Вторичные конечные точки (5)

• Percentage of participants achieving FSGS partial remission endpoint [Срок оценки: At Week 12]
• Percentage of participants achieving CR [Срок оценки: At Week 12]
• Incidence of treatment-emergent adverse events, treatment-emergent serious adverse events (SAEs), treatment-emergent adverse events of special interest (AESIs) and IMP discontinuation due to TEAEs during the study [Срок оценки: Treatment emergent period, up to Week 48]
• Plasma concentrations of frexalimab and rilzabrutinib and serum concentrations of SAR442970 [Срок оценки: Up to Week 48]
• Occurrence of anti-drug antibodies (ADAs) against frexalimab and SAR442970 [Срок оценки: Up to Week 48]

Критерии участия

Критерии включения

• Biopsy report indicative of primary FSGS or MCD, with supportive clinical presentation per Investigator's judgement.
• UPCR ≥3 g/g at screening, or ≥ 1.5 g/g in those with eGFR ≥ 60 mL/min/1.73 m2.
• eGFR ≥45 mL/min/1.73 m\^2 at screening.
• Documented history of UPCR or UACR (or 24-hour urine protein or 24-hour urine albumin) reduction by >40% in response to corticosteroid or other immunosuppressive therapy when pre-treatment UPCR was ≥3.5 g/g or equivalent for UACR (or pre-treatment 24-hr urine protein was ≥3.5 g/day if 24-hour urine protein is used or equivalent for 24-hr urine albumin if 24-hour urine albumin is used).
• ≤10 mg/day prednisone or equivalent and stable starting at least 1 week prior to randomization.
• For those on a RAAS inhibitor prior to screening, the dose must be stable ≥4 weeks prior to screening; starting RAAS inhibitors or changing the dose will not be allowed during the double-blind or OLE treatment period.
• For those on an SGLT2 inhibitor prior to screening, the dose must be stable ≥4 weeks prior to screening; starting SGLT2 inhibitor treatment or changing the dose will not be allowed during the double-blind or OLE treatment periods.
• Body weight within 45 to 120 kg (inclusive) at screening.

Критерии исключения

• Genetic or secondary FSGS or MCD. Those with APOL1 risk alleles are eligible.
• Collapsing variant of FSGS.
• ESKD requiring dialysis or transplantation.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

США · 16 центров

• Investigational Site Number : 8400007 — Birmingham
• Investigational Site Number : 8400015 — Orange
• Investigational Site Number : 8400012 — San Francisco
• Investigational Site Number : 8400025 — Tampa
• Emory Children's Center- Site Number : 8400020 — Atlanta
• Investigational Site Number : 8400014 — Chicago
• Investigational Site Number : 8400017 — Hinsdale
• Investigational Site Number : 8400010 — Ann Arbor
• … и ещё 8 центров

Испания · 5 центров

• Investigational Site Number : 7240001 — Barcelona
• Investigational Site Number : 7240005 — Seville
• Investigational Site Number : 7240002 — Córdoba
• Investigational Site Number : 7240008 — Madrid
• Investigational Site Number : 7240007 — Madrid

Бразилия · 4 центра

• Investigational Site Number: 0760004 — Botucatu
• Synvia Clinical- Site Number : 0760005 — São Paulo
• Investigational Site Number : 0760002 — São Paulo
• Investigational Site Number : 0760001 — São Paulo

Канада · 4 центра

• Investigational Site Number : 1240002 — London
• Investigational Site Number : 1240001 — Montreal
• Investigational Site Number : 1240005 — Montreal
• Investigational Site Number : 1240006 — Québec

Китай · 3 центра

• Investigational Site Number : 1560001 — Пекин
• Investigational Site Number : 1560003 — Чэнду
• Investigational Site Number : 1560004 — Шанхай

Германия · 3 центра

• Investigational Site Number : 2760002 — Berlin
• Investigational Site Number : 2760006 — Dresden
• Investigational Site Number : 2760003 — Hanover

Греция · 3 центра

• Investigational Site Number : 3000002 — Athens
• Investigational Site Number : 3000001 — Heraklion
• Investigational Site Number : 3000003 — Ioannina

Италия · 3 центра

• Investigational Site Number : 3800002 — Florence
• Investigational Site Number : 3800003 — Naples
• Investigational Site Number : 3800001 — Brescia

Мексика · 3 центра

• Investigational Site Number : 4840005 — Mexico City
• Investigational Site Number : 4840001 — Mexico City
• Investigational Site Number : 4840003 — Monterrey

Польша · 3 центра

• Investigational Site Number : 6160004 — Poznan
• Investigational Site Number : 6160001 — Lodz
• Investigational Site Number : 6160002 — Opole

Словакия · 3 центра

• Investigational Site Number : 7030003 — Banská Bystrica
• Investigational Site Number : 7030004 — Bratislava - Kramare
• Investigational Site Number : 7030001 — Martin

Великобритания · 3 центра

• Investigational Site Number : 8260001 — Leicester
• Investigational Site Number : 8260004 — Salford
• Investigational Site Number : 8260005 — Oxford

Аргентина · 2 центра

• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320002 — Córdoba

Австралия · 2 центра

• Investigational Site Number : 0360003 — Garran
• Investigational Site Number : 0360001 — Parkville

Чили · 2 центра

• Investigational Site Number : 1520003 — Temuco
• Investigational Site Number : 1520002 — Santiago

Чехия · 2 центра

• Investigational Site Number : 2030002 — Olomouc
• Investigational Site Number : 2030001 — Prague

Франция · 2 центра

• Investigational Site Number : 2500002 — Créteil
• Investigational Site Number : 2500001 — Paris

Португалия · 2 центра

• Investigational Site Number : 6200003 — Lisbon
• Investigational Site Number : 6200002 — Porto

Тайвань · 2 центра

• Investigational Site Number : 1580001 — Taichung
• Investigational Site Number : 1580002 — Taipei

Turkey (Türkiye) · 2 центра

• Investigational Site Number : 7920001 — İzmit
• Investigational Site Number : 7920002 — Kayseri

Венгрия · 1 центр

• Investigational Site Number : 3480001 — Budapest

Нидерланды · 1 центр

• Investigational Site Number : 5280001 — Amsterdam

Публикации

• Lin J, Radhakrishnan J. What Are Baskets, Umbrellas, and Platforms Doing in Nephrology Clinical Trials? J Am Soc Nephrol. 2025 Feb 3;36(8):1652-1654. doi: 10.1681/ASN.0000000648. No abstract available. PMID 39899371

Идентификаторы

NCT: NCT06500702 · ACT18064 · 2024-511775-15 · U1111-1301-2676

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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