A Study to Assess the Clinical Efficacy of Donidalorsen (Also Known as IONIS-PKK-LRx and ISIS 721744) in Participants With Hereditary Angioedema

Phase 2 Completed 23 enrolled Ionis Pharmaceuticals, Inc.

RandomizedParallel-groupTriple-blindTreatment

Summary

The purpose of this study was to evaluate the clinical efficacy, safety, and tolerability of donidalorsen in participants with hereditary angioedema (HAE) type 1 (HAE-1), HAE type 2 (HAE-2), or HAE with normal C1-inhibitor (C1-INH) and to evaluate the effect of donidalorsen on plasma prekallikrein (PKK) and other relevant biomarkers.

Timeline

Start: 2020-01-07
Primary completion: 2021-01-04
Completion: 2021-03-01

Outcome

Met primary endpoint

registry analysis (superiority test); Part A: Placebo vs Part A: Donidalorsen 80 mg; p = 0.001; Percentage Difference -90.00 (95% CI -96.00 to -76.00); Wald Chi-Square NCT04030598 ↗

paper donidalorsen treatment resulted in a significantly lower rate of angioedema attacks than placebo in this small, phase 2 trial. PMID 35294812 ↗

Publications

Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM. Inhibition of Prekallikrein for Hereditary Angioedema. N Engl J Med. 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Donidalorsen	Antisense oligonucleotide	80 mg	Subcutaneous