Henriette Farkas1, Avner Reshef2, Werner Aberer3, Teresa Caballero4, Laura McCarthy5, James Hao5, Wolfram Nothaft5, Jennifer Schranz5, Jonathan A Bernstein6, H Henry Li7. 1. Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. Electronic address: farkas.henriette@med.semmelweis-univ.hu. 2. Chaim Sheba Medical Center, Allergy, Immunology and Angiodema Center, Tel-Hashomer, Israel. 3. Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria. 4. Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases (CIBERER, U754), Madrid, Spain. 5. Shire, Lexington, Mass. 6. University of Cincinnati Physicians Immunology Research Center, Cincinnati, Ohio. 7. Institute for Asthma and Allergy, Chevy Chase, Md.
Abstract
BACKGROUND: Clinical manifestations of hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) usually begin in childhood, often intensifying during puberty. Currently there are insufficient efficacy/safety data for HAE therapies in children and adolescents due to the small number of pediatric patients enrolled in studies. OBJECTIVE: The objective of this phase 3 study was to evaluate the efficacy/safety of a single subcutaneous dose of icatibant (0.4 mg/kg; maximum 30 mg) in pediatric patients with C1-INH-HAE. METHODS: Patients aged 2 years to younger than 18 years were categorized as prepubertal (children) and pubertal/postpubertal (adolescents). The primary end point was time to onset of symptom relief-earliest time posttreatment to 20% or more improvement in composite symptom score. RESULTS: Thirty-two patients received icatibant (safety population: 11 children with attack, 10 adolescents without attack, and 11 adolescents with attack). The efficacy population consisted of 11 children and 11 adolescents with edematous attacks. Most attacks in the efficacy population (16 [72.7%]) were cutaneous, 5 (22.7%) were abdominal, and 1 (4.5%) was both cutaneous and abdominal; none was laryngeal. Overall, the median time to onset of symptom relief was 1.0 hour, the same for children and adolescents. Thirty-two treatment-emergent adverse events (all mild or moderate) occurred in 9 (28.1%) patients. Gastrointestinal symptoms were most common (9 events in 3 [9.4%] patients). Injection-site reactions affected most (90.6%) patients (particularly erythema and swelling), but almost all resolved by 6 hours postdose. Icatibant demonstrated a monophasic plasma concentration-time profile. Time to peak concentration was approximately 0.5 hours postdose. CONCLUSIONS: Symptom relief was rapid, and a single icatibant injection in pediatric patients with C1-INH-HAE was well tolerated (ClinicalTrials.gov identifier, NCT01386658).
BACKGROUND: Clinical manifestations of hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) usually begin in childhood, often intensifying during puberty. Currently there are insufficient efficacy/safety data for HAE therapies in children and adolescents due to the small number of pediatric patients enrolled in studies. OBJECTIVE: The objective of this phase 3 study was to evaluate the efficacy/safety of a single subcutaneous dose of icatibant (0.4 mg/kg; maximum 30 mg) in pediatric patients with C1-INH-HAE. METHODS:Patients aged 2 years to younger than 18 years were categorized as prepubertal (children) and pubertal/postpubertal (adolescents). The primary end point was time to onset of symptom relief-earliest time posttreatment to 20% or more improvement in composite symptom score. RESULTS: Thirty-two patients received icatibant (safety population: 11 children with attack, 10 adolescents without attack, and 11 adolescents with attack). The efficacy population consisted of 11 children and 11 adolescents with edematous attacks. Most attacks in the efficacy population (16 [72.7%]) were cutaneous, 5 (22.7%) were abdominal, and 1 (4.5%) was both cutaneous and abdominal; none was laryngeal. Overall, the median time to onset of symptom relief was 1.0 hour, the same for children and adolescents. Thirty-two treatment-emergent adverse events (all mild or moderate) occurred in 9 (28.1%) patients. Gastrointestinal symptoms were most common (9 events in 3 [9.4%] patients). Injection-site reactions affected most (90.6%) patients (particularly erythema and swelling), but almost all resolved by 6 hours postdose. Icatibant demonstrated a monophasic plasma concentration-time profile. Time to peak concentration was approximately 0.5 hours postdose. CONCLUSIONS: Symptom relief was rapid, and a single icatibant injection in pediatric patients with C1-INH-HAE was well tolerated (ClinicalTrials.gov identifier, NCT01386658).
Authors: Francesca Gorini; Michele Santoro; Anna Pierini; Lorena Mezzasalma; Silvia Baldacci; Elena Bargagli; Alessandra Boncristiano; Maurizia Rossana Brunetto; Paolo Cameli; Francesco Cappelli; Giancarlo Castaman; Barbara Coco; Maria Alice Donati; Renzo Guerrini; Silvia Linari; Vittoria Murro; Iacopo Olivotto; Paola Parronchi; Francesca Pochiero; Oliviero Rossi; Barbara Scappini; Andrea Sodi; Alessandro Maria Vannucchi; Alessio Coi Journal: Front Pharmacol Date: 2022-05-16 Impact factor: 5.988
Authors: Marcus Maurer; Markus Magerl; Stephen Betschel; Werner Aberer; Ignacio J Ansotegui; Emel Aygören-Pürsün; Aleena Banerji; Noémi-Anna Bara; Isabelle Boccon-Gibod; Konrad Bork; Laurence Bouillet; Henrik Balle Boysen; Nicholas Brodszki; Paula J Busse; Anette Bygum; Teresa Caballero; Mauro Cancian; Anthony J Castaldo; Danny M Cohn; Dorottya Csuka; Henriette Farkas; Mark Gompels; Richard Gower; Anete S Grumach; Guillermo Guidos-Fogelbach; Michihiro Hide; Hye-Ryun Kang; Allen P Kaplan; Constance H Katelaris; Sorena Kiani-Alikhan; Wei-Te Lei; Richard F Lockey; Hilary Longhurst; William Lumry; Andrew MacGinnitie; Alejandro Malbran; Inmaculada Martinez Saguer; Juan José Matta Campos; Alexander Nast; Dinh Nguyen; Sandra A Nieto-Martinez; Ruby Pawankar; Jonathan Peter; Grzegorz Porebski; Nieves Prior; Avner Reshef; Marc Riedl; Bruce Ritchie; Farrukh Rafique Sheikh; William B Smith; Peter J Spaeth; Marcin Stobiecki; Elias Toubi; Lilian Agnes Varga; Karsten Weller; Andrea Zanichelli; Yuxiang Zhi; Bruce Zuraw; Timothy Craig Journal: World Allergy Organ J Date: 2022-04-07 Impact factor: 5.516