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

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Early-Onset Alzheimer Disease

Treatments: Drug: Placebo; Drug: ALN-APP

Study type: Interventional

Funder types: Industry

Identifiers

NCT05231785

2023-508363-79-00 (Other Identifier)

ALN-APP-001

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 / exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

60 participants in 3 patient groups, including a placebo group

Part A: ALN-APP

Experimental group

Description:

Participants will be administered a single dose of ALN-APP.

Treatment:

Drug: ALN-APP

Part A: Placebo

Placebo Comparator group

Description:

Participants will be administered a single dose of placebo.

Treatment:

Drug: Placebo

Part B:

Experimental group

Description:

Participants will be administered multiple doses of ALN-APP.

Treatment:

Drug: ALN-APP