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

Official title

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)

Overview

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.

Interventions

• Drug frexalimab
  frexalimab treatment
• Drug brivekimig
  brivekimig treatment
• Drug rilzabrutinib
  rilzabrutinib treatment
• Drug placebo
  placebo treatment

Primary outcome measures

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

Secondary outcome measures (5)

• Percentage of participants achieving FSGS partial remission endpoint [Time frame: At Week 12]
• Percentage of participants achieving CR [Time frame: 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 [Time frame: Treatment emergent period, up to Week 48]
• Plasma concentrations of frexalimab and rilzabrutinib and serum concentrations of SAR442970 [Time frame: Up to Week 48]
• Occurrence of anti-drug antibodies (ADAs) against frexalimab and SAR442970 [Time frame: Up to Week 48]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 16 centers

• 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
• … and 8 more centers

Spain · 5 centers

• 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

Brazil · 4 centers

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

Canada · 4 centers

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

China · 3 centers

• Investigational Site Number : 1560001 — Beijing
• Investigational Site Number : 1560003 — Chengdu
• Investigational Site Number : 1560004 — Shanghai

Germany · 3 centers

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

Greece · 3 centers

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

Italy · 3 centers

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

Mexico · 3 centers

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

Poland · 3 centers

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

Slovakia · 3 centers

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

United Kingdom · 3 centers

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

Argentina · 2 centers

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

Australia · 2 centers

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

Chile · 2 centers

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

Czechia · 2 centers

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

France · 2 centers

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

Portugal · 2 centers

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

Taiwan · 2 centers

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

Turkey (Türkiye) · 2 centers

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

Hungary · 1 center

• Investigational Site Number : 3480001 — Budapest

Netherlands · 1 center

• Investigational Site Number : 5280001 — Amsterdam

Publications

• 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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗