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

NCT ID: NCT03100149

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-27
• Study Completion Date: 2031-12-01

Brief 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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: RO7046015 High Dose

Participants will receive RO7046015 at high dose level as intravenous (IV) infusion every 4 weeks (Q4W) up to 52 weeks in Part 1.

Group Type: EXPERIMENTAL

RO7046015

Intervention Type: DRUG

RO7046015 will be administered at dose of 4500 milligrams (mg) for participants with body-weight greater than or equal to (\>/=) 65 kilograms (kg) or 3500 mg for participants with body-weight less than (\<) 65 kg.

Part 1: RO7046015 Low Dose

Participants will receive RO7046015 at low dose level as IV infusion Q4W up to 52 weeks in Part 1.

Group Type: EXPERIMENTAL

RO7046015

Intervention Type: DRUG

RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.

Part 1: Placebo

Participants will receive placebo as IV infusion Q4W up to 52 weeks in Part 1.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

RO7046015 placebo will be administered to all participants in the indicated arm.

Part 2: RO7046015 High Dose

Part 1 RO7046015 high dose group participants and placebo group participants randomized to high dose level will receive RO7046015 at high dose level as IV infusion Q4W for additional 52 weeks in Part 2.

Group Type: EXPERIMENTAL

RO7046015

Intervention Type: DRUG

RO7046015 will be administered at dose of 4500 milligrams (mg) for participants with body-weight greater than or equal to (\>/=) 65 kilograms (kg) or 3500 mg for participants with body-weight less than (\<) 65 kg.

Part 2: RO7046015 Low Dose

Part 1 RO7046015 low dose group participants and placebo group participants randomized to low dose level will receive RO7046015 at low dose level as IV infusion Q4W for additional 52 weeks in Part 2.

Group Type: EXPERIMENTAL

RO7046015

Intervention Type: DRUG

RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.

Part 3: RO7046015 Low Dose

All participants who complete Part 1 and Part 2 will receive monthly IV infusions of RO7046015.

Group Type: EXPERIMENTAL

RO7046015

Intervention Type: DRUG

RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.

Interventions

RO7046015

RO7046015 will be administered at dose of 4500 milligrams (mg) for participants with body-weight greater than or equal to (\>/=) 65 kilograms (kg) or 3500 mg for participants with body-weight less than (\<) 65 kg.

Intervention Type: DRUG

RO7046015

RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.

Intervention Type: DRUG

Placebo

RO7046015 placebo will be administered to all participants in the indicated arm.

Intervention Type: DRUG

Other Intervention Names

PRX002; prasinezumab; PRX002; prasinezumab

Eligibility Criteria

Inclusion Criteria

• Idiopathic PD with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity) being present, without any other known or suspected cause of PD untreated or treated with MAO-B inhibitor
• Body weight range between: >/=45 kg/ 99 pounds (lbs) and less than or equal to (</=) 110 kg/242 lbs
• Body mass index (BMI) of 18 to 34 kilograms per meter-squared (kg/m^2)
• A diagnosis of PD for 2 years or less at screening
• Hoehn and Yahr Stage I or II
• A screening brain DaT-SPECT consistent with PD (central reading)
• Clinical status does not require dopaminergic PD medication and is not expected to require dopaminergic treatment within 52 weeks from baseline
• If presently being treated for PD, a stable dose of MAO-B inhibitor (rasagiline or selegiline) for at least 90 days prior to baseline and not expected to change within 52 weeks
• For women of childbearing potential: use of highly effective contraceptive methods (that result in a failure rate of <1 percent [%] per year) during the treatment period and for at least 30 days (or longer if required by local regulations) after the last dose of study drug
• For men with female partners of childbearing potential or pregnant female partners, must use a condom during the treatment period and for at least 30 days (or longer if required by local regulations) after the last dose of study drug to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The female partners should use a contraception method with a failure rate of <1% per year during the treatment period and for at least 30 days (or longer if required by local regulations) after the last dose of study drug. Use of contraceptive measures is not required for male participants enrolled in Part 3.

Exclusion Criteria

• Medical history indicating a Parkinson syndrome other than idiopathic PD, including but not limited to, progressive supranuclear gaze palsy, multiple system atrophy, drug-induced parkinsonism, essential tremor, primary dystonia
• Known carriers of certain familial PD genes (as specified in study protocol)
• History of PD related freezing episodes or falls
• A diagnosis of a significant CNS disease other than Parkinson's disease; history of repeated head injury; history of epilepsy or seizure disorder other than febrile seizures as a child
• Mini Mental State Examination (MMSE) </=25
• Reside in a nursing home or assisted care facility
• History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study or interfere with the participant's ability to comply with study procedures or abide by study restrictions, or with the ability to interpret safety data
• Any significant cardiovascular condition
• Any significant laboratory abnormality
• Lactating women
• Prior treatment with dopaminergic medication (for example, levodopa or a dopaminergic agonist) with no clinical treatment response or a clinical treatment response inconsistent with PD (for example, absence of observable response to a sufficiently high-dose of levodopa [i.e., ≥ 600 mg/day])
• Use of any of the following: catechol-O-methyl transferase (COMT) inhibitors (entacapone, tolcapone), amantadine or anticholinergics, or dopaminergic medication (levodopa and both ergot and non-ergot [pramipexole, ropinirole, rotigotine] dopamine agonists) for more than a total of 60 days or within 60 days of baseline
• Anti-epileptic medication for non-seizure-related treatment which has not remained stable for at least 60 days prior to baseline
• Anti-depressant or anxiolytic use that has not remained stable for at least 90 days prior to baseline. The use of fluoxetine and fluvoxamine is not permitted. For patients treated with a MAO-B inhibitor and an antidepressant (except fluoxetine and fluvoxamine), a 6-month period of stable and tolerated dosing before baseline is required.
• Use of any of the following within 90 days prior to baseline: antipsychotics (including clozapine and olanzapine), metoclopramide, alpha methyldopa, clozapine, olanzapine, flunarizine, amoxapine, amphetamine derivatives, reserpine, bupropion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, and modafinil
• Participated in an investigational drug, device, surgical , or stem cell study in PD
• Any prior treatment with an investigational PD-related vaccine (including active immunization or passive immunotherapy with monoclonal antibodies).
• Prior participation in any RO7046015 or PRX002 study
• Receipt of any non-PD investigational product or device, or participation in a non-PD drug research study within a period of 30 days (or 5 half-lives of the drug, whichever is longer) before baseline
• Receipt of any monoclonal antibody or an investigational immunomodulator within 180 days (or 5 half-lives, whichever is longer) before baseline
• Immunomodulating drugs within 30 days prior to baseline
• Allergy to any of the components of RO7046015 such as citrate, trehalose and polysorbate (Tween) 20 or a known hypersensitivity or an Infusion-related reaction (IRR) to the administration of any other monoclonal antibody
• Any contraindications to obtaining a brain MRI. Patients with a hypersensitivity to iodine may receive an alternative thyroid blocking agent.
• For participants consenting to provide optional cerebrospinal fluid (CSF) samples by lumbar puncture (LP): LP will only be performed if the participant does not have any contraindication to undergoing an LP
• Donation of blood over 500 milliliters (mL) within three months prior to screening

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prothena Biosciences Limited

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Uab Medicine

Birmingham, Alabama, United States

Barrow Neurology Clinics

Phoenix, Arizona, United States

Neurology Center of North Orange County

Fullerton, California, United States

USC Keck Medical Center of USC

Los Angeles, California, United States

University of California at San Francisco

San Francisco, California, United States

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, United States

Associated Neurologists of Southern CT PC

Fairfield, Connecticut, United States

Molecular Neurolmaging

New Haven, Connecticut, United States

Aventura Neurologic Associates

Aventura, Florida, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

USF Parkinsons Disease and Movement Disorders Center

Tampa, Florida, United States

Northwestern University

Evanston, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Quest Research Institute

Farmington Hills, Michigan, United States

Corewell Health Neurology and Epilepsy - Beltline

Grand Rapids, Michigan, United States

Henry Ford Health System

West Bloomfield, Michigan, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

Oregon Health & Science Uni

Portland, Oregon, United States

UNIVERSITY of PENNSYLVANIA

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College

Houston, Texas, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Medizinische Universität Innsbruck

Innsbruck, , Austria

Groupe Hospitalier Pellegrin

Bordeaux, , France

Hopital Gabriel Montpied

Clermont-Ferrand, , France

Hopital Henri Mondor

Créteil, , France

Hôpital Michallon - Centre d'Investigation Clinique

Grenoble, , France

hopital de la Timone

Marseille, , France

CHU de Nice Hopital Pasteur

Nice, , France

Hopital Pitie-Salpetriere APHP

Paris, , France

CHU Poitiers

Poitiers, , France

CHU Rouen Charles Nicolle

Rouen, , France

CHU de Nantes - Hopital Laennec

Saint-Herblain, , France

CIC - Hôpital Purpan

Toulouse, , France

Klinik fur Neurologie

Berlin, , Germany

Heinrich-Heine Universitätsklinik Düsseldorf

Düsseldorf, , Germany

Paracelsus Elena Klinik Kassel

Kassel, , Germany

Klinik und Poliklinik für Neurologie Universitätsklinikum

Leipzig, , Germany

Philipps Universität Marburg

Marburg, , Germany

DZNE Clinical Trial Unit

München, , Germany

Universitaettsklinikum Tübingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Hospital General de Catalunya

Sant Cugat del Vallès, Barcelona, Spain

Policlínica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, Spain

Fundacion Hospital de Alcorcon

Alcorcón, Madrid, Spain

Clinica Universidad de Navarra

Pamplona/iruña, Navarre, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

United States; Austria; France; Germany; Spain

References

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.

Reference Type: DERIVED

PMID: 40523921 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39379705 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35921451 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35840753 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34659081 (View on PubMed)

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.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://forpatients.roche.com/en/trials/neurodegenerative-disorder/pd/a-study-to-evaluate-the-efficacy-of-ro7046015-in-participants-wi.html

Pasadenastudy.com provides information about the Roche clinical trial NCT03100149 and molecule being investigated in Parkinson's Disease

Other Identifiers

2017-000087-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-504472-24-00

Identifier Type: CTIS

Identifier Source: secondary_id

BP39529

Identifier Type: -

Identifier Source: org_study_id