Abstract: PO1833
The NefIgArd trial: The Effect of Nefecon® (Budesonide) in Patients with Primary IgA Nephropathy at Risk of Developing ESRD
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Trials - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Barratt, Jonathan, Mayer IgA Nephropathy Laboratory, University of Leicester, UK, Leicester, United Kingdom
- Kristensen, Jens, Calliditas Therapeutics AB, Stockholm, Sweden
- Stone, Andrew M., Calliditas Therapeutics AB, Stockholm, Sweden
Background
The gut-associated lymphoid tissue (GALT) has been identified as the potential source of poorly O-galactosylated immunoglobulin A (IgA) 1 that triggers the formation of nephritogenic immune complexes in IgA nephropathy (IgAN). The NEFIGAN trial (NCT01738035), which assessed the safety and efficacy of a novel targeted-release formulation of budesonide (NEFECON®), highlighted the potential of selectively targeting GALT in patients with IgAN. After 9 months’ treatment, urine protein–creatinine ratio (UPCR) was reduced by 29.3% in the NEFECON® 16 mg/day group vs placebo. Estimated glomerular filtration rate (eGFR) decreased by 4.7 ml/min/1.73 m2 in the placebo group, but with no deterioration seen with NEFECON® 16 mg/day. The incidence of patient-reported adverse events was similar in all groups. Based on these data, the phase 3 NefIgArd study was designed to assess the efficacy and safety of NEFECON® 16 mg/day in patients with IgAN at risk of end-stage renal disease.
Methods
NefIgArd is a randomized, double-blind, placebo-controlled trial with two parts, recruiting a total of 360 patients across 150 nephrology clinics in 20 countries. Patients must be aged ≥18 years with biopsy-confirmed primary IgAN, proteinuria >1 g/24 h and eGFR 35–90 ml/min/1.73 m2 (CKD-EPI) despite optimized renin–angiotensin system blockade.
Part A of the study, comprising the first 200 dosed patients, will form the basis for submission for accelerated/conditional regulatory approval to the FDA and EMA. The primary outcome will assess the effect of NEFECON® 16 mg/day on UPCR at 9 months vs placebo, consistent with the 2019 Kidney Health Initiative White Paper “Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy”.
Part B is a post-approval confirmatory trial to validate the surrogacy of the Part A UPCR endpoint. For this purpose, and based on the 2018 NKF/FDA/EMA workshop supporting eGFR slope as an endpoint for full approval, the primary outcome will assess the effect of NEFECON® on a 2-year eGFR-based endpoint vs placebo.
Results
In 2019 the 200 patients needed for Part A were randomized, with top-line data expected in Q4 2020.
Conclusion
Randomization will continue until 360 patients are reached for Part B, which is expected to report in 2022.
Funding
- Commercial Support –