Early-Onset Alzheimer DiseasePhase 1NCT05231785
A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD
A Phase 1 study testing ALN-APP in people with Early-Onset Alzheimer Disease, run by Alnylam Pharmaceuticals at 8 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early-Onset Alzheimer Disease
- What is being tested?
- ALN-APP
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 4 Feb 2022to 11 Jan 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
8 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 4 countries
United States2 sites, 1 recruiting
- Recruiting
Clinical Trial Site
Indianapolis, Indiana, 46202
- Completed
Clinical Trial Site
La Jolla, California, 92037
Canada2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Montreal, H3A 2B4
- Recruiting
Clinical Trial Site
Toronto, M3B 2S7
Netherlands2 sites, 1 recruiting
- Recruiting
Clinical Trial Site
Amsterdam, 1081 BT
- Completed
Clinical Trial Site
Groningen, 9713 GG
United Kingdom2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Huntley Street, WC1E 6AG
- Recruiting
Clinical Trial Site
Sheffield, S10 2JF
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Single Ascending Dose and Open-label Multi-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ALN-APP in Adult Patients With Early-onset Alzheimer's Disease (EOAD)
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.
- Conditions
- Early-Onset Alzheimer Disease
- Being tested
- ALN-APP, Placebo
- Keywords
- EOAD
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-APPDrug
Also called mivelsiran
ALN-APP will be administered intrathecally (IT)
PlaceboDrug
Placebo will be administered IT
| Study group | Role | What they receive |
|---|---|---|
| Part A: ALN-APP | Experimental | Participants will be administered a single dose of ALN-APP. Receives: Drug: ALN-APP |
| Part A: Placebo | Placebo comparator | Participants will be administered a single dose of placebo. Receives: Drug: Placebo |
| Part B: | Experimental | Participants will be administered multiple doses of ALN-APP. Receives: Drug: ALN-APP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Frequency of Adverse Events
Measured: Up to 12 months
Part B: Frequency of Adverse Events
Measured: Up to 42 months
Secondary outcomes (5)
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)
Measured: 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
Measured: 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
Measured: 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)
Measured: Up to 1 day
Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF
Measured: Part A up to 12 months; Part B up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start4 Feb 2022
- Primary completion11 Jan 2029 (estimated)
- Study completion11 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-Onset Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231785
- Sponsor's protocol ID
- ALN-APP-001
- Other IDs
- 2023-508363-79-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 30 Jan 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No