Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease
- Registration Number
- NCT03318523
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 357
Not provided
- Presence of freezing of gait.
- Montreal cognitive assessment (MOCA) score <23 or other significant cognitive impairment or clinical dementia that, in the opinion of the Investigator, would interfere with study evaluation.
- History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality, as read by central reader.
- History of severe allergic or anaphylactic reactions, or history of hypersensitivity to BIIB054 or any of the inactive ingredients in the drug product or to radioligands or iodine used in the study.
- Participation in any active immunotherapy study targeting alpha-synuclein.
- Use of allowed medications not previously specified at doses that have not been stable for at least 8 weeks before Day 1, and/or that are not expected to remain stable for the duration of the study.
- Clinically significant abnormal laboratory test values at Screening, as determined by the Investigator.
- Blood donation (1 unit or more) within 8 weeks before Day 1 (must also refrain from donating blood for the duration of the study).
NOTE : Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIIB054 250 mg BIIB054 Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks. BIIB054 1250 mg BIIB054 Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks. Placebo 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. BIIB054 3500 mg BIIB054 Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.
- Primary Outcome Measures
Name Time Method 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 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 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
Name Time Method 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 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.
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 Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) 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 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.
Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96 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 SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52 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.
Percentage of Participants With Anti-BIIB054 Antibodies in the Serum Up to Week 144 Change From Baseline in MDS-UPDRS Subpart I Score at Week 52 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 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 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 SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52 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.
Change From Baseline in MDS-UPDRS Subpart III Score at Week 52 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 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.
Trial Locations
- Locations (52)
Royal Hallamshire Hospital
🇬🇧Sheffield, West Midlands, United Kingdom
University of Kansas Medical Center Research Institute
🇺🇸Kansas City, Kansas, United States
Cedars Sinai
🇺🇸Los Angeles, California, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
University of Colorado Health
🇺🇸Aurora, Colorado, United States
Rocky Mountain Movement Disorders Center, PC
🇺🇸Englewood, Colorado, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Parkinson's Disease and Movement Disorders Centerf
🇺🇸Boca Raton, Florida, United States
Northwestern University PD and Movement Disorders Center
🇺🇸Chicago, Illinois, United States
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
University of Pittsburgh Medical Center Health System
🇺🇸Pittsburgh, Pennsylvania, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Research Site
🇬🇧London, United Kingdom
Mayo Clinic Hospital
🇺🇸Jacksonville, Florida, United States
Bioclinica Research
🇺🇸Orlando, Florida, United States
USF Health Byrd Institute
🇺🇸Tampa, Florida, United States
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
NYU Langone Health Center
🇺🇸New York, New York, United States
Inland Northwest Research
🇺🇸Spokane, Washington, United States
Booth Gardner Parkinson's Care Center at Evergreen Health
🇺🇸Kirkland, Washington, United States
Montreal Neurological Institute Clinical Research Unit
🇨🇦Montréal, Quebec, Canada
Research Name
🇫🇷Toulouse Cedex 09, Haute Garonne, France
Hôpital Henri Mondor
🇫🇷Créteil, Val De Marne, France
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico
🇮🇹Catania, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
CHU Nantes - Hopital Nord Laënnec
🇫🇷Nantes, Loire Atlantique, France
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Klinikum rechts der Isar der TU Muenchen
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Bayern, Germany
Paracelsus-Elena-Klinik
🇩🇪Kassel, Hessen, Germany
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
🇮🇹Pozzilli, Isernia, Italy
Ospedale Bellaria
🇮🇹Bologna, Italy
Seconda Università degli Studi di Napoli
🇮🇹Napoli, Italy
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic De Barcalona
🇪🇸Barcelona, Spain
Biocruces Health Research Institute
🇪🇸Barakaldo, Vizcaya, Spain
Hospital General de Catalunya
🇪🇸Sant Cugat del Vallés, Barcelona, Spain
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
🇮🇹Salerno, Italy
IRCCS San Raffaele
🇮🇹Roma, Italy
Salford Royal
🇬🇧Salford, Greater Manchester, United Kingdom
Clinical Ageing Research Unit
🇬🇧Newcastle upon Tyne, Tyne & Wear, United Kingdom
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Universitaetsklinikum Aachen AOeR
🇩🇪Aachen, Nordrhein Westfalen, Germany
Azienda Ospedaliera Santa Maria di Terni
🇮🇹Terni, Italy
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain