What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease include cholinesterase inhibitors (e.g., donepezil, rivastigmine) and NMDA receptor antagonists (e.g., memantine). Cholinesterase inhibitors can cause side effects such as nausea, vomiting, diarrhea, muscle cramps, and fatigue. Memantine may cause dizziness, headache, confusion, and constipation. Investigational drugs like ALN-APP, which target Alzheimer's pathology, may have unique side effects that are still being studied, but could include injection site reactions, headache, and potential neuropsychiatric symptoms. It is important to discuss these potential side effects with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Alzheimer's Disease, primarily focusing on symptomatic relief and disease modification. Notable among these are cholinesterase inhibitors like donepezil, rivastigmine, and galantamine, which help manage symptoms by increasing levels of acetylcholine in the brain. Additionally, memantine, an NMDA receptor antagonist, is approved for moderate to severe Alzheimer's Disease. More recently, aducanumab, a monoclonal antibody targeting amyloid-beta plaques, was approved as the first disease-modifying therapy aimed at reducing amyloid plaques in the brain, similar to the investigational drug ALN-APP, which also targets Alzheimer's Disease pathology.

What other types of research exist?

Promising novel alternatives to ALN-APP for Alzheimer's Disease patients in 2024 include: 1) Lecanemab, an anti-amyloid beta protofibril antibody recently approved by the FDA, which has shown efficacy in slowing cognitive decline. 2) Donanemab, another anti-amyloid antibody targeting amyloid plaques, currently in late-stage clinical trials. 3) Tau-targeting therapies such as semorinemab, which aim to reduce tau pathology and are in advanced clinical trials. 4) BACE inhibitors like elenbecestat, which reduce amyloid-beta production, though their development has faced challenges. These alternatives represent the forefront of AD treatment research and offer potential options for patients.

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RNAi Therapeutics

ALN-APP for Alzheimer's Disease

Phase 1

Recruiting

Research Sponsored by Alnylam Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has mild cognitive impairment or mild dementia due to EOAD

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up part a up to 12 months; part b up to 24 months

Awards & highlights

Study Summary

This trial is to study the safety of a single dose of ALN-APP, a new drug for Alzheimer's, in adults. Part A is a single dose, and Part B is 12 months.

Who is the study for?

This trial is for adults with early-onset Alzheimer's Disease (EOAD) who have mild cognitive impairment or dementia. Participants should have a CDR score of 0.5 or 1.0 and an MMSE score over 20, indicating some memory issues but not severe dementia. People can't join if they have poor kidney function, recently took experimental drugs, suffer from non-Alzheimer's dementias, or have certain liver enzyme levels that are too high.Check my eligibility

What is being tested?

The study tests the safety and effects of ALN-APP given through spinal injection to EOAD patients compared to a placebo group receiving no active treatment. The drug's behavior in the body (pharmacokinetics) and its impact on disease processes (pharmacodynamics) will be monitored for up to one year.See study design

What are the potential side effects?

While specific side effects aren't listed here, common ones may include discomfort at the injection site, potential allergic reactions to components of ALN-APP, headache, nausea, back pain and possible changes in cognition or mood.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have mild memory problems or mild dementia from early-onset Alzheimer's.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ part a up to 12 months; part b up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~part a up to 12 months; part b up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and part a up to 12 months; part b up to 24 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Part A: Frequency of Adverse Events

Part B: Frequency of Adverse Events

Secondary outcome measures

Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites

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 and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF

+2 more

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Part B:Experimental Treatment1 Intervention

Participants will be administered multiple doses of ALN-APP.

Group II: Part A: ALN-APPExperimental Treatment1 Intervention

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

Group III: Part A: PlaceboPlacebo Group1 Intervention

Participants will be administered a single dose of placebo.

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The investigational drug ALN-APP targets amyloid precursor protein (APP) to reduce the production of amyloid-beta, a protein that forms plaques in the brains of Alzheimer's Disease patients. Similar treatments include aducanumab, which targets amyloid-beta plaques to reduce their accumulation, and cholinesterase inhibitors (donepezil, rivastigmine, galantamine), which increase acetylcholine levels to improve cognitive function. These treatments are important as they aim to address the underlying pathology of Alzheimer's Disease or improve symptoms, thereby managing disease progression and enhancing the quality of life for patients.