AGB101 for Mild Cognitive Impairment
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AgeneBio
Must be taking: Cholinesterase inhibitors, Memantine
Must not be taking: Anticonvulsants, Anti-amyloids
Disqualifiers: ApoE4 allele, Severe renal impairment, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive and functional impairment as measured by reduction in neuronal injury in participants with mild cognitive impairment due to Alzheimer's Disease. Participants will be randomized to receive placebo or AGB101 (220 mg), once daily for 78 weeks. Secondary objectives are to assess the effect of AGB101 compared with placebo on clinical progression as measured by the Clinical Dementia Rating Scale- Sum of Boxes and Memory Box score.
Will I have to stop taking my current medications?
The trial requires that certain medications be at a stable dose for a specific period before and during the study. If you are taking medications with potential pro-cognitive effects, antidepressants, or antipsychotics, they must be stable for at least 3 months before screening. Other medications like estrogen replacement therapy, Ginkgo biloba, and vitamin E must be stable for at least 4 weeks before screening. Some medications, such as anticonvulsants and certain psychotropics, are not allowed.
What evidence supports the effectiveness of the drug AGB101 for mild cognitive impairment?
Levetiracetam, a component of AGB101, has been shown to improve cognitive deficits in Alzheimer's disease and mild cognitive impairment by reducing excess neural activity in the brain, which is linked to memory loss. Additionally, it does not negatively impact cognitive function in patients with epilepsy, suggesting it may be beneficial for cognitive health.12345
Is AGB101 (Levetiracetam) safe for humans?
How does the drug AGB101 (Levetiracetam) differ from other treatments for mild cognitive impairment?
AGB101 (Levetiracetam) is unique because it targets excess neural activity in the hippocampus, which is linked to cognitive decline in conditions like mild cognitive impairment and Alzheimer's disease. Unlike other treatments, it reduces this hyperactivity without negatively impacting cognitive function, potentially improving memory and slowing disease progression.2341011
Research Team
Eligibility Criteria
This trial is for individuals with mild cognitive impairment due to Alzheimer's, who can consent and participate for 78 weeks. They should have at least an eighth-grade education or equivalent work history, adequate sensory abilities for testing, a study partner to assist them, MMSE scores of 24-30, and a specific memory complaint.Inclusion Criteria
I have someone who knows me well to attend major clinic visits and assess my memory changes.
You are able to provide consent and commit to the study's duration.
You have completed at least eight years of schooling, or possess a work record that indicates an absence of mental impairment.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either AGB101 or placebo once daily for 78 weeks
78 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- AGB101 (Anti-amyloid agent)
Trial OverviewThe trial tests AGB101 (220 mg daily) against a placebo to see if it slows down cognitive decline in Alzheimer's patients over 78 weeks. It measures the reduction in neuronal injury and assesses clinical progression using dementia rating scales.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: AGB101 220 mg tabletExperimental Treatment1 Intervention
Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks.
Group II: Placebo Oral TabletPlacebo Group1 Intervention
Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks
AGB101 is already approved in United States, European Union, Canada, China for the following indications:
🇺🇸 Approved in United States as Levetiracetam for:
- Partial onset seizures
- Myoclonic seizures
- Tonic-clonic seizures
🇪🇺 Approved in European Union as Levetiracetam for:
- Epilepsy
- Partial onset seizures
- Myoclonic seizures
- Tonic-clonic seizures
🇨🇦 Approved in Canada as Levetiracetam for:
- Partial onset seizures
- Myoclonic seizures
- Tonic-clonic seizures
🇨🇳 Approved in China as Levetiracetam for:
- Epilepsy
- Partial onset seizures
- Myoclonic seizures
- Tonic-clonic seizures
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns HopkinsBaltimore, MD
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Who Is Running the Clinical Trial?
AgeneBio
Lead Sponsor
Trials
3
Patients Recruited
250+
References
Levetiracetam inhibits interleukin-1 beta inflammatory responses in the hippocampus and piriform cortex of epileptic rats. [2018]Levetiracetam (LEV, 2S-(oxo-1-pyrrolidinyl)butanamide, Keppra, UCB Pharma) is a new anti-epileptic drug used to treat certain types of seizures in epilepsy patients. However, the pharmacodynamics of LEV is still controversial. Recently, interleukin-1 beta (IL-1 beta) has been reported to involve in epileptic phenomena. Therefore, we investigated the effects of LEV on IL-1 beta system in the hippocampus and piriform cortex of chronic epileptic rats. As compared to controls, typical reactive astrogliosis and microgliosis were observed in the hippocampus and piriform cortex of epileptic animals. In addition, both reactive astrocytes and reactive microglia showed strong IL-1 beta and interleukin-1 receptor subtype 1 (IL-1R1) immunoreactivities. LEV reduced reactive gliosis and expression levels of IL-1 beta system in the hippocampus and the piriform cortex, while valproic acid did not. These findings suggest that the LEV may have, at least in part, anti-inflammatory effect, particularly against IL-1 beta system in neuroglia within epileptic brains.
Targeting Neural Hyperactivity as a Treatment to Stem Progression of Late-Onset Alzheimer's Disease. [2019]Sporadic late-onset Alzheimer's disease (LOAD), the most common form of dementia in the elderly, causes progressive and severe loss of cognitive abilities. With greater numbers of people living to advanced ages, LOAD will increasingly burden both the healthcare system and society. There are currently no available disease-modifying therapies, and the failure of several recent pathology-based strategies has highlighted the urgent need for effective therapeutic targets. With aging as the greatest risk factor for LOAD, targeting mechanisms by which aging contributes to disease could prove an effective strategy to delay progression to clinical dementia by intervention in elderly individuals in an early prodromal stage of disease. Excess neural activity in the hippocampus, a recently described phenomenon associated with age-dependent memory loss, was first identified in animal models of aging and subsequently translated to clinical conditions of aging and early-stage LOAD. Critically, elevated activity was similarly localized to specific circuits within the hippocampal formation in aged animals and humans. Here we review evidence for hippocampal hyperactivity as a significant contributor to age-dependent cognitive decline and the progressive accumulation of pathology in LOAD. We also describe studies demonstrating the efficacy of reducing hyperactivity with an initial test therapy, levetiracetam (Keppra), an atypical antiepileptic. By targeting excess neural activity, levetiracetam may improve cognition and attenuate the accumulation of pathology contributing to progression to the dementia phase of LOAD.
Absence of negative impact of levetiracetam on cognitive function and memory in normal and amygdala-kindled rats. [2010]The effect of the new antiepileptic drug (AED) levetiracetam (LEV, Keppra) on cognitive function was studied in normal and amygdala-kindled rats by using the Morris water maze test. In addition, we investigated the effect of LEV on long-term potentiation (LTP) in rat hippocampal slices. Sodium valproate (VPA) was used as comparator in all studies. Clonazepam (CZP) and carbamazepine (CBZ) were used in normal rats. The results indicated that doses of LEV known to suppress motor seizures did not alter cognitive performance. In contrast, similar doses of the classic AEDs all decreased learning performance of the rats. Likewise, VPA did alter LTP but LEV was inactive. Amygdala-kindled rats were more sensitive than normal rats to the effects of VPA. These results suggest that LEV may be devoid of negative impact on cognition in epileptic patients.
Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease. [2019]Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD.
Levetiracetam monotherapy in Alzheimer patients with late-onset seizures: a prospective observational study. [2022]Levetiracetam (LEV) monotherapy was investigated in 25 patients with advanced Alzheimer's disease (AD) and new-onset epileptic seizures in a prospective open-label study. At a daily dose of 1000-1500 mg, 72% were seizure-free for at least one year; 16% discontinued for untolerability; 8% were unresponsive; 4% were lost to follow-up. These results suggest the need for controlled studies to confirm if LEV can be a first-choice drug in AD.
A systematic review of the safety profile of levetiracetam: a new antiepileptic drug. [2022]This report provides detailed review of safety information on levetiracetam (LEV) (Keppra), a new antiepileptic drug.
Spotlight on levetiracetam in epilepsy. [2021]Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial-onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial-onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial-onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracetam and placebo treatment groups, with most events being mild to moderate in severity. Levetiracetam is not associated with cognitive impairment or drug-induced weight gain, but has been associated with behavioural adverse effects in some patients.
Dose-response effect of levetiracetam 1000 and 2000 mg/day in partial epilepsy. [2022]To evaluate the efficacy, dose-response, tolerability, and withdrawal effects of levetiracetam (Keppra) as adjunctive therapy in adult patients with partial epilepsy.
An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy. [2019]The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population.
Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. [2022]Elevated hippocampal activation is observed in conditions that confer risk for Alzheimer's disease, including amnestic mild cognitive impairment (aMCI). Studies in relevant animal models have indicated that overactivity in selective hippocampal circuits contributes to cognitive impairment. Here, we tested the effect of reducing hippocampal activation in aMCI. Under placebo treatment, hippocampal activation in the dentate gyrus/CA3 was elevated in aMCI patients compared to a healthy control group. By using a low dose of the antiepileptic levetiracetam hippocampal activation in aMCI was reduced to a level that did not differ from the control group. Compared to aMCI memory performance under placebo, performance in the scanning task was significantly improved under drug treatment. Contrary to the view that greater hippocampal activation might serve a beneficial function, these results support the view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential.
Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement. [2018]Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.