NCT06372821: NIO-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

Recruiting now Phase 1 Last updated 23 January 2026

What this trial tests

Phase 1 trial testing NIO752 in Alzheimer Disease in 10 participants. Currently enrolling.

Timeline

18 November 2024

Primary endpoint
1 July 2026

1 July 2026

Quick facts

Lead sponsor	University College, London
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	10
Start date	18 November 2024
Primary completion	1 July 2026
Estimated completion	1 July 2026
Sites	2 locations across United States, United Kingdom

Drugs / interventions tested

• NIO752 — full drug profile →
• Placebo

Conditions studied

• Alzheimer Disease — all drugs for Alzheimer Disease →
• Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder) — all drugs for Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder) →
• Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2 (Disorder) — all drugs for Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 2 (Disorder) →
• Autosomal Dominant Alzheimer Disease Due to Mutation of Amyloid Precursor Protein (Disorder) — all drugs for Autosomal Dominant Alzheimer Disease Due to Mutation of Amyloid Precursor Protein (Disorder) →

Sponsor

University College, London

Who can join

Adults 21 to 80, any sex, with Alzheimer Disease or Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder). Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.
   Sharma A, Rudrawar S, Bharate SB, Jadhav HR. · · 2025 · cited 14× · PMID 39790124 · DOI 10.1039/d4md00630e
2. Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials.
   Harris GA, Hirschfeld LR, Gonzalez MI, Pritchard MC, et al · · 2025 · cited 8× · PMID 40462159 · DOI 10.1186/s13195-025-01775-x
3. Biologics as Therapeutical Agents Under Perspective Clinical Studies for Alzheimer's Disease.
   Li H, Shen X, Zhang B, Zhu Z. · · 2025 · cited 7× · PMID 40942007 · DOI 10.3390/molecules30173479
4. CTAD taskforce: genetic therapies in Alzheimer's disease.
   Jakabek D, Isaacs AM, De Strooper B, Tuszynski M, et al · · 2025 · cited 3× · PMID 40634156 · DOI 10.1016/j.tjpad.2025.100269
5. Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.
   Shen X, Li H, Zhang B, Li Y, et al · · 2025 · cited 1× · PMID 41090735 · DOI 10.3390/cells14191506
6. Alzheimer's disease drug development pipeline: 2026.
   Cummings JL, Zhou Y, Yang Y, Zhong K, et al · · 2026 · PMID 42095064 · DOI 10.1002/trc2.70251
7. Health effects of loss of function variants in gene targets for Alzheimer's disease prevention.
   Ma Y, Zhang A, Asri S, Curtis D. · · 2025 · PMID 41123760 · DOI 10.1007/s10072-025-08578-w