A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Dosing of Exidavnemab in Patients With Mild to Moderate Parkinson's Disease on Stable Symptomatic Parkinson's Disease Medication and in Patients With Multiple System Atrophy
The primary objective of this study is to assess the safety and tolerability of exidavnemab after multiple dosing versus placebo.
• Male and female participants 40 to 85 years of age.
• Body weight more than or equal to 50 kg and less than or equal to 120 kg.
• Have idiopathic PD (i.e., not induced by drugs or other diseases) as defined by bradykinesia combined with at least 1 of resting tremor and rigidity, as per the Movement Disorder Society Criteria for PD (Postuma, et al. 2015).
• Classified as Stage 1 to 2.5 on the modified Hoehn and Yahr scale for the staging of PD severity.
• Participants must have cognition inconsistent with dementia as confirmed by a score of more than or equal to 22 on the MoCA.
• Stable and optimized symptomatic PD medication, defined as the same list of medications for at least 3 months prior to the Screening Visit with no change in the dose for at least 1 month prior to the Baseline Visit, and no planned changes in dose-regimen during trial participation.
• Prior (any time; i.e., no time limit) or current DaT-SPECT or DaT-PET consistent with dopamine transporter deficit, as per the Movement Disorder Society Criteria for PD(Postuma, et al. 2015). For participants who have not undergone DaT-SPECT or DaT-PET prior to Screening, or who have previously undergone DaT-SPECT or DaT-PET scan(s) but without results consistent with dopamine transporter deficit, DaT-SPECT or DaT-PET should be performed and read locally as part of the Screening procedures.
• Positive smell test showing hyposmia, as defined by UPSIT scores of around or below the 15% percentile for their relevant sex and age group. Cut-off scores are provided below for reference (Table 5.1; based on Brumm, et al. 2023) Ability to use a tablet device to measure cognitive function, as per Investigator judgment.
• Male and female participants 40 to 85 years of age.
• Body weight more than or equal to 50 kg and less than or equal to 120 kg.
• Have clinically established or clinically probable MSA (either MSA-P or MSA-C), as per the Movement Disorder Society criteria for the diagnosis of MSA (Wenning, et al. 2022).
• Classified as Stage 1 to 3 on the modified Hoehn and Yahr scale for the staging of MSA severity.
• Participants must have cognition inconsistent with dementia as confirmed by a score of more than or equal to 22 on the MoCA.
• Negative urine or serum pregnancy test at the Screening Visit and Baseline for premenopausal women, and for women who have experienced menopause onset less than 12 months prior to the first planned dose of trial medication.
• Males and POCBP must agree to practice an effective means of birth control during their participation in the trial and until 3 months after their last dose of the trial medication. See specific guidelines regarding contraceptive methods in Section 14.1.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and trial procedures.