AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216 Week Study With an Extension Phase to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical Alzheimer's Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (A3 Trial)

Plain English Summary

AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid is a Phase 3 clinical trial sponsored by Eisai Inc. studying Preclinical Alzheimer's Disease, Early Preclinical Alzheimer's Disease. This study tests if a drug called lecanemab can help people with very early signs of Alzheimer's disease. It is for individuals aged 55-80 who have early signs of Alzheimer's and have specific markers of amyloid in their brain. Participants will receive either lecanemab or a placebo through IV infusion for about 4.5 years, with regular check-ups. The main alternative is watchful waiting or participation in other trials, as there are limited treatments for this early stage. The trial aims to enroll 1400 participants.

Official Summary

The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial). This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the Extension Phase.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 55 and 80 years old and have early signs of Alzheimer's with amyloid buildup in your brain. If you are younger than 65, you may need to have a family history of early-onset dementia or a specific gene (APOE4) to qualify. You cannot join if you have had a stroke or seizure recently, have certain medical conditions, or are pregnant or breastfeeding. This trial is studying Preclinical Alzheimer's Disease, Early Preclinical Alzheimer's Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will show if lecanemab is better than a placebo at preserving thinking and memory abilities and at reducing the buildup of amyloid in the brain over nearly four years. The specific primary outcome measures are: A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216 (Baseline, Week 216); A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 (Baseline, Week 216). 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 important because it addresses a critical need for treatments that can intervene in the earliest stages of Alzheimer's disease, potentially slowing its progression before significant sym 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 Preclinical Alzheimer's Disease, Early Preclinical Alzheimer's Disease, where improved treatment options are needed.

Investor Insight

This trial targets a large and growing market for Alzheimer's treatments, with lecanemab representing a significant advancement in disease-modifying therapies, suggesting a strong potential for market Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1400 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the study's goals, potential benefits, and risks, and what lecanemab is. Be prepared for regular clinic visits for infusions, cognitive tests, and medical evaluations over several years. Ensure your study partner is willing and able to provide regular updates on 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: 1,400 participants

Interventions

• DRUG: Lecanemab — IV infusion.
• DRUG: Placebo — IV infusion.

Primary Outcomes

• A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216 (Baseline, Week 216)
• A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 (Baseline, Week 216)

Secondary Outcomes

• A45 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 (Baseline, Week 96, Week 216)
• A45 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 (Baseline, Week 96, Week 216)
• A45 Trial: Change From Baseline in Cognitive Function Index (CFI) at Week 216 (Baseline, Week 216)
• A3 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 (Baseline, Week 216)

Full Eligibility Criteria

Inclusion criteria:

Participants must meet all of the following criteria to be included in this study:

1. Male or female, age 55 to 80 years inclusive at the time of informed consent, with a plasma biomarker result that is predictive of intermediate or elevated brain amyloid at Screening or known before Screening to have elevated or intermediate amyloid according to previous PET, cerebrospinal fluid (CSF), or plasma testing

   • Those 55 to 64 must have 1 of the following additional risk factors, given the relatively low rates of amyloid positivity less than (\<) 65 years, before screening:
   * First degree relative diagnosed with dementia onset before age 75, or
   * Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or
   * Known before screening to have elevated brain amyloid according to previous plasma biomarker results, PET imaging, or CSF testing
2. Global Clinical Dementia Rating (CDR) score of 0 at screening
3. Mini Mental State Examination score greater than or equal to (\>=) 27 (with educational adjustments) at screening.
4. Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at screening of \>=6
5. A45 Trial: Elevated brain amyloid pathology by amyloid PET: defined as approximately greater than (\>) 40 Centiloids on screening scan A3 Trial: Intermediate levels of brain amyloid pathology by amyloid PET: defined as approximately 20 to 40 Centiloids on screening scan
6. Has a study partner that is willing to participate as a source of information and has approximately weekly contact with the participant (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily function
7. Provide written (or electronic, if allowed per country-specific regulations) informed consent
8. Willing and able to comply with all aspects of the protocol

For extension phase :

1. Completed the Core Study, or meet the following progression criteria during the Core Study:

   * Two consecutive CDR visits with Global Scores \> zero when measured at least 6 months apart within the Core Study
   * The principal investigator's confirmation that the participant has clinically declined consistent progression to EAD
2. 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. The study partner must provide separate written informed consent for the Extension Phase. Study partners must continue to have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily functions
3. 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 (capacity to consent and the definition of a 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, Spain), they will not be enrolled
4. Willing and able to comply with all aspects of the protocol

Exclusion criteria:

Participants who meet any of the following criteria will be excluded from this study:

1. Females who are breastfeeding or pregnant at screening or baseline
2. Females of childbearing potential who:

   • Within 28 days before study entry, did not use a highly effective method of contraception For sites outside of Europe, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception
3. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
4. Current or history within the past 2 years of psychiatric diagnosis or symptoms that, in the opinion of the investigator, could interfere with study procedures
5. Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and cardiac devices other than those approved as safe for use in MRI scanners), or exhibit other significant pathological findings on brain MRI at Screening
6. Hypersensitivity to any monoclonal antibody treatment
7. Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
8. Bleeding disorder that is not under adequate control (inc

Trial Locations

• University of Alabama, Birmingham, Birmingham, Alabama, United States
• Banner Alzheimer's Institute, Phoenix, Arizona, United States
• Banner Sun Health Research Institute, Sun City, Arizona, United States
• UCI MIND, Irvine, California, United States
• University of Southern California, Los Angeles, California, United States
• Hoag Memorial Hospital Presbyterian, Newport Beach, California, United States
• Stanford University, Palo Alto, California, United States
• Sharp Mesa Vista Hospital, San Diego, California, United States
• University of California, San Francisco, San Francisco, California, United States
• University of California, Davis, Walnut Creek, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Preclinical Alzheimer's Disease
• Early Alzheimer's Disease
• Mild Cognitive Impairment
• Dementia
• Amyloidosis
• Neurodegenerative Diseases
• Cognitive Impairment
• Geriatric Medicine
• Neurology

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