Efficacy and Safety of NIO752 in Participants with Progressive Supranuclear Palsy Richardson Syndrome: A Phase III Randomized, Placebo-Controlled Study

The primary objective of this study is to evaluate the efficacy of NIO752 in slowing disease progression in individuals with Progressive Supranuclear Palsy, as measured by the rPSPRS-10 scale at week 72. Secondary objectives include:

• Evaluation of disease progression using the PSPRS-28 scale.
• Assessment of the effect on activities of daily living.
• Evaluation of quality of life.
• Assessment of cognition.
• Measurement of specific brain region volumes.
• Assessment of safety and tolerability.

This study involves 149 participants diagnosed with progressive supranuclear palsy Richardson syndrome. The population consists of both male and female individuals between the ages of 41 and 81 years. Inclusion requires a diagnosis of mild-to-moderate disease based on MDS-PSP 2017 criteria, with symptom onset occurring less than 5 years prior to enrollment. Eligible subjects must have a PSPRS total score of less than 40 at baseline and a Mini-Mental State Examination score of 20 or greater. Furthermore, participants must be able to ambulate independently or with minimal assistance. Each subject must be accompanied by a reliable study partner, such as a caregiver or family member, who is capable of providing clinical information and committing at least 5 hours per week to the participant.

This Phase III, randomized, placebo-controlled, parallel group, double-blind study is designed to evaluate the efficacy and safety of NIO752 compared to a placebo in individuals diagnosed with Progressive Supranuclear Palsy. Following the initial treatment period, participants may enter an Open Label Extension. The primary objective is to assess the change from baseline in the rPSPRS-10 score at week 72. The study involves several stages, beginning with a screening visit to confirm eligibility based on criteria such as age, symptom onset, PSPRS total score, and MMSE score. During the trial, participants receive either NIO752 or a placebo via intrathecal use. Secondary endpoints include assessments of the PSPRS-28, activities of daily living, quality of life via the PSP-ShoQoL, cognitive functions, and various brain volumes measured by MRI. Safety is monitored through clinical laboratory evaluations, vital signs, and electrocardiogram. Participant involvement is expected to continue through the end-of-study assessments following the 72-week treatment period.

The experimental medication is NIO752, provided as a concentrate for solution for injection. This substance is administered via the intrathecal route.

The control group receives a placebo consisting of sodium chloride 0.9% solution for infusion. This comparator is administered via intrathecal use.

The efficacy of NIO752 in participants with Progressive Supranuclear Palsy will be evaluated using the rPSPRS-10 score as the primary endpoint. This parameter is measured by calculating the change from baseline at Week 72.

Secondary efficacy assessments include the following evaluations performed at Week 72:

• Change from baseline in the PSPRS-28 score.
• Changes in activities of daily living.
• Change in the Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL).
• Changes in Category Fluency, Phonemic Fluency, Symbol Digit Modality Test (SDMT), and Letter-Number Sequencing (LNS).
• Changes from baseline in ventricle volumes, whole brain, midbrain, pons, superior cerebellar peduncle, third ventricle, and frontal lobe as measured by MRI until Week 72.