A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease

Summary

This multicenter, randomized, double-blind, placebo-controlled, Phase 2 study will evaluate the efficacy of intravenous prasinezumab (RO7046015/PRX002) versus placebo over 52 weeks in participants with early Parkinson's Disease (PD) who are untreated or treated with monoamine oxidase B (MAO-B) inhibitors since baseline. The study will consist of three parts: a 52-week, double-blind, placebo-controlled treatment period (Part 1) after which eligible participants will continue into an all-participants-on-treatment blinded dose extension for an additional 52 weeks (Part 2). Participants who complete Part 2 (including the 12-week treatment-free follow up visit assessing long term safety and efficacy of RO7046015) will be offered participation in Part 3 open-label extension (all-participants-on-RO7046015-treatment) for an additional 520 weeks.

Timeline

Start

2017-06-27

Primary completion

2019-11-27

Completion

2031-12-01

Outcome

Missed primary endpoint

registry analysis (superiority test); Part 1: Placebo vs Part 1: RO7046015 Low Dose; p = 0.2385; Difference in Adjusted Means -2.02 (80% CI -4.21 to 0.18); Mixed Models Analysis NCT03100149 ↗

registry analysis (superiority test); Part 1: Placebo vs Part 1: RO7046015 High Dose; p = 0.7169; Difference in Adjusted Means -0.62 (80% CI -2.82 to 1.58); Mixed Models Analysis NCT03100149 ↗

release “As previously reported, the study did not meet the primary objective, but signals of efficacy showing a reduction in disease progression were observed” prothena.com ↗

Publications

• Taylor KI, Lipsmeier F, Scelsi MA, Volkova-Volkmar E, Rukina D, Popp W, Lambrecht S, Anzures-Cabrera J, Summers D, Abt M, Monnet A, Kilchenmann T, Schjodt-Eriksen J, Essioux L, Kustermann T, Zago W, Svoboda H, Nikolcheva T, Postuma RB, Pagano G, Lindemann M; PASADENA Investigators; Prasinezumab Study Group. Exploratory digital outcome measures of motor sign progression in Parkinson's disease patients treated with prasinezumab. NPJ Digit Med. 2025 Jun 16;8(1):365. doi: 10.1038/s41746-025-01572-8.
• Pagano G, Monnet A, Reyes A, Ribba B, Svoboda H, Kustermann T, Simuni T, Postuma RB, Pavese N, Stocchi F, Brockmann K, Smigorski K, Gerbaldo V, Fontoura P, Doody R, Kerchner GA, Brundin P, Marek K, Bonni A, Nikolcheva T; PASADENA Investigators; Prasinezumab Study Group. Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial. Nat Med. 2024 Dec;30(12):3669-3675. doi: 10.1038/s41591-024-03270-6. Epub 2024 Oct 8.
• Pagano G, Taylor KI, Anzures-Cabrera J, Marchesi M, Simuni T, Marek K, Postuma RB, Pavese N, Stocchi F, Azulay JP, Mollenhauer B, Lopez-Manzanares L, Russell DS, Boyd JT, Nicholas AP, Luquin MR, Hauser RA, Gasser T, Poewe W, Ricci B, Boulay A, Vogt A, Boess FG, Dukart J, D'Urso G, Finch R, Zanigni S, Monnet A, Pross N, Hahn A, Svoboda H, Britschgi M, Lipsmeier F, Volkova-Volkmar E, Lindemann M, Dziadek S, Holiga S, Rukina D, Kustermann T, Kerchner GA, Fontoura P, Umbricht D, Doody R, Nikolcheva T, Bonni A; PASADENA Investigators; Prasinezumab Study Group. Trial of Prasinezumab in Early-Stage Parkinson's Disease. N Engl J Med. 2022 Aug 4;387(5):421-432. doi: 10.1056/NEJMoa2202867.
• Lipsmeier F, Taylor KI, Postuma RB, Volkova-Volkmar E, Kilchenmann T, Mollenhauer B, Bamdadian A, Popp WL, Cheng WY, Zhang YP, Wolf D, Schjodt-Eriksen J, Boulay A, Svoboda H, Zago W, Pagano G, Lindemann M. Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease. Sci Rep. 2022 Jul 15;12(1):12081. doi: 10.1038/s41598-022-15874-4.
• Pagano G, Boess FG, Taylor KI, Ricci B, Mollenhauer B, Poewe W, Boulay A, Anzures-Cabrera J, Vogt A, Marchesi M, Post A, Nikolcheva T, Kinney GG, Zago WM, Ness DK, Svoboda H, Britschgi M, Ostrowitzki S, Simuni T, Marek K, Koller M, Sevigny J, Doody R, Fontoura P, Umbricht D, Bonni A; PASADENA Investigators; Prasinezumab Study Group. A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data. Front Neurol. 2021 Oct 1;12:705407. doi: 10.3389/fneur.2021.705407. eCollection 2021.
• Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, Koller M, Zago W, Ness DK, Griffith SG, Grundman M, Soto J, Ostrowitzki S, Boess FG, Martin-Facklam M, Quinn JF, Isaacson SH, Omidvar O, Ellenbogen A, Kinney GG. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-alpha-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 1;75(10):1206-1214. doi: 10.1001/jamaneurol.2018.1487.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Prasinezumab	Monoclonal antibody	1512 mg	Intravenous
Subject	Prasinezumab	Monoclonal antibody	3500 mg	Intravenous
Subject	Prasinezumab	Monoclonal antibody	4500 mg	Intravenous

Indications