NIO752 treatment for people with Progressive Supranuclear Palsy Richardson syndrome.

A Phase III, Randomized, Placebo-controlled, Parallel Group, Double-blind Study to Evaluate the Efficacy and Safety of NIO752 in Participants With Progressive Supranuclear Palsy Followed by an Open Label Extension

This trial will try NIO752 versus placebo in adults with mild-to-moderate PSP-RS to see if it slows symptom progression.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 41 Years to 81 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Locations: 2 sites (Englewood, Colorado and 1 other locations)
• Trial ID: NCT07498426 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled, parallel-group Phase 3 trial that assigns participants in a 2:1 ratio to NIO752 or placebo, followed by an open-label extension where participants can continue NIO752. NIO752 is an antisense oligonucleotide designed to reduce MAPT (tau) expression, with the goal of slowing neurodegeneration. Eligible participants are adults 41–81 years old with probable/possible PSP-RS of less than 5 years' duration, a PSPRS score under 40, MMSE ≥20, ability to walk at least 10 steps (with minimal assistance if needed), and a reliable study partner. The study includes regular clinical visits and informant-based assessments to measure changes in function, motor signs, and cognition over the double-blind period and extension.

Who should consider this trial

Good fit: Adults aged 41–81 with probable or possible PSP Richardson syndrome of under 5 years' duration, PSPRS <40, MMSE ≥20, able to take at least 10 steps (with minimal assistance if needed), and who have a reliable study partner are the intended participants.

Not a fit: People with more advanced PSP (longer disease duration or higher PSPRS), significant cognitive impairment (MMSE <20), inability to ambulate, or those outside the age range are unlikely to qualify or benefit from this trial.

Why it matters

Potential benefit: If successful, NIO752 could slow disease progression and help preserve function and daily abilities in people with PSP-RS.

How similar studies have performed: Tau-targeting antisense approaches are relatively novel in PSP and have shown limited or mixed results in early-phase studies, so clinical benefit remains unproven to date.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female participants, age between 41-81 yrs inclusive.
3. Diagnosis of mild-moderate, probable/possible PSP Richardson syndrome as per MDS-PSP 2017 criteria with symptoms onset \< 5 years.
4. PSPRS total score less than 40 at Baseline.
5. Reliable study partner such as spouse, sibling, close friend, or caregiver able and willing to provide accurate information (including clinical symptoms and medical history) about the participant and to participate in study visits and informant-based assessments for the duration of the study. A reliable study partner is expected to spend enough time (at least 5 hours per week) with the study participant.
6. Participant is able to ambulate defined as the ability to take at least 10 steps independently or with minimal assistance (stabilization of one arm to minimize fall risk).
7. Mini Mental State Examination (MMSE) score ≥ 20 at Screening.

Exclusion Criteria:

1. Diagnosis of other significant neurological or psychiatric disorders including (but not limited to) Parkinsons' Disease (which has not subsequently been revised to a diagnosis of PSP); Alzheimer's disease (AD), dementia with Lewy bodies; prion disease; any psychotic disorders; severe Major depressive disorder; seizure; brain tumor or other space-occupying lesion; history of clinically significant stroke (e.g., stroke with permanent neurological deficit); history of head injury with loss of consciousness for at least 15 minutes within the past 20 years.
2. Diagnosis of amyotrophic lateral sclerosis or other motor neuron diseases.
3. Diagnosis of cerebellar ataxia, choreoathetosis, and early symptomatic autonomic dysfunction.
4. History of or screening brain MRI scan indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct \>1 cm3, \>3 lacunar infarcts, cerebral contusion, aneurysm, vascular malformation \>1 cm3, subdural hematoma, hydrocephalus, and space-occupying lesion (e.g., abscess or brain tumor).
5. Contraindications to undergo MRI procedure, including metal (ferromagnetic) implants and/or a cardiac pacemaker that is not compatible with MRI.
6. Medical conditions that would, as per Investigator's judgement, prevent the participant from undergoing lumbar puncture, including but not limited to:

   1. Known allergy to local anesthetic
   2. History of back surgery (with the exception of microdiscectomy or laminectomy over 1 level)
   3. Spinal deformities
   4. Current dermatological infection at the lumbar puncture spot and/or significant skin alterations at the planned puncture place
   5. Risk of increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally, could place a participant at an increased risk for procedural bleeding. These could include, but are not limited, to anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms) and underlying disorders of coagulation, platelet function or platelet count (e.g. abnormal coagulation parameters, hemophilia, Von Willebrand's disease, liver disease).
7. History of deep brain stimulator surgery other than sham surgery for participation in a deep brain stimulation clinical trial.

Other protocol-defined inclusion/exclusion criteria may apply

Where this trial is running

Englewood, Colorado and 1 other locations

• CenExcel Rocky Mtn Clin Research — Englewood, Colorado, United States (Recruiting)
• Novartis Investigative Site — Ulm, Germany (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Progressive Supranuclear Palsy Richardson Syndrome; Progressive Supranuclear Palsy; NIO752; Anti-Sense Oligonucleotide; Microtubule Associated Protein Tau