Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE)
Introduction: 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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-09-01
|
| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924018102 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850223445493678080 |
|---|---|
| author | Opeyemi A. Olabisi Nadine J. Barrett Anika Lucas Maurice Smith Kenisha Bethea Karen Soldano Stephanie Croall Azita Sadeghpour Hrishikesh Chakraborty Myles Wolf |
| author_facet | Opeyemi A. Olabisi Nadine J. Barrett Anika Lucas Maurice Smith Kenisha Bethea Karen Soldano Stephanie Croall Azita Sadeghpour Hrishikesh Chakraborty Myles Wolf |
| author_sort | Opeyemi A. Olabisi |
| collection | DOAJ |
| description | Introduction: 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). Methods: 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. Results: 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. Conclusion: 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. |
| format | Article |
| id | doaj-art-eaa6588a552845128170269756dd9468 |
| institution | OA Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-eaa6588a552845128170269756dd94682025-08-20T02:05:57ZengElsevierKidney International Reports2468-02492024-09-01992677268410.1016/j.ekir.2024.06.033Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE)Opeyemi A. Olabisi0Nadine J. Barrett1Anika Lucas2Maurice Smith3Kenisha Bethea4Karen Soldano5Stephanie Croall6Azita Sadeghpour7Hrishikesh Chakraborty8Myles Wolf9Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Correspondence: Opeyemi A. Olabisi, Department of Medicine, Division of Nephrology, Duke University School of Medicine, Duke Molecular Physiology Institute, 300 N. Duke Street., 50-104, Durham, North Carolina 27701, USA.Atrium Health/Wake Forest Comprehensive Cancer Center and Maya Angelo Center for Health Equity, Wake Forest School of Medicine, Wake Forest, North Carolina, USA; Department of Social Science and Health Policy, Division of Population Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Maya Angelo Center for Health Equity, Wake Forest School of Medicine, Winston-Salem, North Carolina, USADivision of Nephrology, Duke University School of Medicine, Durham, North Carolina, USADivision of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USADuke Clinical and Translational Science Institute, Duke University School of Medicine, Durham, North Carolina, USADivision of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USADivision of Nephrology, Duke University School of Medicine, Durham, North Carolina, USADuke Precision Medicine Program, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USADuke Clinical Research Institute, Duke University, Durham, North Carolina, USADivision of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Duke University, Durham, North Carolina, USAIntroduction: 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). Methods: 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. Results: 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S2468024924018102African AmericanAPOL1proteinuria |
| spellingShingle | Opeyemi A. Olabisi Nadine J. Barrett Anika Lucas Maurice Smith Kenisha Bethea Karen Soldano Stephanie Croall Azita Sadeghpour Hrishikesh Chakraborty Myles Wolf Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) Kidney International Reports African American APOL1 proteinuria |
| title | Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) |
| title_full | Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) |
| title_fullStr | Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) |
| title_full_unstemmed | Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) |
| title_short | Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1–Mediated Kidney Disease (JUSTICE) |
| title_sort | design and rationale of the phase 2 baricitinib study in apolipoprotein l1 mediated kidney disease justice |
| topic | African American APOL1 proteinuria |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924018102 |
| work_keys_str_mv | AT opeyemiaolabisi designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT nadinejbarrett designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT anikalucas designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT mauricesmith designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT kenishabethea designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT karensoldano designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT stephaniecroall designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT azitasadeghpour designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT hrishikeshchakraborty designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice AT myleswolf designandrationaleofthephase2baricitinibstudyinapolipoproteinl1mediatedkidneydiseasejustice |