Focal Segmental Glomerulosclerosis, Glomerulonephritis Minimal Lesion
Conditions
Brief summary
This is a parallel, Phase 2a, double-blind, 6-arm study for the treatment of primary focal segmental glomerulosclerosis (FSGS) or primary 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 primary MCD aged 16 to 75 years. Study details for each participant include: The study duration will be up to 76 weeks. The treatment duration will be 24 weeks. There will be up to 18 visits.
Interventions
DRUGfrexalimab
frexalimab treatment
DRUGbrivekimig
brivekimig treatment
DRUGrilzabrutinib
rilzabrutinib treatment
DRUGplacebo
placebo treatment
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy report indicative of primary FSGS or primary 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. * eGFR ≥45 mL/min/1.73 m\^2 at screening. * Documented history of UPCR (or 24-hour urine protein) reduction by \>40% in response to corticosteroid or other immunosuppressive therapy when pre-treatment UPCR was ≥3.5 g/g (or pre-treatment 24-hr urine protein was ≥3.5 g/day if 24-hour urine protein 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent reduction in urine protein to creatinine ratio (UPCR) | From baseline to Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving FSGS partial remission endpoint | At Week 12 | Defined as UPCR ≤1.5 g/g and \>40 % reduction of UPCR from baseline |
| Percentage of participants achieving CR | At Week 12 | Defined as UPCR ≤0.3 g/g |
| 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 | Treatment emergent period, up to Week 48 | TEAEs, including clinically significant changes in vital signs, electrocardiogram \[ECG\], and laboratory evaluation |
| Plasma concentrations of frexalimab and rilzabrutinib and serum concentrations of SAR442970 | Up to Week 48 | — |
| Occurrence of anti-drug antibodies (ADAs) against frexalimab and SAR442970 | Up to Week 48 | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Italy, Mexico, Netherlands, Poland, Portugal, Slovakia, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed