Clinical Trial of AGB101 for Mild Cognitive Impairment

NCT05986721 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: AGB101 NE4
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment; Prodromal Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change in Entorhinal Cortex (EC) Volume From Baseline

  Magnetic resonance imaging (MRI) will be used to assess neuronal injury via change in EC volume from baseline to 78 weeks. Negative change scores indicate reduced volume at 78 weeks and positive change scores indicate increase in volume at 78 weeks. Greater numbers therefore correspond with better outcomes.

  78 weeks

Secondary Outcomes (2)

• Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score From Baseline

  78 weeks

• Change in Clinical Dementia Rating Scale - Memory Box Score From Baseline

  78 weeks

Study Arms (2)

Placebo Oral Tablet

PLACEBO COMPARATOR

Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks

Drug: Placebo

AGB101 220 mg tablet

EXPERIMENTAL

Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks.

Drug: AGB101

Interventions

AGB101 DRUG

low-dose levetiracetam, 220 mg, extended release tablet

Also known as: levetiracetam, keppra

AGB101 220 mg tablet

Placebo DRUG

Placebo oral tablet

Also known as: placebo tablet

Placebo Oral Tablet

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects between 55 and 85 years old (inclusive) in good general health:
• Willing and able to consent and participate for the duration of the study.
• Have eighth-grade education or good work history sufficient to exclude mental retardation.
• Have visual and auditory acuity adequate for neuropsychological testing.
• Have proficient fluency of the native local language to participate in all the neuropsychological test assessments.
• Have a study partner who has sufficient contact with the subject to be able to provide assessment of memory changes, who can accompany the subject to the screening visit and all major clinic visits for the duration of those visits, and who is able to provide an independent evaluation of the subject's functioning.
• Have MCI as defined by all of the following criteria and consistent with the National Institute on Aging-Alzheimer's Association criteria:
• MMSE scores between 24 and 30 (inclusive; exceptions may be made for subjects with \<8 years of education at the discretion of the sponsor).
• A memory complaint reported by the subject or his/her study partner.
• Evidence of lower memory performance based on the delayed recall portion on a list learning task (ISLT or BSRT).
• A CDR score of 0.5 with a memory box score of ≥ 0.5.
• Essentially preserved activities of daily living.
• Cognitive decline not primarily caused by vascular, traumatic, or medical problems (alternative causes of cognitive decline are ruled out).
• Have an Apolipoprotein E (ApoE) genotype that does not include one or more E4 alleles.
• Permitted medications:

You may not qualify if:

• Carrying one or more copies of the apolipoprotein E4 (ApoeE4) allele.
• Use of anticonvulsant medications or excluded psychotropic medications within 3 months prior to the baseline visit.
• Use of anti-amyloid medications at any time prior to screening visit, or at any time during the study.
• Participation in a therapeutic clinical study for any medical or psychiatric indications within 3 months (6 months for biologics) of the screening visit, or at any time during the study. Subjects must understand that they may only enroll in this clinical study once; they may not enroll in any other clinical study while participating in the current study, and they may not participate in a clinical study of a drug, biologic, therapeutic device, or medical food, in which the last dose/administration was received within 3 months (6 months for biologics) prior to screening.
• History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam).
• Severe renal impairment (creatinine clearance of \< 30 mL/minute) or undergoing hemodialysis.
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body that constitute a contraindication to having an MRI.
• Diagnosis of bipolar disorder, or major depression within the past 3 years, as described in the DSM-5. Psychotic features, agitation, or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol. Subjects must not have a major depressive disorder or other types of depression that could confound diagnosis of MCI due to AD, or clinical assessments, in the opinion of the investigator. The Geriatric Depression Scale \[GDS\] (long form score \> 9 suggests depression) results should be reviewed by the investigator to assist in this determination.
• Modified Hachinski Ischemic Scale (HIS) score \> 4.
• History of schizophrenia (DSM-5 criteria).
• History of alcohol or substance abuse or dependence within the past 3 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol requirements.
• Any unstable medical condition that is likely to require new medical or surgical treatment during the course of the study and where such treatments might affect the collection of efficacy data.
• Residence in a skilled nursing facility. Individuals in independent living communities, assisted living facilities, residential care facilities, or continuing care communities are eligible provided they engage in a sufficient spectrum of activity to permit assessment of all 6 domains contributing to the CDR-SB. Individuals in these facilities must also have a study partner who has the ability to observe the subject during the study and can participate in clinical evaluations.
• Any use of excluded medications (eg, antiepileptics, certain antidepressants or antipsychotics, antihistamines with anticholinergic properties, opiates).

Sponsors & Collaborators

• AgeneBio: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 2:1, 3:1, or 4:1, following an escalating randomization scheme. A total of 60 subjects will be randomized (approximately 44 subjects will be randomized to AGB101 and 16 to placebo)

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: December 3, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)