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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

Tracking Information
First Submitted Date  ICMJE October 19, 2017
First Posted Date  ICMJE October 24, 2017
Results First Submitted Date  ICMJE October 25, 2021
Results First Posted Date  ICMJE November 23, 2021
Last Update Posted Date November 23, 2021
Actual Study Start Date  ICMJE January 10, 2018
Actual Primary Completion Date October 26, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2021)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Up to Week 52 ]
    An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, requires inpatient hospitalization, results in persistent or significant disability and/or results in a congenital anomaly.
  • Change From Baseline in Clinical Laboratory Test Data [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Vital Sign Measurements [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Neurological and Physical Examination Findings [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Electrocardiograms (ECGs) [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Brain Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2021)
  • 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.
  • 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.
  • 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 ]
    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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Percentage of Participants With Anti-BIIB054 Antibodies in the Serum [ Time Frame: Up to Week 144 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Change in Striatal Binding Ratio (SBR) in Putamen, Striatum, and Caudate as Measured by Striatal-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter With Ioflupane I123 (DaTscan™) [ Time Frame: Baseline, Week 52 ]
  • Concentration of BIIB054 in the Serum [ Time Frame: Baseline and at multiple time points (up to Week 52) ]
  • Percentage of Participants With Anti-BIIB054 Antibodies in the Serum [ Time Frame: Baseline and at multiple time points (up to Week 52) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE
  • Drug: Placebo
    Administered as specified in the treatment arm
  • Drug: BIIB054
    Administered as specified in the treatment arm.
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Placebo
  • Experimental: BIIB054 250 mg
    Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.
    Intervention: Drug: BIIB054
  • Experimental: BIIB054 1250 mg
    Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.
    Intervention: Drug: BIIB054
  • Experimental: BIIB054 3500 mg
    Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.
    Intervention: Drug: BIIB054
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 21, 2020)
357
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2017)
311
Actual Study Completion Date  ICMJE April 29, 2021
Actual Primary Completion Date October 26, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   France,   Germany,   Israel,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03318523
Other Study ID Numbers  ICMJE 228PD201
2016-004610-95 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP