William R Lumry1, Inmaculada Martinez-Saguer2, William H Yang3, Jonathan A Bernstein4, Joshua Jacobs5, Dumitru Moldovan6, Marc A Riedl7, Douglas T Johnston8, H Henry Li9, Yongqiang Tang10, Jennifer Schranz10, Peng Lu10, Moshe Vardi10, Henriette Farkas11. 1. AARA Research Center, Dallas, Texas. Electronic address: LumryMD@AllergySpecialists.us. 2. Hämophilie-Zentrum Rhein Main (HZRM), Mörfelden-Walldorf, Germany. 3. Ottawa Allergy Research Corporation, University of Ottawa Medical School, Ottawa, Ontario, Canada. 4. Bernstein Clinical Research Center, Cincinnati, Ohio. 5. Allergy and Asthma Clinical Research, Walnut Creek, Calif. 6. MediQuest Medical Center, Sangeorgiu de Mures, Târgu Mureș, Romania. 7. University of California, San Diego, Calif. 8. Asthma & Allergy Specialists, PA, Charlotte, NC. 9. Institute for Asthma and Allergy, Chevy Chase, Md. 10. Shire, now part of Takeda, Lexington, Mass. 11. Hungarian Angioedema Reference Center, Semmelweis University, Budapest, Hungary.
Abstract
BACKGROUND: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. OBJECTIVE: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). METHODS:Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre-long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety. RESULTS:Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least-squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH-treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). CONCLUSIONS: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.
RCT Entities:
BACKGROUND: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. OBJECTIVE: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). METHODS: Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre-long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety. RESULTS: Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least-squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH-treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). CONCLUSIONS: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.
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