- Site Principal Investigator: Julio Rojas-Martinez, MD, PhD
- Sponsor: Eisai Inc.
- Status: Recruiting
- Official Study Title: AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216-Week Study 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)
- ClinicalTrials.gov Identifier: NCT04468659
- Conditions Studied: Preclinical or early preclinical Alzheimer’s disease (AD)
- Intervention: Lecanemab and placebo control
- Phase: Phase 3
- Duration of Participation: 4 years
Purpose of the Study
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). For more details, please see the AHEAD study website.
Eligibility
- 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 PET or CSF testing
- Global Clinical Dementia Rating (CDR) score of 0 at screening
- Mini Mental State Examination score greater than or equal to (>=) 27 (with educational adjustments) at screening
- Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at screening of >=6
- 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
- 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
- Provide written (or electronic, if allowed per country-specific regulations) informed consent
- Willing and able to comply with all aspects of the protocol
- Females who are breastfeeding or pregnant at screening or baseline
- 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
- History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
- 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
- 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
- Hypersensitivity to any monoclonal antibody treatment
- 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
- Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5) at screening
- Results of laboratory tests conducted during the screening that are outside the following limits:
- Thyroid stimulating hormone (TSH) above normal range
- Abnormally low (below lower limit of normal [LLN]) serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the LLN for the testing laboratory). A low vitamin B12 is exclusionary, unless the required follow-up labs (homocysteine and methylmalonic acid [MMA]) indicate that it is not physiologically significant
- Known to be human immunodeficiency virus (HIV) positive
- Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
- Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants with treatment cycles completed at least 6 months before screening). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before screening need not be excluded
- Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before screening, at screening, or at baseline, or has been hospitalized or treated for suicidal behavior in the past 5 years before screening
- Known or suspected history of drug or alcohol abuse or dependence within 2 years before screening or a positive urine drug test at screening. Participants who test positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug testing need not be excluded unless in the clinical opinion of the investigator this is due to potential drug abuse
- Taking prohibited medications
- Participation in a clinical study involving:
- Any anti-amyloid immunotherapy (example, therapeutic monoclonal antibody or active anti-amyloid vaccine) at any time, unless it can be documented that the participant was randomized to placebo or never received study drug
- Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless it can be documented that the participant was randomized to placebo or never received study drug
- Lecanemab
- Any new chemical entities or investigational drug for AD within 6 months before screening unless it can be documented that the participant received only placebo
- Any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the participant was in a placebo treatment arm
- Planned surgery during the prerandomization phase or within 3 months of randomization, which requires general anesthesia
What to Expect
Over the course of the 4 years you will:
- Be randomly assigned to a study group: Lecanemab (study drug) or placebo (saline solution, containing no active drug product). You do not get to pick your study group. You and your study doctor will not know if you are on the study drug or placebo.
- Come into the UCSF clinic for 22 study visits
- Have 55 intravenous (into the vein, or IV) infusions of lecanemab or placebo every 4 weeks for about 4 years
- Undergo brain scans (MRI and PET)
- Complete questionnaires and undergo tests of your memory and daily functioning, including computerized testing
- Undergo blood draws
Materials Needed Before Evaluation: A biomarker result that is predictive of intermediate or elevated brain amyloid at screening
Costs: No costs will be charged for any of the study procedures. Parking will be validated at UCSF public garages for all study visits, and participants will be reimbursed up to $50 for each scheduled visit to the clinic to help defray any incidental expenses incurred in the course of participating in this study.
Contact Information
Coordinator: Claudio Gamboa – [email protected], 415.476.0669
Clinical Trials Nurse: Mary Koestler, RN, PhD, CCRC – [email protected], 415.476.0661
