Antisense Oligonucleotide for Progressive Supranuclear Palsy

Recruiting at 17 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Lithium, Methylene blue, others

Disqualifiers: Motor neuron disease, Major depressive episode, others

Compensation: Varies

Number of Visits: 4

Duration: 3-9 months

59 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, NIO752, for people with progressive supranuclear palsy (PSP). The drug is injected into the spinal fluid to help it reach the brain. The goal is to find out if NIO752 can better manage PSP symptoms.

Do I need to stop my current medications to join the trial?

You can continue taking your current medications if they are stable for at least 30 days before the screening and remain stable during the study. However, you cannot start any new medications during the trial.

What data supports the effectiveness of the drug NIO752 for Progressive Supranuclear Palsy?

Research on similar antisense oligonucleotide drugs shows promise in treating neurological diseases like Parkinson's by reducing harmful protein levels in the brain, suggesting potential for NIO752 in treating Progressive Supranuclear Palsy. ^{1 2 3 4 5}

Is there any safety data available for antisense oligonucleotide treatments in humans?

Research on antisense oligonucleotides (ASOs) for Parkinson's disease in mice suggests they can be safe when targeted to the brain, avoiding unwanted side effects in other body parts. ^{6 7 8 9 10}

How is the drug NIO752 different from other treatments for progressive supranuclear palsy?

NIO752 is an antisense oligonucleotide, which is a type of genetic therapy that targets and modifies the production of specific proteins involved in progressive supranuclear palsy, unlike current treatments that are mainly supportive and symptomatic. This approach is novel as it aims to directly address the underlying disease mechanism rather than just alleviating symptoms. ^{6 10 11 12 13}

Eligibility Criteria

This trial is for adults aged 40-75 with Progressive Supranuclear Palsy (PSP) diagnosed within the last 5 years, able to walk independently or with minimal assistance. Participants must have a history of postural instability or falls and score below certain thresholds on PSP and cognitive scales. They need a reliable study partner and can't be in nursing care, recently hospitalized, or show significant benefit from levodopa.

Inclusion Criteria

My Parkinson's or Alzheimer's medication dose has been stable for at least 30 days.

I have difficulty moving my eyes up or down quickly.

I can safely have lumbar punctures and blood tests.

Exclusion Criteria

I have a diagnosed neurological condition that could explain my symptoms.

You have recently shown signs of wanting to harm yourself or others, have had a major episode of feeling very sad, confused, or violent.

You live in a nursing home or a place for people with memory problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple intrathecal injections of NIO752 or placebo over 3 or 9 months

3-9 months

4 injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

3-9 months

Treatment Details

Interventions

• NIO752
• Placebo

Trial Overview The trial tests multiple doses of NIO752, an antisense oligonucleotide against placebo in people with PSP. It's double-blind meaning neither participants nor researchers know who gets the real treatment versus placebo. The goal is to assess safety, tolerability, and how the body processes the drug.

Participant Groups

Group I: Cohort E NIO752 Experimental Treatment 1 Intervention

4 injections of NIO752 at dose E

Group II: Cohort D NIO752 Experimental Treatment 1 Intervention

4 injections of NIO752 at dose D

Group III: Cohort C NIO752 Experimental Treatment 1 Intervention

4 injections of NIO752 at dose C

Group IV: Cohort B NIO752 Experimental Treatment 1 Intervention

4 injections of NIO752 at dose B

Group V: Cohort A NIO752 Experimental Treatment 1 Intervention

4 injections of NIO752 at dose A

Group VI: Placebo Placebo Group 1 Intervention

4 injections of placebo

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

A new quantitative MRI analysis method was developed to measure disease progression in progressive supranuclear palsy (PSP), using data from 99 patients in two clinical trials, which can help in designing future studies.

The study identified that changes in the volumes of the third ventricle, midbrain, and frontal lobe are effective indicators of disease progression, requiring fewer patients to detect treatment efficacy compared to traditional clinical scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. Höglinger, GU., Schöpe, J., Stamelou, M., et al.[2018]

The NNIPPS study developed a new clinical rating scale to assess disease severity in Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), demonstrating high reliability and validity across 362 PSP and 398 MSA patients over a 3-year period.

The scale effectively correlates with survival rates and shows responsiveness to disease progression, indicating it can be a valuable tool for evaluating treatment effects in clinical studies of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale. Payan, CA., Viallet, F., Landwehrmeyer, BG., et al.[2022]

In a study involving 187 patients with progressive supranuclear palsy (PSP), the PSP-Rating Scale was identified as the most efficient measure for detecting significant changes in disease progression, requiring only 51 patients per group for a 50% change over one year.

The study found no detectable placebo effect on the PSP-Rating Scale or the Schwab and England Activities of Daily Living, suggesting that these scales can reliably assess treatment efficacy in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. Stamelou, M., Schöpe, J., Wagenpfeil, S., et al.[2021]

There is currently no effective treatment for progressive supranuclear palsy (PSP), as most studies have shown negative outcomes and there are no randomized controlled trials to establish therapeutic standards.

The review highlights the ongoing challenges in developing effective therapies for PSP and suggests that future strategies may be needed to address this unmet medical need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward future therapies in progressive supranuclear palsy. Burn, DJ., Warren, NM.[2005]

References

1. United States pubmed.ncbi.nlm.nih.gov

α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson's disease. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson's disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Antisense therapies for movement disorders. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Progress and promise of antisense oligonucleotide therapeutics for central nervous system diseases. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Design and application of a peptide nucleic acid sequence targeting the p75 neurotrophin receptor. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efaroxan, an alpha-2 antagonist, in the treatment of progressive supranuclear palsy. [2012]

10. United States pubmed.ncbi.nlm.nih.gov

Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Progressive supranuclear palsy diagnosis and confounding features: report on 16 autopsied cases. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Progressive supranuclear palsy: Advances in diagnosis and management. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Toward future therapies in progressive supranuclear palsy. [2005]