A Study of Gantenerumab in Participants With Mild Alzheimer Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Placebo; Gantenerumab
Intervention description: Participants received Placebo SC injection Q4W.; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 389.0
Sex: All
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      Part 1 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study
      will evaluate the efficacy and safety of gantenerumab in participants with mild Alzheimer
      disease. Participants will be randomized to receive either gantenerumab subcutaneously every
      4 weeks or placebo subcutaneously every 4 weeks. Approved Alzheimer medication is allowed if
      on stable dose for 3 months prior to screening. Part 2 is an open-label extension (OLE).

      A positron emission tomography (PET) imaging substudy will be conducted within the main
      study. Eligible participants who provide separate informed consent will undergo PET imaging
      scans using the radioligand florbetapir as a pharmacodynamic measure of changes in brain
      amyloid load over time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical diagnosis of probable mild Alzheimer disease (AD) based on National Institute
             of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related
             Disorders Association (NINCDS/ADRDA) criteria or major NCD based whether or not
             receiving AD approved medication

          -  Cerebral spinal fluid (CSF) result consistent with the presence of amyloid pathology

          -  Availability of a person ('caregiver') who in the investigator's judgment has frequent
             and sufficient contact with the participant, and is able to provide accurate
             information regarding the participant's cognitive and functional abilities

          -  Fluency in the language of the tests used at the study site

          -  Willingness and ability to complete all aspects of the study

          -  Adequate visual and auditory acuity, in the investigator's judgment, sufficient to
             perform the neuropsychological testing (eye glasses and hearing aids are permitted)

          -  If currently receiving approved medications for AD, the dosing regimen must have been
             stable for 3 months prior to screening

          -  Agreement not to participate in other research studies for the duration of this trial
             and its associated substudies

        PART 2 - All participants who have been randomized and are actively participating in the
        study are eligible for Part 2

        Exclusion Criteria:

          -  Dementia or neurocognitive disorder (NCD) due to a condition other than AD, including,
             but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy
             bodies, Huntington disease, or vascular dementia

          -  History or presence of clinically evident vascular disease potentially affecting the
             brain that in the opinion of the investigator has the potential to affect cognitive
             function

          -  History or presence of stroke within the past 2 years or documented history of
             transient ischemic attack within the last 12 months

          -  History or presence of systemic autoimmune disorders potentially causing progressive
             neurologic disease with associated cognitive deficits

          -  History of schizophrenia, schizoaffective disorder, or bipolar disorder

          -  Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years
             (nicotine use is allowed)

          -  History or presence of atrial fibrillation

          -  Within the last 2 years, unstable or clinically significant cardiovascular disease
             (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart
             Association Class II or higher)

          -  Uncontrolled hypertension

          -  Chronic kidney disease

          -  Impaired hepatic function

        PET imaging substudy, in addition to above:

        - Prior participation in other research study or clinical care within the last year such
        that the total radiation exposure would exceed the local or national annual limits

        Part 2 Participants who have been discontinued from the study