LONG-TERM PROPHYLACTIC TREATMENT WITH ORAL DEUCRICTIBANT IMPROVED DISEASE CONTROL AND HEALTH-RELATED QUALITY OF LIFE IN PARTICIPANTS WITH HEREDITARY ANGIOEDEMA: FINAL RESULTS OF THE CHAPTER-1 OPEN-LABEL EXTENSION STUDY
Author(s)
Michael E. Manning, MD1, John Anderson, MD2, Francesco Arcoleo, MD3, Mauro Cancian, MD, PhD4, Hugo Chapdelaine, MD, FRCPC5, Niall Conlon, PhD, FRCPath6, Efrem Eren, MBBS, MRCP, FRCPath, PhD7, Mark Gompels, MD8, Sofia Grigoriadou, MD9, Maria D. Guarino, MD, PhD10, Padmalal Gurugama, MBBS, MSc, MD, MRCP, FRCPath11, Sorena Kiani, BSc, MBBS, PhD, FRCP, FRCPath12, Tamar Kinaciyan, MD13, Markus Magerl, MD14, Marcin Stobiecki, MD, PhD15, Michael D. Tarzi, MA, MD, MRCP, FRCPath16, Anna Valerieva, MD, PhD17, H. James Wedner, MD, FACP, FAAAAI18, William H. Yang, MD, FRCPC, FAAAAI19, Andrea Zanichelli, MD, PhD20, Rafael Crabbé, MD21, Susan Mulders, PhD22, Jonathan Levy, PhD23, Ulrich Freudensprung, MS24, Umar Katbeh, MA, PhD24, Jochen Knolle, PhD25, Anne Lesage, PhD26, Peng Lu, MD, PhD23, Emel Aygören-Pürsün, MD27, Marc A. Riedl, MD28.
1Allergy, Asthma and Immunology Associates, Ltd., Scottsdale, AZ, USA, 2AllerVie Health, Clinical Research Center of Alabama, Birmingham, AL, USA, 3AOR Villa Sofia-Cervello, UOC di Patologia Clinica e Immunologia, Palermo, Italy, 4Azienda Ospedale Università di Padova, Padua, Italy, 5CHU de Montréal, Université de Montréal, Montréal, QC, Canada, 6St. James's Hospital and Trinity College, Wellcome Trust CRF, Dublin, Ireland, 7University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, 8North Bristol NHS Trust, Bristol, United Kingdom, 9Barts Health NHS Trust, Department of Immunology, London, United Kingdom, 10U.O.C. Allergologia Ospedale di Civitanova Marche, Civitanova Marche, Italy, 11Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, 12Royal Free London NHS Foundation Trust, Department of Immunology, London, United Kingdom, 13Medical University of Vienna, Department of Dermatology, Vienna, Austria, 14Charité-Universitätsmedizin Berlin, Institute of Allergology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany, 15Jagiellonian University Medical College, Department of Clinical and Environmental Allergology, Kraków, Poland, 16University Hospitals Sussex NHS Foundation Trust, Department of Respiratory Medicine, Brighton, United Kingdom, 17Medical University of Sofia, Department of Allergology, Sofia, Bulgaria, 18Washington University School of Medicine, Division of Allergy and Immunology, Department of Medicine, St. Louis, MO, USA, 19University of Ottawa, Ottawa Allergy Research Corporation, Department of Medicine, Ottawa, ON, Canada, 20Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute; I.R.C.C.S., Policlinico San Donato, Centro Angioedema, UO Medicina, Milan, Italy, 21RC Consultancy, Bassins, Switzerland, 22Mulders Clinical Consulting, Groesbeek, Netherlands, 23Pharvaris Inc., Lexington, MA, USA, 24Pharvaris GmbH, Zug, Switzerland, 25JCK Consult, Frankfurt, Germany, 26GrayMatters Consulting, Schilde, Belgium, 27Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany, 28University of California San Diego, Division of Allergy and Immunology, La Jolla, CA, USA.
1Allergy, Asthma and Immunology Associates, Ltd., Scottsdale, AZ, USA, 2AllerVie Health, Clinical Research Center of Alabama, Birmingham, AL, USA, 3AOR Villa Sofia-Cervello, UOC di Patologia Clinica e Immunologia, Palermo, Italy, 4Azienda Ospedale Università di Padova, Padua, Italy, 5CHU de Montréal, Université de Montréal, Montréal, QC, Canada, 6St. James's Hospital and Trinity College, Wellcome Trust CRF, Dublin, Ireland, 7University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, 8North Bristol NHS Trust, Bristol, United Kingdom, 9Barts Health NHS Trust, Department of Immunology, London, United Kingdom, 10U.O.C. Allergologia Ospedale di Civitanova Marche, Civitanova Marche, Italy, 11Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, 12Royal Free London NHS Foundation Trust, Department of Immunology, London, United Kingdom, 13Medical University of Vienna, Department of Dermatology, Vienna, Austria, 14Charité-Universitätsmedizin Berlin, Institute of Allergology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany, 15Jagiellonian University Medical College, Department of Clinical and Environmental Allergology, Kraków, Poland, 16University Hospitals Sussex NHS Foundation Trust, Department of Respiratory Medicine, Brighton, United Kingdom, 17Medical University of Sofia, Department of Allergology, Sofia, Bulgaria, 18Washington University School of Medicine, Division of Allergy and Immunology, Department of Medicine, St. Louis, MO, USA, 19University of Ottawa, Ottawa Allergy Research Corporation, Department of Medicine, Ottawa, ON, Canada, 20Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute; I.R.C.C.S., Policlinico San Donato, Centro Angioedema, UO Medicina, Milan, Italy, 21RC Consultancy, Bassins, Switzerland, 22Mulders Clinical Consulting, Groesbeek, Netherlands, 23Pharvaris Inc., Lexington, MA, USA, 24Pharvaris GmbH, Zug, Switzerland, 25JCK Consult, Frankfurt, Germany, 26GrayMatters Consulting, Schilde, Belgium, 27Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany, 28University of California San Diego, Division of Allergy and Immunology, La Jolla, CA, USA.
Presentation Documents
OBJECTIVES: Deucrictibant is a potent, selective, orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment of attacks of bradykinin-mediated angioedema, including hereditary angioedema (HAE). During the randomized, placebo-controlled period of the two-part, phase 2 CHAPTER-1 study (NCT05047185), participants with HAE reported improved disease control and health-related quality of life (HRQoL) with deucrictibant vs placebo from as early as week 4 and through week 12. Here, we investigated the impact of deucrictibant on disease control and HRQoL in the subsequent open-label extension (OLE) part of the study.
METHODS: Eligible participants for CHAPTER-1 included adults diagnosed with HAE-1/2. Of 34 participants enrolled, 30 completed the 12-week randomised controlled trial (RCT), during which they self-administered deucrictibant 20 mg/day (n=11), 40 mg/day (n=10), or placebo (n=9). All continued into the OLE and self-administered deucrictibant 40 mg/day. Participants used the 4‑week Angioedema Control Test (AECT-4wk) to assess disease control and Patient Global Assessment of Change (PGA-C) and Angioedema QoL Questionnaire (AE-QoL) to assess HRQoL.
RESULTS: Of the 30 participants who entered the OLE, 24 participants had reached at least the week 86 visit at the time of OLE end. Of these participants, 100% achieved the AECT-4wk definition of well-controlled HAE. At week 86, all (100%) participants reported feeling “much better” on the PGA-C scale compared with RCT baseline, indicating improved HRQoL. The mean AE-QoL total score improved by 26.9 points from RCT baseline to 14.8 points at week 86. The AE-QoL domains showing the greatest improvement with deucrictibant treatment from RCT baseline to week 86 were “functioning” and “fear/shame” (39.4- and 35.5-point improvement, respectively).
CONCLUSIONS: Final patient-reported outcome results from the CHAPTER-1 OLE study provide further evidence on the effects of long-term prophylactic treatment with oral deucrictibant on disease control and HRQoL in participants with HAE.
METHODS: Eligible participants for CHAPTER-1 included adults diagnosed with HAE-1/2. Of 34 participants enrolled, 30 completed the 12-week randomised controlled trial (RCT), during which they self-administered deucrictibant 20 mg/day (n=11), 40 mg/day (n=10), or placebo (n=9). All continued into the OLE and self-administered deucrictibant 40 mg/day. Participants used the 4‑week Angioedema Control Test (AECT-4wk) to assess disease control and Patient Global Assessment of Change (PGA-C) and Angioedema QoL Questionnaire (AE-QoL) to assess HRQoL.
RESULTS: Of the 30 participants who entered the OLE, 24 participants had reached at least the week 86 visit at the time of OLE end. Of these participants, 100% achieved the AECT-4wk definition of well-controlled HAE. At week 86, all (100%) participants reported feeling “much better” on the PGA-C scale compared with RCT baseline, indicating improved HRQoL. The mean AE-QoL total score improved by 26.9 points from RCT baseline to 14.8 points at week 86. The AE-QoL domains showing the greatest improvement with deucrictibant treatment from RCT baseline to week 86 were “functioning” and “fear/shame” (39.4- and 35.5-point improvement, respectively).
CONCLUSIONS: Final patient-reported outcome results from the CHAPTER-1 OLE study provide further evidence on the effects of long-term prophylactic treatment with oral deucrictibant on disease control and HRQoL in participants with HAE.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
PCR66
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Rare & Orphan Diseases