Clinical trial NCT04777331: A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson's Disease
Official title: A Phase IIB, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Parkinsons Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Prothena Biosciences Limited
First posted: 2021-03-02
Enrollment: 586
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy and safety of intravenous (IV) prasinezumab versus placebo in participants with Early Parkinson's Disease (PD) who are on stable symptomatic PD medication.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic PD based on MDS criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism
* On symptomatic PD medication, with stable doses for at least 3 months prior to baseline
* A diagnosis of PD for at least 3 months to maximum 3 years at screening
* MDS-UPDRS Part IV score of 0 at screening and prior to randomization
* Hoehn and Yahr (H\&Y) Stage I or II in OFF medication state at screening and prior to randomization
* Dopamine transporter imaging with single photon emission computed tomography (DaT-SPECT) imaging consistent with dopamine transporter deficit, as assessed by the central reader
* No anticipated changes in PD medication from baseline throughout the study duration based on clinical status during screening
* Willingness and ability to use a smartphone application to measure PD-related symptoms for the duration of the study
* Willingness and ability to wear a smartwatch to measure PD-related motor signs

Exclusion Criteria:

* Medical history indicating a Parkinsonian syndrome other than idiopathic PD
* Diagnosis of PD dementia
* Diagnosis of a significant neurologic disease other than PD
* Within the last year, unstable or clinically significant cardiovascular disease
* Uncontrolled hypertension
* Drug and/or alcohol abuse within 12 months prior to screening, in the investigator's judgment (Nicotine is allowed, Marijuana use is not allowed)
* Clinically significant abnormalities in laboratory test results at the screening visit, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis
* Allergy to any of the components of prasinezumab, a known hypersensitivity, or a previous IRR following administration of any other monoclonal antibody
* Any contraindications to obtaining a brain magnetic resonance imaging (MRI)
* Any contraindications to DaT-SPECT imaging

Primary outcomes:
measure: Time to Confirmed Motor Progression Event
timeFrame: From baseline until 28 days after final dose of study treatment
measure: OLE: Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: From baseline until 70 days after final dose of study treatment
measure: OLE: Number of Participants with Adverse Events of Special Interest (AESI)
timeFrame: From baseline until 70 days after final dose of study treatment
measure: OLE: Number of Participants with Infusion Related Reactions (IRRs)
timeFrame: From baseline until 70 days after final dose of study treatment
measure: OLE: Change from Baseline in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From baseline until 70 days after final dose of study treatment
Secondary outcomes:
measure: Time-to-worsening of Participants Motor Function as Reported by the Participant in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and in the Presence of a Confirmed Motor Progression Event
timeFrame: From baseline until 28 days after final dose of study treatment
measure: Time to Meaningful Worsening in Patient Global Impression of Change (PGI-C, Overall Disease Subscale)
timeFrame: From baseline until 28 days after final dose of study treatment
measure: Time to Meanaingful Worsening in Clinician Global Impression of Change (CGI-C, Overall Disease Subscale)
timeFrame: From baseline until 28 days after final dose of study treatment
measure: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV
timeFrame: From baseline until 28 days after final dose of study treatment
measure: Change in Motor Function from Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score
timeFrame: From baseline to Week 76
measure: Change in Bradykinesia and Rigidity from Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore
timeFrame: From baseline to Week 76
measure: Percentage of Participants With AEs and SAEs
timeFrame: From baseline until 70 days after final dose of study treatment
measure: Number of Participants with AESI
timeFrame: From baseline until 70 days after final dose of study treatment
measure: Number of Participants with IRRs
timeFrame: From baseline until 70 days after final dose of study treatment
measure: Change from Baseline in Suicidal Ideation, as Measured by the C-SSRS
timeFrame: From baseline until 28 days after final dose of study treatment
measure: Serum Concentration of Prasinezumab
timeFrame: From weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 and after week 76 every 12 weeks therafter until end of study (approximately 28 days after the final dose)
measure: Percentage of Participants with Anti-drug Antibodies (ADAs) Against Prasinezumab at Baseline
timeFrame: At Baseline
measure: Percentage of Participants with ADAs Against Prasinezumab During the Study
timeFrame: Up to end of study visit (approximately 76 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research, LLC
state: Colorado
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research LLC
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Winter Park
country: United States
facility: Charter Research - Winter Park/Orlando
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School Of Medicine
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University, School of Medicine
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University Pennsylvania Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Neurology PA
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Norfolk
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Kirkland
country: United States
facility: EvergreenHealth Investigational Drug Services
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck
city: Wien
country: Austria
facility: Klinik Ottakring
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Gatineau
country: Canada
facility: Clinique Neuro Outaouais
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin
city: Bron cedex
country: France
facility: Groupement Hospitalier Est - Hôpital Neurologique
city: Clermont-ferrand
country: France
facility: Hopital Gabriel Montpied
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Grenoble
country: France
facility: Hôpital Michallon - Centre d'Investigation Clinique
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: hopital de la Timone
city: Montpellier
country: France
facility: CHU Gui de Chauliac
city: Nice
country: France
facility: CHU de Nice Hopital Pasteur
city: Paris
country: France
facility: Hopital Pitie-Salpetriere APHP
city: Poitiers
country: France
facility: CHU Poitiers
city: Rouen cedex
country: France
facility: CHU Rouen Charles Nicolle
city: St Herblain
country: France
facility: CHU de Nantes - Hopital Laennec
city: Strasbourg
country: France
facility: CHU Strasbourg Hpital Hautepierre
city: Toulouse
country: France
facility: CIC - Hôpital Purpan
city: Napoli
country: Italy
facility: Università degli studi della Campania Luigi Vanvitelli
state: Campania
city: Salerno
country: Italy
facility: Az. Osp. OO.RR. S. Giovanni di Dio e Ruggi D' Aragona
state: Campania
city: Bologna
country: Italy
facility: Ospedale Bellaria
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Rome
country: Italy
facility: IRCCS San Raffaele;Clinical Trial Center
state: Lazio
city: Genova
country: Italy
facility: Irccs A.O.U.San Martino Ist
state: Liguria
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Istituto Neurologico Carlo Besta
state: Lombardia
city: Pozzilli (IS)
country: Italy
facility: IRCCS Neuromed
state: Molise
city: Catania
country: Italy
facility: A.O.U. Policlinico "G.Rodolico - San Marco"
state: Sicilia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana
state: Toscana
city: Perugia
country: Italy
facility: AO di Perugia - Ospedale S. Maria della Misericordia
state: Umbria
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria
state: Umbria
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
state: Veneto
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
city: ?ód?
country: Poland
facility: NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Gda?sk
country: Poland
facility: Szpital Sw. Wojciecha
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
city: Rzeszów
country: Poland
facility: Nmedis sp. z o.o.
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny im. prof. Orlowskiego
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Bródnowski w Warszawie Sp. z o.o.
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Sant Cugat del Valles
country: Spain
facility: Hospital General De Catalunya
state: Barcelona
city: Donosti-San Sebastián
country: Spain
facility: Policlínica Guipuzkoa
state: Guipuzcoa
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Alcorcon
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Móstoles
country: Spain
facility: HM Universitario Puerta del Sur CINAC (C.Integ.Neuroc);
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Plasencia
country: Spain
facility: Hospital Virgen del Puerto
state: Palencia
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos. Servicio de Neurología
city: Madrid
country: Spain
facility: Hospital Ruber Juan Bravo
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Zaragoza
country: Spain
facility: Servicio de Neurología Hospital Viamed Montecanal.
city: Dundee
country: United Kingdom
facility: Ninewells Hospital, Dundee- Scotland
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Newcastle
country: United Kingdom
facility: Campus for Ageing and Vitality
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Peterborough
country: United Kingdom
facility: North West Anglia NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: