Objective: Assess safety and immunogenicity of UB-312 in a phase 1b trial in Multiple System atrophy (MSA) or Parkinson’s disease (PD).

Background: Abnormal deposition of insoluble a-synuclein (a-syn) in neurons, glia, and other cells plays a key role in the pathophysiology of MSA and PD. UB-312 is a synthetic peptide vaccine designed to induce antibodies against oligomeric and fibrillary forms of a-syn being developed as a disease-modifying therapy in patients with MSA or PD.

Method: Single-center, single-blind, randomized, placebo-controlled, delayed-start, phase-1b trial of UB-312 in MSA or PD to test safety and tolerability, immunogenicity, and explore potential efficacy signals after multiple administrations of UB-312 conducted at NYU Grossman School of Medicine under an investigator IND in collaboration with Vaxxinity. Participants receive priming doses at baseline, weeks 4 and 12, and booster doses at weeks 24, 36, and 48 followed by 24-week safety follow-up. MSA and PD participants receive 300 and 600µg doses, respectively. Motor and non-motor clinical features are being evaluated using standardized rating scales and evaluations, as well as quality of life and global disability. Phosphorylated a-syn in skin biopsies, fMRI, and quantitative EEG to evaluate changes in motor neurocircuitry and functional connectivity are exploratory endpoints. Levels of anti-synuclein antibodies are assessed by ELISA.

Results: To date, we enrolled 4 male patients with MSA (age: 43 to 65; 1 MSA-P, 3 MSA-C), and 3 males with PD (age: 62 to 66). MSA participants disease duration ranged from 1 to 7 years from onset of motor symptoms. UMSARS-I ranged from 8 to 26, UMSARS-II: 5 to 36, and UMSARS-IV: 1 to 4.  PD participants disease duration from diagnosis, ranged from 1 to 9 years.  MDS-UPDRS-I ranged from 9 to 18, MDS-UPDRS-II: 13 to 18, MDS-UPDRS-III (Off): 9 to 25, and MDS-UPDRS-IV: 0 to 5. All skin biopsies were positive for phosphorylated a-syn. All subjects who received 3 priming doses developed antibodies against a-synuclein. To date, there were 7 mild and moderate severity adverse events in 6 patients. There was one serious adverse event (unrelated to the investigational product).

Conclusion: Following immunization with priming doses, UB-312-specific antibodies were detectable. To date, the vaccine demonstrates a well-tolerated safety profile. Data collection is ongoing and additional data will be shared at the conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-1b-randomized-placebo-controlled-delayed-start-trial-of-ub-312-in-synucleinopathies/