Efficacy and Safety Evaluation of BIIB122 in a Randomized, Double-Blind, Placebo-Controlled Phase 2b Study in Parkinson's Disease Patients

The primary objective of this study is to evaluate the **efficacy** of BIIB122 225 mg compared with placebo in participants with **Parkinson's Disease**. This is clinically relevant as it aims to determine the potential therapeutic benefits of BIIB122 in managing symptoms or progression of Parkinson's Disease, which could lead to improved patient outcomes and quality of life.

Secondary objectives include evaluating the **efficacy**, **safety**, and **tolerability** of BIIB122 225 mg compared with placebo. These assessments are crucial for understanding the overall benefit-risk profile of BIIB122, ensuring that it is not only effective but also safe and well-tolerated by patients.

The clinical trial involves a total of **329 participants** diagnosed with **Parkinson's Disease**. The study population includes both male and female subjects, with an age range starting from at least 30 years at the time of diagnosis. Participants were selected based on a clinical diagnosis of Parkinson's Disease meeting the Movement Disorder Society Clinical Diagnostic Criteria within two years of the screening visit. The trial includes individuals with a Modified Hoehn and Yahr scale of stages 1 to 2 in the OFF state and a combined MDS-UPDRS Parts II and III score of 40 or less at screening. Genetic testing was conducted to ensure the absence of specific pathogenic LRRK2 variants. The trial population is considered vulnerable, and lifestyle factors such as diet and physical activity were not specified. The selection criteria ensure a focus on early-stage Parkinson's Disease, allowing for a precise evaluation of the efficacy of BIIB122 225 mg compared with placebo.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of BIIB122 in participants with **Parkinson's Disease**. The trial is conducted in multiple centers and follows a Phase 2b design. Participants are randomly assigned to receive either BIIB122 or a matching placebo, administered orally in tablet form. The primary objective is to assess the time to confirmed worsening in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score over the treatment period. Secondary endpoints include the incidence of adverse events (AEs) and serious adverse events (SAEs), changes in MDS-UPDRS scores, and time to confirmed worsening in the Schwab and England Activities of Daily Living Scale (SEADL).

The trial is expected to last until December 15, 2025, with participant involvement spanning a maximum treatment period of 144 weeks. The study begins with a screening visit to confirm eligibility, which includes a clinical diagnosis of Parkinson's Disease within two years of the screening visit, a Modified Hoehn and Yahr scale stage of 1 to 2, and a combined MDS-UPDRS Parts II and III score of ≤40. Genetic testing is conducted to verify the absence of specific pathogenic leucine-rich repeat kinase 2 (LRRK2) variants. Participants who meet the inclusion criteria proceed to the randomization phase.

Throughout the trial, participants attend regular follow-up visits to monitor their health status, assess treatment efficacy, and record any adverse events. These visits are crucial for collecting data on the primary and secondary endpoints. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted to evaluate the overall impact of the treatment. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety.

The clinical trial involves the administration of **BIIB122**, an experimental medication formulated as a tablet. The active substance in BIIB122 is **N2-(3-(2-(2H-1,2,3-triazol-2-yl)propan-2-yl)-1-cyclopropyl-1H-pyrazol-5-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine**, a chemical compound. The medication is administered orally at a dosage of 225 mg per day. The maximum treatment period for participants is 144 days. The pharmaceutical form of BIIB122 is a tablet, and it is produced by Biogen Idec Research Limited. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **matching placebo** group, which receives tablets without any active substance. These placebo tablets are designed to match the experimental medication in appearance and administration route, ensuring the study remains double-blind. The placebo is administered orally, following the same dosing schedule as the experimental group, to maintain consistency in the trial design. The use of a placebo allows for a controlled comparison to evaluate the efficacy and safety of BIIB122 in participants with Parkinson's Disease.

The efficacy of BIIB122 in participants with **Parkinson's Disease** will be assessed using several endpoints. The primary endpoint is the time to confirmed worsening in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score over the treatment period. Secondary endpoints include the incidence of adverse events (AEs) and serious adverse events (SAEs) during the treatment period, time to confirmed worsening in MDS-UPDRS Part II score, change in MDS-UPDRS Parts II and III combined score, time to confirmed worsening in the Schwab and England Activities of Daily Living Scale (SEADL), and change in MDS-UPDRS Parts I, II, and III combined score.

The MDS-UPDRS is a validated scale used to measure the severity of Parkinson's Disease symptoms, and the SEADL scale assesses the impact on daily living activities. These assessments will be conducted at specified intervals throughout the trial to monitor changes in symptom severity and daily functioning. The data collected will be analyzed to determine the efficacy of BIIB122 compared to placebo in slowing the progression of Parkinson's Disease symptoms.