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

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.

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