A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease

Plain English Summary

A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease is a Phase 3 clinical trial sponsored by Eisai Inc. studying Early Alzheimer's Disease. This study tests lecanemab, an investigational drug, against a placebo to see if it can slow the progression of early Alzheimer's disease. It is for individuals diagnosed with mild cognitive impairment (MCI) due to Alzheimer's disease or mild Alzheimer's disease dementia. Participants will receive either lecanemab or a placebo through IV infusions or injections over 18 months, with a potential for an extended treatment period. Alternative treatments for early Alzheimer's include medications like acetylcholinesterase inhibitors and memantine, which manage symptoms but do not target the underlying disease pathology. The trial aims to enroll 1906 participants.

Official Summary

This study will be conducted to evaluate the efficacy of lecanemab in participants with early Alzheimer's disease (EAD) by determining the superiority of lecanemab compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of lecanemab in participants with EAD in the Extension Phase and whether the long-term effects of lecanemab as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase. Extension Phase Part B will continue dosing with lecanemab in countries where lecanemab may not be commercially available.

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals aged 50-90 with a diagnosis of MCI due to Alzheimer's disease or mild Alzheimer's disease dementia. Must have objective memory impairment and a confirmed presence of amyloid plaques in the brain. Participants cannot have other neurological conditions that could explain their cognitive impairment or a history of stroke or seizures in the past year. Individuals with certain psychiatric conditions like hallucinations or major depression may not be eligible. This trial is studying Early Alzheimer's Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how much a participant's cognitive and functional abilities decline over 18 months, with lower scores indicating slower progression of the disease. The specific primary outcome measures are: Core Study: Change from Baseline in the CDR-SB at 18 Months (Baseline, 18 months); Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) (From first dose of study drug up to approximately 51 months (including 3 months follow up) for the extension phase); Extension Phase: Change from Core Study Baseline in CDR-SB (Baseline up to Month 66); Extension Phase Part B: Number of Participants Exposed to Lecanemab (From 48th month in extension phase part A to the end of extension phase part B (up to 24 months)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is crucial for addressing the significant unmet need in treating early-stage Alzheimer's disease by investigating a therapy that targets the underlying amyloid pathology. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Early Alzheimer's Disease, where improved treatment options are needed.

Investor Insight

This Phase 3 trial for lecanemab, targeting the large and growing market of early Alzheimer's disease, represents a significant potential advancement with a high probability of approval if primary end Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1906 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of lecanemab and how it compares to other available treatments. Participation involves regular clinic visits for drug administration, cognitive assessments, and monitoring for side effects. You will need a study partner who can accompany you to appointments and provide information about your daily functioning. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 1,906 participants

Interventions

• DRUG: Lecanemab IV — Administered as IV infusion.
• DRUG: Placebo — Biweekly (once every 2 weeks) administered as IVinfusion.
• DRUG: Lecanemab SC — Administered weekly as a SC injection.

Primary Outcomes

• Core Study: Change from Baseline in the CDR-SB at 18 Months (Baseline, 18 months)
• Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) (From first dose of study drug up to approximately 51 months (including 3 months follow up) for the extension phase)
• Extension Phase: Change from Core Study Baseline in CDR-SB (Baseline up to Month 66)
• Extension Phase Part B: Number of Participants Exposed to Lecanemab (From 48th month in extension phase part A to the end of extension phase part B (up to 24 months))

Secondary Outcomes

• Core Study: Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at 18 Months (Baseline, 18 months)
• Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months (Baseline, 18 months)
• Core Study: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months (Baseline, 18 months)
• Core Study: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) at 18 Months (Baseline, 18 months)
• Core Study: Number of Participants Reporting One or More TEAEs (From first dose of study drug up to approximately 21 months (including 3 months follow-up))

Full Eligibility Criteria

Core Study: Inclusion Criteria

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer's disease - intermediate likelihood:

* Meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to Alzheimer's disease - intermediate likelihood
* Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of 0.5 or greater at Screening and Baseline
* Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer's disease dementia:

* Meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
* Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline

Key Inclusion Criteria that must be met by all participants:

* Objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II (WMS-IV LMII)
* Positive biomarker for brain amyloid pathology
* Male or female participants aged greater than or equal to (\>=) 50 and less than or equal to (\<=) 90 years, at the time of informed consent
* Mini mental state examination (MMSE) score \>=22 at Screening and Baseline and \<=30 at Screening and Baseline
* Body mass index (BMI) greater than (\>)17 and less than (\<) 35 at Screening
* If receiving an approved Alzheimer's disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer's disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naive participants for Alzheimer's disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non-Alzheimer's disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for participants in Japan
* Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant)
* Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

Extension Phase: Inclusion Criteria:

* Participants who have completed the Core Study (except de novo participants)
* Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase
* Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled
* Participants entering the SC (vial) substudy at Extension Phase Week 1, must be willing to participate, or continue participating in the amyloid positron emission tomography (PET) substudy. All participants must have an amyloid PET scan within 4 weeks before starting SC BAN2401
* Participants enrolling into the SC autoinjector substudy must have had at least 6 months exposure to BAN2401 10 mg/kg IV biweekly or at least 12 months exposure of BAN2401 Dose 1 subcutaneously weekly.
* Participants enrolling into the SC Dose 3 autoinjector substudy must have previously received BAN2401 by either IV administration and/or SC autoinjector administration and must have completed Visit 82 (Extension Week 79) at a minimum, regardless of previous route of administration

Extension Phase Part B: Inclusion Criteria:

• Must have completed Week 207 in the Extension Phase

Exclusion Criteria

* Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease
* History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
* Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or del

Trial Locations

• Banner Alzheimer's Institute- Clinical Trials Department, Phoenix, Arizona, United States
• Banner Sun Health Research, Sun City, Arizona, United States
• Neurological Associates of Tucson dba Center for Neurosciences, Tucson, Arizona, United States
• Neurology Center of North Orange County, Fullerton, California, United States
• Irvine Clinical Research, Irvine, California, United States
• University of California - Los Angeles, Los Angeles, California, United States
• Pacific Neuroscience Medical Group, Oxnard, California, United States
• Stanford University Medical Center, Palo Alto, California, United States
• Pacific Research Network, Inc, San Diego, California, United States
• Sharp Mesa Vista Hospital, San Diego, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment (MCI)
• Dementia
• Neurodegenerative Diseases
• Amyloid Pathology
• Cognitive Impairment
• Memory Loss
• Geriatric Medicine
• Neurology
• Clinical Trials

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