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

Alnylam Pharmaceuticals

Status and phase: Begins enrollment this month; Phase 2

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

Treatments: Drug: Placebo; Drug: Mivelsiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT07636811

2025-523390-42-00 (EU Trial (CTIS) Number)

ALN-APP-003

Details and patient eligibility

About

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.

Enrollment: 58 estimated patients

Sex: All

Ages: 40 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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58 participants in 3 patient groups, including a placebo group

Mivelsiran (Treatment Group A)

Experimental group

Description:

Participants will be administered multiple low doses of mivelsiran.

Treatment:

Drug: Mivelsiran

Mivelsiran (Treatment Group B)

Experimental group

Description:

Participants will be administered multiple high doses of mivelsiran.

Treatment:

Drug: Mivelsiran

Placebo (Treatment Group C)

Placebo Comparator group

Description:

Participants will be administered multiple doses of placebo.

Treatment:

Drug: Placebo