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

NCT04539041 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CNIO752A02101
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 12

Brief Summary

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

Conditions

Progressive Supranuclear Palsy (PSP)

Keywords

progressive supranuclear palsy; PSP; antisense oligonucleotide; ASO; tau; NIO752; adult

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Concentrations of NIO752 in blood 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

  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

  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

  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

  0 to 24 hours after first injection

Study Arms (6)

Cohort A NIO752

EXPERIMENTAL

4 injections of NIO752 at dose A

Drug: antisense oligonucleotide

Cohort B NIO752

EXPERIMENTAL

4 injections of NIO752 at dose B

Drug: antisense oligonucleotide

Placebo

PLACEBO COMPARATOR

4 injections of placebo

Drug: placebo

Cohort C NIO752

EXPERIMENTAL

4 injections of NIO752 at dose C

Drug: antisense oligonucleotide

Cohort D NIO752

EXPERIMENTAL

4 injections of NIO752 at dose D

Drug: antisense oligonucleotide

Cohort E NIO752

EXPERIMENTAL

4 injections of NIO752 at dose E

Drug: antisense oligonucleotide

Interventions

antisense oligonucleotide DRUG

solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels

Also known as: NIO752

Cohort A NIO752; Cohort B NIO752; Cohort C NIO752; Cohort D NIO752; Cohort E NIO752

placebo DRUG

placebo for each dose level

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Between 40 to 75 years old (inclusive)
• 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
• Be able to ambulate independently or able to take at least 5 steps with minimal assistance
• At least a 12-month history of postural instability or falls within 3 years from disease onset as per medical history
• Vertical supranuclear gaze palsy, or reduced velocity of vertical saccade
• 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
• 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.

You may not qualify if:

• Live in a skilled nursing facility or dementia care facility
• Evidence of motor neuron disease, or any other neurological disease that could explain symptoms
• Clinically significant laboratory abnormality
• 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.
• A clear and robust benefit from levodopa by history
• Use of lithium, methylene blue or other putative disease modifying drugs for PSP within 30 days of screening
• Any previous use of experimental therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater
• Any condition that increases risk of meningitis unless participant is receiving appropriate prophylactic treatment
• History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
• \. 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

University of California San Diego

La Jolla, California, 92037, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Vanderbilt University Medical CenterX

Nashville, Tennessee, 37221, United States

Location

Novartis Investigative Site

Montreal, Quebec, H2X 1R9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3A 2B4, Canada

Location

Novartis Investigative Site

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Pick Disease of the Brain

Interventions

Oligonucleotides, Antisense

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Antisense Elements (Genetics); Nucleic Acids, Nucleotides, and Nucleosides; Nucleic Acid Probes; Nucleic Acids; Oligonucleotides; Polynucleotides; Nucleotides; Molecular Probes; Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: September 4, 2020
• Study Start: February 16, 2021
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); DE (6); GB (1); US (3)