Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: Gantenerumab; Placebo
Intervention description: Gantenerumab will be administered as per the schedule specified in the respective arm.; Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 975.0
Sex: All
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      This randomized, double-blind, placebo-controlled, parallel group study will evaluate the
      efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to
      mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible
      participants will be randomized 1:1 to receive either subcutaneous (SC) injection of
      gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the
      double blind period at week 116. Participants will then be offered to enter into an
      open-label extension (OLE). Participants not willing to go to the OLE will participate in a
      long term follow-up period for up to 50 weeks after the last gantenerumab dose.
    

Eligibility criteria:

        Key Inclusion criteria:

          -  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)

          -  Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid
             PET scan

          -  Demonstrated abnormal memory function

          -  MMSE score greater than or equal to 22 (≥ 22)

          -  Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0

          -  Availability of a reliable study partner who accepts to participate in study
             procedures throughout the 2 years duration of study

          -  If receiving symptomatic AD medications, the dosing regimen must have been stable for
             3 months prior to screening and until randomization

          -  For enrollment in the China extension, patients must have residence in mainland China,
             Hong Kong, or Taiwan and be of Chinese ancestry

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods

        Key Exclusion criteria:

          -  Any evidence of a condition other than AD that may affect cognition

          -  History of schizophrenia, schizoaffective disorder, major depression, or bipolar
             disorder

          -  History or presence of clinically evident systemic vascular disease that in the
             opinion of the investigator has the potential to affect cognitive function

          -  History or presence of clinically evident cerebrovascular disease

          -  History or presence of posterior reversible encephalopathy syndrome

          -  History or presence of any stroke with clinical symptoms within the past 12 months, or
             documented history within the last 6 months of an acute event that is consistent with
             a transient ischemic attack

          -  History of severe, clinically significant CNS trauma

          -  History or presence of intracranial mass (e.g., glioma, meningioma) that could
             potentially impair cognition

          -  Presence of infections that affect brain function or history of infections that
             resulted in neurologic sequelae

          -  History or presence of systemic autoimmune disorders that potentially cause
             progressive neurologic disease with associated cognitive deficits

          -  At risk for suicide in the opinion of the investigator

          -  Alcohol and/or substance abuse or dependants in past 2 years

          -  Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

          -  Any contraindications to brain MRI

          -  Unstable or clinically significant cardiovascular, kidney or liver disease

          -  Uncontrolled hypertension

          -  Unstable or clinically significant cardiovascular disease

          -  Abnormal thyroid function

          -  Patients with evidence of folic acid deficiency

        Exclusion for Open-Label Extension (OLE):

          -  Discontinued from study treatment during the double-blind treatment period

          -  Received any other investigational medication during the double-blind treatment period
             or after the end of double-blind treatment

          -  Participation in the OLE deemed inappropriate by the investigator

          -  Presence of ARIA-E findings at the Week 116 MRI scan