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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318523
Recruitment Status : Terminated (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.)
First Posted : October 24, 2017
Results First Posted : November 23, 2021
Last Update Posted : November 23, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: Placebo Drug: BIIB054 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 357 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 10, 2018
Actual Primary Completion Date : October 26, 2020
Actual Study Completion Date : April 29, 2021

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.

  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 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 3 years ]
    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.

  2. Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96 [ Time Frame: Baseline, 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.

  3. 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 ]
  4. Change From Baseline in MDS-UPDRS Subpart I Score 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). 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.

  5. Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96 [ Time Frame: Baseline, 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.

  6. Change From Baseline in MDS-UPDRS Subpart II Score at Week 52 [ Time Frame: Baseline, 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.

  7. Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96 [ Time Frame: Baseline, 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.

  8. Change From Baseline in MDS-UPDRS Subpart III Score at Week 52 [ Time Frame: Baseline, 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.

  9. Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96 [ Time Frame: Baseline, Weeks 72 and 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.

  10. 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 ]
    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.

  11. Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52 [ Time Frame: Baseline, 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.

  12. Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52 [ Time Frame: Baseline, 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.

  13. Percentage of Participants With Anti-BIIB054 Antibodies in the Serum [ Time Frame: Up to Week 144 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318523


Locations
Hide Hide 75 study locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
Research Site
La Jolla, California, United States, 92093-0886
Cedars Sinai
Los Angeles, California, United States, 90048
University of California San Francisco Medical Center
San Francisco, California, United States, 94158
Research Site
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Health
Aurora, Colorado, United States, 80045
Rocky Mountain Movement Disorders Center, PC
Englewood, Colorado, United States, 80113
United States, Florida
Parkinson's Disease and Movement Disorders Centerf
Boca Raton, Florida, United States, 33486
Mayo Clinic Hospital
Jacksonville, Florida, United States, 32224
Bioclinica Research
Orlando, Florida, United States, 32806
USF Health Byrd Institute
Tampa, Florida, United States, 33616
United States, Illinois
Northwestern University PD and Movement Disorders Center
Chicago, Illinois, United States, 60611
Research Site
Chicago, Illinois, United States, 60612
United States, Kansas
University of Kansas Medical Center Research Institute
Kansas City, Kansas, United States, 66160
United States, Louisiana
Ochsner Health System
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston University Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Quest Research Institute
Farmington Hills, Michigan, United States, 48334
United States, New York
NYU Langone Health Center
New York, New York, United States, 10017
Research Site
New York, New York, United States, 10032
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27705
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37232
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Washington
Booth Gardner Parkinson's Care Center at Evergreen Health
Kirkland, Washington, United States, 98034
Inland Northwest Research
Spokane, Washington, United States, 99204
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Austria
Research Site
Innsbruck, Austria, 6020
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
Montreal Neurological Institute Clinical Research Unit
Montréal, Quebec, Canada, H3A 2B4
France
Research Name
Toulouse Cedex 09, Haute Garonne, France, 31059
CHU Nantes - Hopital Nord Laënnec
Nantes, Loire Atlantique, France, 44093
Hopital Roger Salengro - CHU Lille
Lille Cedex, Nord, France, 59037
Hôpital Henri Mondor
Créteil, Val De Marne, France, 94010
Research Site
Paris, France, 75013
Germany
Universitaetsklinikum Ulm
Ulm, Baden Wuerttemberg, Germany, 89081
Klinikum rechts der Isar der TU Muenchen
Muenchen, Bayern, Germany, 81675
Universitaetsklinikum Wuerzburg
Wuerzburg, Bayern, Germany, 97080
Paracelsus-Elena-Klinik
Kassel, Hessen, Germany, 34128
Universitaetsklinikum Aachen AOeR
Aachen, Nordrhein Westfalen, Germany, 52074
Research Site
Bochum, Nordrhein Westfalen, Germany, 44791
Israel
Research Site
Haifa, Israel, 3109601
Research Site
Tel Aviv, Israel, 6423906
Italy
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
Pozzilli, Isernia, Italy, 86077
Ospedale Bellaria
Bologna, Italy, 40139
Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
Catania, Italy, 95125
Research Site
Milano, Italy, 20122
Ospedale San Raffaele
Milano, Italy, 20132
Research Site
Milano, Italy, 20132
Seconda Università degli Studi di Napoli
Napoli, Italy, 80138
Research Site
Pisa, Italy, 56126
IRCCS San Raffaele
Roma, Italy, 00163
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno, Italy, 84131
Azienda Ospedaliera Santa Maria di Terni
Terni, Italy, 05100
Spain
Hospital General de Catalunya
Sant Cugat del Vallés, Barcelona, Spain, 08190
Research Site
Móstoles, Madrid, Spain, 28938
Clinica Universidad de Navarra
Pamplona, Navarra, Spain, 31008
Biocruces Health Research Institute
Barakaldo, Vizcaya, Spain, 48903
Hospital Clinic De Barcalona
Barcelona, Spain, 08036
Hospital Santa Creu i Sant Pau
Barcelona, Spain, 08041
Research Site
Madrid, Spain, 28006
Research Site
Madrid, Spain, 28007
Research Site
Madrid, Spain, 28034
Research Site
Sevilla, Spain, 41013
United Kingdom
Research Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Salford Royal
Salford, Greater Manchester, United Kingdom, M6 8HD
Research Site
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Clinical Ageing Research Unit
Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE4 5PL
Royal Hallamshire Hospital
Sheffield, West Midlands, United Kingdom, S10 2JF
Research Site
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
  Study Documents (Full-Text)

Documents provided by Biogen:
Study Protocol  [PDF] August 13, 2020
Statistical Analysis Plan  [PDF] June 23, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03318523    
Other Study ID Numbers: 228PD201
2016-004610-95 ( EudraCT Number )
First Posted: October 24, 2017    Key Record Dates
Results First Posted: November 23, 2021
Last Update Posted: November 23, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biogen:
BIIB054
Alpha-synuclein
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases