Antisense Oligonucleotide for Progressive Supranuclear Palsy

No longer recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NIO752 (an antisense oligonucleotide) for progressive supranuclear palsy (PSP), a brain disorder affecting movement, balance, and eye movement. Researchers aim to determine the safety and effectiveness of NIO752 by comparing different doses against a placebo (a substance with no active drug). Suitable participants have had a PSP diagnosis for less than five years and experience issues like frequent falls or trouble with eye movement. The trial seeks to learn more about NIO752's effectiveness and potential side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the safety of NIO752 in humans remains under investigation. This phase 1 clinical trial represents an early stage in testing the drug's safety. Phase 1 trials typically involve a small number of participants to identify any side effects and assess how the body processes the treatment.

Previous studies may not clearly indicate how individuals react to NIO752. The goal is to learn more about its safety and how people with progressive supranuclear palsy respond to the drug. Researchers closely monitor participants for any health changes, including unusual lab results or other side effects.

Overall, while NIO752 appears promising, more information is needed to fully understand its safety. Participants in the current trial will contribute to gathering this crucial information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for progressive supranuclear palsy?

Researchers are excited about NIO752 because it offers a novel approach to treating Progressive Supranuclear Palsy (PSP). Unlike current treatments, which mainly focus on managing symptoms, NIO752 uses antisense oligonucleotides to target the genetic underlying causes of the disease. This new mechanism of action could potentially slow down or even halt disease progression, offering hope for more effective long-term management of PSP. Additionally, with multiple dosage options being tested, there is the potential to fine-tune treatment effectiveness and safety for patients.

What evidence suggests that NIO752 might be an effective treatment for progressive supranuclear palsy?

Research has shown that treatments like NIO752, known as antisense oligonucleotides, might help with progressive supranuclear palsy (PSP). These treatments target specific genetic material to reduce the production of harmful proteins that cause PSP symptoms. Although no effective treatment currently exists for PSP, early studies suggest that reducing these proteins might slow the disease's progression. In this trial, participants will receive either NIO752 at various doses or a placebo. Specific clinical data on NIO752's effectiveness for PSP patients is not yet available, but the scientific rationale is strong. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. psp-blog.org psp-blog.org/2024/12/11/nio752-update/

NIO752 update The Phase 1 NIO752 trial ended a month or so ago and Novartis, apparently, is still crunching the numbers. It's typical for that to take 2 or 3 months.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11710339/

Cross‐species systems biology target prioritization leads to ... We plan to translate our findings into safe and effective treatments for PSP using antisense oligonucleotides (ASO).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04539041

Study Details | NCT04539041 | Safety, Tolerability and ... This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation study with NIO752 in progressive supranuclear palsy (PSP) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04539041?term=AREA%5BBasicSearch%5D(antisense%20oligonucleotide)&rank=6

Study Details | Safety, Tolerability and Pharmacokinetics of ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. withpower.com withpower.com/trial/phase-1-supranuclear-palsy-progressive-1-2021-5d636

Antisense Oligonucleotide for Progressive Supranuclear ... There is currently no effective treatment for progressive supranuclear palsy (PSP), as most studies have shown negative outcomes and there are no randomized ...

6. novctrd.com novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18339

Sponsor Generic Drug Name Trial Indication(s) Protocol ... These safety and tolerability data coupled with PK findings support the future development of NIO752 in the PSP program. Date of Clinical Trial ...

7. psp-blog.org psp-blog.org/tag/nio752/

NIO752 For clinicians, patients and families fighting progressive supranuclear palsy ... data analyzed, the drug's safety remains unknown in ...

8. ctv.veeva.com ctv.veeva.com/study/safety-tolerability-and-pharmacokinetics-of-multiple-ascending-doses-of-nio752-in-progressive-supra

Safety, Tolerability and Pharmacokinetics of Multiple ... This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation study with NIO752 in progressive supranuclear palsy (PSP) ...