Evaluation of NEU-411 Maleate in LRRK2-Driven Early Parkinson's Disease: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this Phase 2, randomized, double-blind, placebo-controlled study is to evaluate the **safety** and primary **efficacy** of NEU-411 in participants with LRRK2-driven Parkinson's disease. This objective is clinically relevant as it aims to determine the potential therapeutic benefits and safety profile of NEU-411, which could offer a targeted treatment option for individuals with this specific genetic form of Parkinson's disease.

Secondary objectives include evaluating the secondary safety and efficacy of NEU-411 in the same participant population. These objectives are crucial for understanding the broader impact of NEU-411 on patient outcomes and further validating its use as a treatment option.

The clinical trial involves a total of **90 participants** diagnosed with **Parkinson's disease**, specifically focusing on those with LRRK2-driven Parkinson's disease. The study population includes both male and female subjects, aged between **40 to 80 years**. Participants were selected based on a diagnosis of clinically established or probable Parkinson's disease, confirmed through a genetic test for LRRK2-driven Parkinson's disease. The trial includes individuals with a Modified Hoehn and Yahr stage of 1 to 2.5. The study population is characterized by a diverse age range and includes a vulnerable population. Participants' general health status is consistent with the inclusion criteria, which require a specific diagnosis and genetic confirmation. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of **NEU-411** in participants with early **Parkinson's disease**. The trial will involve participants who are diagnosed with LRRK2-driven Parkinson's disease, as determined by a companion diagnostic genetic test. The study will span a total duration of 54 weeks, with the treatment period lasting 52 weeks. Participants will be randomly assigned to receive either NEU-411 or a placebo, administered orally in tablet form, with a maximum daily dose of 30 mg.

The trial will commence with an inclusion (screening) visit, where participants will be assessed for eligibility based on criteria such as age (40-80 years), diagnosis of Parkinson's disease, and LRRK2-driven status. Following successful screening, participants will be enrolled and randomized into the study. The primary endpoints include the change from baseline in the Roche digital biomarker score and the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) compared to placebo. Secondary endpoints will assess changes in motor and non-motor functions using the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).

Study visits will be scheduled at regular intervals throughout the trial to monitor participants' health, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the conclusion of the 54-week period, where final assessments will be conducted to evaluate the overall outcomes of the trial. Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial aims to provide valuable insights into the therapeutic potential of NEU-411 for individuals with LRRK2-driven Parkinson's disease.

The clinical trial involves the administration of **NEU-411**, an investigational medication developed by Neuron23, Inc. NEU-411 is formulated as a **tablet** and contains the active substance **NEU-411 maleate**, a chemical compound. The medication is administered **orally** with a maximum daily dose of **30 mg**. The treatment period extends up to **52 weeks**. The primary objective of the trial is to evaluate the safety and efficacy of NEU-411 in participants with LRRK2-driven Parkinson's disease. The investigational drug is designed to target specific genetic modifiers associated with the disease, and its administration is guided by a companion diagnostic test to identify suitable participants.

The study also includes a **placebo** group, which receives a placebo formulation of NEU-411 maleate. The placebo is used as a comparator to assess the efficacy of the investigational drug in a double-blind manner. The placebo does not contain any active substance and is administered in a manner identical to the experimental treatment to maintain the study's blinding. The use of a placebo control is essential in determining the true therapeutic effect of NEU-411 by providing a baseline for comparison.

Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the prescribed treatment schedule. The trial employs a blood-based in vitro diagnostic test, the QIAseq Exome Complete System, co-developed by Neuron23, Inc. and QIAGEN Manchester Limited. This test utilizes Next-Generation Sequencing to detect specific single nucleotide polymorphisms in LRRK2 genetic modifiers, categorizing patients into LRRK2-active or LRRK2-normal Parkinson's disease groups. This stratification is crucial for selecting participants who are most likely to benefit from NEU-411 treatment and excluding those less likely to respond.

The efficacy of NEU-411 in the treatment of early Parkinson's disease will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint involves evaluating the change from baseline in the Roche digital biomarker score using the Roche Parkinson's Disease application (v3.0) compared to placebo. This assessment will be conducted from enrollment to the end of treatment at 52 weeks. Additionally, the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be compared to placebo from enrollment to the end of the study at 54 weeks.

Secondary efficacy will be measured by the change from baseline to Week 52 in motor and nonmotor function, as assessed by the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). These assessments will provide a comprehensive evaluation of the therapeutic impact of NEU-411 on patients with LRRK2-driven Parkinson's disease. The investigational companion diagnostic genetic test (CDx) will be utilized to select participants with LRRK2-driven Parkinson's disease, ensuring that the study population is appropriately targeted for the intervention.