preclinical AD early preclinical AD
Conditions
Sponsors
Eisai Co., Ltd.
Alzheimer's Clinical Trial Consortium (ACTC), Biogen, National Institute on Aging (NIA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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: -First degree relative diagnosed with dementia onset before age 75, or -Known to possess at least 1 apolipoprotein EKnown 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 CDR score of 0 at Screening 3. Mini Mental State Examination (MMSE) score >-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
Exclusion criteria: 1. Females who are breastfeeding or pregnant at Screening or Baseline 2. Females of childbearing potential who wiithin 28 days before study entry, did not use a highly effective method of contraception, or who do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation 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 (including a platelet count 1.5) at Screening 9. Results of laboratory tests conducted during Screening that are outside the following limits: -Thyroid stimulating hormone (TSH) above normal range -Abnormally low (below lower limit of normal) 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 10. Known to be human immunodeficiency virus (HIV) positive 11. Any other clinically significant abnormalities that require further investigation or treatment or may interfere with study procedures or safety 12. 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 13. 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. 14. 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 15. Taking prohibited medications 16. Participation in a clinical study involving: -Any anti-amyloid plaque lowering immunotherapy (eg, 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 stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy A45 Trial : -Change from baseline of the PACC5 at 216 weeks of treatment A3 Trial : -Brain amyloid accumulation as measured by amyloid PET at 216 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy A45 Trial : -Brain amyloid levels as measured by amyloid PET at 96 and 216 weeks of treatment -Brain tau pathology as measured by tau PET at 96 and 216 weeks of treatment A3 Trial : -Brain amyloid accumulation as measured by amyloid PET at 216 weeks of treatment Safety A45 Trial : -Safety and tolerability of BAN2401 relative to placebo A3 Trial : -Safety and tolerability of BAN2401 relative to placebo | — |
Countries
Australia, Canada, Japan, Netherlands, North America, Singapore, Spain, Sweden, United Kingdom
Outcome results
None listed