Clinical trial NCT03318523: Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, With an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: BIIB054
Alpha-synuclein
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 357
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the clinical efficacy of BIIB054 via dose response using the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score.

The secondary objectives of the study are to evaluate the dose-related safety of BIIB054, to evaluate the clinical efficacy of BIIB054 via MDS-UPDRS total score, to assess the pharmacokinetic (PK) profile of BIIB054, to evaluate the clinical efficacy of BIIB054 based on MDS-UPDRS subparts, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals and to evaluate the immunogenicity of BIIB054.


Eligibility criteria: Inclusion Criteria

* Diagnosed with Parkinson's disease (PD) within a maximum of 3 years prior to Screening.
* Score of ≤2.5 on the Modified Hoehn and Yahr Scale.
* Has not received any medication for the treatment of the motor symptoms of PD for at least 12 weeks prior to Day 1 and, in the opinion of the Investigator, is not expected to require PD treatment for at least 6 months following Day 1. Maximum total duration of prior PD regimens should not exceed 30 days. Stable (at least 8 weeks) dosages of medications that are used to treat conditions other than PD tremor are allowed. Further guidance will be provided by the study's Medical Monitor on a case by case basis.
* Screening dopamine transporter (DaT)/ single-photon emission computed tomography (SPECT) results consistent with neurodegenerative Parkinsonism (central reading).
* All women of childbearing potential and all men must practice highly effective contraception during the study and for 6 months after their last dose of study treatment.

Exclusion Criteria:

* Presence of freezing of gait.
* Montreal cognitive assessment (MOCA) score \<23 or other significant cognitive impairment or clinical dementia that, in the opinion of the Investigator, would interfere with study evaluation.
* History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality, as read by central reader.
* History of severe allergic or anaphylactic reactions, or history of hypersensitivity to BIIB054 or any of the inactive ingredients in the drug product or to radioligands or iodine used in the study.
* Participation in any active immunotherapy study targeting alpha-synuclein.
* Use of allowed medications not previously specified at doses that have not been stable for at least 8 weeks before Day 1, and/or that are not expected to remain stable for the duration of the study.
* Clinically significant abnormal laboratory test values at Screening, as determined by the Investigator.
* Blood donation (1 unit or more) within 8 weeks before Day 1 (must also refrain from donating blood for the duration of the study).

NOTE : Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72
timeFrame: Baseline, Week 72
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 3 years
measure: Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96
timeFrame: Baseline, Week 96
measure: Serum Concentration of BIIB054
timeFrame: Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144
measure: Change From Baseline in MDS-UPDRS Subpart I Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96
timeFrame: Baseline, Weeks 72 and 96
measure: Change From Baseline in MDS-UPDRS Subpart II Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96
timeFrame: Baseline, Weeks 72 and 96
measure: Change From Baseline in MDS-UPDRS Subpart III Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96
timeFrame: Baseline, Weeks 72 and 96
measure: Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
timeFrame: Up to Week 144
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: University of Colorado Health
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center, PC
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Centerf
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University PD and Movement Disorders Center
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: New York
country: United States
facility: NYU Langone Health Center
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center at Evergreen Health
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Innsbruck
country: Austria
facility: Research Site
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute Clinical Research Unit
state: Quebec
city: Toulouse Cedex 09
country: France
facility: Research Name
state: Haute Garonne
city: Nantes
country: France
facility: CHU Nantes - Hopital Nord Laënnec
state: Loire Atlantique
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Créteil
country: France
facility: Hôpital Henri Mondor
state: Val De Marne
city: Paris
country: France
facility: Research Site
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
state: Bayern
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik
state: Hessen
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen AOeR
state: Nordrhein Westfalen
city: Bochum
country: Germany
facility: Research Site
state: Nordrhein Westfalen
city: Haifa
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Pozzilli
country: Italy
facility: I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
state: Isernia
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Catania
country: Italy
facility: Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: IRCCS San Raffaele
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Sant Cugat del Vallés
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Móstoles
country: Spain
facility: Research Site
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barakaldo
country: Spain
facility: Biocruces Health Research Institute
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Clinic De Barcalona
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Salford
country: United Kingdom
facility: Salford Royal
state: Greater Manchester
city: Oxford
country: United Kingdom
facility: Research Site
state: Oxfordshire
city: Newcastle upon Tyne
country: United Kingdom
facility: Clinical Ageing Research Unit
state: Tyne & Wear
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: West Midlands
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Lang AE, Siderowf AD, Macklin EA, Poewe W, Brooks DJ, Fernandez HH, Rascol O, Giladi N, Stocchi F, Tanner CM, Postuma RB, Simon DK, Tolosa E, Mollenhauer B, Cedarbaum JM, Fraser K, Xiao J, Evans KC, Graham DL, Sapir I, Inra J, Hutchison RM, Yang M, Fox T, Budd Haeberlein S, Dam T; SPARK Investigators. Trial of Cinpanemab in Early Parkinson's Disease. N Engl J Med. 2022 Aug 4;387(5):408-420. doi: 10.1056/NEJMoa2203395.
citation: Hutchison RM, Evans KC, Fox T, Yang M, Barakos J, Bedell BJ, Cedarbaum JM, Brys M, Siderowf A, Lang AE. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson's disease trial. BMC Neurol. 2021 Nov 23;21(1):459. doi: 10.1186/s12883-021-02470-8.