Parkinson's DiseasePhase 2SPARKNCT03318523

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

A Phase 2 study testing BIIB054 in people with Parkinson's Disease, run by Biogen at 75 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Parkinson's Disease
What is being tested?: BIIB054
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 357 participants
Where: 75 sitesin 9 countries
Study dates: 10 Jan 2018to 29 Apr 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 9Show fewer

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

Trial locations and contacts

75 sites in 9 countries.

Country

City, postcode or hospital

75 sites in 9 countries

United States32 sites

University of Colorado Health
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Parkinson's Disease and Movement Disorders Centerf
Boca Raton, Florida, 33486
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston University Medical Center
Boston, Massachusetts, 02118
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University PD and Movement Disorders Center
Chicago, Illinois, 60611
Research Site
Chicago, Illinois, 60612
The Cleveland Clinic Foundation
Cleveland, Ohio, 44106
Research Site
Durham, North Carolina, 27705
Rocky Mountain Movement Disorders Center, PC
Englewood, Colorado, 80113
Quest Research Institute
Farmington Hills, Michigan, 48334
Research Site
Houston, Texas, 77030
Mayo Clinic Hospital
Jacksonville, Florida, 32224
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160
Booth Gardner Parkinson's Care Center at Evergreen Health
Kirkland, Washington, 98034
Research Site
La Jolla, California, 92093-0886
Cedars Sinai
Los Angeles, California, 90048
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Research Site
Nashville, Tennessee, 37232
Ochsner Health System
New Orleans, Louisiana, 70121
NYU Langone Health Center
New York, New York, 10017
Research Site
New York, New York, 10032
Bioclinica Research
Orlando, Florida, 32806
Research Site
Philadelphia, Pennsylvania, 19107
St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
Phoenix, Arizona, 85013
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, 15213
University of California San Francisco Medical Center
San Francisco, California, 94158
Inland Northwest Research
Spokane, Washington, 99204
Research Site
Stanford, California, 94305
USF Health Byrd Institute
Tampa, Florida, 33616
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157

Other trials in United States

Italy11 sites

Ospedale Bellaria
Bologna, 40139
Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
Catania, 95125
Research Site
Milan, 20122
Ospedale San Raffaele
Milan, 20132
Research Site
Milan, 20132
Seconda Università degli Studi di Napoli
Naples, 80138
Research Site
Pisa, 56126
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
Pozzilli, Isernia, 86077
IRCCS San Raffaele
Roma, 00163
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno, 84131
Azienda Ospedaliera Santa Maria di Terni
Terni, 05100

Other trials in Italy

Spain10 sites

Biocruces Health Research Institute
Barakaldo, Vizcaya, 48903
Hospital Clinic De Barcalona
Barcelona, 08036
Hospital Santa Creu i Sant Pau
Barcelona, 08041
Research Site
Madrid, 28006
Research Site
Madrid, 28007
Research Site
Madrid, 28034
Research Site
Móstoles, Madrid, 28938
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Hospital General de Catalunya
Sant Cugat Del Vallés, Barcelona, 08190
Research Site
Seville, 41013

Other trials in Spain

Germany6 sites

Universitaetsklinikum Aachen AOeR
Aachen, North Rhine-Westphalia, 52074
Research Site
Bochum, North Rhine-Westphalia, 44791
Paracelsus-Elena-Klinik
Kassel, Hesse, 34128
Klinikum rechts der Isar der TU Muenchen
Munich, Bavaria, 81675
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Universitaetsklinikum Wuerzburg
Würzburg, Bavaria, 97080

Other trials in Germany

United Kingdom6 sites

Research Site
Cambridge, Cambridgeshire, CB2 0QQ
Research Site
London, WC1N 3BG
Clinical Ageing Research Unit
Newcastle upon Tyne, Tyne & Wear, NE4 5PL
Research Site
Oxford, Oxfordshire, OX3 9DU
Salford Royal
Salford, Greater Manchester, M6 8HD
Royal Hallamshire Hospital
Sheffield, West Midlands, S10 2JF

Other trials in United Kingdom

France5 sites

Hôpital Henri Mondor
Créteil, Val De Marne, 94010
Hopital Roger Salengro - CHU Lille
Lille, Nord, 59037
CHU Nantes - Hopital Nord Laënnec
Nantes, Loire Atlantique, 44093
Research Site
Paris, 75013
Research Name
Toulouse, Haute Garonne, 31059

Other trials in France

Canada2 sites

Montreal Neurological Institute Clinical Research Unit
Montreal, Quebec, H3A 2B4
University Health Network
Toronto, Ontario, M5T 2S8

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Israel2 sites

Research Site
Haifa, 3109601
Research Site
Tel Aviv, 6423906

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Austria1 site

Research Site
Innsbruck, 6020

Other trials in Austria

About this study

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

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.

Conditions: Parkinson's Disease
Being tested: Placebo, BIIB054
Keywords: BIIB054, Alpha-synuclein
Medical subject headings: Parkinson Disease, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Administered as specified in the treatment arm
BIIB054Drug
Administered as specified in the treatment arm.

Study groups in NCT03318523
Study group	Role	What they receive
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. Receives: Drug: Placebo
BIIB054 250 mg	Experimental	Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks. Receives: Drug: BIIB054
BIIB054 1250 mg	Experimental	Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks. Receives: Drug: BIIB054
BIIB054 3500 mg	Experimental	Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks. Receives: Drug: BIIB054

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline, Week 72

Secondary outcomes (13)

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.
Measured: 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.
Measured: Baseline, Week 96
Serum Concentration of BIIB054
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 52
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
Measured: Up to Week 144

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jan 201829 Apr 2021

First posted24 Oct 2017
Study start10 Jan 2018
Primary completion26 Oct 2020
Study completion29 Apr 2021

Why it stopped: SPARK did not meet it's primary outcome measure for year 1 and failed to meet secondary outcome measures resulting in the development of BIIB054 (cinpanemab) for Parkinson's disease to be discontinued and SPARK study was closed.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 357 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03318523
Sponsor's protocol ID: 228PD201
Other IDs: 2016-004610-95, 2016
Acronym: SPARK
Status last verified: Feb 2022
First submitted: 19 Oct 2017
Last updated: 28 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

Publications

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.
PubMed 38315945
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.
PubMed 35921450
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.
PubMed 34814867

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03318523
Acronym / sponsor ID: SPARK / 228PD201
Conditions: Parkinson's Disease
Keywords: BIIB054, Alpha-synuclein
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: SPARK did not meet it's primary outcome measure for year 1 and failed to meet secondary outcome measures resulting in the development of BIIB054 (cinpanemab) for Parkinson's disease to be discontinued and SPARK study was closed.
Enrolment: 357 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 10 Jan 2018 (actual)
Primary completion: 26 Oct 2020 (actual)
Study completion: 29 Apr 2021 (actual)
First posted: 24 Oct 2017 (actual)
Results: Posted 23 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboYear 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.
BIIB054 250 mg	Experimental	Drug: BIIB054Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.
BIIB054 1250 mg	Experimental	Drug: BIIB054Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.
BIIB054 3500 mg	Experimental	Drug: BIIB054Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboAdministered as specified in the treatment arm	Drug	Placebo
BIIB054Administered as specified in the treatment arm.	Drug	BIIB054 1250 mg, BIIB054 250 mg, BIIB054 3500 mg

Primary outcome

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
Time frame: Baseline, 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.
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
Time frame: Baseline, 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.

13 secondary outcomes

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 3 years
Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96
Time frame: Baseline, Week 96
Serum Concentration of BIIB054
Time frame: 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
Time frame: Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96
Time frame: Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart II Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96
Time frame: Baseline, Weeks 72 and 96
Change From Baseline in MDS-UPDRS Subpart III Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96
Time frame: 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
Time frame: Baseline, Week 52
Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52
Time frame: Baseline, Week 52
Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52
Time frame: Baseline, Week 52
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum
Time frame: Up to Week 144

Results and safety

Results posted to the registry on 23 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PC Period: Placebo	100	96
PC Period: BIIB054 250 mg (Early Start)	55	53
PC Period: BIIB054 1250 mg (Early Start)	102	100
PC Period: BIIB054 3500 mg (Early Start)	100	96
DBE Period: Placebo to BIIB054 250 mg (Delayed Start)	0	0
DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)	0	0
DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)	0	0
DBE Period: BIIB054 250 mg (Early Start)	0	0
DBE Period: BIIB054 1250 mg (Early Start)	0	0
DBE Period: BIIB054 3500 mg (Early Start)	0	0

Primary outcome: 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

Time frame: Baseline, Week 52. Mean (Standard Error). Unit: score on a scale

Measure	PC Period: Placebo n = 53	PC Period: BIIB054 250 mg (Early Start) n = 29	PC Period: BIIB054 1250 mg (Early Start) n = 57	PC Period: BIIB054 3500 mg (Early Start) n = 51
Value	10.78 (1.490)	10.48 (1.951)	11.29 (1.446)	10.86 (1.518)

PC Period: Placebo vs PC Period: BIIB054 250 mg (Early Start): Difference: -0.30 (95% CI -4.888 to 4.287), p = 0.8976, Mixed Model for Repeated Measures
PC Period: Placebo vs PC Period: BIIB054 1250 mg (Early Start): Difference: 0.50 (95% CI -3.310 to 4.312), p = 0.7960, Mixed Model for Repeated Measures
PC Period: Placebo vs PC Period: BIIB054 3500 mg (Early Start): Difference: 0.08 (95% CI -3.805 to 3.956), p = 0.9695, Mixed Model for Repeated Measures

Population analysed: The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). Number of participants analyzed were participants analyzed for this outcome measure.

Primary outcome: 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

Time frame: Baseline, Week 72. Mean (Standard Error). Unit: score on a scale

Measure	PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) n = 68	PC Period: Early Start BIIB054 250 mg n = 32	PC Period: Early Start BIIB054 1250 mg n = 62	PC Period: Early Start BIIB054 3500 mg n = 64
Value	7.11 (1.476)	6.83 (2.032)	8.66 (1.496)	6.94 (1.508)

PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) vs PC Period: Early Start BIIB054 250 mg: Difference: -0.28 (95% CI -5.035 to 4.483), p = 0.9093, Mixed Model for Repeated Measures
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) vs PC Period: Early Start BIIB054 1250 mg: Difference: 1.55 (95% CI -2.336 to 5.440), p = 0.4327, Mixed Model for Repeated Measures
PC Period: Placebo to BIIB054 250 mg/ 1250 mg / 3500 mg (Delayed Start - Pooled) vs PC Period: Early Start BIIB054 3500 mg: Difference: -0.17 (95% CI -4.051 to 3.719), p = 0.9330, Mixed Model with repeated Measures

Population analysed: The ITT population was defined as all randomized participants who received at least one dose of study treatment (BIIB054 or placebo). As prespecified in the protocol, the data for the delayed start BIIB054 were pooled from Placebo/BIIB054 250/1250/3500 mg for the analysis of this outcome measure. Number of participants analyzed were participants analyzed for this outcome measure.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 3 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PC Period: Placebo	7 of 100 (7%)	58 of 100 (58%)	0 of 100
PC Period: BIIB054 250 mg (Early Start)	4 of 55 (7.3%)	32 of 55 (58.2%)	0 of 55
PC Period: BIIB054 1250 mg (Early Start)	4 of 102 (3.9%)	61 of 102 (59.8%)	0 of 102
PC Period: BIIB054 3500 mg (Early Start)	6 of 100 (6%)	63 of 100 (63%)	0 of 100
DBE Period: Placebo to BIIB054 250 mg (Delayed Start)	2 of 20 (10%)	16 of 20 (80%)	0 of 20
DBE Period: Placebo to BIIB054 1250 mg (Delayed Start)	3 of 37 (8.1%)	22 of 37 (59.5%)	0 of 37
DBE Period: Placebo to BIIB054 3500 mg (Delayed Start)	3 of 39 (7.7%)	22 of 39 (56.4%)	0 of 39
DBE Period: BIIB054 250 mg (Early Start)	3 of 52 (5.8%)	25 of 52 (48.1%)	0 of 52
DBE Period: BIIB054 1250 mg (Early Start)	5 of 100 (5%)	51 of 100 (51%)	0 of 100
DBE Period: BIIB054 3500 mg (Early Start)	7 of 94 (7.4%)	56 of 94 (59.6%)	1 of 94

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38315945Hutchison 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.
Derived from this study: PubMed 35921450Lang 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.
Derived from this study: PubMed 34814867Hutchison 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.
Fox Trial FinderLink provided by the sponsor.
Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

75 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIIB054 in people with Parkinson's Disease, run by Biogen at 75 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, Italy, Spain, Germany, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Baseline, Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03318523, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.