A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, randomizované kontrolované studie, klinické zkoušky, fáze II, multicentrická studie
PubMed
38552841
DOI
10.1016/j.kint.2024.03.012
PII: S0085-2538(24)00236-9
Knihovny.cz E-zdroje
- Klíčová slova
- B-cell modulator, IgA nephropathy, glomerular disease,
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- IgA nefropatie * farmakoterapie moč diagnóza MeSH
- kreatinin * moč krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- proteinurie farmakoterapie moč MeSH
- receptory Fc terapeutické užití MeSH
- rekombinantní fúzní proteiny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- kreatinin * MeSH
- receptory Fc MeSH
- rekombinantní fúzní proteiny * MeSH
- TACI receptor-IgG Fc fragment fusion protein MeSH Prohlížeč
Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks. Primary and key secondary endpoints were changes in urine protein creatinine ratio based on 24-hour urine collection at weeks 24 and 36, respectively, in the combined atacicept 150 mg and 75 mg group versus placebo. The primary endpoint was met at week 24 as the mean urine protein creatinine ratio was reduced from baseline by 31% in the combined atacicept group versus 8% with placebo, resulting in a significant 25% reduction with atacicept versus placebo. At week 36, the key secondary endpoint was met as the mean urine protein creatinine ratio reduced from baseline by 34% in the combined atacicept group versus a 2% increase with placebo, resulting in a significant 35% reduction with atacicept versus placebo. The reduction in proteinuria was accompanied by stabilization in endpoint eGFR with atacicept compared to a decline with placebo at week 36, resulting in significant between-group geometric mean difference of 11%, approximating an absolute difference of 5.7 mL/min/1.73m2. Endpoint galactose deficient IgA1 levels significantly decreased from baseline by 60% versus placebo. The safety profile of atacicept was like placebo. Thus, our results provide evidence to support a pivotal, phase 3 study of atacicept in IgA nephropathy.
Biostatistics Vera Therapeutics Inc Brisbane California USA
Clinical Development Vera Therapeutics Inc Brisbane California USA
Department of Nephrology AZ Delta Roeselare Belgium
Department of Nephrology Faculty of Medicine Kocaeli University Kocaeli Turkey
Division of Nephrology Department of Medicine Stanford University Stanford California USA
Division of Nephrology Department of Medicine The University of British Columbia Vancouver Canada
Hallym University Sacred Heart Hospital Anyang Korea
Medical Vera Therapeutics Inc Brisbane California USA
Western Nephrology Arvada Colorado USA
Westmead Clinical School The University of Sydney Sydney Australia
Citace poskytuje Crossref.org
Advances in Multitarget Therapeutic Approaches for Immune-Mediated Glomerular Diseases
