NCT03318523

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
357

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2018

Typical duration for phase_2

Geographic Reach
9 countries

75 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 19, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

October 24, 2017

Completed
3 months until next milestone

Study Start

First participant enrolled

January 10, 2018

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2020

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 29, 2021

Completed
7 months until next milestone

Results Posted

Study results publicly available

November 23, 2021

Completed
Last Updated

February 28, 2022

Status Verified

February 1, 2022

Enrollment Period

2.8 years

First QC Date

October 19, 2017

Results QC Date

October 25, 2021

Last Update Submit

February 15, 2022

Conditions

Keywords

BIIB054Alpha-synuclein

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (13)

  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Up to 3 years

  • Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96

    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

    Baseline, Week 52

  • Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96

    Baseline, Weeks 72 and 96

  • +8 more secondary outcomes

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

BIIB054 250 mg

EXPERIMENTAL

Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.

Drug: BIIB054

BIIB054 1250 mg

EXPERIMENTAL

Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.

Drug: BIIB054

BIIB054 3500 mg

EXPERIMENTAL

Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.

Drug: BIIB054

Interventions

Administered as specified in the treatment arm

Placebo

Administered as specified in the treatment arm.

BIIB054 1250 mgBIIB054 250 mgBIIB054 3500 mg

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (75)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Research Site

La Jolla, California, 92093-0886, United States

Location

Cedars Sinai

Los Angeles, California, 90048, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94158, United States

Location

Research Site

Stanford, California, 94305, United States

Location

University of Colorado Health

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Movement Disorders Center, PC

Englewood, Colorado, 80113, United States

Location

Parkinson's Disease and Movement Disorders Centerf

Boca Raton, Florida, 33486, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

USF Health Byrd Institute

Tampa, Florida, 33616, United States

Location

Northwestern University PD and Movement Disorders Center

Chicago, Illinois, 60611, United States

Location

Research Site

Chicago, Illinois, 60612, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Ochsner Health System

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

NYU Langone Health Center

New York, New York, 10017, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

Durham, North Carolina, 27705, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44106, United States

Location

Research Site

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Research Site

Nashville, Tennessee, 37232, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Booth Gardner Parkinson's Care Center at Evergreen Health

Kirkland, Washington, 98034, United States

Location

Inland Northwest Research

Spokane, Washington, 99204, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Research Site

Innsbruck, 6020, Austria

Location

University Health Network

Toronto, Ontario, M5T 2S8, Canada

Location

Montreal Neurological Institute Clinical Research Unit

Montreal, Quebec, H3A 2B4, Canada

Location

Research Name

Toulouse, Haute Garonne, 31059, France

Location

CHU Nantes - Hopital Nord Laënnec

Nantes, Loire Atlantique, 44093, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

Hôpital Henri Mondor

Créteil, Val De Marne, 94010, France

Location

Research Site

Paris, 75013, France

Location

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum rechts der Isar der TU Muenchen

Munich, Bavaria, 81675, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, Bavaria, 97080, Germany

Location

Paracelsus-Elena-Klinik

Kassel, Hesse, 34128, Germany

Location

Universitaetsklinikum Aachen AOeR

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Research Site

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Research Site

Haifa, 3109601, Israel

Location

Research Site

Tel Aviv, 6423906, Israel

Location

I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo

Pozzilli, Isernia, 86077, Italy

Location

Ospedale Bellaria

Bologna, 40139, Italy

Location

Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico

Catania, 95125, Italy

Location

Research Site

Milan, 20122, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Research Site

Milan, 20132, Italy

Location

Seconda Università degli Studi di Napoli

Napoli, 80138, Italy

Location

Research Site

Pisa, 56126, Italy

Location

IRCCS San Raffaele

Roma, 00163, Italy

Location

Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, 84131, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, 05100, Italy

Location

Hospital General de Catalunya

Sant Cugat Del Vallés, Barcelona, 08190, Spain

Location

Research Site

Móstoles, Madrid, 28938, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Biocruces Health Research Institute

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Clinic De Barcalona

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Research Site

Madrid, 28006, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Seville, 41013, Spain

Location

Research Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Salford Royal

Salford, Greater Manchester, M6 8HD, United Kingdom

Location

Research Site

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Clinical Ageing Research Unit

Newcastle upon Tyne, Tyne & Wear, NE4 5PL, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, West Midlands, S10 2JF, United Kingdom

Location

Research Site

London, WC1N 3BG, United Kingdom

Location

Related Publications (3)

  • Hutchison RM, Fraser K, Yang M, Fox T, Hirschhorn E, Njingti E, Scott D, Bedell BJ, Kistner KM, Cedarbaum JM, Evans KC, Graham D, Martarello L, Mollenhauer B, Lang AE, Dam T, Beaver J. Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial. Neurology. 2024 Mar 12;102(5):e209137. doi: 10.1212/WNL.0000000000209137. Epub 2024 Feb 5.

  • 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.

Related Links

MeSH Terms

Conditions

Parkinson DiseaseParkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative Diseases

Limitations and Caveats

The study did not meet its primary outcome measure for year 1 and did not demonstrate efficacy on key secondary outcome measures; additional pre-specified analyses at week 72 confirmed the study did not provide evidence of efficacy; resulting in the development of BIIB054 for Parkinson's disease to be discontinued and SPARK study was closed.

Results Point of Contact

Title
US Biogen Clinical Trial Center
Organization
Biogen

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

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

October 19, 2017

First Posted

October 24, 2017

Study Start

January 10, 2018

Primary Completion

October 26, 2020

Study Completion

April 29, 2021

Last Updated

February 28, 2022

Results First Posted

November 23, 2021

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will share

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

More information

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