A DOSE-BLINDED EXTENSION STUDY TO EVALUATE THE LONG-TERM EFFICACY, SAFETY, AND TOLERABILITY OF UCB0599 IN STUDY PARTICIPANTS WITH PARKINSON’S DISEASE

The primary objective of this study is to estimate the **pharmacodynamic** effects of minzasolmin (UCB0599) on brain pathophysiology in participants with early-start versus delayed-start treatment, who were originally diagnosed with new onset **Parkinson's disease**. This objective is clinically relevant as it aims to understand the impact of minzasolmin on the progression of brain changes associated with Parkinson's disease, potentially informing treatment strategies and improving patient outcomes.

Secondary objectives include estimating the pharmacodynamic effects of minzasolmin on the need for symptomatic treatment in early-start versus delayed-start participants, and assessing the safety and tolerability of minzasolmin in participants with new onset Parkinson's disease. These objectives are crucial for evaluating the overall therapeutic profile of minzasolmin, ensuring its efficacy and safety for long-term use in managing Parkinson's disease symptoms.

The clinical trial involves a total of **131 participants** diagnosed with **Parkinson's disease**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their completion of a previous treatment period in study PD0053, with the baseline visit for the current study (PD0055) scheduled within four weeks following the end of treatment in the prior study. The trial includes individuals who are capable of providing informed consent and are compliant with contraceptive guidelines if applicable. The study population is characterized by a vulnerable group, as it includes individuals with a new onset of Parkinson's disease. Participants' general health status is not specified beyond their diagnosis, and no specific lifestyle considerations such as diet or physical activity are detailed in the available data.

The clinical trial is designed to evaluate the long-term efficacy, safety, and tolerability of **minzasolmin** in participants with **Parkinson's disease**. This study is a randomized, double-blind, controlled trial, which includes a placebo group to ensure the reliability of the results. The trial is expected to run until April 2027, with recruitment having started in November 2022. Participants will be involved in the study for a duration that includes multiple visits over an 18-month period, with the primary endpoint being the baseline-adjusted Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) whole striatum specific binding ratio at Month 18.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as completion of a prior treatment period and agreement to use contraception. This is followed by a baseline visit, which must occur no later than four weeks after the end of treatment in the previous study. Subsequent follow-up visits are scheduled to monitor the pharmacodynamic effects of the investigational product and to assess safety and efficacy outcomes. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include the occurrence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) that lead to withdrawal from the study. The study protocol outlines that participants must adhere to the requirements and restrictions specified in the informed consent form, and any deviation from these may also result in early termination. The investigational product, **minzasolmin**, is administered orally in a capsule form, with a maximum daily dose of 360 mg, while the placebo is designed to match the investigational product in appearance but contains no active substance.

The clinical trial involves the administration of **UCB0599**, a hard capsule formulation containing the active substance **minzasolmin**. This investigational medication is administered orally with a maximum daily dose of 360 mg. The treatment period for UCB0599 is set to a maximum of 30 days. The medication is developed by UCB Biopharma SPRL and is intended for participants diagnosed with Parkinson's disease. The study aims to evaluate the long-term efficacy, safety, and tolerability of UCB0599.

A placebo matching UCB0599 is also utilized in the study. This placebo is designed to mimic the appearance of the UCB0599 capsules but does not contain any active substance. The placebo serves as a control to assess the effects of the investigational drug against a non-active comparator. The placebo is administered in the same manner as UCB0599, ensuring blinding of the study participants and investigators.

Additionally, the study employs **Iodine Ioflupane (123I)**, a radiopharmaceutical used as an auxiliary substance. It is administered as a solution for injection with a maximum dose of 74 MBq. Iodine Ioflupane (123I) is utilized for imaging purposes to assess brain pathophysiology in participants. The administration of this substance is limited to a single day during the trial. This auxiliary treatment aids in evaluating the pharmacodynamic effects of UCB0599 on brain function in participants with Parkinson's disease.

The efficacy of the investigational product UCB0599, containing the active substance **minzasolmin**, will be assessed in a clinical trial involving participants with Parkinson's disease. The primary endpoint for evaluating efficacy is the baseline-adjusted Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) whole striatum specific binding ratio (SBR) at Month 18 of the trial (PD0055). This imaging technique will provide insights into the pharmacodynamic effects of minzasolmin on brain pathophysiology.

Secondary endpoints include the Cumulative Levodopa Equivalent Daily Dose (LEDD) at Month 18, as well as the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to withdrawal from the study. These parameters will be measured and collected at specified timepoints throughout the trial to ensure comprehensive analysis of the drug's efficacy and safety profile. The trial is designed to provide a robust evaluation of the long-term efficacy, safety, and tolerability of UCB0599 in participants with Parkinson's disease.