BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

AARA Research Center Dallas Texas

Allergy and Asthma Clinical Research Walnut Creek Calif

Allergy Asthma and Immunology Center Tulsa Okla

Barzilai University Medical Center Allergy Immunology and Angioedema Ashkelon Israel

Bernstein Clinical Research Center LLC Cincinnati Ohio

Clinical Allergy and Immunology Section University of California San Diego School of Medicine La Jolla Calif

Clinical Research Center of Alabama Alabama Allergy and Asthma Birmingham Ala

Clinical Research Centre Hautklinik und Poliklinik der Universitätsklinik Mainz Mainz Germany

Clinique Specialisée en Allergie de la Capitale Québec QC Canada

CSL Behring LLC King of Prussia Pa

CSL Behring Marburg Germany

Department of Biomedical and Clinical Sciences L Sacco University of Milan ASST Fatebenefratelli Sacco Milan Italy

Department of Dermatology and Allergy Charité Universitätsmedizin Berlin Berlin Germany

Department of Dermatology Johannes Gutenberg University Mainz Germany

Department of Internal Medicine Virginia Commonwealth University Richmond Va

Department of Medicine Immunology and Allergy Campbelltown Hospital Campbelltown NSW Australia

Department of Medicine Pediatrics and Graduate Studies Penn State University Hershey Medical Center Hershey Pa

Department of Medicine University of California San Diego and San Diego VA Healthcare La Jolla Calif

Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele Catania Italy

Dr Donald Levy MD Orange Calif

Fakultni nemocnice Plzen Ustav Imunologie a Alergologie Plzen Czech Republic

Gordon Sussman Clinical Research Inc Toronto ON Canada

Hospital General Universitario Gregorio Marañón Servicio de Alergología Instituto de Investigación Gregorio Marañón Centro de Investigacion Biomédica en Red de Enfermedades Raras U761 Madrid Spain

Hospital Universitario La Fe Servicio de Alergia Bulevar del Sur Valencia Spain

Hungarian Angioedema Reference Center 3rd Department of Internal Medicine Semmelweis University Budapest Hungary

HZRM Haemophilia Center Rhein Main Moerfelden Walldorf Germany

Immunology Department Barts Health NHS Trust The Royal London Hospital London United Kingdom

Institute for Asthma and Allergy Chevy Chase Md

Klinikum der Johann Wolfgang Goethe Universität Klinik für Kinder und Jugendmedizin Frankfurt Germany

McMaster University Medical Center Site Hamilton ON Canada

Medical Research of Arizona Scottsdale Ariz

Ottawa Allergy Research Corp Ottawa ON Canada

Servicio de Alergia Hospital La Paz Institute for Health Research U754 Madrid Spain

Spitalul Clinic Municipal Cluj Cluj Napoca Romania

St John's Institute of Dermatology Tower Wing Guy's Hospital London United Kingdom

Tel Aviv Sourasky Medical Center Allergy and Immunology Unit Tel Aviv Israel

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ClinicalTrials.gov
NCT02316353