A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD

Conditions

Early-Onset Alzheimer Disease

Keywords

EOAD

Brief summary

The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose and multiple doses of ALN-APP administered by intrathecal (IT) injection in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment duration for Part B: 12 months.

Dominique Taillie, Diana Cha, Gina Ferraro, K Bittner, Alexandre Sostelly et al. (7 authors)

Alzheimer s & Dementia2025-12-01

10.1002/alz70859_098351

Multiple‐Dose Results from an Ongoing Phase 1 Study of Mivelsiran, an Investigational RNA Interference Therapeutic Targeting Amyloid‐Beta Precursor Protein for Alzheimer’s Disease

Sharon Cohen, Simon Ducharme, Jared R. Brosch, Everard G.B. Vijverberg, D. Blackburn et al. (12 authors)

Alzheimer s & Dementia2025-12-01

10.1002/alz70859_097989

Single ascending dose results from an ongoing Phase 1 study of mivelsiran (ALN‐APP), the first investigational RNA interference therapeutic targeting amyloid precursor protein for Alzheimer’s disease

Sharon Cohen, Simon Ducharme, Jared R. Brosch, Everard G.B. Vijverberg, Alexandre Sostelly et al. (10 authors)

Alzheimer s & Dementia2024-12-016 citations

10.1002/alz.084521

Interim phase 1 part A results for ALN‐APP, the first investigational RNAi therapeutic in development for Alzheimer’s disease

Sharon Cohen, Simon Ducharme, Jared R. Brosch, Everard G.B. Vijverberg, Liana G. Apostolova et al. (12 authors)

Alzheimer s & Dementia2023-12-0112 citations

10.1002/alz.082650

Interventions

DRUGALN-APP

ALN-APP will be administered intrathecally (IT)

DRUGPlacebo

Placebo will be administered IT

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Has mild cognitive impairment or mild dementia due to EOAD * Has Clinical Dementia Rating (CDR) global score 0.5 or 1.0 and Mini Mental State Examination (MMSE) \>20

Exclusion criteria

* Has Non-Alzheimer's disease dementia * Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2×upper limit of normal (ULN) * Has estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m\^2 at Screening * Has recently received an investigational agent * Has recent treatment with amyloid-targeting antibody Note: other protocol defined inclusion /

Design outcomes

Primary

Measure	Time frame
Part A: Frequency of Adverse Events	Up to 12 months
Part B: Frequency of Adverse Events	Up to 42 months

Secondary

Measure	Time frame
Part A and Part B: Change from Baseline in Levels of Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein Alpha (sAPPα) and Soluble Amyloid Precursor Protein Beta (sAPPβ)	Part A up to 12 months; Part B up to 24 months
Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites	Part A up to 12 months; Part B up to 24 months
Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites	Part A up to 12 months; Part B up to 24 months
Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)	Up to 1 day
Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF	Part A up to 12 months; Part B up to 24 months

Countries

Canada, Netherlands, United Kingdom, United States

Contacts

CONTACTAlnylam Clinical Trial Information Line

clinicaltrials@alnylam.com1-877-ALNYLAM

STUDY_DIRECTORMedical Director

Alnylam Pharmaceuticals

Outcome results

None listed