The study is designed as a multicenter, randomized, double-blind, placebo controlled study to demonstrate the superiority of iptacopan (LNP023) at a dose of 200 mg b.i.d. compared to placebo on top of maximally tolerated ACEi or ARB on reduction of proteinuria and slowing renal disease progression in primary IgA Nephropathy patients.
The purpose of the study is to evaluate the efficacy and safety of iptacopan (LNP023) compared to placebo on proteinuria reduction and slowing disease progression in primary IgAN patients. The study will be the pivotal trial for registration of LNP023 in IgA Nephropathy patients with the aim to demonstrate a clinically meaningful reduction in proteinuria by LNP023 vs. placebo as assessed by reduction in urine protein to creatinine ratio (UPCR) sampled from a 24 hour urine collection at an IA at 9 months. The trial will continue in a blinded fashion to confirm long-term efficacy based on annualized total slope of eGFR decline over 24 months to provide confirmatory evidence of LNP023 efficacy and safety in treating patients with IgAN. The trial will enroll approximately 470 participants; 430 biopsy-proven IgAN participants with eGFR ≥30 mL /min/1.73m2 (main study population) and up to approximately 40 participants with eGFR 20 to \<30 mL/min/1.73m2 (severe renal impairment (SRI) population).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
518
Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at 9 months
Evaluated at interim analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein to Creatinine Ratio sampled from a 24h urine collection.
Time frame: Baseline and 9 months
Annualized total estimated Glomerular Filtration Rate (eGFR) slope over 24 months).
Evaluated at the final analysis - to demonstrate superiority of LNP023 vs. placebo in slowing IgAN progression measured by the annualized total slope of Estimated Glomerular Filtration Rate (eGFR) change over 24 months.
Time frame: Baseline and 24 months
Change from baseline in estimated glomerular filtration rate at 9 months
Evaluated at interim analysis - To evaluate the effect of LNP023 vs. placebo on slowing estimated glomerular filtration rate decrease as measured by the change from baseline in eGFR
Time frame: Baseline and 9 months
Proportion of participants reaching Urine Protein To Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant or other newly approved drugs or initiating new background therapy for treatment of IgAN or Kidney Replacement Therapy (KRT)
Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.
Time frame: Baseline and 9 months
Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months
Evaluated at interim analysis - To evaluate the effect of LNP023 vs. placebo on slowing IgAN progression measured by the annualized total slope of Estimated Glomerular Filtration Rate change over 1 year.
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AZ Kidney Dise and Hypertension Ctr
Glendale, Arizona, United States
AKDHC Medical Research ServicesLLC
Phoenix, Arizona, United States
UCLA Medical Center
Los Angeles, California, United States
Kaiser Permanente
San Diego, California, United States
North America Research Institute
San Dimas, California, United States
University of Colorado Anschutz
Aurora, Colorado, United States
Nephrology Associates PA
Newark, Delaware, United States
Boise Kidney and Hypertension
Boise, Idaho, United States
CaRe Research
Chubbuck, Idaho, United States
Nep Assoc of Northern Illinois
Hinsdale, Illinois, United States
...and 167 more locations
Time frame: Baseline and 12 months
Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire
Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the change from baseline to 9 months in fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.
Time frame: Baseline and 9 months
Time from randomization to first occurrence of composite kidney failure endpoint event
Evaluated at final analysis - demonstrate the superiority of LNP023 vs. placebo on delaying the time to first occurrence of a composite kidney failure endpoint, defined as reaching either sustained ≥30% decline in Estimated Glomerular Filtration Rate (eGFR) relative to baseline or sustained eGFR \<15 mL/min/1.73m2 or maintenance dialysis or receipt of kidney transplant or death from kidney failure.
Time frame: Up to 24 months
Ratio to baseline in Urine Protein-To-Creatinine Ratio (sampled from 24h urine collection) at 9 months
Evaluated at final analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein To Creatinine Ratio sampled from a 24h urine collection.
Time frame: Baseline and 9 months
Proportion of participants reaching Urine Protein-To-Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant Therapy or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating KRT
Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.
Time frame: Baseline and 9 months
Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.
Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the change from baseline to 9 months in the fatigue scale measured by Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.
Time frame: Baseline and 9 months