{"doi":"10.1016/j.ekir.2022.07.004","title":"Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial","abstract":"Introduction: Complement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. About 50% of patients with C3G progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapeutic agents for C3G. Iptacopan is an oral, first-in-class, potent, and selective inhibitor of factor B, a key component of the AP. In a Phase II study, treatment with iptacopan was associated with a reduction in proteinuria and C3 deposit scores in C3G patients with native and transplanted kidneys, respectively. Methods: . All patients will receive maximally tolerated angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and vaccination against encapsulated bacteria. Patients with any organ transplantation, progressive crescentic glomerulonephritis (GN), monoclonal gammopathy of undetermined significance, or kidney biopsy with >50% interstitial fibrosis/tubular atrophy, will be excluded. Patients will be randomized 1:1 to receive either iptacopan 200 mg twice daily or placebo for 6 months, followed by open-label treatment with iptacopan 200 mg twice daily for all patients for 6 months. The primary objective is to evaluate the efficacy of iptacopan versus placebo on proteinuria reduction urine protein:creatinine ratio (UPCR) (24 h urine). Key secondary endpoints will assess kidney function measured by eGFR, histological disease total activity score, and fatigue. Conclusion: This study aims to demonstrate the clinical benefits of AP inhibition with iptacopan in C3G.","journal":"Kidney International Reports","year":2022,"id":235672,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":62377,"name":"David Kavanagh","orcid":"0000-0003-4718-0072","position":1,"is_corresponding":false},{"id":614255,"name":"Marina Vivarelli","orcid":"0000-0002-2448-1959","position":2,"is_corresponding":false},{"id":12839,"name":"Matthias Meier","orcid":"0000-0001-9455-4538","position":3,"is_corresponding":false},{"id":854508,"name":"Yaqin Wang","orcid":"0000-0003-1927-5840","position":4,"is_corresponding":false},{"id":604557,"name":"Nicholas J.A. Webb","orcid":"0000-0001-8572-5446","position":5,"is_corresponding":false},{"id":855388,"name":"Angelo J. Trapani","orcid":null,"position":6,"is_corresponding":false},{"id":291758,"name":"Richard J. Smith","orcid":"0000-0003-1201-6731","position":7,"is_corresponding":false},{"id":242625,"name":"Andrew S. Bomback","orcid":"0000-0001-5449-1667","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T00:21:53.333008Z","pmid":"36217526","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}