NMRA-323511 for Agitation in Alzheimer's Disease

No longer recruiting at 22 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Neumora Therapeutics, Inc.

Must not be taking: Anticonvulsants

Disqualifiers: Epilepsy, Suicidal, Neurologic disorder, others

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is studying a new treatment called NMRA-323511, which aims to help with agitation in people with Alzheimer's disease. For healthy participants aged 65 to 80, the trial will assess the treatment's safety and how the body processes it. For those aged 55 to 90 with Alzheimer's and noticeable agitation, the trial will evaluate if the treatment effectively reduces agitation. Individuals diagnosed with Alzheimer's for at least a year and experiencing regular agitation may be a good fit. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding how it works in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NMRA-323511 is likely to be safe for humans?

Research has shown that NMRA-323511 has promising safety results from early studies. In past trials, participants tolerated it well at different doses, and no major side effects were reported. These findings suggest that NMRA-323511 could be safe for humans, but ongoing research will provide more information. Remember, this treatment is still being tested, so new safety data will become available as more studies are completed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about NMRA-323511 for treating agitation in Alzheimer's disease because it offers a novel approach compared to current options like antipsychotics and anxiolytics. Unlike these traditional treatments, which often manage symptoms through sedation, NMRA-323511 targets the underlying neurochemical pathways associated with agitation. This could potentially lead to more effective and specific symptom relief without the common side effects associated with existing medications. Additionally, NMRA-323511 might provide faster results, improving patient quality of life more quickly.

What evidence suggests that NMRA-323511 might be an effective treatment for agitation in Alzheimer's disease?

Initial findings suggest that NMRA-323511, one of the treatments studied in this trial, might help with agitation—restlessness or irritability—in people with Alzheimer's disease. Early studies showed that this drug was well-tolerated, meaning participants didn't experience serious side effects. Preclinical studies demonstrated its promise, as it worked well in lab tests before human trials. This research offers hope that NMRA-323511 could become a new option for calming agitation in Alzheimer's patients. However, more data is needed to confirm its effectiveness in treating this condition. Participants in this trial will receive either NMRA-323511 or a placebo to further evaluate its potential benefits. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for healthy elderly individuals and adults with agitation due to Alzheimer's dementia. Participants must pass a screening and be eligible based on specific criteria not detailed here.

Inclusion Criteria

I am between 65 and 80 years old with a BMI between 18 and 32.

I am 55-90 years old, diagnosed with Alzheimer's, have agitation, and my MMSE score is 5-24.

Do you experience agitation or irritation related to not being able to remember things?

Exclusion Criteria

I have dementia or memory issues not caused by Alzheimer's, or another significant neurological condition.

Have you been diagnosed with a serious health condition outside of Alzheimer's?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment (Part A)

Participants receive NMRA-323511 or placebo for 10 days to evaluate safety, tolerability, and pharmacokinetics

10 days

Follow-up (Part A)

Participants are monitored for safety and effectiveness after treatment

10 days

1 clinic visit

Treatment (Part B)

Participants receive NMRA-323511 or placebo for 8 weeks to evaluate safety, tolerability, and efficacy

8 weeks

Follow-up (Part B)

Participants are monitored for safety and effectiveness after treatment

10 days

1 clinic visit

What Are the Treatments Tested in This Trial?

Interventions

• NMRA-323511

Trial Overview The study tests NMRA-323511 against a placebo in two parts: Part A focuses on safety in healthy elderly, while Part B assesses safety and effectiveness in those with Alzheimer's-related agitation.

How Is the Trial Designed?

Group I: Part B: NMRA-323511 Experimental Treatment 1 Intervention

Group II: Part A: NMRA-323511 Experimental Treatment 1 Intervention

Group III: Part A: Placebo Placebo Group 1 Intervention

Group IV: Part B: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Neumora Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

2,100+

Published Research Related to This Trial

In a study involving 10 patients with probable Alzheimer's disease, buspirone was found to significantly reduce agitation scores, indicating its potential efficacy for managing agitation in this population.

The optimal average dose for achieving a significant decrease in agitation was 35 mg/day, suggesting that lower doses may be effective before reaching the maximum dose of 60 mg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Buspirone on Agitation Associated With Dementia. Sakauye, KM., Camp, CJ., Ford, PA.[2019]

In a study involving 149 participants with moderate-to-severe Alzheimer's disease, memantine did not show a significant improvement in clinically significant agitation compared to placebo after 6 weeks, indicating it may not be effective for this symptom.

However, memantine did demonstrate a positive effect on cognitive function and showed some benefits in reducing neuropsychiatric symptoms, suggesting it may still have a role in managing other aspects of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. Fox, C., Crugel, M., Maidment, I., et al.[2022]

Switching from donepezil to galantamine in patients with Alzheimer's disease showed improvements in agitation after 8 weeks, indicating that this switch is a safe and effective treatment option.

Adding memantine to existing donepezil therapy was also found to be effective in reducing agitation compared to simply increasing the donepezil dose, suggesting that both strategies can provide meaningful benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer's disease receiving donepezil. Kano, O., Ito, H., Takazawa, T., et al.[2021]

In two 12-week studies involving a total of 703 patients with agitation in Alzheimer's dementia, brexpiprazole at a dose of 2 mg/day showed significant improvement in agitation symptoms compared to placebo, indicating its efficacy in this patient population.

Brexpiprazole was generally well tolerated, with most treatment-emergent adverse events being mild to moderate, although headaches and insomnia were reported more frequently than with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. Grossberg, GT., Kohegyi, E., Mergel, V., et al.[2021]

Memantine 20 mg once daily has been shown to improve cognition, functional ability, and behavioral symptoms in patients with moderate to severe Alzheimer's disease, based on pooled clinical trials and real-world studies.

The use of memantine is associated with delays in the need for full-time care, potentially leading to cost savings compared to standard care, and it has a safety profile similar to that of a placebo, indicating it is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily memantine: a guide to its use in moderate to severe Alzheimer's disease in the EU. Lyseng-Williamson, KA., McKeage, K.[2021]

Citations

1. ir.neumoratx.com ir.neumoratx.com/news-releases/news-release-details/neumora-therapeutics-announces-initiation-phase-1b-study-nmra

Neumora Therapeutics Announces Initiation of Phase 1b ... Based on data available to date, Neumora believes NMRA-511 has the potential to be a promising novel medication for multiple neuropsychiatric ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06546995

NCT06546995 | Study to Evaluate the Effects of NMRA- ... Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease.

3. synapse.patsnap.com synapse.patsnap.com/article/neumora-begins-phase-1b-study-of-nmra-511-for-alzheimers-agitation

Neumora Begins Phase 1b Study of NMRA-511 for ... The drug has shown promising results in preclinical studies and a Phase 1a trial, where it was well-tolerated across various doses without any ...

4. firstwordpharma.com firstwordpharma.com/story/5987019

Neumora Therapeutics Reports Second Quarter 2025 ... Neumora is on track to report data from a Phase 1b signal-seeking study evaluating NMRA-511 as a treatment for AD agitation around the end of ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06546995/study-to-evaluate-the-effects-of-nmra-323511-among-healthy-elderly-and-adults-with-agitation-associated-with-dementia-due-to-alzheimers-disease

Study to Evaluate the Effects of NMRA-323511 Among ... Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease.

6. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/nmra-511-neumora-therapeutics-net-present-value/

Risk Adjusted Net Present Value: What is the current ... NMRA-511 is under development for the treatment of agitation in alzheimer's disease. The drug candidate is administered by oral route and acts ...