Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of NIO752 in Progressive Supranuclear Palsy

A Randomized, Participant, Investigator and Sponsor Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of Intrathecally Administered NIO752 in Participants With Progressive Supranuclear Palsy

This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation study with NIO752 in progressive supranuclear palsy (PSP) participants.

Study Overview

• Status: Completed
• Conditions: Progressive Supranuclear Palsy (PSP)
• Intervention / Treatment: Drug: antisense oligonucleotide; Drug: placebo

Detailed Description

This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation study with NIO752 in progressive supranuclear palsy (PSP) participants.

Approximately 58 PSP participants in 5 cohorts will be randomized to receive NIO752 or placebo in a ratio of 3:1. Intrathecal (IT) injections will be given multiple times over 3 months and participants will remain in study for an additional 9-month follow-up period; or will be given multiple times over 9 months and participants will remain in study for an additional 3-month follow-up period.

Cohorts will be enrolled sequentially.

Safety assessments will include physical and neurological examinations, ECGs, vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), CSF laboratory test, adverse event, and serious adverse event monitoring.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 1R9
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 2B4
      • Novartis Investigative Site
• Germany
  • Düsseldorf, Germany, 40225
    • Novartis Investigative Site
  • Hanover, Germany, 30625
    • Novartis Investigative Site
  • München, Germany, 81377
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Novartis Investigative Site
• United Kingdom
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Tennessee
    • Nashville, Tennessee, United States, 37221
      • Vanderbilt University Medical CenterX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. Between 40 to 75 years old (inclusive)
3. Have PSP diagnosed for less than 5 years with a current classification of probable PSP Richardson syndrome, a progressive supranuclear palsy rating scale (PSPRS) score < 40 and MOCA score >17 at screening
4. Be able to ambulate independently or able to take at least 5 steps with minimal assistance
5. At least a 12-month history of postural instability or falls within 3 years from disease onset as per medical history
6. Vertical supranuclear gaze palsy, or reduced velocity of vertical saccade

7. Able and willing to meet all study requirements including:

   Have a study partner who is reliable, competent, and at least 18 years of age, and will be able to accompany the participant to study visits, be knowledgeable of the participant's ongoing condition during the study to provide study related information to study site when required both in person and via a phone Reside in a proximity to the study site to allow a timely unscheduled visit if necessary (ideally less than 2 hours) Able to undergo lumbar puncture (LP), CSF draws and blood draws

8. If the participant is receiving levodopa/carbidopa, levodopa/benserazide, a dopamine agonist, catechol-o-methyltransferase (COMT) inhibitor, rasagiline, CoQ10 or other Parkinson's medications, acetylcholinesterase inhibitors, antipsychotics, memantine, or other non-tau modifying Alzheimer's medication the dose must have been stable for at least 30 days prior to the screening visit and must remain stable for the duration of the study. No such medication can be initiated during the study.

Exclusion Criteria:

1. Live in a skilled nursing facility or dementia care facility
2. Evidence of motor neuron disease, or any other neurological disease that could explain symptoms
3. Clinically significant laboratory abnormality
4. Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening. In addition, patients deemed by the Investigator to be at significant risk of suicide, major depressive episode, psychosis, confusion state, or violent behavior should be excluded.
5. A clear and robust benefit from levodopa by history
6. Use of lithium, methylene blue or other putative disease modifying drugs for PSP within 30 days of screening
7. Any previous use of experimental therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater
8. Any condition that increases risk of meningitis unless participant is receiving appropriate prophylactic treatment
9. History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch

11. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study 12. Unable to undergo magnetic resonance imaging (MRI) due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator) 13. Patients with other significant brain MRI abnormalities by history or at screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A NIO752; 4 injections of NIO752 at dose A	Drug: antisense oligonucleotide; solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels; Other Names: NIO752
Experimental: Cohort B NIO752; 4 injections of NIO752 at dose B	Drug: antisense oligonucleotide; solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels; Other Names: NIO752
Placebo Comparator: Placebo; 4 injections of placebo	Drug: placebo; placebo for each dose level
Experimental: Cohort C NIO752; 4 injections of NIO752 at dose C	Drug: antisense oligonucleotide; solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels; Other Names: NIO752
Experimental: Cohort D NIO752; 4 injections of NIO752 at dose D	Drug: antisense oligonucleotide; solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels; Other Names: NIO752
Experimental: Cohort E NIO752; 4 injections of NIO752 at dose E	Drug: antisense oligonucleotide; solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels; Other Names: NIO752

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events and serious adverse events	Adverse events will be collected at clinical visits and other contacts. All abnormalities from safety assessments (physical exams and neurological exams and clinical safety labs) considered clinically significant will be recorded as adverse events	Baseline up to approximately one year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)
Change in severity scores for Columbia-Suicide Severity Rating Scale (C-SSRS)	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire that prospectively assesses Suicidal Ideation and Suicidal Behavior. The C-SSRS must be administered at visits. If, at any time after "screening and/or baseline" version, the score is "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS or "yes" on any item of the Suicidal Behavior section, the participant must be referred to a mental health care professional for further assessment and/or treatment.	Baseline up to approximately 1 year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)
Levels of infection indicators in Cerebrospinal fluid (CSF)	CSF safety labs measure levels of proteins, glucose, lactate and white blood cell counts with differential indicating infections.	Baseline up to approximately 1 year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of NIO752 in blood plasma	concentrations of NIO752 in plasma	From the 1st dose administration (day 1), through study completion, where the longest duration would be approximately 1 year for those who receive 4 treatment doses
Concentrations of NIO752 in CSF	concentrations of NIO752 in CSF	From the 1st dose administration (day 1), through study completion, where the longest duration would be approximately 1 year for those who receive 4 treatment doses
Cmax, Ctrough in blood plasma	Maximum and trough level concentrations of NIO752 in plasma	From the 1st dose administration (day 1), through study completion, where the longest duration would be approximately 1 year for those who receive 4 treatment doses
Tmax in blood plasma	Time of Cmax in plasma post first injection	From the 1st dose administration (day 1), through study completion, where the longest duration would be approximately 1 year for those who receive 4 treatment doses
AUClast in blood plasma	Area under curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)	0 to 24 hours after first injection
AUCinf in blood plasma	The AUC from time zero to infinity (mass x time x volume-1)	0 to 24 hours after first injection

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Link to study results
• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): October 17, 2024
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Estimated): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: adult; tau; PSP; ASO; antisense oligonucleotide; progressive supranuclear palsy; NIO752
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Eye Diseases; Dementia; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Frontotemporal Lobar Degeneration; Frontotemporal Dementia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pick Disease of the Brain; Supranuclear Palsy, Progressive; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; Chemical Actions and Uses; Specialty Uses of Chemicals; Nucleotides; Laboratory Chemicals; Antisense Elements (Genetics); Polynucleotides; Nucleic Acid Probes; Oligonucleotides; Molecular Probes; Oligonucleotides, Antisense
• Other Study ID Numbers: CNIO752A02101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No