Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants with Parkinson’s Disease (SPARK)

Status: 
Recruiting
Sponsor: 
Biogen
Enrollment: 
311
Study Design: 
SPARK is a multi-centre, randomized, double-blind, placebo-controlled study, with an active treatment dose-blinded period, to evaluate the safety, pharmacokinetics and pharmacodynamics of BIIB054 in subjects with Parkinson’s. The study is conducted in patients who have been diagnosed with clinically established PD within a maximum of 3 years with no other known or suspected cause of Parkinsonism. Patients should have a score of ≤2.5 on the Modified Hoehn and Yahr Scale. There will be 2 cohorts. Cohort A will be randomized first and will include approximately 24 patients (completed). Cohort B (on-going) was launched after all patients in Cohort A completed Week 12 assessments and had safety read out. Cohort 2 will include approximately 287 patients. In Year 1 (the placebo-controlled portion of the study), patients will be randomized into the following 4 parallel dosing arms, to receive treatment every 4 weeks via IV infusion: Arm 1: Placebo. Arm 2: BIIB054 - 250 mg. Arm 3: BIIB054 - 1250 mg. Arm 4: BIIB054 - 3500 mg. Patients will continue treatment in Year 2 (the active-treatment dose-blinded portion of the study). Those who received placebo in Year 1 will be randomized to one of the active treatment arms to receive BIIB054 in Year 2. Subjects who received BIIB054 in Year 1 will continue with the same dose regimen in Year 2. The total duration of study participation for each patient will be approximately 113 weeks, including a 5-week screening period, a 48-week placebo-controlled treatment period, a 48-week active-treatment dose-blinded period, and a 12-week follow-up period.
Rationale: 
BIIB054 is a human monoclonal antibody that targets aggregated forms of α-synuclein. Pre-clinical work1 showed >800-fold binding to aggregated α-synuclein compared to monomer, with epitope mapping showing that the antibody binds to residues 1-10. BIIB054 treatment in three different mouse models showed that it reduces the spread of α-synuclein pathology, improves motor function and reduces the loss of dopamine transporter density in dopaminergic terminals. The successful pre-clinical work supported the initiation of a Phase 1 trial (NCT02459886). This study, entitled “Single Ascending Dose Study of BIIB054 in Healthy Participants and Early Parkinson’s Disease”, was randomized, double-blind and placebo-controlled. Eighteen patients received a single dose of 15 or 45mg/kg of BIIB054, or placebo. Results2 showed favourable pharmacokinetic, safety and tolerability, with a serum half-life of 30 days.
Comments: 
As with all the other α-synuclein targeting therapeutics, this is still an early phase study focusing on the safety and tolerability, however a number of the secondary and exploratory outcome measures will inform the design of the future studies. The study is enriched with a large number of biomarkers that hopefully will contribute to better mechanistic understanding of these targets.
Results: 
PRIMARY OUTCOME MEASURE: Percentage of participants with adverse events (AEs) and serious adverse events (SAEs) up to week 52. SECONDARY OUTCOME MEASURES: 1. Change in striatal binding ratio (SBR) in putamen, striatum, and caudate (Timeframe: baseline, week 52). SBR will be measured by Striatal-Photon Emission Computed Tomography (SPECT) imaging of the Dopamine Transporter with Ioflupane 123I (DaTscan™). 2. Concentration of BIIB054 in the serum (Timeframe: baseline up to week 108). 3. Percentage of participants with anti-BIIB054 antibodies in the serum (Timeframe: baseline up to week 108).