Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II

Summary

This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

Timeline

Start

2022-04-19

Primary completion

2025-06-30

Completion

2025-06-30

Outcome

Met primary endpoint

paper percent reduction in attack rate compared with placebo was 79·2% (95% CI 47·2-91·8) for deucrictibant 20 mg (p=0·0010) PMID 41865746 ↗

paper 84·5% (95% CI 53·8-94·8) for deucrictibant 40 mg (p=0·0008) PMID 41865746 ↗

release “CHAPTER-1, a double-blind, placebo-controlled Phase 2 proof-of-concept study of deucrictibant for the prophylactic treatment of HAE attacks, demonstrated statistically significant reduction” pharvaris.com ↗

Publications

• Aygoren-Pursun E, Stobiecki M, Valerieva A, Cancian M, Gompels M, Grigoriadou S, Kiani-Alikhan S, Kinaciyan T, Yang WH, Anderson J, Arcoleo F, Chapdelaine H, Conlon N, Eren E, Guarino MD, Gurugama P, Magerl M, Manning ME, Tarzi MD, Wedner HJ, Zanichelli A, Crabbe R, Mulders S, Levy J, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA. Oral deucrictibant for prophylaxis of hereditary angioedema attacks (CHAPTER-1): primary analysis of a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2026 Apr;13(4):e215-e226. doi: 10.1016/S2352-3026(26)00004-9. Epub 2026 Mar 19.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	CRICTIBANT	Small molecule	20 mg	Oral
Subject	CRICTIBANT	Small molecule	40 mg	Oral

Indications