Mild Cognitive ImpairmentPhase 2NCT05986721
Clinical Trial of AGB101 for Mild Cognitive Impairment
A Phase 2 study testing AGB101 in people with Mild Cognitive Impairment and Prodromal Alzheimer's Disease, run by AgeneBio at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Mild Cognitive Impairment, Prodromal Alzheimer's Disease
- What is being tested?
- AGB101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Dec 2024to Dec 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- With potential pro-cognitive effects, such as cholinesterase inhibitors and memantine, must be at a stable dose for ≥ 3 months prior to screening and expected to remain stable throughout the study; estrogen replacement therapy, Ginkgo biloba, and vitamin E must be at a stable dose for ≥ 4 weeks prior to screening and expected to remain stable throughout the study.
- Other psychotropics, such as antidepressants and antipsychotics, must be at a stable dose for ≥ 3 months prior to screening and expected to remain stable throughout the study.
- Willing and able to undergo imaging procedures:
- An amyloid-imaging PET scan with 11C-PiB or documented evidence of an amyloid-positive PET scan.
- The amyloid PET scan performed at baseline must be read by a qualified physician with experience in reading amyloid PET scans, and it should be consistent with the presence of amyloid plaques.
- Repeated MRI scans (3 Tesla) with no contraindications to MRI. The MRI scan performed at baseline must be read by a physician with experience in evaluating brain-imaging studies in dementia. MRI scan results are consistent with the diagnosis of amnestic MCI due to AD with no clinically significant findings of non-AD pathology that could account for the observed cognitive impairment.
- Willing to allow collection of blood for apolipoprotein E (ApoE) genotyping and banking.
Who cannot join
- 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.
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- Any significant neurological disease other than suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder (lifetime history; infant febrile seizures are not exclusionary), subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities.
- 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.
- Clinically significant abnormalities in B12 or thyroid function test that might interfere with the study. A low B12 (below normative range for elderly) is exclusionary, unless follow-up labs (homocysteine and methylmalonic acid) indicate that it is not physiologically significant. If the B12 deficiency is treated, subjects may become eligible to participate in the study.
- 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).
- Participation in clinical studies using the ISLT/BSRT, BPS-O task, or the trail making test (A, B) within 1 month of screening.
- Female subjects must not be pregnant, lactating, or of childbearing potential (ie, they must be 2 years postmenopause or surgically sterile).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101 on Slowing Progression of Mild Cognitive Impairment Due to Alzheimer's Disease in Apolipoprotein E4 Non-carriers
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.
Read the detailed description
AGB101 is hypothesized to slow the progression of MCI due to AD by restoring the entorhinal/hippocampal network balance. During this phase of the disease, fMRI studies show hippocampal over-activity and EC under-activity. As shown in the phase 2 study, AGB101 restores this network balance by attenuating hippocampal over-activity and restoring EC activity. Hippocampal over-activity predicts progression on EC atrophy (primary endpoint) and on CDR-SB (secondary endpoint). By restoring network balance, AGB101 is hypothesized to improve cognitive function (CDR-SB) and reduce neuronal injury (EC atrophy).
- Being tested
- AGB101, Placebo
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGB101Drug
Also called levetiracetam, keppra
low-dose levetiracetam, 220 mg, extended release tablet
PlaceboDrug
Also called placebo tablet
Placebo oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Placebo Oral Tablet | Placebo comparator | Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks Receives: Drug: Placebo |
| AGB101 220 mg tablet | Experimental | Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. Receives: Drug: AGB101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 78 weeks
Secondary outcomes (2)
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score From Baseline
CDR-SB scores at baseline will be subtracted from CDR-SB scores at week 78 to generate the change score from baseline, with a possible total range of -18 to 18. Positive change scores reflect greater impairment on the CDR-SB at week 78, while negative change scores reflect less impairment on the CDR-SB at week 78.
Measured: 78 weeks
Change in Clinical Dementia Rating Scale - Memory Box Score From Baseline
The CDR- memory box score at baseline will be subtracted from the CDR- memory box score at week 78 to generate the change score from baseline, with a possible total range of -3 to 3. Positive change scores reflect greater impairment on the CDR-SB at week 78, while negative change scores reflect less impairment on the CDR-SB at week 78.
Measured: 78 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start3 Dec 2024
- Primary completionJul 2028 (estimated)
- Study completionDec 2028 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AgeneBio
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05986721
- Sponsor's protocol ID
- AGB101 NE4
- Status last verified
- May 2025
- First submitted
- 3 Aug 2023
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101 on Slowing Progression of Mild Cognitive Impairment Due to Alzheimer's Disease in Apolipoprotein E4 Non-carriers
- ClinicalTrials.gov ID
- NCT05986721
- Acronym / sponsor ID
- AGB101 NE4
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AgeneBioIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 3 Dec 2024 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
AGB101 is hypothesized to slow the progression of MCI due to AD by restoring the entorhinal/hippocampal network balance. During this phase of the disease, fMRI studies show hippocampal over-activity and EC under-activity. As shown in the phase 2 study, AGB101 restores this network balance by attenuating hippocampal over-activity and restoring EC activity. Hippocampal over-activity predicts progression on EC atrophy (primary endpoint) and on CDR-SB (secondary endpoint). By restoring network balance, AGB101 is hypothesized to improve cognitive function (CDR-SB) and reduce neuronal injury (EC atrophy).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Placebo Oral Tablet | Placebo comparator | Drug: PlaceboMatching placebo to AGB101 tablet once daily, taken orally, for 78 weeks |
| AGB101 220 mg tablet | Experimental | Drug: AGB101Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Subjects between 55 and 85 years old (inclusive) in good general health:
- 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:
- Have an Apolipoprotein E (ApoE) genotype that does not include one or more E4 alleles.
- Permitted medications:
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGB101Also: levetiracetam, keppralow-dose levetiracetam, 220 mg, extended release tablet | Drug | AGB101 220 mg tablet |
| PlaceboAlso: placebo tabletPlacebo oral tablet | Drug | Placebo Oral Tablet |
Primary outcome
Change in Entorhinal Cortex (EC) Volume From Baseline
Time frame: 78 weeks
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.
2 secondary outcomes
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score From Baseline
Time frame: 78 weeks
Change in Clinical Dementia Rating Scale - Memory Box Score From Baseline
Time frame: 78 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AGB101 in people with Mild Cognitive Impairment and Prodromal Alzheimer's Disease, run by AgeneBio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Entorhinal Cortex (EC) Volume From Baseline (time frame: 78 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.