Dataset Information

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria.

ABSTRACT:

Introduction

Patients with IgA nephropathy (IgAN) and persistent proteinuria are at risk of progression to kidney failure. Atacicept is a novel B-cell-targeted immunomodulator, shown to reduce immunoglobulin levels in patients with autoimmune diseases.

Methods

JANUS (NCT02808429) was a phase II study that assessed the safety, pharmacodynamic effects, and efficacy of atacicept in patients with IgAN and proteinuria ≥1 g/d or 0.75 mg/mg on 24-hour UPCR despite maximal standard of care therapy.

Results

A total of 16 patients were randomized 1:1:1 to placebo (n = 5), atacicept 25 mg (n = 6), or atacicept 75 mg (n = 5) once weekly using subcutaneous injection. Twelve (75%) completed ≥48 weeks of treatment; 8 (50%) completed 72 weeks of treatment and the 24-week safety follow-up period. Fourteen patients reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild or moderate in severity. Three patients (placebo n = 1; atacicept 25 mg n = 2) reported serious TEAEs, none of which were treatment related. Dose-dependent reductions in IgA, IgG, IgM, and galactose-deficient (Gd)-IgA1 with atacicept at week 24 were maintained to week 72. Early reduction in proteinuria was observed at week 24 with atacicept. Renal function progressively declined with placebo but remained stable under exposure to atacicept.

Conclusion

Atacicept has an acceptable safety profile in patients with IgAN and is effective at reducing the levels of pathogenic factor Gd-IgA1, with potential improvements in proteinuria and renal function.

SUBMITTER: Barratt J

PROVIDER: S-EPMC9366370 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria.

Barratt Jonathan J Tumlin James J Suzuki Yusuke Y Kao Amy A Aydemir Aida A Pudota Kishore K Jin Hulin H Gühring Hans H Appel Gerald G

Kidney international reports 20220526 8

<h4>Introduction</h4>Patients with IgA nephropathy (IgAN) and persistent proteinuria are at risk of progression to kidney failure. Atacicept is a novel B-cell-targeted immunomodulator, shown to reduce immunoglobulin levels in patients with autoimmune diseases.<h4>Methods</h4>JANUS (NCT02808429) was a phase II study that assessed the safety, pharmacodynamic effects, and efficacy of atacicept in patients with IgAN and proteinuria ≥1 g/d or 0.75 mg/mg on 24-hour UPCR despite maximal standard of car ...[more]

PMID: 35967104

Similar Datasets

Project description:BackgroundThe serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China.MethodsWe recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR).ResultsWe found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis.ConclusionsThe present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

Dataset Information

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria.

Introduction

Methods

Results

Conclusion

Publications

Randomized Phase II JANUS Study of Atacicept in Patients With IgA Nephropathy and Persistent Proteinuria.

Similar Datasets

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