A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Gantenerumab; Placebo
Intervention description: Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.; Participants received Placebo SC injection Q4W.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 799.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This multi-center, randomized, double-blind, placebo-controlled parallel-group study will
      evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety
      and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be
      randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo.
      Participants who consent to be part of the sub study will undergo positron emission
      tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is
      104 weeks in Part 1, with an option for an additional up to 2 years of treatment in Part 2,
      followed by an open-label extension (Part 3) until July 2020.

      The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a
      low probability of meeting the primary outcome measure with the doses studied. The study has
      converted to open-label to investigate higher gantenerumab doses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants, 50-85 years of age

          -  Participants with prodromal Alzheimer's disease who are not receiving memantine or
             cholinesterase inhibitors

          -  Has a study partner who in the investigator's judgement has frequent and sufficient
             contact with the participant as to be able to provide accurate information as to the
             participant's cognitive and functional abilities, who agrees to provide information at
             clinic visits which require partner input for scale completion

          -  Has had sufficient education or work experience to exclude mental retardation

          -  Study partner has noticed a recent gradual decrease in participant's memory (over the
             last 12 months), which the participant may or may not be aware of

          -  Screening Mini Mental State Exam (MMSE) score of 24 or above

        Additional inclusion criteria for sub study:

          -  Able and willing to travel to PET imaging center and complete the planned scanning
             sessions

          -  Past and planned exposure to ionizing radiation not exceeding safe and permissible
             levels

        Exclusion Criteria:

          -  Other prior or current neurologic or medical disorder which may currently or during
             the course of the study impair cognition or psychiatric functioning

          -  A history of stroke

          -  A documented history of transient ischemic attack within the last 12 months

          -  History of schizophrenia, schizoaffective or bipolar disorder

          -  Currently meets criteria for major depression

          -  Within the last 2 years, unstable or clinical significant cardiovascular disease
             (myocardial infarction, angina pectoris)

        Additional exclusion criteria for sub study:

          -  Inclusion in a research and/or medical protocol involving PET ligands or other
             radioactive agents within 12 months

          -  Present or planned participation in a research and/or medical protocol involving PET
             ligands or radioactive agents other than study WN25203

          -  Have planned or are planning to have exposure to ionizing radiation that in
             combination with the planned administration with study amyloid PET ligand would result
             in a cumulative exposure that exceeds local recommended exposure limits