A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Dyskinesia Due to Cerebral Palsy

The primary objective of this study is to evaluate the **efficacy** of valbenazine compared to placebo in improving chorea in pediatric and adult subjects with **dyskinesia due to cerebral palsy** (DCP) characterized by choreiform movements. This is clinically relevant as chorea significantly impacts the quality of life and daily functioning of individuals with DCP, and effective management could lead to improved patient outcomes.

Secondary objectives include:

• Evaluating the efficacy of valbenazine versus placebo on improving dyskinesia severity, functioning, pain, and quality of life in subjects with DCP and choreiform movements.
• Assessing the safety and tolerability of valbenazine administered once daily, including the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs).

The clinical trial involves a total of **44 participants** diagnosed with **dyskinesia due to cerebral palsy (DCP)**, characterized by choreiform movements. The study population includes both **male and female subjects**, encompassing a broad **age range** from children to adults. Participants were selected based on a medically confirmed diagnosis of DCP, with their medical conditions being stable and expected to remain so throughout the study. The trial includes a vulnerable population, indicating careful consideration of ethical standards in participant selection. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **Phase 3, randomized, double-blind, placebo-controlled** study designed to assess the efficacy, safety, and tolerability of **Valbenazine** for the treatment of **dyskinesia due to cerebral palsy (DCP)**. The primary objective is to evaluate the efficacy of Valbenazine versus placebo in improving chorea in pediatric and adult subjects with DCP. The trial is expected to run from October 2023 to January 2026, with an estimated duration of 12 weeks for each participant's involvement. Participants will be randomly assigned to receive either Valbenazine or a matching placebo, administered orally in the form of hard capsules.

The study will include several key visits: an initial **screening visit** to confirm eligibility based on inclusion criteria such as a medically confirmed diagnosis of DCP with choreiform movements and stable medical conditions. Following randomization, participants will attend regular follow-up visits to monitor efficacy and safety outcomes. The primary endpoint is the change in the Total Maximal Chorea (TMC) score of the Unified Huntington Disease Rating Scale (UHDRS) from baseline to the average of the Week 12 and Week 14 assessments. Secondary endpoints include changes in the Clinical Global Impression of Severity (CGI-S) score, Movement Disorders - Childhood Rating Scale (MD-CRS) Part I score, and other relevant measures.

The end-of-study visit will occur at Week 14, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if their medical condition worsens. The trial is not categorized as low intervention, and it involves a drug not currently authorized for the indication being studied. The study aims to provide valuable data on the potential benefits of Valbenazine in managing dyskinesia associated with cerebral palsy.

The clinical trial involves the administration of **Valbenazine**, a chemical compound known as valbenazine ditosylate, provided in the form of hard capsules. The pharmaceutical product is manufactured by Neurocrine Biosciences Inc. The trial includes several dosing regimens of Valbenazine, with the maximum daily doses being 30 mg, 40 mg, 60 mg, and 80 mg, depending on the specific formulation. The maximum treatment periods for these doses are 88 days, 96 days, 28 days, and 12 days, respectively. The administration route for Valbenazine is oral, and the dosing schedule is designed to ensure participant compliance, with monitoring mechanisms in place to track adherence to the prescribed regimen.

In addition to the experimental medication, the study utilizes a **matching placebo** for Valbenazine. The placebo is designed to mimic the appearance of the active drug to maintain the double-blind nature of the trial. The placebo does not contain any active pharmaceutical ingredients and serves as a comparator to evaluate the efficacy and safety of Valbenazine in treating dyskinesia due to cerebral palsy. The placebo is administered orally, following the same dosing schedule as the active treatment to ensure consistency in the trial protocol.

The efficacy of **Valbenazine** in the treatment of dyskinesia due to cerebral palsy will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change in the Total Maximal Chorea (TMC) score of the Unified Huntington Disease Rating Scale (UHDRS) from baseline to the average of the Week 12 and Week 14 assessments. This endpoint is designed to measure the improvement in chorea, a key symptom of the condition.

Secondary endpoints include several measures to evaluate broader aspects of the condition and treatment impact. These include the change in the Clinical Global Impression of Severity (CGI-S) score from baseline to Week 14, and the change in the Movement Disorders - Childhood Rating Scale (MD-CRS) Part I score from baseline to the average of the Week 12 and Week 14 assessments. Additional secondary endpoints involve the change in the Total Maximal Dystonia (TMD) score of the UHDRS, the Patient Global Impression of Improvement (PGI-I) score, the Caregiver Global Impression of Improvement (CaGI-I) score, and the Clinical Global Impression of Improvement (CGI-I) score, all assessed at Week 14. The Goal Attainment Scale (GAS) will be used to measure goal attainment at Week 14, and the Faces Pain Scale-Revised (FPS-R) will assess changes in pain from baseline to Week 14. The UHDRS Total Motor Score (TMS) will also be evaluated from baseline to the average of the Week 12 and Week 14 assessments.

These efficacy parameters will be collected and analyzed at specified timepoints, including baseline, Week 12, and Week 14, using validated scales and patient-reported outcomes. The trial is structured to provide a comprehensive assessment of the efficacy of Valbenazine in improving symptoms and overall condition in patients with dyskinesia due to cerebral palsy.