Safety and efficacy study of LNP023 in IgA Nephropathy
Research type
Research Study
Full title
An adaptive seamless randomized, double-blind, placebo-controlled, dose ranging study to investigate the efficacy and safety of LNP023 in primary IgA nephropathy patients
IRAS ID
234907
Contact name
Lisa Willcocks
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2017-000891-27
Duration of Study in the UK
years, 24 months, days
Research summary
Research Summary
IgA nephropathy (IgAN) is a kidney disease that occurs when an antibody called immunoglobulin A (IgA) lodges in the kidneys. When antibodies lodge in the kidneys, local inflammation occurs that can cause the kidneys to leak blood and protein, and over time, may hamper the kidneys' ability to filter wastes from blood. Approximately 25% of IgAN patients develop proteinuria and hypertension. Many of these patients develop End Stage Renal Disease (ESRD) within 10 years.
There is no cure for IgAN. The goal of IgAN treatment is to prevent or delay ESRD. Treatment of IgAN has not changed significantly during the last three decades and effective, approved therapy is lacking. Guidelines recommend therapy based on angiotensin converting enzyme inhibitor (ACEis) or angiotensin receptor blocker (ARBs) with or without high dose steroids and cytotoxic agents, for blood pressure control and proteinuria reduction (KDIGO 2012). However, immunosuppressive agents (including steroids), have considerable side-effects and are only moderately effective in treating IgAN.
LNP023 is a drug that blocks key steps in the “alternative complement pathway”, which is known to be activated in the kidney of most patients with IgAN, and as such may improve IgA nephropathy.
The purpose of the study is to find out if LNP023 is safe; can reduce renal inflammation, proteinuria, and improve renal function in patients with IgAN. The study will also provide information on the appropriate dose of LNP023 to treat patients diagnosed with IgAN.
The study will run for ~2 years with 7-11 patients to be enrolled across 3 sites in the UK. Participants will receive either active drug or placebo, and will visit the study doctor 10 times over 7-9 months for assessments and monitoring of their condition as part of the study.
Summary of Results
: LNP023 b.i.d. ranging from 10 mg to 200 mg was safe and well tolerated. The LNP023 safety profile was similar to the placebo safety profile and there was no evident dose effect on the incidence of adverse events.
This study met its primary objective by demonstrating a statistically significant dose response effect of LNP023 vs. placebo on the reduction in proteinuria (24h urine sample) after 90 days of treatment (one-sided multiplicity adjusted p-value=0.038).
At Day 90, the highest reduction of 23% (80% CI: 8, 34) from baseline in urine protein to creatinine ratio as compared to placebo was estimated for the LNP023 dose of 200 mg b.i.d.
In the subgroup of patients who received treatment for 180 days, urine protein to creatinine ratio continued to decrease between 90 and 180 days of treatment except in placebo and iptacopan 10 mg b.i.d. group.
LNP023 b.i.d. induced a clear dose-dependent inhibition of the complement alternative pathway up to 90 days of treatment. In the subgroup of patients who received treatment for 180 days, only the LNP023 dose of 200 mg b.i.d. was able to sustain a strong inhibition with all the biomarkers tested up to Day 180.The results of this study support the LNP023 dose of 200 mg b.i.d. for subsequent clinical development of LNP023 for IgAN as well as other indications.
This trial helped researchers learn how well LNP023 works at different doses and if it is safe to use in people with IgA nephropathy. They learned that protein levels in urine went down more in participants who took the 200 mg dose of LNP023 twice a day than those who took the placebo and other doses of LNP023 twice a day. The researchers found no new safety concerns for LNP023 in people with IgA nephropathy.
This was the first trial of LNP023 in people with IgA nephropathy. More research is needed to confirm its results. Another trial, CLNP023A2301 (NCT04578834), is a larger trial to learn more about the safety and effects of the 200 mg dose of LNP023 for people with IgA nephropathyREC name
East Midlands - Leicester South Research Ethics Committee
REC reference
17/EM/0412
Date of REC Opinion
15 Nov 2017
REC opinion
Further Information Favourable Opinion