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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

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ClinicalTrials.gov Identifier: NCT04468659
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : November 23, 2020
Sponsor:
Collaborators:
Alzheimer's Clinical Trial Consortium (ACTC)
Biogen
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Eisai Inc.

Brief 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).

Condition or disease Intervention/treatment Phase
Preclinical Alzheimer's Disease Early Alzheimer's Disease Drug: Lecanemab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : July 13, 2020
Estimated Primary Completion Date : October 25, 2027
Estimated Study Completion Date : October 25, 2027


Arm Intervention/treatment
Experimental: A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg
Participants will receive lecanemab 5 milligram per kilogram (mg/kg), administered as intravenous (IV) infusion, every two weeks through 8 weeks, then 10 mg/kg, administered as IV infusion, every two weeks through 96 weeks, and 10 mg/kg, administered as IV infusion, every four weeks through 216 weeks.
Drug: Lecanemab
IV infusion.
Other Name: BAN2401

Placebo Comparator: A45 Trial: Placebo
Participants will receive placebo (0.9 percent [%] sodium chloride solution), administered as IV infusion, every two weeks through 96 weeks then every four weeks through 216 weeks.
Drug: Placebo
IV infusion.

Experimental: A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg
Participants will receive lecanemab 5 mg/kg, administered as IV infusion, every four weeks through 8 weeks, then 10 mg/kg, administered as IV infusion, every four weeks through 216 weeks.
Drug: Lecanemab
IV infusion.
Other Name: BAN2401

Placebo Comparator: A3 Trial: Placebo
Participants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks through 216 weeks.
Drug: Placebo
IV infusion.




Primary Outcome Measures :
  1. A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216 [ Time Frame: Baseline, Week 216 ]
    PACC5(5 components):Free/cued selective reminding test:number of words recalled without cuing/with cuing(0[worst]-96[best recall]);Delayed Paragraph Recall test:free recall of 1 short story(25 bits information),immediately after reading and again after delay of 30 minutes.Total bits of information recalled is noted(0[worst]-25[best recall]);Digital-symbol substitution test:small blank squares with 1 of 9 numbers printed and key above square.Participant use key to fill in blank squares as fast in 90 seconds(0[none]-91[best performance]);Mini Mental State Score:to evaluate orientation,memory,attention,concentration,naming,repetition,comprehension and ability to create sentence,to copy 2 overlapping pentagons,scored as number of correctly completed items(0[worse]-30[perfect performance]);Category fluency task:participants generating words in 60 second belonging to semantic category(total score:number of appropriate words generated per task,higher values indicate better performance).

  2. A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 [ Time Frame: Baseline, Week 216 ]

Secondary Outcome Measures :
  1. A45 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 [ Time Frame: Baseline, Week 96, Week 216 ]
  2. A45 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 [ Time Frame: Baseline, Week 96, Week 216 ]
  3. A45 Trial: Change From Baseline in Cognitive Function Index (CFI) at Week 216 [ Time Frame: Baseline, Week 216 ]
    CFI assessment includes 15 questions that assess the participant's perceived ability to perform high-level functional tasks in daily life and sense of overall cognitive functional ability. Study participants and their study partners independently rate the participant's abilities. Total scores range from 0 to 15 (yes=1; no=0; maybe=0.5 for each question) with higher scores indicating greater impairment.

  4. A3 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 [ Time Frame: Baseline, Week 216 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

    • 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:

    • 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 cerebrospinal fluid (CSF) testing. Individuals with historical amyloid PET scans with intermediate brain amyloid (example, from preclinical Alzheimer's disease (AD) studies such as A4 or EARLY) are eligible to be screened, provided the participant did not participate in any clinical studies involving anti-amyloid therapies subsequent to the PET assessment
  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 informed consent
  8. 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 the European union (EU), 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 magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants 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 <50,000 or international normalized ratio [INR] >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 [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
  10. Known to be human immunodeficiency virus (HIV) positive
  11. 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
  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 therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months before screening (anti-amyloid therapies within 1 year 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
  17. Planned surgery during the prerandomization phase or within 3 months of randomization, which requires general anesthesia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04468659


Contacts
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Contact: Eisai Medical Information +1-888-274-2378 esi_medinfo@eisai.com
Contact: ACTC Recruitment Unit ahead-participate@usc.edu

Locations
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United States, Florida
University of South Florida - Health Byrd Alzheimer Institute Recruiting
Tampa, Florida, United States, 33613
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40504
United States, Rhode Island
Butler Hospital Memory and Aging Program Recruiting
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
Eisai Inc.
Alzheimer's Clinical Trial Consortium (ACTC)
Biogen
National Institute on Aging (NIA)
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT04468659    
Other Study ID Numbers: BAN2401-G000-303
R01AG054029 ( U.S. NIH Grant/Contract )
R01AG063689 ( U.S. NIH Grant/Contract )
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: November 23, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
BAN2401
Preclinical Alzheimer's disease
Elevated amyloid
Early preclinical Alzheimer's disease
Intermediate amyloid
A45 Trial
A3 Trial
AHEAD 3-45
Lecanemab
Additional relevant MeSH terms:
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Alzheimer Disease
Amyloidosis
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Proteostasis Deficiencies
Metabolic Diseases