AGB101 for Dementia

(AGB101-CN Trial)

Overseen By Caroline L Wagandt, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Anticonvulsants, Anticoagulants

Disqualifiers: Neurological disease, Major depression, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new slow-release form of levetiracetam, called AGB101, to determine if it helps maintain normal brain function in adults without cognitive issues. The study compares AGB101 with a placebo (a non-active pill) to assess its effect on brain imaging over two weeks. It suits individuals aged 50 to 80 who have no memory complaints and are willing to undergo MRI scans. Participants will first take either AGB101 or the placebo, have a break, and then switch to the other treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticonvulsant or anticoagulant medications at least 1 month before starting. If you're on antidepressants, the dose must be stable for 1 month before and during the study.

Is there any evidence suggesting that AGB101 is likely to be safe for humans?

Research shows that AGB101, a slow-release version of the drug levetiracetam, has been tested for safety in people with memory and thinking problems. Earlier studies found that levetiracetam is usually well-tolerated, with most people experiencing few side effects. Serious issues were rare. Some common mild side effects included dizziness and tiredness, but these occurred infrequently. The FDA has already approved levetiracetam for other uses, indicating that its safety is fairly well-known. However, AGB101 is still under investigation for use in dementia, so ongoing research is essential to fully understand its safety for this purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AGB101 for dementia because it offers a new approach by using low-dose levetiracetam, an extended-release tablet, which is not typically used for this condition. Most existing dementia treatments focus on managing symptoms with drugs like donepezil or memantine, which target neurotransmitter systems. AGB101, however, is believed to modulate neuronal activity differently, potentially addressing the underlying disruptions in brain signaling associated with dementia. This unique mechanism of action might lead to improved cognitive function and better overall outcomes for patients.

What evidence suggests that AGB101 might be an effective treatment for dementia?

Research has shown that AGB101, a slow-release version of the drug levetiracetam, might aid memory and brain function. In this trial, participants will receive either AGB101 followed by a placebo, or a placebo followed by AGB101. The HOPE4MCI study found that AGB101 slowed memory problems in individuals without the APOE ε4 genetic variant. While one study found that levetiracetam did not change overall thinking abilities, it did improve tasks involving planning and remembering locations. These early results suggest that AGB101 could enhance memory and brain activity, particularly for those without the APOE ε4 variant. ^{1 2 6 7 8}

Who Is on the Research Team?

Marilyn Albert, PhD

Principal Investigator

Johns Hopkins University

Arnold Bakker, Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for cognitively normal adults aged 50-80 with no memory complaints, good general health, and a reliable study partner. They must be able to undergo PET and MRI scans, have stable antidepressant use if applicable, and agree to effective contraception if of childbearing age. Exclusions include recent participation in other clinical studies, significant neurological diseases or conditions that might interfere with the study, major depression within the last 3 years or psychotic disorders history.

Inclusion Criteria

Subjects must be willing and able to undergo a Tau positron emission tomography (PET) scan with 18F MK-6240 tracer

I am between 50 and 80 years old and in good health.

I have someone who can report on my health changes and how I'm doing weekly.

Exclusion Criteria

Subjects must not have any other reason, which in the opinion of the investigator, would confound proper interpretation of the study

Subjects must not participate in a therapeutic clinical study for any medical or psychiatric indications within 1 month of the screening visit or at any time during the study

I do not have any major neurological conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGB101 or placebo once daily for 2 weeks

2 weeks

1 visit (in-person) at the end of each treatment period

Washout

Participants undergo a washout period between treatment phases

4 weeks

Crossover Treatment

Participants receive the alternate treatment (AGB101 or placebo) once daily for 2 weeks

2 weeks

1 visit (in-person) at the end of each treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AGB101

Trial Overview AGB101 (a slow-release form of levetiracetam) is being tested for its ability to reduce hippocampal overactivity in older adults without dementia. The trial uses a randomized crossover design where participants receive both AGB101 and placebo at different times during the two-week treatment period while undergoing imaging measures.

How Is the Trial Designed?

Group I: placebo first, then AGB101 Experimental Treatment 2 Interventions

Placebo capsule once daily for 2 weeks, washout (4 weeks), then AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks.

Group II: AGB101 first, then placebo Experimental Treatment 2 Interventions

AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks, washout (4 weeks), then placebo capsule once daily for 2 weeks.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

AgeneBio

Industry Sponsor

Trials

3

Recruited

250+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10865488/

The HOPE4MCI study: A randomized double‐blind ... This trial, HOPE4MCI (Hippocampal Overactivity Prevention in the Elderly with MCI due to AD), was conducted to assess the efficacy of AGB101.

2. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2784539

Effect of Levetiracetam on Cognition in Patients With ... In this randomized clinical trial of 34 adults with AD, treatment with levetiracetam did not significantly modify cognitive function.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06919926

Study Details | NCT06919926 | Clinical Trial Evaluating the ... This randomized, crossover, placebo controlled clinical study will assess the efficacy and safety of a slow release form of levetiracetam (AGB101) in the ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70004

The HOPE4MCI study: AGB101 treatment slows progression ... The HOPE4MCI study showed that APOE ε4 non-carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0011393X25000232

Cognitive Effect of Levetiracetam in Patients with ... They reported that LEV did not improve primary outcome, but in further analysis, LEV improved spatial memory performance and executive function tasks in ...

6. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/trc2.12446

A randomized double‐blind assessment of AGB101 for the ... The primary endpoint was the change in Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB) comparing follow up at 18 months to baseline.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/461457

Clinical Trial of AGB101 for Mild Cognitive Impairment The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive and functional impairment as measured by ...

8. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Levetiracetam_UPDATE_%28drug%29.pdf

Levetiracetam In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. Levetiracetam. Evidence Summary.