A Randomized First-in-Human Study With UB-312, a UBITh® α-Synuclein Peptide Vaccine.

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Alpha-synuclein (αSyn) aggregation is central to Parkinson's disease (PD) pathology.
• UB-312 is an experimental immunotherapeutic designed to target pathological αSyn forms.
• Developing disease-modifying therapies for synucleinopathies is a critical unmet need.

Purpose of the Study:

• To evaluate the safety, tolerability, and immunogenicity of UB-312 in healthy volunteers.
• To identify a safe and immunologically effective dose for future Parkinson's disease trials.

Main Methods:

• A 44-week, randomized, placebo-controlled, double-blind study in 50 healthy participants.
• Participants received three intramuscular injections of UB-312 or placebo across seven dose cohorts (40-2000 μg).
• Safety was monitored via adverse events and clinical assessments; immunogenicity was assessed by anti-αSyn antibody levels in serum and CSF.

Main Results:

• UB-312 was generally safe and well-tolerated, with mostly mild, transient adverse events.
• Dose- and time-dependent anti-αSyn antibody production was observed.
• Antibodies were detected in serum and CSF at the 300 μg dose, with a CSF/serum ratio of 0.2%.

Conclusions:

• UB-312 is a safe and well-tolerated immunotherapeutic agent that elicits an anti-αSyn antibody response.
• The 100 μg and 300 μg doses of UB-312 were selected for further clinical development in Parkinson's disease patients.