Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial

This 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated the safety, tolerability, and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with Parkinson's disease (PD). Primary outcome measures were adverse event frequency and changes in anti-αSyn antibody titers. Exploratory outcomes included changes in clinical scales and biomarker-based target engagement. Twenty patients were randomized (UB-312:placebo, 7:3) into dose groups. Safety was similar across groups; adverse events were mostly mild and transient. Anti-αSyn antibodies in serum and CSF of UB-312-treated patients confirmed immunogenicity. Exploratory analyses showed no statistical differences in clinical scales but a significant reduction of αSyn seeds in CSF of a subset of UB-312-treated patients. These data support further UB-312 development. ClinicalTrials.gov: NCT04075318.

Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D. Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M. Vroom, Carly M. Farris, Yihua Ma, Marieke L. de Kam, Igor Radanovic, Maurits F. J. M. Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart