Alzheimer DiseasePhase 1NIO-SILKNCT06372821
A Trial Evaluating the Effect of NIO752 on Tau Synthesis Measured by a Process Known as SILK
A Phase 1 study testing NIO752 in people with Alzheimer Disease and Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder), run by University College, London at 2 sites in 2 countries.
Trial summary
This study will assess if drug (NIO752) reduces production of a protein, tau, by the brain. Normally tau maintains the internal skeleton of nerve cells. In Alzheimer's disease (AD) it builds up in the brain, causing damage. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Alzheimer Disease, Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder), Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2 (Disorder)
- What is being tested?
- NIO752
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 18 Nov 2024to Jul 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide signed informed consent.
- Between 21 to 80 years old (inclusive).
- 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.
- 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.
- Fluency in English
- Participant has a reliable study partner or caregiver
- Able to undergo lumbar punctures, magnetic resonance imaging (MRI), cerebrospinal fluid draws, and blood draws.
- Individuals will be willing to consent for their biological samples and personal data to be shared with the commercial partner (Novartis)
Who cannot join
- Live in a skilled nursing facility or dementia care facility.
- Any clinically significant laboratory abnormality
- Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening
- Any previous use of experimental therapy within 180 days or 5 half-lives prior to Day 1, whichever is greater.
- Any previous use of MAPT antisense oligonucleotides (ASO) or any other ASO or other gene therapy meant as treatment for Alzheimer's disease.
- History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
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- Any condition that increases risk of meningitis unless participant is receiving appropriate prophylactic treatment.
- Current medical or non-Alzheimer's disease neurological condition that might impact cognition or performance on cognitive assessments
- 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.
- 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.
- 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.
- 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.
- Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
- Significant signs of major cerebrovascular disease
- 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.
- Breast feeding women, pregnant women, and females of reproductive potential unless they use highly effective contraception methods, as specified in the protocol.
- Patients on regular anticoagulants or anti-platelets that would preclude lumbar puncture are not eligible to participate
- Seropositive for human immunodeficiency virus (HIV), Hepatitis B or hepatitis C.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Lisa French contact
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Washington University in St. Louis
St Louis, Missouri, 63110
Tina Nolte, 314-362-3839, nolte.tina@wustl.edu
Nupur Ghoshal, MD, PhD
United Kingdom1 site, 1 recruiting
- Recruiting
University College London Hospitals NHS Foundation Trust
London, NW1 2PG
Joe Mwanza, +44(0)2034567890, joe.mwanza@nhs.net
Ross Paterson
About this study
Official title: 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 study will assess if drug (NIO752) reduces production of a protein, tau, by the brain. Normally tau maintains the internal skeleton of nerve cells. In Alzheimer's disease (AD) it builds up in the brain, causing damage. Abnormal tau proteins cling to each other forming 'tangles' inside nerve cells, which interfere with how the nerve cells work, and eventually die. This is what causes the symptoms of dementia. It is thought that NIO752 reduces production of tau.
- Conditions
- Alzheimer Disease, Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder), Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2 (Disorder), Autosomal Dominant Alzheimer Disease Due to Mutation of Amyloid Precursor Protein (Disorder)
- Being tested
- NIO752, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIO752Drug
Antisense oligonucleotide
PlaceboOther
Saline
| Study group | Role | What they receive |
|---|---|---|
| NIO752 | Experimental | Intrathecal administration. Receives: Drug: NIO752 |
| Saline | Placebo comparator | 10mL of saline (placebo) is administered intrathecally. Receives: Drug: NIO752; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tau synthesis rate inhibition in individuals with sporadic AD and ADAD
Tau synthesis rate calculated using tracer to tracee ratio of tau specific peptide calculated on day 20 post leucine administration in individuals with sporadic and ADAD (analyzed collectively) receiving intrathecal NIO752 compared to placebo.
Measured: Day 23
Secondary outcomes (5)
Compare efficacy of knockdown of tau production in sporadic AD and ADAD by measuring the synthesis rate of tau by determining the ratio of labelled to unlabeled tau (tracer to tracee ratio) in serial cerebrospinal fluid samples.
Measured: Day 23
Number of participants with adverse events [safety and tolerability]
Measured: Day 0 to Day 145
Comparison of number of Adverse Events reported between participants receiving one dose of NIO752 versus those receiving two doses of NIO752.
Compare safety between 1 and 2 doses.
Measured: Day 0 to Day 145
Compare rates of tau synthesis and clearance in sporadic AD and ADAD
Measured: Day 23
Determine CSF tau concentration to tau production relationships in humans
Measured: 120 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start18 Nov 2024
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine, University of Washington, Alzheimer's Association, Sigrid Rausing Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06372821
- Sponsor's protocol ID
- 158160
- Acronym
- NIO-SILK
- Status last verified
- Jan 2026
- First submitted
- 13 Mar 2024
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06372821
- Acronym / sponsor ID
- NIO-SILK / 158160
- Conditions
- Alzheimer Disease, Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder), Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2 (Disorder), Autosomal Dominant Alzheimer Disease Due to Mutation of Amyloid Precursor Protein (Disorder)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Washington University School of Medicine, University of Washington, Alzheimer's Association, Sigrid Rausing Trust
- Study start
- 18 Nov 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 18 Apr 2024 (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 study will assess if drug (NIO752) reduces production of a protein, tau, by the brain. Normally tau maintains the internal skeleton of nerve cells. In Alzheimer's disease (AD) it builds up in the brain, causing damage. Abnormal tau proteins cling to each other forming 'tangles' inside nerve cells, which interfere with how the nerve cells work, and eventually die. This is what causes the symptoms of dementia. It is thought that NIO752 reduces production of tau.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIO752 | Experimental | Drug: NIO752Intrathecal administration. |
| Saline | Placebo comparator | Drug: NIO752, Other: Placebo10mL of saline (placebo) is administered intrathecally. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able to provide signed informed consent.
- Between 21 to 80 years old (inclusive).
- 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.
- 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.
- Fluency in English
Key exclusion criteria (18 listed)
- Live in a skilled nursing facility or dementia care facility.
- Any clinically significant laboratory abnormality
- Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening
- Any previous use of experimental therapy within 180 days or 5 half-lives prior to Day 1, whichever is greater.
- Any previous use of MAPT antisense oligonucleotides (ASO) or any other ASO or other gene therapy meant as treatment for Alzheimer's disease.
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 |
|---|---|---|
| NIO752Antisense oligonucleotide | Drug | NIO752, Saline |
| PlaceboSaline | Other | Saline |
Primary outcome
Tau synthesis rate inhibition in individuals with sporadic AD and ADAD
Time frame: Day 23
Tau synthesis rate calculated using tracer to tracee ratio of tau specific peptide calculated on day 20 post leucine administration in individuals with sporadic and ADAD (analyzed collectively) receiving intrathecal NIO752 compared to placebo.
5 secondary outcomes
Compare efficacy of knockdown of tau production in sporadic AD and ADAD by measuring the synthesis rate of tau by determining the ratio of labelled to unlabeled tau (tracer to tracee ratio) in serial cerebrospinal fluid samples.
Time frame: Day 23
Number of participants with adverse events [safety and tolerability]
Time frame: Day 0 to Day 145
Comparison of number of Adverse Events reported between participants receiving one dose of NIO752 versus those receiving two doses of NIO752.
Time frame: Day 0 to Day 145
Compare rates of tau synthesis and clearance in sporadic AD and ADAD
Time frame: Day 23
Determine CSF tau concentration to tau production relationships in humans
Time frame: 120 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- 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.
Lisa French contact
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NIO752 in people with Alzheimer Disease and Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder), run by University College, London at 2 sites in 2 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 8 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ross Paterson (+44(0)2074483875, r.paterson@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tau synthesis rate inhibition in individuals with sporadic AD and ADAD (time frame: Day 23). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2026.