A Study to Evaluate the Efficacy of NIO752 in Participants With Progressive Supranuclear Palsy

May 25, 2026 updated by: Novartis Pharmaceuticals

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 Phase III study is intended to evaluate the efficacy and safety of NIO752 in participants with Progressive Supranuclear Palsy (PSP). Eligible participants will be randomized to receive either NIO752 or placebo followed by an open-label extension.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel group, study to evaluate the efficacy of NIO752 in participants with Progressive Supranuclear Palsy followed by an open-label extension (OLE).

The participants with or without symptomatic therapy will be randomly allocated to either NIO752 or placebo treatment in a 2:1 randomization ratio.

Upon completion of the core double-blind treatment period, participants will be offered to continue with NIO752 treatment in the OLE.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Novartis Investigative Site
      • Stadtroda, Germany, 07646
        • Recruiting
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Recruiting
        • Novartis Investigative Site
    • Saxony
      • Leipzig, Saxony, Germany, 04103
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Recruiting
        • CenExcel Rocky Mtn Clin Research
        • Principal Investigator:
          • Meagen Salinas
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NIO752
NIO752 solution
Other: NIO752
Solution of antisense oligonucleotide.
Placebo Comparator: Placebo
Placebo in solution
Drug: Placebo
Placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in the mPSPRS-10 score
Time Frame: Baseline, Week 72
The 10-item Progressive Supranuclear Palsy Rating Scale (mPSPRS-10) is a modified version of the original 28 item PSPRS developed to improve clinical meaningfulness and statistical performance. The 10 items measure three key motor domains: gait, limb function, and bulbar. The mPSPRS-10 ranges between 0 and 30, with higher scores indicating greater disability.
Baseline, Week 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in the PSPRS-28 items score
Time Frame: Baseline, Week 72
28-item Progressive Supranuclear Palsy Rating Scale (PSPRS-28) , scale ranges between 0 and 100 with higher scores indicating greater disability.
Baseline, Week 72
Changes from baseline in activities of daily living on the Cortical Basal ganglia Functional Scale (CBFS)
Time Frame: From baseline up to week 72

The CBFS is a patient/study partner reported rating scale designed to evaluate the functional impact of 4 repeat tauopathies (4RTs), including PSP. The level of disability assessed by the CBFS correlates with motor, cognitive and psychiatric impairments.

The CBFS consists of 14 questions on Motor experiences in daily living (EDL's) and 17 questions on non-Motor EDL's, each rated on a Likert 5-point scale that goes from 0 (Normal/No problems) to 4 (Severe problems).
From baseline up to week 72
Change from baseline on the PSP-ShoQoL
Time Frame: From baseline up to week 72
The Progressive Supranuclear Palsy - Short version Quality of Life (PSP-ShoQoL) is a patient reported outcome that comprises 12 items, covering phyisical (7 items) and mental health (5 items) states. Items are scored from 0 (no problem) to 4 (extreme problems), total score ranges from 0 to 48 with higher scores indicating greater impact of the disease on the quality of life.
From baseline up to week 72
Change from baseline in Category (or Semantic) Fluency test over time
Time Frame: From baseline up to week 72
The Category Fluency test is a measure of semantic retrieval and executive functions. It requires the study participant to name as many objects as possible belonging to a given category within one minute. The total score is given by the number of correct words generated within the time limit.
From baseline up to week 72
Change from baseline in Letter (or Phonemic) Fluency test over time
Time Frame: From baseline up to week 72
The Letter Fluency test is a measure of language and executive functions. It requires the study participant to name as many words as possible starting with a certain letter within one minute. The total score is given by the number of correct words generated within the time limit.
From baseline up to week 72
Change from baseline in Symbol Digit Modality Test (SDMT) over time
Time Frame: From baseline up to week 72
The SDMT is a measure of attention and processing speed. It requires the study participant to orally pair specific numbers with symbols as quickly and as accurately as possible using a reference key.
From baseline up to week 72
Change from baseline in Letter-Number Sequencing task (LNS) over time
Time Frame: From baseline up to week 72
The LNS is a sub-test of the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) and it is a measure of working memory and executive function. The study participant is read a sequence of numbers and letters and is required to recall the numbers in ascending order followed by the letters in alphabetical order.
From baseline up to week 72
Ratio to baseline of NfL (CSF)
Time Frame: From baseline up to week 72
Neurofilament light chain (NfL) is a specific marker of neuroaxonal damage. NfL in CSF will be used to assess the effect of NIO752 on neurodegeneration.
From baseline up to week 72
Ratio to baseline of CSF phospho-Tau-181 and CSF Total-Tau
Time Frame: From baseline up to week 72
Ratio to baseline in Total -Tau and Phospho-Tau-181 will be used as measures of target engagement
From baseline up to week 72
Changes from baseline in volumes of brain structures as measured by MRI
Time Frame: From baseline up to week 72
MRI measured volumes will be collected for ventricles, whole brain, midbrain, pons, superior cerebellar peduncle, third ventricle and frontal lobe
From baseline up to week 72
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From first treatment administration up to 72 weeks
Incidence and severity of AEs and SAEs by treatment group, including clinical laboratory evaluations, vital signs, ECG, C-SSRS qualifying and reported as AEs.
From first treatment administration up to 72 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 29, 2026

Primary Completion (Estimated)

July 20, 2029

Study Completion (Estimated)

July 18, 2031

Study Registration Dates

First Submitted

March 23, 2026

First Submitted That Met QC Criteria

March 23, 2026

First Posted (Actual)

March 27, 2026

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 25, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CNIO752A12301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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