A Study of Gantenerumab in Patients With Prodromal Alzheimer's Disease

• To evaluate the effect on the change in the Clinical Dementia Rating scale Sum of Boxes (CDR-SOB), a global measure of cognition and functional ability [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Substudy: Change in brain amyloid over time assessed with Positron Emission Tomography [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Effect on cognition assessed with the Alzheimer Disease Assessment Scale-Cognition [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Effect on functioning assessed with the Functional Activities Questionnaire [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Safety (nature and incidence of adverse events) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• Pharmacokinetics: gantenerumab levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Effect on cognition assessed with Alzheimer Disease Assessment Scale-Cognition [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Effect on functioning assessed with Functional Activities Questionnaire [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Safety (nature and incidence of adverse events) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Pharmacokinetics: gantenerumab levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]

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 patients with prodromal Alzheimer's Disease. Patients will be randomized to receive subcutaneous injections of either gantenerumab or placebo. Patients 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, with an option for an additional 2 years of treatment.

• Drug: gantenerumab
  225 mg subcutaneous doses every 4 weeks for 104 weeks
• Drug: gantenerumab
  105 mg subcutaneous doses every 4 weeks for 104 weeks
• Drug: placebo
  subcutaneous doses every 4 weeks for 104 weeks

• Experimental: 1
  Intervention: Drug: gantenerumab
• Experimental: 2
  Intervention: Drug: gantenerumab
• Placebo Comparator: 3
  Intervention: Drug: placebo

Inclusion Criteria:

• Adult patients, 50-85 years of age
• Patients 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 subject as to be able to provide accurate information as to the patient'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 patient's memory (e.g. over the last 12 months), which the patient may or may not be aware of
• Screening MMSE score of 24 or above

Additional inclusion criteria for sub study:

• Able and willing to travel to Positron Emission Tomography 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 (e.g. 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