Phase 1 Trial Suggests PD01A Is Safe in Parkinson Disease Treatment

Parkinson’s disease. 3D illustration showing neurons containing Lewy bodies small red spheres which are deposits of proteins (alpha-synuclein) accumulated in the brain cells.
A Phase 1 trial suggested that PD01A was safe and well tolerated over an extended period in patients with Parkinson disease.

Repeated administrations of PD01A were found to be safe and well tolerated over an extended time period in patients with Parkinson disease (PD), according to phase 1 study results published in Lancet Neurology.

PD01A is an immunotherapy that targets oligomeric α-synuclein, a potential driver of neuronal dysfunction in patients with PD. Study researchers sought to evaluate the safety and tolerability of PD01A in patients with PD. A total of 24 patients with PD aged between 45 and 65 years (mean age, 54.9 years) were recruited from a single center in Austria and enrolled into this first-in-human phase 1 trial of PD01A.

All patients were on a stable treatment regimen for PD for ≥3 months prior to enrollment. Patients were randomly assigned to receive 4 subcutaneous administrations of either 15 μg (n=12) or 75 μg (n=12) PD01A that were injected into the upper arms. These patients were followed up for 52 weeks and then an additional 39 weeks.

After the 39-week follow-up, patients were randomly assigned to receive the first booster immunization with PD01A at 15 μg (n=10) or 75 μg (n=12). The follow-up period after the second randomization was 24 weeks. Patients then received a second booster of 75 μg PD01A and were followed up for another 52 weeks. Study researchers examined the primary outcomes — safety and tolerability — with patient diary data and investigator assessments at each visit. These outcome assessments focused on all local or systemic treatment-emergent adverse events (TEAEs).

Approximately 87% of patients (n=21) received all 6 administrations of PD01A and completed between 221 and 259 weeks in the study. All patients in the study experienced ≥1 adverse event (AE), but the majority of these events were deemed unrelated to treatment from this study. Local injection site reactions, while transient, were the only treatment-related AE reported in this study (n=23). A total of 500 TEAEs were reported by all patients across the follow-up period. The systemic TEAEs possibly related to treatment and reported in ≥2 patients were fatigue (n=4), headache (n=3), myalgia (n=3), muscle rigidity (n=2), and tremor (n=2).

Investigators observed no abnormalities on MRI after baseline; however, they observed 1 treatment-unrelated microhemorrhage event in the 15 μg group. In the 15 μg dose group, the geometric group mean titer of antibodies against the immunizing peptide PD01 increased from a baseline of 1:46 to 1:3580 at 12 weeks. In the 75 μg dose group, the geometric group mean titer of antibodies increased from 1:76 at baseline to 1:2462 at week 12. Over a 2-year period, antibody titers returned to baseline. These titers were capable of being reactivated following a booster immunization from week 116 onwards, subsequently reaching geometric group mean titers of up to 1:20218.

Limitations of the study included the small sample size, the lack of a placebo group, and the inclusion of patients from a single center in Austria, which may reduce generalizability of the findings.

Investigators concluded that their “findings of a sustained α-synuclein-specific antibody response, suggests immunization with PD01A might be a promising strategy for long-term management of PD.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Volc D, Poewe W, Kutzelnigg A, et al. Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson’s disease: a randomised, single-blinded, phase 1 trial. Lancet Neurol. 2020;19(7):591-600.