Pharvaris reports the first qualitative AAE-C1INH study validating patient-reported outcomes and informing endpoint selection for the Phase 3 CREAATE trial.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Pharvaris N.V. has announced the publication of the first in-depth qualitative study exploring the experiences of people living with acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) and validating patient-reported outcome (PRO) measures for this ultra-rare disease. Published in Frontiers in Immunology, the findings directly informed the design and endpoint selection of the ongoing Phase 3 CREAATE trial (NCT07266805), which is evaluating deucrictibant for the prophylaxis and on-demand treatment of AAE-C1INH attacks.
AAE-C1INH is an ultra-rare bradykinin-mediated disorder that typically develops later in life due to autoimmune or hematologic diseases. Unlike hereditary angioedema, there are currently no approved therapies specifically for preventing or treating AAE-C1INH attacks, leaving patients dependent on off-label use of hereditary angioedema treatments.
Study Design
Researchers conducted a cross-sectional qualitative study to better understand the disease burden and determine whether existing PRO instruments are appropriate for use in AAE-C1INH clinical trials. Because the condition is extremely rare, only eight eligible adults in the United States were enrolled from 169 individuals screened through the Hereditary Angioedema Association. Participants completed approximately 90-minute semi-structured interviews combining concept elicitation with cognitive debriefing of several PRO instruments.
Significant Disease Burden
Participants consistently described prolonged diagnostic delays and frequent misdiagnoses before receiving the correct diagnosis. Misdiagnoses included cellulitis, insect bites, and conversion disorder, while six of the eight participants required emergency department care during their first attack.
All participants reported relying on off-label therapies approved for hereditary angioedema because no treatments are approved specifically for AAE-C1INH. The abdomen (87.5%) and face (75.0%) were the most common attack sites.
Beyond physical symptoms, interviews demonstrated that AAE-C1INH substantially affects quality of life. Participants reported disruption of daily activities, work, travel, family and social relationships, emotional well-being, and hobbies. Based on these interviews, investigators also developed the first conceptual disease model for AAE-C1INH, providing a framework for future clinical endpoint selection.
Validation of Patient-Reported Outcome Measures
The study evaluated the relevance and interpretability of four patient-reported outcome instruments: the Patient Global Impression of Change (PGI-C), Patient Global Impression of Severity (PGI-S), Patient Global Assessment of Status (PGA-S), and Patient Global Assessment of Change (PGA-C).
Among these, PGI-C showed the strongest content validity, with all participants correctly interpreting the response scale. PGI-S was correctly understood by three of the seven participants who reviewed it, while PGA-S and PGA-C were understood by 86% and 83% of respondents, respectively.
Importantly, participants consistently identified a PGI-C rating of “better” as representing a meaningful treatment benefit at assessment time points up to four hours after treatment, supporting its use as a clinically relevant patient-centered endpoint.
Supporting the CREAATE Trial
According to Pharvaris, these findings directly informed endpoint selection for the ongoing Phase 3 CREAATE study evaluating oral deucrictibant in patients with AAE-C1INH. The company said the research provides an evidence-based framework for incorporating outcomes that reflect improvements considered meaningful by patients.
Danny M. Cohn, M.D., Ph.D., principal investigator of the CREAATE study, said patients with AAE-C1INH often face painful attacks, prolonged misdiagnoses, and repeated emergency care because of limited disease awareness. He noted that the absence of approved therapies makes patient-centered clinical research particularly important.
Pharvaris President Peng Lu, M.D., Ph.D., added that the study aligns with U.S. Food and Drug Administration guidance on incorporating patient experience into drug development and strengthens the scientific foundation for evaluating treatment benefit in this underserved patient population.
Although limited by its small sample size and recruitment from a patient advocacy group, the study represents the first comprehensive qualitative assessment of AAE-C1INH. The authors concluded that it establishes a foundation for selecting meaningful patient-centered endpoints in future clinical trials for this ultra-rare disease.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.