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.