{"doi":"10.1093/cid/ciaa1725","title":"Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model","abstract":"BACKGROUND: It is imperative to identify new targets for improved vaccines and therapeutics against influenza. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. METHODS: We conducted a randomized, double-blind, phase 2, placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50 mg/kg dose of CR6261 was infused 24 hours after challenge. The primary efficacy outcome was area under the curve (AUC) of viral RNA detection over time. RESULTS: Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 received placebo. CR6261 had no statistically significant effect on AUC (AUC, 48.56 log [copies/mL] × days, interquartile range [IQR], 202 vs AUC, 25.53 log [copies/mL] × days, IQR, 155; P = .315) and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or inFLUenza Patient-Reported Outcome (FLU-PRO) scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1 × 106 ng/mL 15 minutes after infusion and a mean peak of 5.97 × 102 ng/mL in the nasal mucosa 2-3 days after infusion. CONCLUSIONS: The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multifaceted strategy rather than as a stand-alone therapeutic. CLINICAL TRIALS REGISTRATION: NCT02371668.","journal":"Clinical Infectious Diseases","year":2020,"id":62179,"datarank":1.7003962923052414,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":1.1020486853206002,"self_endowment_contribution":0.5983476069846413,"citer_contribution":1.1020486853206002,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":50,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02371668"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":327663,"name":"Lindsay Czajkowski","orcid":null,"position":1,"is_corresponding":false},{"id":295529,"name":"Luz Angela Rosas","orcid":"0000-0002-8743-7189","position":2,"is_corresponding":false},{"id":296900,"name":"Adriana Cervantes-Medina","orcid":null,"position":3,"is_corresponding":false},{"id":327657,"name":"Yongli Xiao","orcid":null,"position":4,"is_corresponding":false},{"id":327659,"name":"Monica Gouzoulis","orcid":null,"position":5,"is_corresponding":false},{"id":330234,"name":"Keith Lumbard","orcid":null,"position":6,"is_corresponding":false},{"id":295533,"name":"Sally Hunsberger","orcid":"0000-0002-4251-5622","position":7,"is_corresponding":false},{"id":327661,"name":"Susan Reed","orcid":null,"position":8,"is_corresponding":false},{"id":327662,"name":"Rani Athota","orcid":null,"position":9,"is_corresponding":false},{"id":330235,"name":"Holly Ann Baus","orcid":null,"position":10,"is_corresponding":false},{"id":330236,"name":"Amy Lwin","orcid":null,"position":11,"is_corresponding":false},{"id":328876,"name":"Jerald Sadoff","orcid":"0000-0002-4839-3013","position":12,"is_corresponding":false},{"id":233147,"name":"Jeffery K. Taubenberger","orcid":"0000-0002-9694-7228","position":13,"is_corresponding":false},{"id":233146,"name":"Matthew J. Memoli","orcid":"0000-0001-6393-5178","position":14,"is_corresponding":false},{"id":326313,"name":"Alison Han","orcid":"0000-0002-7622-7696","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T21:10:11.612909Z","pmid":"33211860","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":[]}