Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1-Mediated Kidney Disease (JUSTICE)

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Individuals of West African ancestry have a 4x higher rate of developing focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (HTN-ESKD) compared to White Americans.
• Two Apolipoprotein L1 (APOL1) gene variants, G1 and G2, account for 50-70% of this excess risk, with their increased kidney expression driven by Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling.
• Baricitinib, a JAK1/2 inhibitor, effectively reduces APOL1 synthesis, offering a potential therapeutic target.

Purpose of the Study:

• To evaluate the antiproteinuric efficacy and safety of baricitinib in patients with APOL1-associated FSGS and hypertension-attributed chronic kidney disease (HTN-CKD).

Main Methods:

• The Janus kinase-STAT Inhibition to Reduce APOL1-Associated Kidney Disease (JUSTICE) trial is a pilot phase 2, single-center, randomized, double-blind, placebo-controlled study.
• 75 African American patients with APOL1-associated CKD (25 with FSGS, 50 with HTN-CKD), aged 18-70, were randomized 2:1 to receive daily baricitinib or placebo.
• Primary efficacy endpoint: percent change in urine albumin-to-creatinine ratio (UACR) at 6 months. Primary safety endpoint: incidence of hemoglobin decrease ≥1 g/dL.

Main Results:

• The study is designed to characterize the antiproteinuric efficacy and safety of baricitinib.
• Data collection and analysis are ongoing to determine the primary efficacy and safety outcomes.

Conclusions:

• Baricitinib demonstrates potential as a treatment for APOL1-mediated kidney diseases by inhibiting JAK-STAT signaling and reducing APOL1 synthesis.
• The JUSTICE trial will provide crucial data on the efficacy and safety of baricitinib for FSGS and HTN-CKD in at-risk populations.