Recruiting
Phase 2

Mivelsiran

Sponsor:

Alnylam Pharmaceuticals

Code:

NCT07636811

Conditions

Down Syndrome-Associated Alzheimer's Disease (DS-AD)

Eligibility Criteria

Sex: All

Age: 40 - 55

Healthy Volunteers: Not accepted

Interventions

Mivelsiran

Placebo

Study Details

Brief summary:

The purpose of the study is to evaluate the effect of mivelsiran in adult participants with early-stage DS-AD and to characterize the safety, tolerability, and pharmacodynamics (PD) of mivelsiran. The study will be conducted over 2 periods: a 24-month double-blind period and an optional 12-month open-label treatment extension (OLE) period. The estimated duration of study participation, inclusive of screening, treatment, and additional safety follow-up, is up to 39 months.

Conditions

Down Syndrome-Associated Alzheimer's Disease (DS-AD)

Study ID

NCT07636811

Start date

Aug 17, 2026

Status verified date

Oct, 2026

Completion date

Jul 30, 2031

Anticipated

Primary completion date

May 18, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Clinical diagnosis of Down-Syndrome (DS) associated with trisomy 21
  • Positive amyloid PET scan
  • Cognitively stable in the opinion of the investigator
  • Seizures must be well controlled with no occurrence of seizures in the 6 months prior to screening

Exclusion Criteria:

  • Has severe intellectual disability (ID)
  • Has a history of DS regression disorder
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2×upper limit of normal (ULN) at Screening
  • Has estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m\^2 at Screening
  • Has recently received an investigational agent
  • Has had treatment with amyloid-targeting antibody
  • Comorbidities such as obstructive sleep apnea and hypothyroidism that are not well controlled

Note: other protocol defined inclusion / exclusion criteria apply

Study Design

Enrollment

58 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Mivelsiran (Treatment Group A)

Participants will be administered multiple low doses of mivelsiran.

experimental: Mivelsiran (Treatment Group B)

Participants will be administered multiple high doses of mivelsiran.

placebo comparator: Placebo (Treatment Group C)

Participants will be administered multiple doses of placebo.

Interventions

Mivelsiran

Mivelsiran will be administered intrathecally

Placebo

Placebo will be administered intrathecally

Primary outcome measure

  • Double-Blind Period: Change from baseline in brain amyloid burden measured in centiloids (CLs) [ Time Frame: Up to 24 months ]

Central Contacts and Locations

Central contacts

Alnylam Clinical Trial Information Line

1-877-ALNYLAMclinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

1-877-256-9526clinicaltrials@alnylam.com

Locations

Clinical Trial Site

Recruiting

Maitland, Florida, United States, 32751

Clinical Trial Site

Recruiting

Naples, Florida, United States, 34105

Clinical Trial Site

Recruiting

Indianapolis, Indiana, United States, 46037

Clinical Trial Site

Recruiting

St Louis, Missouri, United States, 63110

More Information

Sponsor

Alnylam Pharmaceuticals

Last update posted

Oct 13, 2026

Last verified

Oct, 2026

Keywords

  • Alzheimer's; DS-AD; Down Syndrome; ALZ

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-25. This information was provided to ClinicalTrials.gov by Alnylam Pharmaceuticals on 2026-10-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.