A Study to Evaluate Mivelsiran in Adult Participants With Early-Stage Down Syndrome-Associated Alzheimer's Disease (DS-AD)

NCT07636811 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ALN-APP-0032025-523390-42-00
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Double-Blind Period: Change from baseline in brain amyloid burden measured in centiloids (CLs)

  Up to 24 months

Secondary Outcomes (5)

• Double-Blind Period: Change from baseline in APP protein concentration in cerebrospinal fluid (CSF)

  Up to 24 months

• Double-Blind Period: Change from baseline in the concentration of amyloid beta proteins in CSF

  Up to 24 months

• Double-Blind Period: Change from baseline in the concentration of tau proteins in plasma

  Up to 24 months

• Double-Blind Period: Change from baseline on a cognitive scale

  Up to 24 months

• Double-blind Period and Open-label Extension (OLE) Period: Frequency of adverse events (AEs)

  Up to 36 months

Study Arms (3)

Mivelsiran (Treatment Group A)

EXPERIMENTAL

Participants will be administered multiple low doses of mivelsiran.

Drug: Mivelsiran

Mivelsiran (Treatment Group B)

EXPERIMENTAL

Participants will be administered multiple high doses of mivelsiran.

Drug: Mivelsiran

Placebo (Treatment Group C)

PLACEBO COMPARATOR

Participants will be administered multiple doses of placebo.

Drug: Placebo

Interventions

Mivelsiran DRUG

Mivelsiran will be administered intrathecally

Also known as: ALN-APP

Mivelsiran (Treatment Group A); Mivelsiran (Treatment Group B)

Placebo DRUG

Placebo will be administered intrathecally

Placebo (Treatment Group C)

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (2)

Clinical Study Site

Maitland, Florida, 32751, United States

Location

Clinical Study Site

Naples, Florida, 34105, United States

Location

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM; clinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 9, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 18, 2030
• Study Completion (Estimated): July 23, 2031
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)