A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

Summary

This study is a randomized, double-blind, placebo-controlled, phase III, three-way crossover clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adolescent and adult Patients

Timeline

Start

2022-02-22

Primary completion

2023-12-31

Completion

2023-12-31

Outcome

Met primary endpoint

registry analysis (superiority test); KVD900 300 mg vs Placebo; p <0.0001; Gehan score transformation test NCT05259917 ↗

registry analysis (superiority test); KVD900 600 mg vs Placebo; p = 0.0013; Gehan score transformation test NCT05259917 ↗

Publications

• Background Riedl MA, Farkas H, Aygoren-Pursun E, Psarros F, Soteres DF, Staevska M, Cancian M, Hagin D, Honda D, Melamed I, Savic S, Stobiecki M, Busse PJ, Dias de Castro E, Agmon-Levin N, Gower R, Kessel A, Kurowski M, Lleonart R, Grivcheva Panovska V, Wedner HJ, Audhya PK, Hao J, Iverson M, Smith MD, Yea CM, Lumry WR, Zanichelli A, Bernstein JA, Maurer M, Cohn DM; KONFIDENT Investigators. Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks. N Engl J Med. 2024 Jul 4;391(1):32-43. doi: 10.1056/NEJMoa2314192. Epub 2024 May 31.
• Aygoren-Pursun E, Cohn DM, Agmon-Levin N, Banerji A, Bernstein JA, Busse P, Cancian M, de Castro ED, Farkas H, Grivcheva-Panovska V, Hagin D, Hakl R, Honda D, Kessel A, Kinaciyan T, Ifaad, Kurowski M, Li HH, Lleonart R, Longhurst HJ, Lumry WR, Magerl M, Martinez-Saguer I, Melamed I, Psarros F, Savic S, Soteres DF, Staevska M, Stobiecki M, Wedner HJ, Zanichelli A, Hao J, Patil K, Iverson M, Owiredu-Yeboa S, Smith MD, Yea CM, Audhya PK, Riedl MA, Kiani-Alikhan S, Maurer M. Sebetralstat for on-demand treatment of hereditary angioedema: A pooled analysis of placebo-controlled clinical trials. World Allergy Organ J. 2026 Jun 9;19(7):101401. doi: 10.1016/j.waojou.2026.101401. eCollection 2026 Jul.
• Farkas H, Anderson J, Bouillet L, Caballero T, Cancian M, Craig T, Fukunaga A, Grivcheva-Panovska V, Guilarte M, Honda D, Kanarek H, Kiani-Alikhan S, Kinaciyan T, Leguevaques D, Longhurst HJ, Magerl M, Manning ME, Martinez-Saguer I, Melamed I, O'Connor ME, Peter J, Savic S, Soteres DF, Staevska M, Staubach P, Stobiecki M, Tachdjian R, Valerieva A, Yong PFK, Hao J, Iverson M, Smith MD, Yea CM, Audhya PK, Aygoren-Pursun E, Bernstein JA, Cohn DM, Lumry WR, Riedl MA, Zanichelli A, Maurer M. Long-Term Safety and Effectiveness of Sebetralstat: Interim Analysis of KONFIDENT-S Open-label Extension. J Allergy Clin Immunol Pract. 2025 Nov;13(11):3094-3103.e5. doi: 10.1016/j.jaip.2025.08.020. Epub 2025 Aug 29.
• Aygoren-Pursun E, Zanichelli A, Cohn DM, Cancian M, Hakl R, Kinaciyan T, Magerl M, Martinez-Saguer I, Stobiecki M, Farkas H, Kiani-Alikhan S, Grivcheva-Panovska V, Bernstein JA, Li HH, Longhurst HJ, Audhya PK, Smith MD, Yea CM, Maetzel A, Lee DK, Feener EP, Gower R, Lumry WR, Banerji A, Riedl MA, Maurer M. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet. 2023 Feb 11;401(10375):458-469. doi: 10.1016/S0140-6736(22)02406-0.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Sebetralstat	Small molecule	300 mg	Oral
Subject	Sebetralstat	Small molecule	600 mg	Oral

Indications