This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.
The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic IC-MPGN. The study aims to demonstrate a reduction in proteinuria and improvement in estimated glomerular filtration rate (eGFR) in participants treated with iptacopan compared to placebo. Change in patient-reported fatigue will also be evaluated. Alternative complement pathway (AP) dysregulation is believed to underlie the clinical manifestations and progression of IC-MPGN. Upon completion of study treatment, participants will have the option to discontinue iptacopan treatment and enter a 30 day safety follow-up or continue iptacopan treatment by transitioning to an open label extension study (CLNP023B12001B; NCT03955445) and continue iptacopan treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
106
Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months.
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
Time frame: 6 months (double-blind)
Log-transformed ratio to baseline in UPCR at the 18-month visit (each study treatment arm)
To evaluate the effect of iptacopan on proteinuria at 18 months.
Time frame: 18 months
Log-transformed ratio to 12-month visit in UPCR at the 18-month visit in the placebo arm.
To evaluate the effect of iptacopan on proteinuria at 18 months.
Time frame: 18 months
Change from baseline in eGFR
To demonstrate the superiority of iptacopan vs. placebo in improving estimated glomerular filtration rate (eGFR).
Time frame: 12 months and 18 months
Change in eGFR from the 12-month visit to the 18- month visit of the placebo arm
To evaluate the effect at 18 months of iptacopan in improving eGFR
Time frame: 18 months
Proportion of patients achieved a composite renal endpoint
To demonstrate the superiority of iptacopan vs. placebo in the proportion of participant who achieved a composite renal endpoint at 6 and 12 months (each study arm).
Time frame: 6 and 12 months
Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
To demonstrate the superiority of iptacopan compared to placebo in improvement of patient-reported fatigue at 12 months (each study arm).
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Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
RECRUITINGUniv Cali Irvine ALS Neuromuscular
Orange, California, United States
RECRUITINGUCSF
San Francisco, California, United States
RECRUITINGOlive View UCLA Medical Center
Sylmar, California, United States
RECRUITINGChildrens Hospital Colorado
Aurora, Colorado, United States
RECRUITINGNicklaus Childrens Hospital
Miami, Florida, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGBoston Univ School of Medicine
Boston, Massachusetts, United States
RECRUITINGUniversity of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGUniversity of New Mexico
Albuquerque, New Mexico, United States
RECRUITING...and 107 more locations
Time frame: 12 months
Number of participants with abnormal vital signs, ECGs and safety laboratory measurements as well as study drug discontinuation due to an AE
To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with abnormal vital signs (msDBP/msSBP/heart rate), ECGs, safety laboratory measurements and study drug discontinuation due to an AE will be collected. msDBP: mean sitting diastolic blood pressure msSBP: mean sitting systolic blood pressure
Time frame: up to 18 months
Number of participants with clinically significant changes in heart rate, blood pressure, echocardiography parameters in adolescent patients
To evaluate the effect of iptacopan compared to placebo, number of participants with clinically significant changes in heart rate, blood pressure (msDBP/ msSBP), echocardiography parameters in adolescent patients will be collected
Time frame: up to 18 months
Annualized total eGFR slope estimated over 12 months.
To demonstrate the superiority of iptacopan vs. placebo in stabilizing eGFR
Time frame: 12 months
Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 12 months.
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 12 months of treatment.
Time frame: 12 months
Proportion of participants who achieved the composite renal endpoint at 18 months
To evaluate the effect of iptacopan on proteinuria at 18 months
Time frame: 18 months