Study of AGB101 in Mild Cognitive Impairment Due to Alzheimer's Disease

NCT03486938 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: AGB101 MCDR56AG055416R01AG048349R01AG061091
• Study Type: interventional
• Target: 164
• Locations: 2 countries
• Sites: 24

Brief Summary

The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with mild cognitive impairment due to Alzheimer's Disease (MCI due to AD) also known as prodromal AD. 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 Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ).

Conditions

Mild Cognitive Impairment; Prodromal Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

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

  CDR-SB scores at baseline were 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.

  78 weeks

Secondary Outcomes (2)

• Change in Mini Mental Status Exam (MMSE) Score From Baseline

  78 weeks

• Change in Functional Activities Questionnaire (FAQ) 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 Oral Tablet

AGB101 220 mg tablet

EXPERIMENTAL

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

Drug: AGB101 220 mg tablet

Interventions

Placebo Oral Tablet DRUG

Placebo oral tablet

Placebo Oral Tablet

AGB101 220 mg tablet DRUG

220 mg AGB101 active compound

AGB101 220 mg 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 all the clinic visits for the duration of each visit, and who is able to provide an independent evaluation of the subject's functioning
• Have MCI due to AD 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 delayed recall in the International Shopping List Test (ISLT)
• A clinical dementia rating (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)
• 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 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 remain stable throughout the study

You may not qualify if:

• Use of anticonvulsant medications or excluded psychotropic medications within 3 months prior to the baseline visit
• 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
• Diagnosis of major depression or bipolar disorder, as described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed (DSM-5), within the past 3 years.
• 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 (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.
• Clinically significant abnormalities in B12 or thyroid function test that might interfere with 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 caregiver who has the ability to observe the subject during the study and can participate in clinical evaluations.
• Any use of excluded medications (e.g., antiepileptics, certain antidepressants or antipsychotics, antihistamines with anticholinergic properties, opiates)

Sponsors & Collaborators

• AgeneBio: lead
• National Institute on Aging (NIA): collaborator

Study Sites (24)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Senior Clinical Trials, Inc.

Laguna Hills, California, 92653, United States

Location

Excell Research Inc

Oceanside, California, 92056, United States

Location

The Mile High Research Center

Denver, Colorado, 80218, United States

Location

Boynton Beach Medical Research Institite

Boynton Beach, Florida, 33437, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Miami Jewish Health

Miami, Florida, 33137, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

IMIC Research

Palmetto Bay, Florida, 33157, United States

Location

The Roskamp Institute, Inc

Sarasota, Florida, 34243, United States

Location

Brain Matters Research

Stuart, Florida, 34997, United States

Location

NeuroStudies.net, LLC

Decatur, Georgia, 30033, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Memory Center/Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Global Medical Institutes LLC; Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Neurology Specialist of Monmouth County, PA

West Long Branch, New Jersey, 07764, United States

Location

Neurological Associates of Albany PC

Albany, New York, 12208, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Clinical Biotechnology Research Institute at RSFH

Charleston, South Carolina, 29401, United States

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Tablets

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Richard Mohs
• Organization: agenebio

richard.mohs@agenebio.com

317-997-3241

Study Officials

• Richard Mohs, PhD

  AgeneBio

  PRINCIPAL INVESTIGATOR

• Sharon Rosenzweig-Lipson, PhD

  AgeneBio

  STUDY DIRECTOR

• Russell Barton, MS

  AgeneBio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: April 3, 2018
• Study Start: December 13, 2018
• Primary Completion: November 2, 2022
• Study Completion: November 2, 2022
• Last Updated: May 17, 2024
• Results First Posted: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (23); CA (1)