{"doi":"10.1016/j.cmi.2024.10.020","title":"Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomized, double-blind, placebo-controlled phase 2/3 trial","abstract":null,"journal":"Clinical Microbiology and Infection","year":2025,"id":595643,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":15748,"name":"Gang Wang","orcid":"0000-0001-7264-2457","position":1,"is_corresponding":false},{"id":416216,"name":"Yan Gao","orcid":"0000-0003-0122-1561","position":2,"is_corresponding":false},{"id":1525330,"name":"Lihong Qu","orcid":null,"position":3,"is_corresponding":false},{"id":598781,"name":"Hong Wang","orcid":"0000-0002-0213-3523","position":4,"is_corresponding":false},{"id":348332,"name":"Min Deng","orcid":"0000-0003-1987-9775","position":5,"is_corresponding":false},{"id":74353,"name":"Hainv Gao","orcid":"0000-0003-4590-9181","position":6,"is_corresponding":false},{"id":1235956,"name":"Yilin Li","orcid":"0000-0003-2610-7730","position":7,"is_corresponding":false},{"id":494520,"name":"Nan Yang","orcid":"0000-0003-1253-2154","position":8,"is_corresponding":false},{"id":1525337,"name":"Baogui Wang","orcid":null,"position":9,"is_corresponding":false},{"id":1525339,"name":"Rongge Liu","orcid":null,"position":10,"is_corresponding":false},{"id":1525341,"name":"Xuzhu Ma","orcid":null,"position":11,"is_corresponding":false},{"id":1086812,"name":"Zhen Tao","orcid":"0000-0002-5413-7112","position":12,"is_corresponding":false},{"id":798931,"name":"Guoqiang Zhang","orcid":"0000-0002-4132-1690","position":13,"is_corresponding":false},{"id":796260,"name":"Qian Wang","orcid":"0000-0002-8980-4915","position":14,"is_corresponding":false},{"id":1525343,"name":"Weifeng Zhao","orcid":null,"position":15,"is_corresponding":false},{"id":618250,"name":"Yunsong Yu","orcid":"0000-0003-2903-918X","position":16,"is_corresponding":false},{"id":753263,"name":"Lin Chen","orcid":"0000-0001-5905-7368","position":17,"is_corresponding":false},{"id":1525344,"name":"Lianchun Liang","orcid":null,"position":18,"is_corresponding":false},{"id":1221967,"name":"Shengyu Wang","orcid":"0000-0002-9774-8319","position":19,"is_corresponding":false},{"id":1525347,"name":"Lei Shao","orcid":null,"position":20,"is_corresponding":false},{"id":273537,"name":"Tao Yang","orcid":"0000-0002-8439-8575","position":21,"is_corresponding":false},{"id":1525350,"name":"Jinglei Cao","orcid":null,"position":22,"is_corresponding":false},{"id":79107,"name":"Yuan Cao","orcid":"0009-0005-9401-276X","position":23,"is_corresponding":false},{"id":1525352,"name":"Xiaoli Qin","orcid":null,"position":24,"is_corresponding":false},{"id":636753,"name":"Jingwen Ai","orcid":"0000-0002-5152-1557","position":25,"is_corresponding":false},{"id":1346302,"name":"Huadong Zhu","orcid":"0000-0002-1592-3188","position":26,"is_corresponding":false},{"id":514458,"name":"Wenhong Zhang","orcid":"0000-0002-9165-3212","position":27,"is_corresponding":false},{"id":199540,"name":"Hongyu Wang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomized, double-blind, placebo-controlled phase 2/3 trial","abstract":"<h4>Objectives</h4>To evaluate the efficacy and safety of ZX-7101A: an inhibitor of influenza viral cap-dependent endonuclease, in adults with uncomplicated influenza and explore treatment-emergent resistance.<h4>Methods</h4>We conducted a randomized, double-blind, placebo-controlled, adaptive-design phase 2 and phase 3 studies (ZX-7101A-202) in adults with uncomplicated influenza. Eligible patients were randomized 1:1:1 to receive a single dose of 40 or 80 mg ZX-7101A or placebo, stratified by body weight and baseline composite symptom score. The primary efficacy endpoint was time to alleviation of influenza symptoms (TTAS) in intention-to-treat infected population.<h4>Results</h4>The phase 2 trial suggested significantly shorter TTAS for ZX-7101A compared with placebo: the median TTAS of 40 or 80 mg ZX-7101A groups were 34.7 hours (95% CI, 22.8-43.4; p 0.005) and 45.8 hours (95% CI, 32.0-66.3; p 0.020), compared with 63.6 hours (95% CI, 43.9-93.4) in the placebo group. In the phase 3 trial, the TTAS of both ZX-7101A dose groups was significantly shortened relative to the that of placebo group: the median TTAS was shortened to 48.4 hours (95% CI, 40.5-55.6) for 40 mg group and 39.4 hours (95% CI, 35.8-49.3) for 80 mg group, compared with 62.9 hours (95% CI, 56.4-69.3) for placebo group (p 0.003 and p < 0.001, respectively). In the safety population, ZX-7101A treatment was associated with fewer adverse events, with 41.8% (100/239) in the 40 mg group, 44.2% (106/240) in the 80 mg group, and 53.8% (129/240) in the placebo group. The majority of adverse events were mild or moderate. Emergence of resistance to ZX-7101A through I38T amino acid substitution was detected in 5/278 (1.8%) patients.<h4>Discussion</h4>ZX-7101A was an effective treatment for influenza with a single dose of either 40 mg or 80 mg, with more rapid alleviation of influenza symptoms vs. placebo. No safety concerns were identified with single dose treatment of ZX-7101A.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39490410","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"","title":null},{"funder_name":"Shanghai Science and Technology University","grant_id":"","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(24)00502-0/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1198743X24005020?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1198743X24005020?httpAccept=text/plain","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Endonucleases","Placebos","Antiviral Agents","Treatment Outcome","Double-Blind Method","Adolescent","Adult","Aged","Middle Aged","Female","Male","Influenza, Human","Young Adult"],"keywords":["Rct","I38t Substitutions","Influenza Cap-dependent Endonuclease Inhibitor","Uncomplicated Influenza","Zx-7101a"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:44:25.583218Z","pmid":null,"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":[]}