ALN-APP for Alzheimer's Disease

Recruiting at9 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Alnylam Pharmaceuticals

Must not be taking: Amyloid antibodies

Disqualifiers: Non-Alzheimer's dementia, High ALT/AST, Low eGFR, others

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called ALN-APP, given through a spinal injection, in adults with early-onset Alzheimer's Disease. The goal is to see if it is safe and how it behaves in the body. The treatment aims to reduce a protein linked to Alzheimer's to slow down the disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have recently received an investigational agent or treatment with an amyloid-targeting antibody, you may not be eligible to participate.

How is the drug ALN-APP for Alzheimer's disease different from other drugs?

The drug ALN-APP is unique because it is being tested specifically for Alzheimer's disease, whereas other treatments like idebenone and acetyl-L-carnitine have been used for cognitive impairment in Alzheimer's but with varying results. ALN-APP's specific mechanism of action or administration details are not provided, making it distinct from existing options that have shown limited efficacy. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Eligibility Criteria

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.

Inclusion Criteria

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

You have mild cognitive impairment with a specific score on two different memory tests.

Exclusion Criteria

Your ALT or AST levels are more than twice the normal limit.

My kidney function is reduced, with an eGFR below 45.

My condition is dementia, but not Alzheimer's disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of ALN-APP or placebo administered by intrathecal injection

Single dose

Treatment Part B

Participants receive multiple doses of ALN-APP administered by intrathecal injection over 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ALN-APP (RNAi Therapeutics)
• Placebo (Other)

Trial Overview 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.

Participant Groups

Group I: Part B: Experimental Treatment 1 Intervention

Participants will be administered multiple doses of ALN-APP.

Group II: Part A: ALN-APP Experimental Treatment 1 Intervention

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

Group III: Part A: Placebo Placebo Group 1 Intervention

Participants will be administered a single dose of placebo.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Findings from Research

In a pooled analysis of eight Japanese Phase II and III studies, it was found that Alzheimer's patients in placebo groups showed a more significant decline in cognitive function at weeks 22 and 24 compared to week 12, indicating a rapid progression of symptoms over time.

The study revealed that patients with moderate Alzheimer's disease experienced a faster deterioration in cognitive scores (ADAS-cog) than those with mild Alzheimer's, which is crucial for clinicians in managing treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo-controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease. Watanabe, M., Nakamura, Y., Yoshiyama, Y., et al.[2022]

In a review of 23 randomized, placebo-controlled trials for Alzheimer's disease lasting 18 months, no trial demonstrated statistically significant benefits for the test drug, highlighting challenges in detecting modest drug efficacy in this timeframe.

The placebo groups showed a consistent decline in cognitive function (measured by the ADAS-cog) over 18 months, with variability in outcomes suggesting that many patients do not experience significant worsening, complicating the ability to identify effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Alzheimer's disease clinical trials: methods and placebo outcomes. Schneider, LS., Sano, M.[2022]

In a 1-year study involving 431 patients with probable Alzheimer's disease, acetyl-L-carnitine hydrochloride (ALCAR) did not show a significant difference in cognitive decline compared to placebo for the overall group, indicating similar efficacy between the two treatments.

However, a subanalysis suggested that early-onset Alzheimer's patients (aged 65 or younger) may experience a slower decline with ALCAR compared to those on placebo, while late-onset patients may progress more rapidly on ALCAR, highlighting the need for further research in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Thal, LJ., Carta, A., Clarke, WR., et al.[2019]

In a review of 69 Alzheimer's disease clinical trials, study duration was found to be the most consistent predictor of cognitive decline in placebo-treated subjects, indicating that longer trials may lead to more observable changes.

Factors such as the number of investigational sites, frequency of evaluations, and the severity of dementia at baseline were inversely related to cognitive decline, suggesting that these elements should be carefully considered in the design of future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design factors and patient demographics and their effect on the decline of placebo-treated subjects in randomized clinical trials in Alzheimer's disease. Gold, M.[2022]

In a multicenter trial involving 92 patients with Alzheimer's disease, idebenone treatment over 90 days showed effectiveness in improving memory, attention, and orientation, while also slowing disease progression.

The treatment was generally well-tolerated, with mild side effects such as insomnia and nausea, which did not require specific medical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idebenone, a new drug in the treatment of cognitive impairment in patients with dementia of the Alzheimer type. Bergamasco, B., Scarzella, L., La Commare, P.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo-controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Current Alzheimer's disease clinical trials: methods and placebo outcomes. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Study design factors and patient demographics and their effect on the decline of placebo-treated subjects in randomized clinical trials in Alzheimer's disease. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Idebenone, a new drug in the treatment of cognitive impairment in patients with dementia of the Alzheimer type. [2022]