About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 m² 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).
Disqualifiers
Genetic or secondary FSGS or MCD. Those with APOL1 risk alleles are eligible.
Collapsing variant of FSGS.
ESKD requiring dialysis or transplantation.
Trial design
Parallel
Treatments tested in this trial
frexalimab
Drugfrexalimab treatment
brivekimig
Drugbrivekimig treatment
rilzabrutinib
Drugrilzabrutinib treatment
placebo
Drugplacebo treatment
Treatment groups
Trial outcomes
Primary outcomes
Percent reduction in urine protein to creatinine ratio (UPCR)
Secondary outcomes
Percentage of participants achieving FSGS partial remission endpoint
Defined as UPCR ≤1.5 g/g and \>40 % reduction of UPCR from baseline
Percentage of participants achieving CR
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
TEAEs, including clinically significant changes in vital signs, electrocardiogram \[ECG\], and laboratory evaluation
Plasma concentrations of frexalimab and rilzabrutinib and serum concentrations of SAR442970