{"doi":"10.1093/ofid/ofad500.1532","title":"1699. Safety and Outcomes of Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis or Invasive Mucormycosis in Pediatric Patients","abstract":"Abstract Background Invasive aspergillosis (IA) and invasive mucormycosis (IM) are life-threatening invasive fungal diseases (IFDs) that occur in critically ill and/or immunocompromised patients. Approved treatment options have significant limitations in pediatric patients. This study assessed the safety and outcomes of isavuconazonium sulfate (ISAV) for the treatment of IFD in this patient population. Methods This phase 2, open-label, non-comparative study enrolled patients at 10 centers in Belgium, Spain, and the US between 2019 and 2022. Patients aged 1 to < 18 years with possible, probable or proven IA or IM per the 2008 (EORTC/MSG) criteria received ISAV 10 mg/kg (max. 372 mg) every 8 h on days 1 and 2, and once-daily thereafter (intravenous or oral), for ≤ 84 days (IA) or ≤ 180 days (IM). Primary objectives were safety, including treatment-emergent adverse events (TEAEs), drug-related TEAEs, vital signs, electrocardiograms and laboratory parameters. Other key outcomes included all-cause case fatality through Day 42, overall response as assessed by an independent committee, and plasma ISAV levels. Data were summarized descriptively. Results Overall, 31 patients aged 1–17 years were enrolled; 80.6% were female and 61.3% were White (Table 1). The most common primary underlying condition was hematologic malignancy (58.1%). Patients received ISAV for a median (range) duration of 55 (2–181) days. Plasma ISAV levels were consistent with those seen in adults receiving the standard dose (Table 2). TEAEs occurred in 29 (93.5%) patients for a total of 415 events. Nine (29.0%) patients experienced drug-related TEAEs, and treatment was withdrawn in 2 patients due to TEAEs. Serious TEAEs occurred in 18 (58.1%) patients and were assessed as drug-related by the investigator in 1 patient (3.2%). All-cause case fatality through Day 42 was 6.5%. Overall, successful response rates were 54.8% at the end of treatment (EOT, Table 3). Table 1: Demographics and baseline characteristics (FAS) ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia (includes relapsed disease); B-LL, B-cell lymphoblastic leukemia/lymphoma; EORTC/MSG, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Mycoses Study Group; FAS, full analysis set; IA, invasive aspergillosis; IFD, invasive fungal disease; IM, invasive mucormycosis; MDS to AML, myelodysplastic syndrome transformed to AML; NHL, non-Hodgkin lymphoma; SD, standard deviation. An investigator assessment of IFD diagnosis was used. The FAS included all patients who are enrolled and receive at least one dose of study drug. Patients with possible IFD were eligible for enrollment; diagnostic tests to confirm the disease as ‘probable’ or ‘proven’ according to EORTC/MSG 2008 criteria were completed within 10 days after first dose of study drug. Other IFDs were defined as IFDs confirmed not to be IA or IM.Table 2:Overview of study drug exposure (SAF) and pharmacokinetic evaluation (PKAS) EORTC/MSG, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the Mycoses Study Group; IA, invasive aspergillosis; IFD: invasive fungal disease; IM, invasive mucormycosis; IV, intravenous; PKAS, pharmacokinetic analysis set; SAF, safety analysis set; SD, standard deviation. An investigator assessment of IFD diagnosis was used. Possible IFD was defined according to EORTC/MSG 2008 mycological criteria. Other IFDs were defined as IFDs confirmed not to be either IA or IM. The FAS included all patients who are enrolled and receive at least one dose of study drug. The PKAS consisted of all patients who took at least 1 dose of study drug and recorded least 1 plasma concentration measurement.Table 3:Overview of adverse events (SAF), all-cause case fatalities and clinical response outcomes (FAS) AC, adjudication committee; FAS, full analysis set; IA, invasive aspergillosis; IFD: invasive fungal disease; IM, invasi","journal":"Open Forum Infectious Diseases","year":2023,"id":382779,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1149227,"name":"Heidi Segers","orcid":"0000-0002-3604-7850","position":1,"is_corresponding":false},{"id":346914,"name":"Jaime G. Deville","orcid":"0000-0002-7523-0658","position":2,"is_corresponding":false},{"id":342568,"name":"William J. Muller","orcid":"0000-0001-7690-0695","position":3,"is_corresponding":false},{"id":1149228,"name":"Ángela Manzanares","orcid":"0000-0002-4230-5035","position":4,"is_corresponding":false},{"id":364681,"name":"Michael Neely","orcid":"0000-0002-1675-8276","position":5,"is_corresponding":false},{"id":753509,"name":"Victoria Bordon","orcid":"0000-0001-8446-0220","position":6,"is_corresponding":false},{"id":673574,"name":"Benjamin Hanisch","orcid":"0000-0003-3387-9093","position":7,"is_corresponding":false},{"id":607792,"name":"Álvaro Lassaletta","orcid":"0000-0003-2881-1473","position":8,"is_corresponding":false},{"id":337614,"name":"Brian T. Fisher","orcid":"0000-0002-8224-4281","position":9,"is_corresponding":false},{"id":602132,"name":"Julie Autmizguine","orcid":"0000-0001-8975-5052","position":10,"is_corresponding":false},{"id":263108,"name":"Andreas H. Groll","orcid":"0000-0003-1188-393X","position":11,"is_corresponding":false},{"id":348442,"name":"Shamim A. Sinnar","orcid":"0000-0002-6625-181X","position":12,"is_corresponding":false},{"id":1149685,"name":"Rodney Croos‐Dabrera","orcid":null,"position":13,"is_corresponding":false},{"id":1149229,"name":"Marc Engelhardt","orcid":"0000-0003-2432-0212","position":14,"is_corresponding":false},{"id":1149686,"name":"Mark E. Jones","orcid":null,"position":15,"is_corresponding":false},{"id":1149230,"name":"Laura Kovanda","orcid":"0000-0002-4493-4652","position":16,"is_corresponding":false},{"id":342565,"name":"Antonio Arrieta","orcid":"0000-0001-9281-8915","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:17:20.969491Z","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":[]}