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

• Published in: Kidney international reports Vol. 9; no. 9; pp. 2677 - 2684
• Main Authors: Olabisi, Opeyemi A., Barrett, Nadine J., Lucas, Anika, Smith, Maurice, Bethea, Kenisha, Soldano, Karen, Croall, Stephanie, Sadeghpour, Azita, Chakraborty, Hrishikesh, Wolf, Myles
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024; Elsevier
• Subjects: African American; APOL1; Clinical Research; proteinuria; APOL1; proteinuria; African American
• ISSN: 2468-0249; 2468-0249
• DOI: 10.1016/j.ekir.2024.06.033

Individuals of recent West African ancestry develop focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (HTN-ESKD) at 4 times the rate of White Americans. Two protein-coding variants of the Apolipoprotein L1 (APOL1) gene, G1 and G2, explain 50% to 70% of the excess risk of HTN-ESKD and FSGS among this group. Increased expression of G1 and G2 in the kidney, mediated by Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, drive pathogenesis of these kidney diseases. Baricitinib is an orally active inhibitor of JAK1/2 that blocks APOL1 synthesis. The Janus kinase-STAT Inhibition to Reduce APOL1-Associated Kidney Disease (JUSTICE) trial is evaluating the antiproteinuric efficacy and safety of baricitinib in patients with APOL1-associated FSGS and HTN-attributed chronic kidney disease (HTN-CKD). JUSTICE is a single-center, randomized, double-blind, placebo-controlled, pilot phase 2 trial of baricitinib in patients with proteinuria, APOL1-associated FSGS or APOL1-associated HTN-CKD without diabetes. A total of 75 African American patients with APOL1-associated CKD, including 25 with FSGS and 50 with HTN-CKD, aged 18 to 70 years will be randomized 2:1 to daily treatment with baricitinib or placebo, respectively. The primary efficacy end point will be percent change in urine albumin-to-creatinine ratio (UACR) from baseline to end of month 6. The primary safety end point will be incidence of clinically significant decreases in hemoglobin of ≥ 1g/dl. The phase 2 JUSTICE study will characterize the antiproteinuric efficacy and safety of JAK1/2 inhibition with baricitinib in patients with APOL1-associated FSGS and APOL1-associated HTN-CKD. [Display omitted]