Abstract: TH-PO0604
Inaxaplin for a Broad Population with APOL1-Mediated Kidney Disease and Comorbid Conditions: Phase 2 Proof-of-Concept Study
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States
- Ferreira, Anna, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
- Barisoni, Laura, Duke University, Durham, North Carolina, United States
- Dell, Katherine MacRae, Cleveland Clinic Children's Hospital, Cleveland, Ohio, United States
- Pollak, Martin, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Friedman, David, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Ojo, Akinlolu, The University of Kansas School of Medicine, Kansas City, Kansas, United States
- Bramham, Kate, King's College London, London, England, United Kingdom
- Lipkowitz, Michael, Georgetown University, Washington, District of Columbia, United States
- Falk, Ronald, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Gbadegesin, Rasheed A., Duke University, Durham, North Carolina, United States
- Delestre-Levai, Irisz K., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
- Yang, Ce, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
Background
Persons with 2 APOL1 variants (G1 or G2) are at an increased risk of developing proteinuric nephropathies called APOL1-mediated kidney disease (AMKD) compared with persons with one or no APOL1 variants. Inaxaplin (IXP), an oral APOL1 inhibitor, reduced proteinuria by 47.6% in participants with 2 APOL1 variants and focal segmental glomerulosclerosis (type of AMKD), and no comorbidities. Given the potential of IXP to treat AMKD, it is essential to assess its efficacy in a broader population, including many of whom have comorbidities that may independently contribute to chronic kidney disease and accelerate disease progression. The phase 2/3 randomized, placebo-controlled AMPLITUDE trial is evaluating the effects of IXP on preserving kidney function and reducing proteinuria in non-diabetic persons with AMKD and severe proteinuria (UPCR ≥0.7 to <10g/g). Here we describe the design of the proof-of-concept AMPLIFIED study evaluating IXP in persons with AMKD with mild to moderate proteinuria and no comorbidities and people with AMKD with mild to severe proteinuria and significant comorbidities that may worsen kidney dysfunction.
Methods
AMPLIFIED is a phase 2, open-label study evaluating the efficacy of IXP to reduce proteinuria in 45 participants (ages 18-67yrs) with proteinuric AMKD who have none (Cohort 1,n=15) or one of the following significant comorbidities: type 2 diabetes mellitus (Cohort 2,n=15), sickle-cell disease (Cohort 3,n=5), human immunodeficiency virus (Cohort 3,n=5), or lupus nephritis (Cohort 3,n=5). Participants in Cohort 1 have mild to moderate proteinuria defined as urine albumin-creatinine ratio (UACR) ≥100mg/g to <420mg/g and participants in Cohorts 2 and 3 have mild to severe proteinuria defined as UACR ≥100mg/g to <6000mg/g.
Results
The primary efficacy endpoint will be the percent change from baseline in proteinuria at week 13. Safety will be evaluated.
Conclusion
The AMPLIFIED study will provide safety and efficacy data on the potential for IXP to treat a diverse population of AMKD patients with concurrent significant comorbidities associated with proteinuric kidney disease.
Funding
- Commercial Support – Vertex Pharmaceuticals