Efficacy and Safety of Bradykinin B2 Receptor Antagonism With Oral Deucrictibant in Prophylaxis of Hereditary Angioedema Attacks - Results of CHAPTER-1 Phase 2 Trial

Aug 23, 2026

Upload by Finn

Bradykinin overactivity drives the clinical manifestations of hereditary angioedema (HAE) attacks, creating a need for prophylactic options that combine injectable-like efficacy, good tolerability, and convenient administration. CHAPTER-1 is a two-part Phase 2 study evaluating oral deucrictibant for long-term prevention in participants with HAE-1/2. In the placebo-controlled period, deucrictibant (20 mg/day or 40 mg/day) significantly reduced the monthly investigator-confirmed attack rate versus placebo, meeting the primary endpoint, with additional outcomes assessed for moderate/severe events and on-demand treated attacks.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages1

Reading Time3 min

AccessFree to download

Rationale

Deucretibant development and unmet need

Methods

Study design and eligibility

Dosing and endpoints

Results

Participant enrollment

Primary endpoint outcomes

Efficacy and Safety of Bradykinin B2 Receptor Antagonism With Oral Deucrictibant in Prophylaxis of Hereditary Angioedema Attacks: Results of CHAPTER-1 Phase 2 Trial Marc A. Riedl1, John Anderson2, Francesco Arcoleo3, Mauro Cancian4, Hugo Chapdelaine5, Niall Conlon6, Efrem Eren7, Mark Gompels8, Sofia Grigoriadou9, Maria D. Guarino10, Padmalal Gurugama11, Tamar Kinaciyan12, Markus Magerl13,14, Michael E. Manning15, Marcin Stobiecki16, Michael D. Tarzi17, Anna Valerieva18, H. James Wedner19, William H. Yang20, Andrea Zanichelli21, Rafael Crabbé22, Susan Mulders23, Minying Royston24, Li Zhu24, Jochen Knolle25, Anne Lesage26, Peng Lu24, Emel Aygören-Pürsün27 1Division of Allergy and Immunology, University of California San Diego, La Jolla, CA, USA; 2Clinical Research Center of Alabama, AllerVie Health, Birmingham, AL, USA; 3UOC di Patologia Clinica e Immunologia, AOR Villa Sofia-Cervello, Palermo, Italy; 4Department of Systems Medicine, University Hospital of Padua, Padua, Italy; 5CHU de Montréal, Université de Montréal, Montréal, Canada; 6Wellcome Trust CRF, St. James's Hospital and Trinity College, Dublin, Ireland; 7University Hospital Southampton NHS Foundation Trust, Southampton, UK; 8North Bristol NHS Trust, Bristol, UK; 9Barts Health NHS Trust, London, UK; 10Ospedale di Civitanova Marche, Civitanova Marche, Italy; 11Department of Clinical Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 12Department of Dermatology, Medical University of Vienna, Vienna, Austria; 13Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 14Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany; 15Allergy, Asthma and Immunology Associates, Ltd., Scottsdale, AZ, USA; 16Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland; 17Department of Immunology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK; 18Department of Allergology, Clinic of Allergology, University Hospital Alexandrovska, Medical University of Sofia, Sofia, Bulgaria; 19Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 20Ottawa Allergy Research Corporation, Department of Medicine, University of Ottawa, Ottawa, Canada; 21Operative Unit of Medicine, Angioedema Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy, and Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; 22RC Consultancy, Bassins, Switzerland; 23Mulders Clinical Consulting, Groesbeek, The Netherlands; 24Pharvaris Inc., Lexington, MA, USA; 25JCK Consult, Frankfurt, Germany; 26GrayMatters Consulting, Schilde, Belgium; 27Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany Rationale • Excess bradykinin is the cause of the clinical manifestations of hereditary angioedema (HAE) attacks.1 • Despite the availability of approved therapies, an unmet need remains for additional prophylactic treatments combining injectable-like efficacy, a well-tolerated profile, and ease of administration.2-5 • Deucrictibant is an orally administered, highly potent, specific antagonist of the bradykinin B2 receptor under development for on-demand and prophylactic treatment of HAE attacks.3,6-10 Methods • CHAPTER-1 (NCT05047185)10,† is a two-part, Phase 2 study evaluating the efficacy, safety, and tolerability of deucrictibant for long-term prophylaxis against angioedema attacks in HAE-1/2 . • Eligible participants were ≥18 and ≤75 years, diagnosed with HAE-1/2, were not receiving other prophylactic treatments at the time of screening, and experienced ≥3 attacks within the past 3 consecutive months prior to screening or ≥2 attacks during screening (up to 8 weeks) . • In placebo-controlled

FAQs

What is the rationale for using bradykinin B2 receptor antagonism in hereditary angioedema?

Excess bradykinin is identified as the cause of hereditary angioedema attack manifestations. Blocking the bradykinin B2 receptor is expected to reduce attack frequency and impact.

How was the CHAPTER-1 Phase 2 study structured and what were the main outcomes?

CHAPTER-1 was a two-part Phase 2 study evaluating oral deucrictibant for long-term prophylaxis in HAE-1/2. The primary endpoint was the time-normalized number of investigator-confirmed HAE attacks, expressed as the monthly attack rate.

Did oral deucrictibant reduce HAE attack rates compared with placebo?

Yes. The primary endpoint was met, with deucrictibant 20 mg/day and 40 mg/day significantly reducing the monthly attack rate by 79.3% and 84.5%, respectively, versus placebo.

Aug 23, 2026

Upload by Finn