A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Elenbecestat; Placebo
Intervention description: Oral tablet.; Oral tablet.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2212.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Elenbecestat; E2609; Alzheimer's Disease; Early Alzheimer's Disease; Prodromal Alzheimer's Disease; Dementia; Dementia, Alzheimer's type; Mild Cognitive Impairment; MissionAD1

Summary:

      The name of this trial is MissionAD1. This phase 3 study consists of a Core and Open Label
      Extension (OLE) Phase in participants with Early Alzheimer's Disease (EAD), and will be
      conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment,
      multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month
      treatment, one group study. The data for the studies E2609-G000-301 (NCT02956486, MissionAD1)
      and E2609-G000-302 (NCT03036280, MissionAD2) will be pooled.
    

Eligibility criteria:

        Inclusion Criteria:

        Core Study

          -  Mild cognitive impairment due to Alzheimer's disease (AD) or mild AD dementia
             including

               1. Mini Mental State Examination score equal to or greater than 24

               2. Clinical Dementia Rating (CDR) global score of 0.5

               3. CDR Memory Box score of 0.5 or greater

          -  Impaired episodic memory confirmed by a list learning task

          -  Positive biomarker for brain amyloid pathology as indicated by either amyloid positron
             emission tomography or cerebrospinal fluid AD assessment or both

        Extension Phase

        • Participants who complete the Core Study

        Exclusion Criteria:

        Core Study

          -  Females who are breastfeeding or pregnant at Screening or Baseline. Females of
             child-bearing potential must use a highly effective method of contraception throughout
             the entire study period and for 28 days after study drug discontinuation

          -  Any condition that may be contributing to cognitive impairment above and beyond that
             caused by the participant's AD

          -  Participants with a history of seizures within 5 years of Screening

          -  History of transient ischemic attacks or stroke within 12 months of Screening

          -  Psychiatric diagnosis or symptoms (example, hallucinations, major depression,
             delusions etc.)

          -  Suicidal ideation or any suicidal behavior within 6 months before Screening or has
             been hospitalized or treated for suicidal behavior in the past 5 years

          -  Have any contraindications to magnetic resonance imaging (MRI) scanning or

               1. Have lesions that could indicate a dementia diagnosis other than AD on brain MRI

               2. Exhibit other significant pathological findings on brain MRI.

          -  Participants who have a history of moderate to severe hepatic impairment (example,
             Child-Pugh Class B or C)

          -  Results of laboratory tests conducted during Screening that are outside the following
             limits:

               1. Absolute lymphocyte count below the lower limit of normal (LLN)

               2. Thyroid stimulating hormone above normal range

               3. Abnormally low Vitamin B12 levels

          -  Participants at increased risk of infection

          -  Have received any live vaccine/live attenuated vaccine in the 3 months before
             randomization

          -  Any chronic inflammatory disease that is not adequately controlled or that requires
             systemic immunosuppressive or immunomodulatory therapy

          -  Any other clinically significant abnormalities

          -  Severe visual or hearing impairment

          -  A prolonged corrected QT (QTc) interval (QT interval with Fridericia's correction
             [QTcF] greater than 450 milliseconds [ms])

          -  Malignant neoplasms within 5 years of Screening

          -  Known or suspected history of drug or alcohol abuse

          -  Taking prohibited medications, which must be reviewed with the Investigator

          -  Have participated in a recent clinical study

        Note: Other protocol-defined Inclusion/Exclusion Criteria may apply.