levetiracetam low dose (AGB101) / AgeneBio - LARVOL DELTA

Population Pharmacokinetics of Intravenous Levetiracetam in Neurosurgical Patients: Dosage Optimization Based on CrCl and Mannitol Use. (PubMed, Pharm Res) - "Standard LEV prophylaxis dosing often yields inadequate exposure in neurosurgical patients. LEV clearance is influenced by CrCl and mannitol use, higher doses is required for patients with concurrent mannitol therapy."

Journal • PK/PD data • CNS Disorders • Epilepsy

Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW) (clinicaltrials.gov) - P4 | N=58 | Completed | Sponsor: Mario Negri Institute for Pharmacological Research | Active, not recruiting ➔ Completed | N=374 ➔ 58

Enrollment change • Trial completion • CNS Disorders • Epilepsy

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: AgeneBio | N=60 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia (clinicaltrials.gov) - P=N/A | N=18 | Completed | Sponsor: University of Colorado, Denver | Recruiting ➔ Completed | N=30 ➔ 18 | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

AGB101-CN: Clinical Trial Evaluating the Efficacy of AGB101 for Reducing Hippocampal Overactivity in Older Adults (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Johns Hopkins University

New P2 trial • Alzheimer's Disease • CNS Disorders • Dementia

The Bidirectional Relationship Between Epilepsy and Alzheimer's Disease. (PubMed, Curr Neurol Neurosci Rep) - "Anti-seizure medications (ASMs), particularly low-dose levetiracetam, show potential not only for seizure control but also for mitigating amyloid deposition, tau hyperphosphorylation, and cognitive decline...The bidirectional nature of AD and epilepsy emphasizes the need for integrated diagnostics, including EEG and biomarker assessments, to guide early intervention and targeted therapies. Future research should focus on the mechanistic interplay between amyloid, tau, and hyperexcitability, alongside trials of ASM regimens, to refine therapeutic strategies and improve outcomes in this population."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Epilepsy • Geriatric Disorders

Biomarkers. (PubMed, Alzheimers Dement) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex. That reduction in atrophy was significantly coupled with the change in CDR-SB and with plasma biomarkers of disease. These exploratory analyses would be consistent with a reduction in neurodegeneration in the non-carriers of ApoE4 treated with AGB101 prior to a clinical diagnosis of dementia."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Alzheimer's Imaging Consortium. (PubMed, Alzheimers Dement) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex. That reduction in atrophy was significantly coupled with the change in CDR-SB and with plasma biomarkers of disease. These exploratory analyses would be consistent with a reduction in neurodegeneration in the non-carriers of ApoE4 treated with AGB101 prior to a clinical diagnosis of dementia."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: AgeneBio | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: AgeneBio | Phase classification: P3 ➔ P2 | N=1040 ➔ 60

Enrollment change • Phase classification • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

The HOPE4MCI study: AGB101 treatment reduces entorhinal cortex atrophy in patients with amnestic mild cognitive impairment due to Alzheimer’s Disease who are ApoE-4 non-carriers (AAIC 2024) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

The HOPE4MCI study: AGB101 treatment reduces entorhinal cortex atrophy in patients with amnestic mild cognitive impairment due to Alzheimer's Disease who are ApoE-4 non-carriers (AAIC 2024) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW) (clinicaltrials.gov) - P4 | N=374 | Active, not recruiting | Sponsor: Mario Negri Institute for Pharmacological Research | Unknown status ➔ Active, not recruiting | Trial completion date: Dec 2021 ➔ Aug 2024 | Trial primary completion date: Jul 2021 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

The HOPE4MCI study: A randomized double-blind assessment of AGB101 for the treatment of MCI due to AD. (PubMed, Alzheimers Dement (N Y)) - "The possibility that ApoE-4 carriers and noncarriers will respond differently to therapeutic intervention is consistent with recently reported findings from biologics and the present results show further testing of AGB101 in patients with MCI due to AD who are noncarriers of the ApoeE-4 allele is warranted. Conclusions from the HOPE4MCI study are limited primarily due to the small sample size and results can only be regarded as a guide to future research."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE

Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials. (PubMed, CNS Drugs) - "This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution."

Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Fatigue • Pain • Psychiatry • Schizophrenia

Dosage, time, and polytherapy dependent effects of different levetiracetam regimens on cognitive function. (PubMed, Epilepsy Behav) - "When taken in small doses, for brief periods as monotherapy, levetiracetam minimally influences cognition. At higher doses, as part of long-term seizure management, in conjunction with multiple ASMs, LEV is associated with cognitive impairment."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Epilepsy • Psychiatry

Efficacy of Low Dose Levetiracetam for Status Epilepticus in Pediatric Patients: A Retrospective Study (ASHP 2023) - No abstract available

Retrospective data • Epilepsy • Pediatrics

AGB101 PDP: Clinical Trial Evaluating the Efficacy and Safety of AGB101 for Treatment of Parkinson's Disease Related Psychosis (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Low dose of levetiracetam counteracts amyloid β-induced alterations of hippocampal gamma oscillations by restoring fast-spiking interneuron activity. (PubMed, Exp Neurol) - "In addition, we found that LEV counteracts the hippocampal γ-Osc alterations in the early prodromal stage of the disease in App mice by recovering the rhythmicity of γ-Osc and the synchronicity in the firing of FS-IN. Altogether the results show that the precise modulation of neuronal circuits with LEV is a promising strategy to counteract early-stage alterations in hippocampal activity by modulating FS-IN in a memory-relevant neuronal network state like γ-Osc."

Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Epilepsy

Study of AGB101 in Mild Cognitive Impairment Due to Alzheimer's Disease (clinicaltrials.gov) - P3 | N=1040 | Not yet recruiting | Sponsor: AgeneBio

New P3 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

AGB101 PDP: Clinical Trial Evaluating the Efficacy and Safety of AGB101 for Treatment of Parkinson's Disease Related Psychosis (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Johns Hopkins University

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Hope4MCI: Study of AGB101 in Mild Cognitive Impairment Due to Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=164 | Completed | Sponsor: AgeneBio | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

STANDARD VERSUS LOW-DOSE LEVETIRACETAM FOR SEIZURE PROPHYLAXIS IN ELDERLY TRAUMATIC BRAIN INJURIES (SCCM 2023) - "The 2016 Brain Trauma Foundation TBI guidelines recommend 7 days of phenytoin for early PTS prophylaxis. Levetiracetam utilized at a dose of 250 mg twice daily may be an option for seizure prophylaxis in elderly TBI patients and may be considered as a strategy to mitigate levetiracetam-related behavioral events. Further randomized controlled trials with larger sample sizes are needed to confirm efficacy of low-dose levetiracetam and better quantify behavioral event rates associated with different regimens."

Clinical • CNS Disorders • Epilepsy • Vascular Neurology

HOPE4MCI Trial Targeting Hippocampal Overactivity for the treatment of Mild Cognitive Impairment due to Alzheimer’s disease with AGB101: Baseline Tau and MRI imaging characteristics (CTAD 2022) - P2/3 | "The current study includes multiple measures relevant to dementia due to AD in a prodromal condition recognized as transitional between normal aging and progression to a clinical AD diagnosis. The use of additional biomarkers in the subset of patients is informative for further characterization of MCI due to AD. The association between structural MRI and FMK-6240 Tau PET in this sample will also be informative bridging to the full dataset of 164 enrollees in which structural MRI was obtained in all participants."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia