Objective: To evaluate the efficacy of the anti-alpha-synuclein monoclonal antibody PRX002/RG7935 in a proof-of-concept Phase 2 study in patients with early Parkinson’s disease (PD).

Background: PD is a chronic, progressive neurological disorder associated with intraneuronal accumulation of aggregated alpha-synuclein protein. Current treatments target PD symptoms but do not address the underlying pathology; neuroprotective, disease-modifying treatments are needed. PRX002/RG7935 is designed to target neurotoxic (aggregated) forms of alpha-synuclein, inhibiting neuron-to-neuron transfer of pathogenic alpha-synuclein. This may result in neuronal protection and slowing of disease progression. In Phase 1, single and multiple doses of PRX002/RG7935 were generally safe and well tolerated, reaching cerebrospinal fluid concentrations that may engage extracellular aggregated alpha-synuclein in the brain.

Methods: PASADENA is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study to evaluate the efficacy of intravenous administration (every 4 weeks) of PRX002/RG7935 in participants with recently diagnosed (≤2 years) PD (Hoehn and Yahr Stages I-II), either untreated or treated with monoamine oxidase B inhibitors at baseline. The study comprises two parts: a 52-week, double-blind, placebo-controlled treatment period (Part 1) after which eligible participants will continue into an all participants-on-treatment PRX002/RG7935, blinded-to-dose extension for an additional 52 weeks (Part 2). Approximately 300 participants will be randomized 1:1:1 to placebo, high dose (4500 mg [≥65-kg body weight], 3500 mg [<65 kg]) or low dose (1500 mg). Primary outcome measure will be the change from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (Parts I-III) at week 52. Secondary outcomes include change from baseline in dopamine transporter imaging using single photon emission computed tomography, MDS-UPDRS motor subscale (Part III), time to start of dopaminergic symptomatic treatment, pharmacokinetics, safety and tolerability. Exploratory outcomes include remote and frequent symptom monitoring via a smartphone and wrist-worn wearable.

Results: This study is currently recruiting.

Conclusions: PASADENA (NCT03100149) is a proof-of-concept study to demonstrate a slowing of progression in recently diagnosed, early PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-study-to-evaluate-the-efficacy-of-prx002-rg7935-in-participants-with-early-parkinsons-disease-pasadena-study-design/