A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD).
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Crenezumab; Placebo
Intervention description: Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.; Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 813.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This randomized, double-blind, placebo-controlled, parallel group study will evaluate the
      efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD.
      Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab
      or placebo every 4 weeks (Q4W) for 100 weeks. The final efficacy and safety assessment will
      be performed 52 weeks after the last crenezumab dose. Participants will then have the option
      to enter the Open Label Extension (OLE) study if eligible. Participants who do not enter the
      OLE study will have additional follow-up visits at 16 and 52 weeks after the last dose,
      primarily for safety and also for limited efficacy assessments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Weight between 40 and 120 kilograms (Kg) inclusive

          -  Availability of a person (referred to as the "caregiver") who in the investigator's
             judgment:

          -  Has frequent and sufficient contact with the participant to be able to provide
             accurate information regarding the participant's cognitive and functional abilities,
             agrees to provide information at clinic visits (which require partner input for scale
             completion), signs the necessary consent form, and has sufficient cognitive capacity
             to accurately report upon the participant's behavior and cognitive and functional
             abilities

          -  Fluency in the language of the tests used at the study site

          -  Adequate visual and auditory acuity, in the investigator's judgment, sufficient to
             perform the neuropsychological testing (eye glasses and hearing aids are permitted)

          -  Evidence of the AD pathological process, by a positive amyloid assessment either on
             cerebrospinal fluid (CSF) amyloid beta 1-42 levels as measured on the Elecsys
             beta-amyloid(1-42) test system or amyloid PET scan by qualitative read by the
             core/central PET laboratory

          -  Demonstrated abnormal memory function at screening (up to 4 weeks before screening
             begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)

          -  Screening mini mental state examination (MMSE) score of greater than or equal to (>=)
             22 points and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1.0

          -  Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical
             criteria for probable AD dementia or prodromal AD (consistent with the NIAAA
             diagnostic criteria and guidelines for mild cognitive impairment (MCI)

          -  If receiving symptomatic AD medications, the dosing regimen must have been stable for
             3 months prior to screening

          -  Participant must have completed at least 6 years of formal education after the age of
             5 years

        Exclusion Criteria:

          -  Any evidence of a condition other than AD that may affect cognition such as other
             dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or
             infections with neurological sequelae.

          -  History of major psychiatric illness such as schizophrenia or major depression (if not
             considered in remission)

          -  At risk of suicide in the opinion of the investigator

          -  Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical
             stroke, etc or inability to tolerate MRI procedures or contraindication to MRI

          -  Unstable or clinically significant cardiovascular (e.g., myocardial infarction),
             kidney or liver disease

          -  Uncontrolled hypertension

          -  Screening hemoglobin A1c (HbA1C) >8%

          -  Poor peripheral venous access

          -  History of cancer except:

        If considered to be cured or If not being actively treated with anti-cancer therapy or
        radiotherapy

        - Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to
        chimeric, human, or humanized antibodies or fusion proteins