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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05231785
- Acronym / sponsor ID
- ALN-APP-001
- Conditions
- Early-Onset Alzheimer Disease
- Keywords
- EOAD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Feb 2022 (actual)
- Primary completion
- 11 Jan 2029 (estimated)
- Study completion
- 11 Jan 2029 (estimated)
- First posted
- 9 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A: ALN-APP | Experimental | Drug: ALN-APPParticipants will be administered a single dose of ALN-APP. |
| Part A: Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered a single dose of placebo. |
| Part B: | Experimental | Drug: ALN-APPParticipants will be administered multiple doses of ALN-APP. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALN-APPAlso: mivelsiranALN-APP will be administered intrathecally (IT) | Drug | Part A: ALN-APP, Part B: |
| PlaceboPlacebo will be administered IT | Drug | Part A: Placebo |
Primary outcome
Part A: Frequency of Adverse Events
Time frame: Up to 12 months
Part B: Frequency of Adverse Events
Time frame: Up to 42 months
5 secondary outcomes
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)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Up to 1 day
Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF
Time frame: Part A up to 12 months; Part B up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Director study director
Alnylam Pharmaceuticals
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-APP in people with Early-Onset Alzheimer Disease, run by Alnylam Pharmaceuticals at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alnylam Clinical Trial Information Line (1-877-ALNYLAM, clinicaltrials@alnylam.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Frequency of Adverse Events (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.