A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)

Summary

The objectives of this time-to-event study were to assess the efficacy and safety of eculizumab as compared with placebo in participants with neuromyelitis optica spectrum disorder (NMOSD) who were anti-aquaporin-4 (AQP4) antibody-positive.

Timeline

Start

2014-04-11

Primary completion

2018-07-17

Completion

2018-07-17

Outcome

Met primary endpoint

registry analysis (other test); Eculizumab vs Placebo; p <0.0001; Hazard Ratio (HR) 0.058 (95% CI 0.017 to 0.197); Stratified Log-Rank Test NCT01892345 ↗

paper Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group PMID 31050279 ↗

Publications

• Background Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O'Toole O, Wingerchuk DM. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013 Jun;12(6):554-62. doi: 10.1016/S1474-4422(13)70076-0. Epub 2013 Apr 26.
• Results Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-625. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3.
• Singh P, Gao X, Kleijn HJ, Bellanti F, Pelto R. Eculizumab Pharmacokinetics and Pharmacodynamics in Patients With Neuromyelitis Optica Spectrum Disorder. Front Neurol. 2021 Nov 3;12:696387. doi: 10.3389/fneur.2021.696387. eCollection 2021.
• Pittock SJ, Fujihara K, Palace J, Berthele A, Kim HJ, Oreja-Guevara C, Nakashima I, Levy M, Shang S, Yountz M, Miller L, Armstrong R, Wingerchuk DM; PREVENT Study Group. Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension. Mult Scler. 2022 Mar;28(3):480-486. doi: 10.1177/13524585211038291. Epub 2021 Sep 9.
• Kim HJ, Nakashima I, Viswanathan S, Wang KC, Shang S, Miller L, Yountz M, Wingerchuk DM, Pittock SJ, Levy M, Berthele A, Totolyan N, Palace J, Barnett MH, Fujihara K; PREVENT Study Group. Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder: A subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension. Mult Scler Relat Disord. 2021 May;50:102849. doi: 10.1016/j.msard.2021.102849. Epub 2021 Feb 20.
• Palace J, Wingerchuk DM, Fujihara K, Berthele A, Oreja-Guevara C, Kim HJ, Nakashima I, Levy M, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Yountz M, Miller L, Armstrong R, Pittock S; PREVENT Study Group. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial. Mult Scler Relat Disord. 2021 Jan;47:102641. doi: 10.1016/j.msard.2020.102641. Epub 2020 Nov 26.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Eculizumab	Monoclonal antibody	1200 mg	Intravenous

Indications