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

NCT03100149 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: BP395292017-000087-152023-504472-24-00
• Study Type: interventional
• Target: 316
• Locations: 5 countries
• Sites: 55

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52

  The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of Parkinson's disease.

  From baseline to Week 52

Secondary Outcomes (15)

• Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores

  From baseline to Week 52

• Change From Baseline in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Striatal Binding Ratio (SBR) in the Putamen Ipsilateral to the Clinically Most Affected Side

  From baseline to Week 52

• Change From Baseline in Montreal Cognition Assessment (MoCA) Total Score

  From baseline to Week 52

• Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Score

  From baseline to Week 52

• Change From Baseline in Patient Global Impression of Change (PGIC) Score

  From baseline to Week 52

Study Arms (6)

Part 1: RO7046015 High Dose

EXPERIMENTAL

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

Drug: RO7046015

Part 1: RO7046015 Low Dose

EXPERIMENTAL

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

Drug: RO7046015

Part 1: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part 2: RO7046015 High Dose

EXPERIMENTAL

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.

Drug: RO7046015

Part 2: RO7046015 Low Dose

EXPERIMENTAL

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.

Drug: RO7046015

Part 3: RO7046015 Low Dose

EXPERIMENTAL

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

Drug: RO7046015

Interventions

RO7046015 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.

Also known as: PRX002; prasinezumab

Part 1: RO7046015 High Dose; Part 2: RO7046015 High Dose

Placebo DRUG

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

Part 1: Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Prothena Biosciences Limited: collaborator

Study Sites (55)

Uab Medicine

Birmingham, Alabama, 35233, United States

Location

Barrow Neurology Clinics

Phoenix, Arizona, 85013, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

USC Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

University of California at San Francisco

San Francisco, California, 94115, United States

Location

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, 80113, United States

Location

Associated Neurologists of Southern CT PC

Fairfield, Connecticut, 06824, United States

Location

Molecular Neurolmaging

New Haven, Connecticut, 06510, United States

Location

Aventura Neurologic Associates

Aventura, Florida, 33180, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

USF Parkinsons Disease and Movement Disorders Center

Tampa, Florida, 33613, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Corewell Health Neurology and Epilepsy - Beltline

Grand Rapids, Michigan, 49525, United States

Location

Henry Ford Health System

West Bloomfield, Michigan, 48322, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14618, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

Oregon Health & Science Uni

Portland, Oregon, 97239, United States

Location

UNIVERSITY of PENNSYLVANIA

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College

Houston, Texas, 77030, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Groupe Hospitalier Pellegrin

Bordeaux, 33000, France

Location

Hopital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hôpital Michallon - Centre d'Investigation Clinique

Grenoble, 38043, France

Location

hopital de la Timone

Marseille, 13385, France

Location

CHU de Nice Hopital Pasteur

Nice, 06002, France

Location

Hopital Pitie-Salpetriere APHP

Paris, 75013, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

CHU Rouen Charles Nicolle

Rouen, 76031, France

Location

CHU de Nantes - Hopital Laennec

Saint-Herblain, 44800, France

Location

CIC - Hôpital Purpan

Toulouse, 31059, France

Location

Klinik fur Neurologie

Berlin, 10117, Germany

Location

Heinrich-Heine Universitätsklinik Düsseldorf

Düsseldorf, 40225, Germany

Location

Paracelsus Elena Klinik Kassel

Kassel, 34128, Germany

Location

Klinik und Poliklinik für Neurologie Universitätsklinikum

Leipzig, 04103, Germany

Location

Philipps Universität Marburg

Marburg, 35043, Germany

Location

DZNE Clinical Trial Unit

München, 81377, Germany

Location

Universitaettsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Hospital General de Catalunya

Sant Cugat del Vallès, Barcelona, 08195, Spain

Location

Policlínica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Fundacion Hospital de Alcorcon

Alcorcón, Madrid, 28922, Spain

Location

Clinica Universidad de Navarra

Pamplona/iruña, Navarre, 31008, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Related Publications (6)

• 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.

  PMID: 40523921 DERIVED

• 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.

  PMID: 39379705 DERIVED

• 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.

  PMID: 35921451 DERIVED

• 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.

  PMID: 35840753 DERIVED

• 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.

  PMID: 34659081 DERIVED

• 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.

  PMID: 29913017 DERIVED

Related Links

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

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 4, 2017
• Study Start: June 27, 2017
• Primary Completion: November 27, 2019
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 17, 2026
• Results First Posted: February 8, 2021

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (26); FR (11); ES (9); AU (1); DE (8)