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

Study Overview
=================
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.

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

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: BIIB054


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Administered as specified in the treatment arm<br>|
| Experimental: BIIB054 250 mg<br>Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks. | Drug: BIIB054<br>* Administered as specified in the treatment arm.<br>|
| Experimental: BIIB054 1250 mg<br>Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks. | Drug: BIIB054<br>* Administered as specified in the treatment arm.<br>|
| Experimental: BIIB054 3500 mg<br>Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks. | Drug: BIIB054<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52 | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values. | Baseline, Week 52 | 
| Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72 | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values. | Baseline, Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Baseline, Week 96 | 
| Serum Concentration of BIIB054 |  | Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144 | 
| Change From Baseline in MDS-UPDRS Subpart I Score at Week 52 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline, Week 52 | 
| Percentage of Participants With Anti-BIIB054 Antibodies in the Serum |  | Up to Week 144 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BIIB054, Alpha-synuclein