Use of Multimodal Imaging in a Phase 2 Study in Participants with Parkinson’s Disease (SPARK) (1516)

Objective: Assess the utility and inter-modality relationships of non-invasive imaging biomarkers to evaluate Parkinson’s Disease (PD) within the ongoing SPARK (NCT03318523) study. Background: PD is characterized by nigral-striatal neurodegeneration that may be quantified by imaging of the striatal dopamine transporters via (DaT)-SPECT or via MRI sequences sensitive to paramagnetic properties of neuromelanin within cell bodies of substantia nigra (SN) neurons. Design/Methods: SPARK is an ongoing, randomized, placebo-controlled, Phase-2 study to evaluate the safety, pharmacokinetics, and pharmacodynamics of Cinpanemab (BIIB054, anti–α-synuclein monoclonal antibody) in patients with early PD. Patients undergo DaT-SPECT imaging with 123Ioflupane and MRI at screening and follow-up visits (only screening data reported here). DaT-SPECT acquisition and image processing were standardized across sites. Striatal binding ratios (SBRs) of a-priori defined regions were calculated following anatomical and atlas co-registration. 3T MRI acquisition was harmonized to a common standard and included T1 anatomical, neuromelanin T1 turbo-spin-echo (NM-TSE), and 3D gradient-echo (NM-GRE) sequences. Results: 3.8% of screened patients were excluded due to normal striatal binding (via DaT-SPECT). The mean±SD SBR of randomized subjects (n=357) was 1.34±0.34 and correlated negatively with age (rho=−0.21, p Conclusions: The SPARK baseline imaging data provide a preliminary framework to assess inter-modal-neuroimaging relationships in a standardized, large-scale trial. Disclosure: Dr. Hutchison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Evans has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Yang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Biogen. Dr. Xiao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Biogen. Dr. Hirschhorn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Kisch-Hancock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Bioclinica. Dr. Scott has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Bioclinica. Dr. Bedell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Biospective Inc.. Dr. Bedell holds stock and/or stock options in Stock: Biospective Inc. which sponsored research in which Dr. Bedell was involved as an investigator. Dr. Auclair has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Biospective Inc.. Dr. Cedarbaum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Cedarbaum has received personal compensation in an editorial capacity for Biogen. Dr. Cedarbaum has received compensation for serving on the Board of Directors of Biogen. Dr. Brys has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Biogen.