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

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)

The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.

Time frame: Baseline, Week 104

Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)

Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.

Time frame: Baseline, Week 104

Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)

The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.

Time frame: Baseline, Week 104

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)

FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (\*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words\*4. The minimum score is 0 (worse).

Time frame: Baseline, Week 104

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)

Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.

Time frame: Baseline, Week 104

Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)

The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.

Time frame: Baseline, Week 104

Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)

The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).

Time frame: Baseline, Week 104

Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)

CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.

Time frame: Baseline, Week 104

Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.

Time frame: Baseline, Week 104

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)

The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.

Time frame: Baseline, Week 156

Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)

The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.

Time frame: Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)

The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

Time frame: Baseline, Week 104

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)

An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Baseline up until a maximum of 4.5 years

Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)

Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Time frame: Baseline up until a maximum of 4.5 years

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)

The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.

Time frame: Baseline, Week 156

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)

The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.

Time frame: Baseline, Week 156

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)

The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.

Time frame: Baseline, Week 156

Time to Onset of Dementia at Week 156 (OLE Phase)

Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.

Time frame: Baseline, Week 156

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)

FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (\*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words\*4. The minimum score is 0 (worse).

Time frame: Baseline, Week 156

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)

Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.

Time frame: Baseline, Week 156

Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)

The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.

Time frame: Baseline, Week 156

Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.

Time frame: Baseline, Week 152

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)

The regions of the brain that were analyzed included cerebellum gray and composite reference.

Time frame: Baseline, Week 156

Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)

The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.

Time frame: Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)

The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

Time frame: Baseline, Week 156

Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)

Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Time frame: Baseline up until a maximum of 5 years