Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1-Mediated Kidney Disease (JUSTICE)
The JUSTICE trial is a Phase 2 study testing whether baricitinib, a JAK1/2 inhibitor, can reduce proteinuria in patients with APOL1-associated FSGS and hypertension-attributed chronic kidney disease by blocking APOL1 gene expression.
Background
Two APOL1 gene variants (G1 and G2), common in people of recent West African ancestry, account for 50-70% of the excess risk of hypertension-attributed end-stage kidney disease and FSGS in this population; increased APOL1 expression via JAK-STAT signaling drives disease pathogenesis.
Study design
JUSTICE is a single-center, randomized, double-blind, placebo-controlled pilot Phase 2 trial randomizing 75 African American patients with APOL1-associated FSGS (n=25) or hypertension-attributed CKD (n=50) 2:1 to baricitinib or placebo, with percent change in urine albumin-to-creatinine ratio at 6 months as the primary efficacy endpoint.
Clinical implications
If successful, this would be among the first genetically-targeted therapies for APOL1-mediated kidney disease, offering a precision-medicine alternative to standard immunosuppression or RAAS blockade for a population that experiences disproportionately rapid CKD progression.
Category
Research
Source
Kidney International Reports
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