Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease (SPARK)

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

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.

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: BIIB054

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute Clinical Research Unit
• France
  • Paris, France, 75013
    • Research Site
  • Haute Garonne
    • Toulouse Cedex 09, Haute Garonne, France, 31059
      • Research name
  • Loire Atlantique
    • Nantes, Loire Atlantique, France, 44093
      • CHU Nantes - Hopital Nord Laënnec
  • Nord
    • Lille Cedex, Nord, France, 59037
      • Hopital Roger Salengro - CHU Lille
  • Val De Marne
    • Créteil, Val De Marne, France, 94010
      • Hôpital Henri Mondor
• Germany
  • Baden Wuerttemberg
    • Ulm, Baden Wuerttemberg, Germany, 89081
      • Universitaetsklinikum Ulm
  • Bayern
    • Muenchen, Bayern, Germany, 81675
      • Klinikum rechts der Isar der TU Muenchen
    • Wuerzburg, Bayern, Germany, 97080
      • Universitaetsklinikum Wuerzburg
  • Hessen
    • Kassel, Hessen, Germany, 34128
      • Paracelsus-Elena-Klinik
  • Nordrhein Westfalen
    • Aachen, Nordrhein Westfalen, Germany, 52074
      • Universitaetsklinikum Aachen AOeR
    • Bochum, Nordrhein Westfalen, Germany, 44791
      • Research Site
• Israel
  • Haifa, Israel, 3109601
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Italy
  • Bologna, Italy, 40139
    • Ospedale Bellaria
  • Catania, Italy, 95125
    • Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
  • Milano, Italy, 20122
    • Research Site
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20132
    • Research Site
  • Napoli, Italy, 80138
    • Seconda Università degli Studi di Napoli
  • Pisa, Italy, 56126
    • Research Site
  • Roma, Italy, 00163
    • IRCCS San Raffaele
  • Salerno, Italy, 84131
    • Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
  • Terni, Italy, 05100
    • Azienda Ospedaliera Santa Maria di Terni
  • Isernia
    • Pozzilli, Isernia, Italy, 86077
      • I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
• Spain
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcalona
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28006
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Barcelona
    • Sant Cugat del Vallés, Barcelona, Spain, 08190
      • Hospital General de Catalunya
  • Madrid
    • Móstoles, Madrid, Spain, 28938
      • Research Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Biocruces Health Research Institute
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Research Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Research Site
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Research Site
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE4 5PL
      • Clinical Ageing research Unit
  • West Midlands
    • Sheffield, West Midlands, United Kingdom, S10 2JF
      • Royal Hallamshire Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
  • California
    • La Jolla, California, United States, 92093-0886
      • Research Site
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • San Francisco, California, United States, 94158
      • University of California San Francisco Medical Center
    • Stanford, California, United States, 94305
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center, PC
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Centerf
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Tampa, Florida, United States, 33616
      • USF Health Byrd Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Chicago, Illinois, United States, 60611
      • Northwestern University PD and Movement Disorders Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • New York
    • New York, New York, United States, 10032
      • Research Site
    • New York, New York, United States, 10017
      • NYU Langone Health Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Health System
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center at Evergreen Health
    • Spokane, Washington, United States, 99204
      • Inland Northwest Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Year 1: Participants will receive matching placebo to BIIB054 on Day 1 and then every 4 weeks. Year 2: Participants who received placebo in year 1 will be randomized into one of the active treatment arms in year 2 and will receive BIIB054 intravenous (IV) infusion on Week 52 and then every 4 weeks.	Drug: Placebo; Administered as specified in the treatment arm
Experimental: BIIB054 250 mg; Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.	Drug: BIIB054; Administered as specified in the treatment arm.
Experimental: BIIB054 1250 mg; Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.	Drug: BIIB054; Administered as specified in the treatment arm.
Experimental: BIIB054 3500 mg; Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.	Drug: BIIB054; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
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	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.	Up to 3 years
Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 96
Serum Concentration of BIIB054		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
Change From Baseline in MDS-UPDRS Subpart I Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart II Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart III Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assessed the motor signs of 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
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	SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52	SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52	SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum		Up to Week 144

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Fox Trial Finder

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): October 26, 2020
• Study Completion (Actual): April 29, 2021

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Alpha-synuclein; BIIB054
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 228PD201; 2016-004610-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No