Down Syndrome-Associated Alzheimer's Disease (DS-AD)Phase 2NCT07636811
A Study to Evaluate Mivelsiran in Adult Participants With Early-Stage Down Syndrome-Associated Alzheimer's Disease (DS-AD)
A Phase 2 study testing Mivelsiran in people with Down Syndrome-Associated Alzheimer's Disease (DS-AD), run by Alnylam Pharmaceuticals at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 55 years
- Conditions the study is for
- Down Syndrome-Associated Alzheimer's Disease (DS-AD)
- What is being tested?
- Mivelsiran
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 17 Aug 2026to 30 Jul 2031
- Phase
- Phase 2
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 40 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 2 countries
Spain6 sites, 6 recruiting
- Recruiting
Clinical Trial Site
Barcelona
- Recruiting
Clinical Trial Site
Dos Hermanas
- Recruiting
Clinical Trial Site
Madrid
- Recruiting
Clinical Trial Site
Pamplona
- Recruiting
Clinical Trial Site
Seville
- Recruiting
Clinical Trial Site
Valencia
United States4 sites, 4 recruiting
- Recruiting
Clinical Trial Site
Indianapolis, Indiana, 46037
- Recruiting
Clinical Trial Site
Maitland, Florida, 32751
- Recruiting
Clinical Trial Site
Naples, Florida, 34105
- Recruiting
Clinical Trial Site
St Louis, Missouri, 63110
About this study
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study, to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Intrathecally Administered Mivelsiran in Adult Participants With Early-Stage Down Syndrome-Associated Alzheimer's Disease (DS-AD)
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.
- Being tested
- Mivelsiran, Placebo
- Keywords
- Alzheimer's; DS-AD; Down Syndrome; ALZ
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MivelsiranDrug
Also called ALN-APP
Mivelsiran will be administered intrathecally
PlaceboDrug
Placebo will be administered intrathecally
| Study group | Role | What they receive |
|---|---|---|
| Mivelsiran (Treatment Group A) | Experimental | Participants will be administered multiple low doses of mivelsiran. Receives: Drug: Mivelsiran |
| Mivelsiran (Treatment Group B) | Experimental | Participants will be administered multiple high doses of mivelsiran. Receives: Drug: Mivelsiran |
| Placebo (Treatment Group C) | Placebo comparator | Participants will be administered multiple doses of placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Double-Blind Period: Change from baseline in brain amyloid burden measured in centiloids (CLs)
Measured: Up to 24 months
Secondary outcomes (5)
Double-Blind Period: Change from baseline in APP protein concentration in cerebrospinal fluid (CSF)
Measured: Up to 24 months
Double-Blind Period: Change from baseline in the concentration of amyloid beta proteins in CSF
Measured: Up to 24 months
Double-Blind Period: Change from baseline in the concentration of tau proteins in plasma
Measured: Up to 24 months
Double-Blind Period: Change from baseline on a cognitive scale
Measured: Up to 24 months
Double-blind Period and Open-label Extension (OLE) Period: Frequency of adverse events (AEs)
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2026
- Study start17 Aug 2026
- Primary completion18 May 2030 (estimated)
- Study completion30 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down Syndrome-Associated Alzheimer's Disease (DS-AD)Studies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07636811
- Sponsor's protocol ID
- ALN-APP-003
- Other IDs
- 2025-523390-42-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 4 Jun 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.