Alzheimer's Disease
Conditions
Brief 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.
Interventions
DRUGGantenerumab
Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
DRUGPlacebo
Participants received Placebo SC injection Q4W.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) | Baseline up until a maximum of 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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). |
| Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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). |
| 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) | Baseline, Week 104 | 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. |
| Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging. |
| Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) | Baseline, Week 156 | The regions of the brain that were analyzed included cerebellum gray and composite reference. |
| Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101 | 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. |
| Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
| Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | Baseline up until a maximum of 4.5 years | 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. |
| Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Baseline, Week 156 | The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference. |
| Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) | Baseline, Week 156 | 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 to Onset of Dementia at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) | Baseline, Week 156 | 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). |
| Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) | Baseline, Week 152 | Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging. |
| Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101 | 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. |
| Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) | Baseline, Week 156 | 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. |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) | Baseline up until a maximum of 5 years | 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. |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Baseline up until a maximum of 4.5 years | 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. |
| Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) | Baseline, Week 104 | 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, Denmark, Finland, France, Germany, Italy, Mexico, Netherlands, Poland, Portugal, Russia, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 128 centers in 24 countries.
Pre-assignment details
A total of 799 participants were randomised in this study. Of these, a total of 797 participants were enrolled and received at least one dose of any study drug and represented the Safety population during the Double-Blind Treatment Phase (Parts 1 and 2 of the study). From the Double-Blind Treatment Phase, a total of 154 participants (at 53 sites) were enrolled into Open-Label Extension (OLE) Phase (Part 3 of the study).
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Parts 1 and 2) Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. | 266 |
| Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. | 271 |
| Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. | 260 |
| Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. | 49 |
| Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. | 105 |
| Total | 951 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind Treatment Phase | Adverse Event | 0 | 5 | 3 | 0 | 0 |
| Double-Blind Treatment Phase | Death | 3 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Phase | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Other | 0 | 0 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Participant/legal guardian decision | 7 | 8 | 8 | 0 | 0 |
| Double-Blind Treatment Phase | Parts 1 and 2 Termination by Sponsor | 62 | 68 | 63 | 0 | 0 |
| Double-Blind Treatment Phase | Physician Decision | 6 | 5 | 4 | 0 | 0 |
| Open-Label Extension (OLE) Phase | Adverse Event | 0 | 0 | 0 | 2 | 6 |
| Open-Label Extension (OLE) Phase | Death | 0 | 0 | 0 | 1 | 3 |
| Open-Label Extension (OLE) Phase | Other | 0 | 0 | 0 | 5 | 3 |
| Open-Label Extension (OLE) Phase | Physician Decision | 0 | 0 | 0 | 2 | 7 |
| Open-Label Extension (OLE) Phase | Withdrawal by Subject | 0 | 0 | 0 | 6 | 15 |
Baseline characteristics
| Characteristic | Placebo (Parts 1 and 2) | Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab 225 mg (Parts 1 and 2) | Total | Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) | Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) |
|---|---|---|---|---|---|---|
| Age, Continuous | 69.5 years STANDARD_DEVIATION 7.5 | 70.3 years STANDARD_DEVIATION 7 | 71.3 years STANDARD_DEVIATION 7.1 | 74.3 years STANDARD_DEVIATION 6.9 | 75.5 years STANDARD_DEVIATION 5.8 | 73.7 years STANDARD_DEVIATION 7.3 |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 Participants | 6 Participants | 5 Participants | 12 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 4 Participants | 7 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 2 Participants | 2 Participants | 5 Participants | — | — |
| Race/Ethnicity, Customized Hispanic | 41 Participants | 39 Participants | 47 Participants | 127 Participants | 10 Participants | 17 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 217 Participants | 221 Participants | 210 Participants | 648 Participants | 39 Participants | 88 Participants |
| Race/Ethnicity, Customized Not Available | 24 Participants | 18 Participants | 10 Participants | 52 Participants | — | — |
| Race/Ethnicity, Customized Unknown | — | — | — | 6 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 239 Participants | 252 Participants | 239 Participants | 730 Participants | 42 Participants | 101 Participants |
| Sex: Female, Male Female | 149 Participants | 152 Participants | 0 Participants | 91 Participants | 27 Participants | 64 Participants |
| Sex: Female, Male Male | 117 Participants | 119 Participants | 0 Participants | 63 Participants | 0 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 266 | 0 / 271 | 2 / 260 | 1 / 49 | 3 / 105 |
| other Total, other adverse events | 163 / 266 | 188 / 271 | 189 / 260 | 40 / 49 | 87 / 105 |
| serious Total, serious adverse events | 55 / 266 | 48 / 271 | 46 / 260 | 18 / 49 | 28 / 105 |
Outcome results
Primary
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment 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 104
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) | 1.19 Scores on a Scale | Standard Deviation 1.68 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) | 1.41 Scores on a Scale | Standard Deviation 2.02 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) | 1.47 Scores on a Scale | Standard Deviation 1.89 |
p-value: 0.674495% CI: [-0.248, 0.161]Mixed Models Analysis
p-value: 0.449495% CI: [-0.304, 0.135]Mixed Models Analysis
Primary
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE 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 5 years
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) | AEs | 46 Participants |
| Placebo (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) | SAEs | 18 Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) | AEs | 100 Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) | SAEs | 28 Participants |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 53 (Post-Dose) | 6.77 µg/ml (micrograms per milliliter) | Standard Deviation 3.94 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 20 (Pre-Dose) | 3.7 µg/ml (micrograms per milliliter) | Standard Deviation 2.15 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 68 (Pre-Dose) | 3.95 µg/ml (micrograms per milliliter) | Standard Deviation 2.35 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 1 (Post-Dose) | 3.56 µg/ml (micrograms per milliliter) | Standard Deviation 2.36 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 100 (Pre-Dose) | 4.35 µg/ml (micrograms per milliliter) | Standard Deviation 2.34 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 44 (Pre-Dose) | 4.08 µg/ml (micrograms per milliliter) | Standard Deviation 2.44 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 101 (Post-Dose) | 7.32 µg/ml (micrograms per milliliter) | Standard Deviation 3.53 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 8 (Pre-Dose) | 2.87 µg/ml (micrograms per milliliter) | Standard Deviation 1.84 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 101 (Post-Dose) | 16.63 µg/ml (micrograms per milliliter) | Standard Deviation 7.96 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 1 (Post-Dose) | 7.4 µg/ml (micrograms per milliliter) | Standard Deviation 4.28 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 20 (Pre-Dose) | 7.66 µg/ml (micrograms per milliliter) | Standard Deviation 4.14 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 44 (Pre-Dose) | 8.22 µg/ml (micrograms per milliliter) | Standard Deviation 4.51 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 53 (Post-Dose) | 15 µg/ml (micrograms per milliliter) | Standard Deviation 9.34 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 68 (Pre-Dose) | 8.91 µg/ml (micrograms per milliliter) | Standard Deviation 4.86 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 100 (Pre-Dose) | 9.4 µg/ml (micrograms per milliliter) | Standard Deviation 4.69 |
| Gantenerumab 105 mg (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) | Week 8 (Pre-Dose) | 5.92 µg/ml (micrograms per milliliter) | Standard Deviation 3.16 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 64 (Pre-Dose) | 33.0 µg/ml (micrograms per milliliter) | Standard Deviation 21.7 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 100 (Pre-Dose) | 39.2 µg/ml (micrograms per milliliter) | Standard Deviation 22.7 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 101 (Post-Dose) | 80.5 µg/ml (micrograms per milliliter) | Standard Deviation 37.8 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 104 (Pre-Dose) | 40.5 µg/ml (micrograms per milliliter) | Standard Deviation 22.5 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 136 (Pre-Dose) | 45.2 µg/ml (micrograms per milliliter) | Standard Deviation 22.4 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 156 (Pre-Dose) | 39.6 µg/ml (micrograms per milliliter) | Standard Deviation 28.2 |
| Placebo (Parts 1 and 2) | Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) | Week 208 (Pre-Dose) | 37.1 µg/ml (micrograms per milliliter) | Standard Deviation 29.2 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) | 3.68 Scores on a Scale | Standard Deviation 6.64 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) | 3.52 Scores on a Scale | Standard Deviation 6.28 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) | 3.97 Scores on a Scale | Standard Deviation 6.89 |
p-value: 0.745895% CI: [-0.179, 0.25]Mixed Models Analysis
p-value: 0.72395% CI: [-0.191, 0.275]Mixed Models Analysis
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) | 5.8 Scores on a Scale | Standard Deviation 7.3 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) | 8.9 Scores on a Scale | Standard Deviation 9.7 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) | 8.0 Scores on a Scale | Standard Deviation 8.2 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) | 10.4 Scores on a Scale | Standard Deviation 10.6 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) | -1.72 Z-Score | Standard Deviation 2.99 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) | -1.37 Z-Score | Standard Deviation 2.74 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) | -1.4 Z-Score | Standard Deviation 3.11 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) | -1.93 Z-Score | Standard Deviation 3.08 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) | 0.1 Scores on a Scale | Standard Deviation 0.29 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) | 0.18 Scores on a Scale | Standard Deviation 0.36 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) | 0.14 Scores on a Scale | Standard Deviation 0.33 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) | 0.1 Scores on a Scale | Standard Deviation 0.31 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) | 0.6 Scores on a Scale | Standard Deviation 0.6 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) | 0.5 Scores on a Scale | Standard Deviation 0.6 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) | 3.3 Scores on a Scale | Standard Deviation 2.4 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) | 2.8 Scores on a Scale | Standard Deviation 3 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) | -4.05 Scores on a Scale | Standard Deviation 8.73 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) | -4.11 Scores on a Scale | Standard Deviation 8.57 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) | -6.42 Scores on a Scale | Standard Deviation 8.45 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) | -4.05 Scores on a Scale | Standard Deviation 8.68 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) | -7.7 Scores on a Scale | Standard Deviation 9.3 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) | -4.1 Scores on a Scale | Standard Deviation 8.3 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) | 3.59 Scores on a Scale | Standard Deviation 4.93 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) | 4.89 Scores on a Scale | Standard Deviation 6.2 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) | 4.03 Scores on a Scale | Standard Deviation 5.75 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) | 3.6 Scores on a Scale | Standard Deviation 4.93 |
p-value: 0.082595% CI: [-0.407, 0.025]Mixed Models Analysis
p-value: 0.717195% CI: [-0.19, 0.276]Mixed Models Analysis
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) | 8.1 Scores on a Scale | Standard Deviation 5.3 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) | 6.8 Scores on a Scale | Standard Deviation 6.8 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) | -2.31 Scores on a Scale | Standard Deviation 3.23 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) | -2.46 Scores on a Scale | Standard Deviation 3.68 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) | -2.25 Scores on a Scale | Standard Deviation 3.31 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) | -4.3 Scores on a Scale | Standard Deviation 4.3 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) | -4.7 Scores on a Scale | Standard Deviation 4.6 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) | 0.6 Scores on a Scale | Standard Deviation 3.22 |
| Gantenerumab 105 mg (Parts 1 and 2) | Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) | 0.39 Scores on a Scale | Standard Deviation 2.57 |
| Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) | 0.34 Scores on a Scale | Standard Deviation 2.84 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) | 0.72 Scores on a Scale | Standard Deviation 3.35 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | AEs | 250 Participants |
| Placebo (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | SAEs | 55 Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | AEs | 241 Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | SAEs | 48 Participants |
| Gantenerumab 225 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | AEs | 240 Participants |
| Gantenerumab 225 mg (Parts 1 and 2) | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) | SAEs | 46 Participants |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | 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) | p-tau (Week 104) | 2.77 Percentage Change | Standard Deviation 20.69 |
| Placebo (Parts 1 and 2) | 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) | Abeta (Week 104) | 4.87 Percentage Change | Standard Deviation 36.14 |
| Placebo (Parts 1 and 2) | 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) | t-tau (Week 104) | 3.43 Percentage Change | Standard Deviation 19.95 |
| Gantenerumab 105 mg (Parts 1 and 2) | 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) | p-tau (Week 104) | -4.78 Percentage Change | Standard Deviation 11.9 |
| Gantenerumab 105 mg (Parts 1 and 2) | 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) | Abeta (Week 104) | 2.45 Percentage Change | Standard Deviation 24.57 |
| Gantenerumab 105 mg (Parts 1 and 2) | 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) | t-tau (Week 104) | -1.36 Percentage Change | Standard Deviation 12.89 |
| Gantenerumab 225 mg (Parts 1 and 2) | 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) | t-tau (Week 104) | -2.12 Percentage Change | Standard Deviation 11.01 |
| Gantenerumab 225 mg (Parts 1 and 2) | 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) | p-tau (Week 104) | -7.34 Percentage Change | Standard Deviation 10.09 |
| Gantenerumab 225 mg (Parts 1 and 2) | 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) | Abeta (Week 104) | 15.2 Percentage Change | Standard Deviation 45.24 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | 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) | p-tau (Week 104) | 2.84 Percentage Change | Standard Deviation 23.19 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | 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) | Abeta (Week 104) | 4.3 Percentage Change | Standard Deviation 39.31 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | 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) | t-tau (Week 104) | 3.46 Percentage Change | Standard Deviation 22.32 |
Comparison: Statistical analysis of the Abeta 1-42 CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 105 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.9734Mixed Models Analysis
Comparison: Statistical analysis of the Abeta 1-42 CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 225 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.0629Mixed Models Analysis
Comparison: Statistical analysis of the p-tau CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 105 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.0084Mixed Models Analysis
Comparison: Statistical analysis of the p-tau CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 225 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.0003Mixed Models Analysis
Comparison: Statistical analysis of the t-tau CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 105 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.0903Mixed Models Analysis
Comparison: Statistical analysis of the t-tau CSF biomarker between Placebo (Parts 1 and 2) and Gantenerumab 225 mg (Parts 1 and 2) treatment arms at Week 104.p-value: 0.0434Mixed Models Analysis
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Cerebellum gray (Week 156) | 6.26 Percentage Change | Standard Deviation 9.1 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Whole Cerebellum (Week 156) | 5.41 Percentage Change | Standard Deviation 7.13 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite White Matter (Week 156) | 2.75 Percentage Change | Standard Deviation 3.18 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Subcortical White Matter (Week 156) | 4.83 Percentage Change | Standard Deviation 4.95 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Pons (Week 156) | 1.72 Percentage Change | Standard Deviation 2.51 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite Reference (Week 156) | 4.5 Percentage Change | Standard Deviation 3.48 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite Reference (Week 156) | 1.19 Percentage Change | Standard Deviation 5.63 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Subcortical White Matter (Week 156) | 1.69 Percentage Change | Standard Deviation 4.45 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Cerebellum gray (Week 156) | 2.7 Percentage Change | Standard Deviation 10.59 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite White Matter (Week 156) | -0.87 Percentage Change | Standard Deviation 2.95 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Whole Cerebellum (Week 156) | 2.07 Percentage Change | Standard Deviation 8.65 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Pons (Week 156) | -2.83 Percentage Change | Standard Deviation 3.39 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Whole Cerebellum (Week 156) | -8.44 Percentage Change | Standard Deviation 8.06 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite White Matter (Week 156) | -4.86 Percentage Change | Standard Deviation 6.35 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Subcortical White Matter (Week 156) | -0.42 Percentage Change | Standard Deviation 8.26 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite Reference (Week 156) | -6.75 Percentage Change | Standard Deviation 6.1 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Pons (Week 156) | -6.99 Percentage Change | Standard Deviation 5.65 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Cerebellum gray (Week 156) | -8.36 Percentage Change | Standard Deviation 9.11 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Pons (Week 156) | 2.1 Percentage Change | Standard Deviation 2.73 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite Reference (Week 156) | 4.46 Percentage Change | Standard Deviation 4.49 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Whole Cerebellum (Week 156) | 5.17 Percentage Change | Standard Deviation 8.66 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Subcortical White Matter (Week 156) | 4.59 Percentage Change | Standard Deviation 0.55 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Cerebellum gray (Week 156) | 5.95 Percentage Change | Standard Deviation 11.13 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) | Composite White Matter (Week 156) | 3.07 Percentage Change | Standard Deviation 2.07 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) | Cerebellum gray (Week 156) | -0.2 Percentage Change | Standard Deviation 0.2 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) | Composite Reference (Week 156) | -41.4 Percentage Change | Standard Deviation 29.9 |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HRV (Week 104) | -7.61 Percentage Change | Standard Deviation 4.03 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HLV (Week 104) | -7.8 Percentage Change | Standard Deviation 4.28 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HLV (Week 104) | -7.76 Percentage Change | Standard Deviation 3.74 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HRV (Week 104) | -7.52 Percentage Change | Standard Deviation 3.96 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HRV (Week 104) | -7.34 Percentage Change | Standard Deviation 3.84 |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HLV (Week 104) | -7.27 Percentage Change | Standard Deviation 3.78 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HRV (Week 104) | -7.7 Percentage Change | Standard Deviation 4.01 |
| Placebo Match Gantenerumab 225 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) | HLV (Week 104) | -8.12 Percentage Change | Standard Deviation 4.19 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) | HRV (Week 152) | 16.7 Percentage Change | Standard Deviation 8.4 |
| Placebo (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) | HLV (Week 152) | 16.2 Percentage Change | Standard Deviation 13 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) | HRV (Week 152) | 16.1 Percentage Change | Standard Deviation 8.2 |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) | HLV (Week 152) | 18.0 Percentage Change | Standard Deviation 8.9 |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Baseline ADAs | 5.8 Percentage of Participants |
| Placebo (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Treatment Emergent ADAs | 5.0 Percentage of Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Baseline ADAs | 7.5 Percentage of Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Treatment Emergent ADAs | 7.0 Percentage of Participants |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Baseline ADAs | 5.5 Percentage of Participants |
| Gantenerumab 225 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) | Treatment Emergent ADAs | 6.4 Percentage of Participants |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) | Baseline ADAs | 2.0 Percentage of Participants |
| Placebo (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) | Treatment Emergent ADAs | 2.2 Percentage of Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) | Baseline ADAs | 5.8 Percentage of Participants |
| Gantenerumab 105 mg (Parts 1 and 2) | Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) | Treatment Emergent ADAs | 2.9 Percentage of Participants |
Secondary
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
Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Parts 1 and 2) | Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) | 63.64 Days |
| Gantenerumab 105 mg (Parts 1 and 2) | Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) | 62.98 Days |
| Gantenerumab 225 mg (Parts 1 and 2) | Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) | 70.64 Days |
Secondary
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
Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Parts 1 and 2) | Time to Onset of Dementia at Week 156 (OLE Phase) | 38.18 Days |
| Gantenerumab 105 mg (Parts 1 and 2) | Time to Onset of Dementia at Week 156 (OLE Phase) | 50.82 Days |