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

NCT ID: NCT04539041

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-16

Study Completion Date

2024-10-17

Brief Summary

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

Detailed Description

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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.

Conditions

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Progressive Supranuclear Palsy (PSP)

Keywords

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progressive supranuclear palsy PSP antisense oligonucleotide ASO tau NIO752 adult

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort A NIO752

4 injections of NIO752 at dose A

Group Type EXPERIMENTAL

antisense oligonucleotide

Intervention Type DRUG

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

Cohort B NIO752

4 injections of NIO752 at dose B

Group Type EXPERIMENTAL

antisense oligonucleotide

Intervention Type DRUG

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

Placebo

4 injections of placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo for each dose level

Cohort C NIO752

4 injections of NIO752 at dose C

Group Type EXPERIMENTAL

antisense oligonucleotide

Intervention Type DRUG

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

Cohort D NIO752

4 injections of NIO752 at dose D

Group Type EXPERIMENTAL

antisense oligonucleotide

Intervention Type DRUG

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

Cohort E NIO752

4 injections of NIO752 at dose E

Group Type EXPERIMENTAL

antisense oligonucleotide

Intervention Type DRUG

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

Interventions

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antisense oligonucleotide

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

Intervention Type DRUG

placebo

placebo for each dose level

Intervention Type DRUG

Other Intervention Names

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NIO752

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California San Diego

La Jolla, California, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

Vanderbilt University Medical CenterX

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Bonn, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Düsseldorf, , Germany

Site Status

Novartis Investigative Site

Hanover, , Germany

Site Status

Novartis Investigative Site

München, , Germany

Site Status

Novartis Investigative Site

Tübingen, , Germany

Site Status

Novartis Investigative Site

Ulm, , Germany

Site Status

Novartis Investigative Site

Southampton, , United Kingdom

Site Status

Countries

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United States Canada Germany United Kingdom

Related Links

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Other Identifiers

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CNIO752A02101

Identifier Type: -

Identifier Source: org_study_id