Progressive Supranuclear Palsy (PSP)Phase 1NCT04539041
Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of NIO752 in Progressive Supranuclear Palsy
A Phase 1 study testing antisense oligonucleotide in people with Progressive Supranuclear Palsy (PSP), run by Novartis Pharmaceuticals at 12 sites in 4 countries.
Trial summary
This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation study with NIO752 in progressive supranuclear palsy (PSP) participants. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Progressive Supranuclear Palsy (PSP)
- What is being tested?
- antisense oligonucleotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 16 Feb 2021to 17 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
- 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.
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
Germany6 sites
Novartis Investigative Site
Bonn, North Rhine-Westphalia, 53127
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
München, 81377
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Ulm, 89081
United States3 sites
University of California San Diego
La Jolla, California, 92037
Vanderbilt University Medical CenterX
Nashville, Tennessee, 37221
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H2X 1R9
Novartis Investigative Site
Montreal, Quebec, H3A 2B4
About this study
Official title: 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.
Read the 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.
- Conditions
- Progressive Supranuclear Palsy (PSP)
- Being tested
- antisense oligonucleotide, placebo
- Keywords
- progressive supranuclear palsy, PSP, antisense oligonucleotide, ASO, tau, NIO752, adult
- Medical subject headings
- Supranuclear Palsy, Progressive, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
antisense oligonucleotideDrug
Also called NIO752
solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels
placeboDrug
placebo for each dose level
| Study group | Role | What they receive |
|---|---|---|
| Cohort A NIO752 | Experimental | 4 injections of NIO752 at dose A Receives: Drug: antisense oligonucleotide |
| Cohort B NIO752 | Experimental | 4 injections of NIO752 at dose B Receives: Drug: antisense oligonucleotide |
| Placebo | Placebo comparator | 4 injections of placebo Receives: Drug: placebo |
| Cohort C NIO752 | Experimental | 4 injections of NIO752 at dose C Receives: Drug: antisense oligonucleotide |
| Cohort D NIO752 | Experimental | 4 injections of NIO752 at dose D Receives: Drug: antisense oligonucleotide |
| Cohort E NIO752 | Experimental | 4 injections of NIO752 at dose E Receives: Drug: antisense oligonucleotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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
concentrations of NIO752 in plasma
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 0 to 24 hours after first injection
AUCinf in blood plasma
The AUC from time zero to infinity (mass x time x volume-1)
Measured: 0 to 24 hours after first injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2020
- Study start16 Feb 2021
- Primary completion17 Oct 2024
- Study completion17 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Supranuclear Palsy (PSP)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04539041
- Sponsor's protocol ID
- CNIO752A02101
- Status last verified
- Dec 2025
- First submitted
- 25 Aug 2020
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rahim AA, Kurian MA, Zhou H, Ferguson R, Tabrizi SJ, Lignani G, Aquilina K, Waddington SN. Genetic therapies for neurological diseases. Pharmacol Rev. 2026 Jan;78(1):100093. doi: 10.1016/j.pharmr.2025.100093. Epub 2025 Oct 3.
PubMed 41389437
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04539041
- Acronym / sponsor ID
- CNIO752A02101
- Conditions
- Progressive Supranuclear Palsy (PSP)
- Keywords
- progressive supranuclear palsy, PSP, antisense oligonucleotide, ASO, tau, NIO752, adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Feb 2021 (actual)
- Primary completion
- 17 Oct 2024 (actual)
- Study completion
- 17 Oct 2024 (actual)
- First posted
- 4 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort A NIO752 | Experimental | Drug: antisense oligonucleotide4 injections of NIO752 at dose A |
| Cohort B NIO752 | Experimental | Drug: antisense oligonucleotide4 injections of NIO752 at dose B |
| Placebo | Placebo comparator | Drug: placebo4 injections of placebo |
| Cohort C NIO752 | Experimental | Drug: antisense oligonucleotide4 injections of NIO752 at dose C |
| Cohort D NIO752 | Experimental | Drug: antisense oligonucleotide4 injections of NIO752 at dose D |
| Cohort E NIO752 | Experimental | Drug: antisense oligonucleotide4 injections of NIO752 at dose E |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| antisense oligonucleotideAlso: NIO752solution of antisense oligonucleotide injected intrathecally (spine tap) at multiple dose levels | Drug | Cohort A NIO752, Cohort B NIO752, Cohort C NIO752, Cohort D NIO752, Cohort E NIO752 |
| placeboplacebo for each dose level | Drug | Placebo |
Primary outcome
Number of adverse events and serious adverse events
Time frame: Baseline up to approximately one year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)
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
Change in severity scores for Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline up to approximately 1 year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)
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.
Levels of infection indicators in Cerebrospinal fluid (CSF)
Time frame: Baseline up to approximately 1 year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)
CSF safety labs measure levels of proteins, glucose, lactate and white blood cell counts with differential indicating infections.
6 secondary outcomes
Concentrations of NIO752 in blood plasma
Time frame: 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
Time frame: 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
Time frame: 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 frame: 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
Time frame: 0 to 24 hours after first injection
AUCinf in blood plasma
Time frame: 0 to 24 hours after first injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2025.
- Derived from this study: PubMed 41389437Rahim AA, Kurian MA, Zhou H, Ferguson R, Tabrizi SJ, Lignani G, Aquilina K, Waddington SN. Genetic therapies for neurological diseases. Pharmacol Rev. 2026 Jan;78(1):100093. doi: 10.1016/j.pharmr.2025.100093. Epub 2025 Oct 3.
- Link to study resultsLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing antisense oligonucleotide in people with Progressive Supranuclear Palsy (PSP), run by Novartis Pharmaceuticals at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, United States, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events and serious adverse events (time frame: Baseline up to approximately one year (3-month treatment plus 9-month follow-up or 9-month treatment plus 3-month follow-up)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04539041, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2025.