Down Syndrome-Associated Alzheimer's Disease (DS-AD)
Conditions
Keywords
Alzheimer's; DS-AD; Down Syndrome; ALZ
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.
Interventions
DRUGMivelsiran
Mivelsiran will be administered intrathecally
DRUGPlacebo
Placebo will be administered intrathecally
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 55 Years
Healthy volunteers
No
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 /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Double-Blind Period: Change from baseline in brain amyloid burden measured in centiloids (CLs) | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Spain, United States
Contacts
CONTACTAlnylam Clinical Trial Information Line
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Outcome results
None listed