NIO752 to reduce tau production measured with SILK

A Randomized, Participant & Investigator Blinded, Placebo-Controlled Study to Evaluate the Ability of Intrathecally Administered NIO752 to Lower CSF Total Tau Synthesis in Participants With AD Measured by Stable Isotope Labelling Kinetics

This Phase 1 trial will test whether the drug NIO752 lowers production of the tau protein in people with mild to moderate Alzheimer's disease or with genetic APP/PSEN mutations.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 21 Years to 80 Years
• Sex: All
• Sponsor: University College, London (Academic / other)
• Locations: 2 sites (St Louis, Missouri and 1 other locations)
• Trial ID: NCT06372821 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 interventional trial comparing NIO752 with placebo to measure effects on tau synthesis using the SILK (stable isotope labeling kinetics) method and cerebrospinal fluid sampling. Participants are adults aged 21–80 with mild to moderate Alzheimer's disease or symptomatic APP/PSEN mutation carriers and must have biomarker evidence of Alzheimer's pathology or confirmatory testing. The study includes lumbar punctures, MRI, blood draws, and clinical assessments to evaluate drug effect on tau production and safety. The goal is to characterize pharmacodynamic effects and early safety signals to inform later-stage development.

Who should consider this trial

Good fit: Ideal candidates are adults 21–80 with mild to moderate Alzheimer’s disease or symptomatic APP/PSEN mutation carriers who have biomarker evidence of AD, a reliable study partner, and are able to undergo lumbar punctures, MRI, and blood draws.

Not a fit: Patients with advanced dementia, no biomarker evidence of Alzheimer pathology, inability to undergo required procedures, or who cannot comply with study visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, lowering tau production could reduce tau buildup in the brain and potentially slow cognitive decline.

How similar studies have performed: Other tau-lowering approaches such as antisense oligonucleotides and small molecules have shown biomarker changes in early studies but have limited proven clinical benefit to date, so the approach is promising but still experimental.

Eligibility criteria

Inclusion Criteria:

1. Able to provide signed informed consent.
2. Between 21 to 80 years old (inclusive).
3. A diagnosis of mild or moderate Alzheimer's disease by a Clinical Dementia Rating score of 0.5 to 2, where the investigator believes they will be able to complete the study.
4. A history of cerebrospinal fluid, Positron Emission Topography (PET), or blood-based biomarkers supporting the diagnosis of Alzheimer's disease, or symptomatic approved presenilin (PSEN) or amyloid precursor protein (APP) mutation carriers. If blood biomarkers are equivocal then amyloid status can be confirmed using cerebrospinal fluid.
5. Fluency in English
6. Participant has a reliable study partner or caregiver
7. Able to undergo lumbar punctures, magnetic resonance imaging (MRI), cerebrospinal fluid draws, and blood draws.
8. Individuals will be willing to consent for their biological samples and personal data to be shared with the commercial partner (Novartis)

Exclusion Criteria:

1. Live in a skilled nursing facility or dementia care facility.
2. Any clinically significant laboratory abnormality
3. Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening
4. Any previous use of experimental therapy within 180 days or 5 half-lives prior to Day 1, whichever is greater.
5. Any previous use of MAPT antisense oligonucleotides (ASO) or any other ASO or other gene therapy meant as treatment for Alzheimer's disease.
6. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
7. Any condition that increases risk of meningitis unless participant is receiving appropriate prophylactic treatment.
8. Current medical or non-Alzheimer's disease neurological condition that might impact cognition or performance on cognitive assessments
9. Have any other conditions which, in the opinion of the investigator, would make the participant unsuitable for inclusion or could interfere with the patient participating in or completing the study.
10. Unlikely to cooperate in the study; not able to attend scheduled examinations and visits; or not able to follow study instructions per the judgement of the investigator.
11. Current alcohol (\>14 units per week) or current cannabis use; or history of alcohol or drug abuse or dependence (except nicotine dependence) within 2-years before the screening visit.
12. Treatment with immunosuppressants, antipsychotics, lithium, neuroleptics, dopaminergic agonists, L-dopa, or monoamine oxidase inhibitors at the time of screening. Current use of medications, other than cholinesterase inhibitors and/or memantine, that could alter cognition, as determined by the Investigator. If patients are taking cholinesterase inhibitors and/or memantine at screening, the dose must have been stable within 12-weeks prior to screening and must remain stable during the duration of the study.
13. Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
14. Significant signs of major cerebrovascular disease
15. Sexually active males, unless they agree to use a condom during intercourse from the time of consent until a minimum of 15 weeks after treatment.
16. Breast feeding women, pregnant women, and females of reproductive potential unless they use highly effective contraception methods, as specified in the protocol.
17. Patients on regular anticoagulants or anti-platelets that would preclude lumbar puncture are not eligible to participate
18. Seropositive for human immunodeficiency virus (HIV), Hepatitis B or hepatitis C.

Where this trial is running

St Louis, Missouri and 1 other locations

• Washington University in St. Louis — St Louis, Missouri, United States (Recruiting)
• University College London Hospitals NHS Foundation Trust — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Ross Paterson

Conditions Alzheimer Disease; Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1; Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2; Autosomal Dominant Alzheimer Disease Due to Mutation of Amyloid Precursor Protein