Abstract Details

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

Topic Movement Disorders

Presentation(s) S41 - Parkinson's Disease Interventions and Clinical Trials (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

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<0.001) and clinical scores (MDS-UPDRSI+II+III, rho=-0.38, p<0.0001). SN volume (via NM-GRE) correlated negatively with age (rho=−0.30, p<0.0001). SN volume measures were moderately correlated between TSE and GRE sequences (rho=0.46, p<0.0001), whereas correlation in intensity measures between sequences was weak (rho=0.34, p<0.0001), and GRE was associated with higher mean intensity values. There was no significant correlation between clinical scores and NM-MRI metrics. DaT-SPECT and MRI correlations were mixed depending on the sequence, hemisphere, and metric (all rho≤0.30). Volumetric assessment of the nucleus basalis showed correlation with age (rho=-0.40, p<0.0001), DaT-SPECT (putamen, rho=0.17, p<0.0001), and NM-MRI SN volume (rho=0.25, p<0.0001).

Conclusions The SPARK baseline imaging data provide a preliminary framework to assess inter-modal-neuroimaging relationships in a standardized, large-scale trial.

Authors/Disclosures
PRESENTER	No disclosure on file
Karleyton Evans, MD	No disclosure on file
Minhua Yang	No disclosure on file
Zhen Xiao, PhD	No disclosure on file
Tara Fox (BIOGEN)	No disclosure on file
	No disclosure on file
	No disclosure on file
David Scott	No disclosure on file
	No disclosure on file
	No disclosure on file
Jesse M. Cedarbaum, MD, FAAN (Coeruleus Clinical Sciences LLC)	No disclosure on file
Miroslaw Brys, MD, PhD	No disclosure on file

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