Alzheimer Disease
Conditions
Brief summary
This is an open-label, multicenter, rollover study to evaluate the safety, tolerability, and efficacy of long-term administration of open-label gantenerumab in participants with AD who completed Study WN29922 or WN39658, either the double-blind or open-label extension (OLE) part.
Detailed description
Participants who were in the active arm in the double blind part and those who have completed OLE part in the parent study, will continue receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W). Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme as in the parent study before receiving target dose of open label gantenerumab.
Interventions
DRUGGantenerumab
Group 1 participants who were in the active arm in the double blind part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg SC, Q2W. Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme before receiving target dose of open label gantenerumab, 510 mg SC, Q2W.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Completed Study WN29922 or WN39658, either its double-blind part or OLE part, and did not discontinue study drug early * The participant should be capable of completing assessments either alone or with the help of the caregiver * Availability of a person (referred to as the caregiver) * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception methods with a failure rate of \<1% per year (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices) during the treatment period and for at least 16 weeks after the final dose of gantenerumab * Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug
Exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant during the study or within at least 16 weeks after the final dose of study drug * Prematurely discontinued from Study WN29922 or WN39658 * Any medical condition that may jeopardize the participant's safety if he or she continues to receive study treatment * Received any investigational treatment other than gantenerumab during or since completion of Study WN29922 or WN39658, either its double-blind or OLE part * Evidence of disseminated leptomeningeal hemosiderosis * Evidence of intracerebral macrohemorrhage * Use of prohibited medication * Evidence of ARIA-E on the last MRI scan report in Study WN29922 or WN39658, either its double-blind or OLE part
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. A SAE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug or a significant medical event in the investigator's judgment. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | C-SSRS= assesses lifetime suicidality of participant (at baseline) & any new instances of suicidality (since last visit). Structured interview prompts recollection of suicidal ideation (intensity of ideation, behavior, & attempts with actual/potential lethality). Categories have yes/no responses, include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted/Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior= yes to any of listed categories. Score of 0= no suicide risk. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here. First dosing visit in OLE (first dosing in current study or OLE period of parent GRADUATE studies)=baseline (OLE Day 1). |
| Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants With Injection-Site Reactions (ISRs) | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, regardless of casual attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants Who Discontinued the Study Due an AE | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants With at Least One Adverse Event of Special Interest (AESI) | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. AEs that were considered to be of special interest for this study included cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law and suspected transmission of an infectious agent by the study drug. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Functional Activities Questionnaire (FAQ) Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | FAQ is a rater-administered observer-reported outcome (ObsRO) (informant-based measure) that measures a participant's functional ability to perform complex higher-order activities. The observer provides performance ratings of the target person on ten complex higher-order activities. Total score that ranges from 0-30, with higher scores reflecting greater functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=normal, 0.5=very mild dementia, 1=mild dementia, 2=moderate dementia, and 3= severe dementia. The score range for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks) | The number of participants with positive results for ADA against gantenerumab at any of the post-baseline assessment time-points were reported. Evaluable participant during OLE was participant with an ADA assay result from at least one sample during OLE. Treatment Emergent ADA = A participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | ADCS-ADL is a 23-item rater-administered, ObsRO that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. Total score ranges from 0-30, with lower scores indicating greater impairment. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | The ADAS-Cog13 total score includes all of the items in the ADAS-Cog11 in addition to delayed word recall and the number cancellation. For the ADAS-cog 13 the range is 0-85 (score range for Delayed Word Recall \[DWR\] score is 0-10 and for Number Cancellation \[NC\] is 0-5, thus the score is ADAS-cog 11\[0-70\] plus the scores for DWR and NC). A higher score indicates worse performance. A negative change from baseline indicates improvement in cognitive function. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Verbal Fluency Task Score | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | VFT is a rater administered PerfO that measures speed and flexibility of verbal thought with a total score that ranges from 0-99 (lower scores indicating lower performance). A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
| Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104 | Coding, also called DSST is a rater administered PerfO that measures speed of processing and associative memory with a total score that ranges from 0-135 (lower scores indicating lower performance). The DSST was adapted from the Wechsler Adult Intelligence Scale. The 120-second version of the test was used in this study. Positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Denmark, Finland, France, Germany, Hungary, Italy, Japan, Lithuania, Mexico, Netherlands, Peru, Poland, Portugal, Puerto Rico, Russia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in this study at 258 investigative centers across 28 countries from 26 January 2021 to 06 March 2023. A total of 1382 participants who completed either the double-blind (DB) part or open-label extension (OLE) part in parent GRADUATE studies WN29922 (NCT03444870) or WN39658 (NCT03443973) were enrolled in this study to receive open-label gantenerumab.
Pre-assignment details
Participants who completed DB and OLE part received gantenerumab approximately 2 weeks after OLE Week 34 visit or final OLE dose visit in the parent study. Participants who completed DB part and did not enter the OLE part received gantenerumab approximately 2 weeks after the Week 116 visit of the parent study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo: Participated in Graduate OLE Participants treated with placebo in the DB part and who completed the DB and OLE up titration in study WN29922 (GRADUATE I) or WN39658 (GRADUATE II), continued receiving open-label gantenerumab, 510 mg, SC, Q2W. | 15 |
| Placebo: No Participation in Graduate OLE Participants treated with placebo in the DB part and who did not enter the OLE part of study WN29922 (GRADUATE I) or WN39658 (GRADUATE II) received gantenerumab SC injections with gradual up titration starting at a dose of 120 mg, Q4W for 3 doses, followed by 255 mg, Q4W for 3 doses, and then at a dose of 510 mg, Q4W for 3 doses before receiving open-label gantenerumab, 510 mg SC injections, Q2W. To maintain the blind to previous treatment assignment, participants received Q2W, SC injections, with alternate doses containing gantenerumab matching placebo. | 696 |
| Gantenerumab: Participated in Graduate OLE Participants treated with gantenerumab in the DB part and who completed the DB and OLE part of study WN29922 (GRADUATE I) or WN39658 (GRADUATE II) continued receiving open-label gantenerumab, 510 mg, SC, Q2W. | 28 |
| Gantenerumab: No Participation in Graduate OLE Participants treated with gantenerumab in the DB part and who did not enter the OLE part of study WN29922 (GRADUATE I) or WN39658 (GRADUATE II) continued receiving open-label gantenerumab 510 mg SC, Q2W. | 642 |
| Total | 1,381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 26 | 2 | 12 |
| Overall Study | Death | 0 | 3 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 10 | 1 | 10 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 2 |
| Overall Study | Reason Not Specified | 0 | 8 | 0 | 8 |
| Overall Study | Study terminated by sponsor | 13 | 593 | 21 | 567 |
| Overall Study | Withdrawal by Subject | 0 | 55 | 3 | 40 |
Baseline characteristics
| Characteristic | Placebo: Participated in Graduate OLE | Placebo: No Participation in Graduate OLE | Gantenerumab: Participated in Graduate OLE | Gantenerumab: No Participation in Graduate OLE | Total |
|---|---|---|---|---|---|
| Age, Continuous | 76.7 years STANDARD_DEVIATION 7.8 | 73.6 years STANDARD_DEVIATION 7.4 | 74.1 years STANDARD_DEVIATION 8 | 73.0 years STANDARD_DEVIATION 7.7 | 73.4 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 116 Participants | 14 Participants | 89 Participants | 225 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 576 Participants | 14 Participants | 548 Participants | 1147 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 0 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 25 Participants | 4 Participants | 18 Participants | 47 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 104 Participants | 1 Participants | 87 Participants | 193 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 0 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 12 Participants | 1 Participants | 15 Participants | 28 Participants |
| Race (NIH/OMB) White | 14 Participants | 549 Participants | 22 Participants | 518 Participants | 1103 Participants |
| Sex: Female, Male Female | 11 Participants | 387 Participants | 14 Participants | 382 Participants | 794 Participants |
| Sex: Female, Male Male | 4 Participants | 309 Participants | 14 Participants | 260 Participants | 587 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 5 / 691 | 2 / 29 | 4 / 647 |
| other Total, other adverse events | 13 / 14 | 395 / 691 | 21 / 29 | 358 / 647 |
| serious Total, serious adverse events | 2 / 14 | 72 / 691 | 4 / 29 | 54 / 647 |
Outcome results
Primary
Number of Participants Who Discontinued the Study Due an AE
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set included all participants enrolled who received at least one dose of study drug in this study or in the OLE part of the parent studies (GRADUATE I or GRADUATE II). Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants Who Discontinued the Study Due an AE | 0 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants Who Discontinued the Study Due an AE | 9 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants Who Discontinued the Study Due an AE | 1 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants Who Discontinued the Study Due an AE | 7 Participants |
Primary
Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. A SAE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug or a significant medical event in the investigator's judgment. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set included all participants enrolled who received at least one dose of study drug in this study or in the OLE part of the parent studies (GRADUATE I or GRADUATE II). Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | AEs | 13 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | SAEs | 2 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | SAEs | 72 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | AEs | 510 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | SAEs | 4 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | AEs | 25 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | SAEs | 54 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) | AEs | 487 Participants |
Primary
Number of Participants With at Least One Adverse Event of Special Interest (AESI)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. AEs that were considered to be of special interest for this study included cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law and suspected transmission of an infectious agent by the study drug. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set included all participants enrolled who received at least one dose of study drug in this study or in the OLE part of the parent studies (GRADUATE I or GRADUATE II). Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event of Special Interest (AESI) | 0 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event of Special Interest (AESI) | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With at Least One Adverse Event of Special Interest (AESI) | 0 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With at Least One Adverse Event of Special Interest (AESI) | 0 Participants |
Primary
Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: M-SE analysis set included all participants in the SE analysis set who had at least one post-baseline safety MRI scan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI | 6 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI | 104 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI | 5 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI | 27 Participants |
Primary
Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: M-SE analysis set included participants in the SE analysis set who had at least one post-baseline safety MRI scan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI | 3 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI | 85 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI | 4 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI | 40 Participants |
Primary
Number of Participants With Injection-Site Reactions (ISRs)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, regardless of casual attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set included all participants enrolled who received at least one dose of study drug in this study or in the OLE part of the parent studies (GRADUATE I or GRADUATE II). Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With Injection-Site Reactions (ISRs) | 3 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Injection-Site Reactions (ISRs) | 63 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Injection-Site Reactions (ISRs) | 1 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Injection-Site Reactions (ISRs) | 80 Participants |
Primary
Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score
C-SSRS= assesses lifetime suicidality of participant (at baseline) & any new instances of suicidality (since last visit). Structured interview prompts recollection of suicidal ideation (intensity of ideation, behavior, & attempts with actual/potential lethality). Categories have yes/no responses, include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted/Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior= yes to any of listed categories. Score of 0= no suicide risk. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here. First dosing visit in OLE (first dosing in current study or OLE period of parent GRADUATE studies)=baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set included all participants enrolled who received at least one dose of study drug in this study or in the OLE part of the parent studies. Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Passive | 1 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Nonspecific (No Method, Intent, or Plan) | 0 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Method, but No Intent or Plan | 1 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: No event | 12 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Completed Suicide | 0 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Aborted Attempt | 0 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Preparatory Actions Toward Imminent Suicidal Behaviors | 0 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: No event | 14 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-injurious Behavior, Without Suicidal Intent: Self-Injurious Behavior - No Suicidal Intent | 0 Participants |
| Placebo: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-Injurious Behavior Without Suicidal Intent: No event | 14 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Method, but No Intent or Plan | 0 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-injurious Behavior, Without Suicidal Intent: Self-Injurious Behavior - No Suicidal Intent | 2 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: No event | 617 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Completed Suicide | 0 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Aborted Attempt | 1 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Preparatory Actions Toward Imminent Suicidal Behaviors | 1 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-Injurious Behavior Without Suicidal Intent: No event | 629 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: No event | 629 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Passive | 11 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Nonspecific (No Method, Intent, or Plan) | 3 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: No event | 29 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Preparatory Actions Toward Imminent Suicidal Behaviors | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-Injurious Behavior Without Suicidal Intent: No event | 29 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Passive | 1 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: No event | 27 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Aborted Attempt | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-injurious Behavior, Without Suicidal Intent: Self-Injurious Behavior - No Suicidal Intent | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Nonspecific (No Method, Intent, or Plan) | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Completed Suicide | 0 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Method, but No Intent or Plan | 1 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Completed Suicide | 2 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: No event | 586 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Aborted Attempt | 0 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-Injurious Behavior Without Suicidal Intent: No event | 588 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Behavior: Preparatory Actions Toward Imminent Suicidal Behaviors | 0 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Nonspecific (No Method, Intent, or Plan) | 2 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Active-Method, but No Intent or Plan | 0 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: No event | 575 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal Ideation: Passive | 11 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Self-injurious Behavior, Without Suicidal Intent: Self-Injurious Behavior - No Suicidal Intent | 0 Participants |
Secondary
Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score
ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 36 | 12.0 score on a scale | Standard Deviation 10 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 76 | 6.6 score on a scale | Standard Deviation 10.9 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 104 | 8.4 score on a scale | Standard Deviation 14.12 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 52 | 5.6 score on a scale | Standard Deviation 9.55 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 24 | 2.4 score on a scale | Standard Deviation 5.56 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 52 | 3.7 score on a scale | Standard Deviation 6.13 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 76 | 5.9 score on a scale | Standard Deviation 7.52 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 104 | 7.8 score on a scale | Standard Deviation 7.65 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 36 | 3.9 score on a scale | Standard Deviation 6.8 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 24 | 2.4 score on a scale | Standard Deviation 5.47 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 52 | 1.9 score on a scale | Standard Deviation 5.89 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 24 | 1.6 score on a scale | Standard Deviation 5.29 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 36 | -3.7 score on a scale | Standard Deviation 5.5 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 76 | 7.0 score on a scale | Standard Deviation 9.5 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 104 | 3.8 score on a scale | Standard Deviation 6.67 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 76 | 6.1 score on a scale | Standard Deviation 7.8 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 36 | 4.0 score on a scale | Standard Deviation 5.46 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 24 | 2.8 score on a scale | Standard Deviation 5.22 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 52 | 4.7 score on a scale | Standard Deviation 6.61 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score | Change from Baseline at Week 104 | 8.2 score on a scale | Standard Deviation 10.26 |
Secondary
Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score
The ADAS-Cog13 total score includes all of the items in the ADAS-Cog11 in addition to delayed word recall and the number cancellation. For the ADAS-cog 13 the range is 0-85 (score range for Delayed Word Recall \[DWR\] score is 0-10 and for Number Cancellation \[NC\] is 0-5, thus the score is ADAS-cog 11\[0-70\] plus the scores for DWR and NC). A higher score indicates worse performance. A negative change from baseline indicates improvement in cognitive function. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 36 | 13.2 score on a scale | Standard Deviation 11.52 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 24 | 2.9 score on a scale | Standard Deviation 6.29 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 52 | 6.7 score on a scale | Standard Deviation 10.13 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 104 | 10.4 score on a scale | Standard Deviation 14.98 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 76 | 7.9 score on a scale | Standard Deviation 11.89 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 104 | 8.7 score on a scale | Standard Deviation 8.13 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 24 | 3.0 score on a scale | Standard Deviation 5.73 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 36 | 4.7 score on a scale | Standard Deviation 7.05 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 52 | 4.3 score on a scale | Standard Deviation 6.45 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 76 | 6.8 score on a scale | Standard Deviation 7.85 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 36 | -3.4 score on a scale | Standard Deviation 5.39 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 52 | 2.7 score on a scale | Standard Deviation 6.01 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 76 | 7.7 score on a scale | Standard Deviation 9.76 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 24 | 2.0 score on a scale | Standard Deviation 5.53 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 104 | 4.8 score on a scale | Standard Deviation 6.74 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 36 | 4.7 score on a scale | Standard Deviation 5.85 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 76 | 6.7 score on a scale | Standard Deviation 8.22 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 52 | 5.3 score on a scale | Standard Deviation 6.94 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 24 | 3.3 score on a scale | Standard Deviation 5.45 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score | Change from Baseline at Week 104 | 8.8 score on a scale | Standard Deviation 10.22 |
Secondary
Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB)
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 76 | 2.68 score on a scale | Standard Deviation 3.133 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 36 | 2.90 score on a scale | Standard Deviation 2.608 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 104 | 3.80 score on a scale | Standard Deviation 3.213 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 52 | 2.57 score on a scale | Standard Deviation 2.286 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 24 | 2.10 score on a scale | Standard Deviation 2.473 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 52 | 1.60 score on a scale | Standard Deviation 1.906 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 76 | 2.20 score on a scale | Standard Deviation 1.994 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 104 | 3.26 score on a scale | Standard Deviation 2.751 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 36 | 1.39 score on a scale | Standard Deviation 2.397 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 24 | 0.83 score on a scale | Standard Deviation 1.787 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 52 | 0.80 score on a scale | Standard Deviation 1.351 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 24 | 1.00 score on a scale | Standard Deviation 2.529 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 36 | 0.72 score on a scale | Standard Deviation 2.265 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 76 | 1.95 score on a scale | Standard Deviation 3.218 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 104 | 1.15 score on a scale | Standard Deviation 2.47 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 76 | 1.97 score on a scale | Standard Deviation 2.249 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 36 | 1.11 score on a scale | Standard Deviation 2.161 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 24 | 0.70 score on a scale | Standard Deviation 1.754 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 52 | 1.50 score on a scale | Standard Deviation 2.051 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) | Change from Baseline at Week 104 | 1.80 score on a scale | Standard Deviation 1.949 |
Secondary
Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS)
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=normal, 0.5=very mild dementia, 1=mild dementia, 2=moderate dementia, and 3= severe dementia. The score range for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 76 | 0.5 score on a scale | Standard Deviation 0.69 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 36 | 0.4 score on a scale | Standard Deviation 0.55 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 104 | 0.6 score on a scale | Standard Deviation 0.89 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 52 | 0.3 score on a scale | Standard Deviation 0.46 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 24 | 0.4 score on a scale | Standard Deviation 0.5 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 52 | 0.2 score on a scale | Standard Deviation 0.44 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 76 | 0.3 score on a scale | Standard Deviation 0.47 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 104 | 0.6 score on a scale | Standard Deviation 0.52 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 36 | 0.3 score on a scale | Standard Deviation 0.55 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 24 | 0.1 score on a scale | Standard Deviation 0.43 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 52 | -0.1 score on a scale | Standard Deviation 0.43 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 24 | 0.1 score on a scale | Standard Deviation 0.53 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 36 | 0.1 score on a scale | Standard Deviation 0.42 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 76 | 0.2 score on a scale | Standard Deviation 0.75 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 104 | 0.2 score on a scale | Standard Deviation 0.43 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 76 | 0.3 score on a scale | Standard Deviation 0.44 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 36 | 0.2 score on a scale | Standard Deviation 0.47 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 24 | 0.1 score on a scale | Standard Deviation 0.41 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 52 | 0.2 score on a scale | Standard Deviation 0.46 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) | Change from Baseline at Week 104 | 0.3 score on a scale | Standard Deviation 0.5 |
Secondary
Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset
Coding, also called DSST is a rater administered PerfO that measures speed of processing and associative memory with a total score that ranges from 0-135 (lower scores indicating lower performance). The DSST was adapted from the Wechsler Adult Intelligence Scale. The 120-second version of the test was used in this study. Positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 76 | -3.4 score on a scale | Standard Deviation 8.49 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 36 | -8.0 score on a scale | Standard Deviation 10 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 104 | 0.4 score on a scale | Standard Deviation 9.94 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 52 | -3.1 score on a scale | Standard Deviation 7.61 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 24 | -0.5 score on a scale | Standard Deviation 6.31 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 52 | -5.0 score on a scale | Standard Deviation 8.6 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 76 | -7.2 score on a scale | Standard Deviation 10.12 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 104 | -4.5 score on a scale | Standard Deviation 13.25 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 36 | -4.8 score on a scale | Standard Deviation 8.09 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 24 | -2.8 score on a scale | Standard Deviation 7.84 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 52 | -2.8 score on a scale | Standard Deviation 14 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 24 | -0.3 score on a scale | Standard Deviation 9.02 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 36 | 6.2 score on a scale | Standard Deviation 13.96 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 76 | -7.1 score on a scale | Standard Deviation 8.99 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 104 | -5.2 score on a scale | Standard Deviation 11.95 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 76 | -6.0 score on a scale | Standard Deviation 9.71 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 36 | -3.0 score on a scale | Standard Deviation 9.66 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 24 | -2.3 score on a scale | Standard Deviation 8.04 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 52 | -4.7 score on a scale | Standard Deviation 8.79 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset | Change from Baseline at Week 104 | -7.0 score on a scale | Standard Deviation 11.04 |
Secondary
Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score
MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. Total score ranges from 0-30, with lower scores indicating greater impairment. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 24 | -0.3 score on a scale | Standard Deviation 2.41 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 76 | -2.9 score on a scale | Standard Deviation 3.2 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 104 | -3.6 score on a scale | Standard Deviation 5.13 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 52 | -1.9 score on a scale | Standard Deviation 2.94 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 36 | -1.8 score on a scale | Standard Deviation 3.35 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 52 | -2.3 score on a scale | Standard Deviation 3.15 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 76 | -3.2 score on a scale | Standard Deviation 3.39 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 104 | -4.3 score on a scale | Standard Deviation 3.93 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 36 | -1.6 score on a scale | Standard Deviation 2.83 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 24 | -1.2 score on a scale | Standard Deviation 2.87 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 52 | -2.0 score on a scale | Standard Deviation 3.49 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 24 | -0.9 score on a scale | Standard Deviation 2.39 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 36 | -0.3 score on a scale | Standard Deviation 1.66 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 76 | -2.9 score on a scale | Standard Deviation 3.97 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 104 | -2.9 score on a scale | Standard Deviation 3.92 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 76 | -3.0 score on a scale | Standard Deviation 3.56 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 36 | -1.7 score on a scale | Standard Deviation 3.18 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 24 | -1.1 score on a scale | Standard Deviation 2.69 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 52 | -2.1 score on a scale | Standard Deviation 3.14 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score | Change from Baseline at Week 104 | -3.0 score on a scale | Standard Deviation 4.12 |
Secondary
Change From Baseline Over Time in Verbal Fluency Task Score
VFT is a rater administered PerfO that measures speed and flexibility of verbal thought with a total score that ranges from 0-99 (lower scores indicating lower performance). A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 52 | -1.5 score on a scale | Standard Deviation 3.02 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 24 | 0.2 score on a scale | Standard Deviation 2.73 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 76 | -1.3 score on a scale | Standard Deviation 2.83 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 36 | -2.2 score on a scale | Standard Deviation 3.42 |
| Placebo: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 104 | -0.6 score on a scale | Standard Deviation 4.22 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 52 | -1.5 score on a scale | Standard Deviation 3.6 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 36 | -1.2 score on a scale | Standard Deviation 3.07 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 76 | -2.1 score on a scale | Standard Deviation 3.66 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 24 | -0.9 score on a scale | Standard Deviation 3.15 |
| Placebo: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 104 | -3.8 score on a scale | Standard Deviation 3.79 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 104 | -0.8 score on a scale | Standard Deviation 4.09 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 24 | -1.0 score on a scale | Standard Deviation 2.83 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 36 | -0.6 score on a scale | Standard Deviation 2.7 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 52 | -0.4 score on a scale | Standard Deviation 2.39 |
| Gantenerumab: Participated in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 76 | -1.3 score on a scale | Standard Deviation 4.36 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 104 | -3.3 score on a scale | Standard Deviation 2.5 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 76 | -2.8 score on a scale | Standard Deviation 7.54 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 36 | -1.4 score on a scale | Standard Deviation 3.45 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 24 | -0.6 score on a scale | Standard Deviation 4.73 |
| Gantenerumab: No Participation in Graduate OLE | Change From Baseline Over Time in Verbal Fluency Task Score | Change from Baseline at Week 52 | -1.5 score on a scale | Standard Deviation 5.77 |
Secondary
Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score
ADCS-ADL is a 23-item rater-administered, ObsRO that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 24 | -4.7 score on a scale | Standard Deviation 5.15 |
| Placebo: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 76 | -10.8 score on a scale | Standard Deviation 11.19 |
| Placebo: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 104 | -11.6 score on a scale | Standard Deviation 17.99 |
| Placebo: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 36 | -12.5 score on a scale | Standard Deviation 12.4 |
| Placebo: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 52 | -9.4 score on a scale | Standard Deviation 7.49 |
| Placebo: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 36 | -5.6 score on a scale | Standard Deviation 9.55 |
| Placebo: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 104 | -6.6 score on a scale | Standard Deviation 10.2 |
| Placebo: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 76 | -7.8 score on a scale | Standard Deviation 9.87 |
| Placebo: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 52 | -5.9 score on a scale | Standard Deviation 8.97 |
| Placebo: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 24 | -2.9 score on a scale | Standard Deviation 7.07 |
| Gantenerumab: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 52 | -4.4 score on a scale | Standard Deviation 8.09 |
| Gantenerumab: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 36 | -2.1 score on a scale | Standard Deviation 6.23 |
| Gantenerumab: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 76 | -8.3 score on a scale | Standard Deviation 11.22 |
| Gantenerumab: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 104 | -6.3 score on a scale | Standard Deviation 13.52 |
| Gantenerumab: Participated in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 24 | -2.0 score on a scale | Standard Deviation 7.1 |
| Gantenerumab: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 36 | -4.9 score on a scale | Standard Deviation 8.53 |
| Gantenerumab: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 76 | -6.9 score on a scale | Standard Deviation 9.62 |
| Gantenerumab: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 52 | -6.2 score on a scale | Standard Deviation 8.38 |
| Gantenerumab: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 24 | -3.2 score on a scale | Standard Deviation 6.69 |
| Gantenerumab: No Participation in Graduate OLE | Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score | Change from Baseline at Week 104 | -9.9 score on a scale | Standard Deviation 12.21 |
Secondary
Change in Functional Activities Questionnaire (FAQ) Score
FAQ is a rater-administered observer-reported outcome (ObsRO) (informant-based measure) that measures a participant's functional ability to perform complex higher-order activities. The observer provides performance ratings of the target person on ten complex higher-order activities. Total score that ranges from 0-30, with higher scores reflecting greater functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Population: ITT analysis set included all enrolled participants, who received at least one dose of study drug. Participants will be analyzed by the treatment they were randomized to in the parent studies (GRADUATE I or GRADUATE II). Overall number analyzed is the number of participants with data available for analyses. The number of participants analyzed indicates the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 24 | 1.2 score on a scale | Standard Deviation 4.04 |
| Placebo: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 36 | -1.0 score on a scale | Standard Deviation 1.87 |
| Placebo: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 76 | 2.3 score on a scale | Standard Deviation 3.66 |
| Placebo: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 104 | 3.2 score on a scale | Standard Deviation 4.92 |
| Placebo: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 52 | 2.1 score on a scale | Standard Deviation 3.8 |
| Placebo: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 104 | 4.5 score on a scale | Standard Deviation 4.09 |
| Placebo: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 24 | 1.6 score on a scale | Standard Deviation 4.36 |
| Placebo: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 76 | 4.0 score on a scale | Standard Deviation 4.55 |
| Placebo: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 52 | 2.6 score on a scale | Standard Deviation 4.39 |
| Placebo: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 36 | 2.7 score on a scale | Standard Deviation 5.07 |
| Gantenerumab: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 36 | 1.3 score on a scale | Standard Deviation 6.18 |
| Gantenerumab: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 24 | 0.1 score on a scale | Standard Deviation 3.15 |
| Gantenerumab: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 52 | 2.7 score on a scale | Standard Deviation 3.73 |
| Gantenerumab: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 76 | 3.3 score on a scale | Standard Deviation 3.95 |
| Gantenerumab: Participated in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 104 | 4.1 score on a scale | Standard Deviation 4.91 |
| Gantenerumab: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 76 | 3.5 score on a scale | Standard Deviation 5.12 |
| Gantenerumab: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 36 | 1.7 score on a scale | Standard Deviation 4.92 |
| Gantenerumab: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 24 | 1.5 score on a scale | Standard Deviation 4.09 |
| Gantenerumab: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 52 | 2.6 score on a scale | Standard Deviation 4.81 |
| Gantenerumab: No Participation in Graduate OLE | Change in Functional Activities Questionnaire (FAQ) Score | Change from Baseline at Week 104 | 1.7 score on a scale | Standard Deviation 5.07 |
Secondary
Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab
The number of participants with positive results for ADA against gantenerumab at any of the post-baseline assessment time-points were reported. Evaluable participant during OLE was participant with an ADA assay result from at least one sample during OLE. Treatment Emergent ADA = A participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).
Time frame: From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Population: SE analysis set: all participants enrolled who received at least one dose of study drug in this study or in OLE part of parent studies (GRADUATE I or GRADUATE II). Six participants randomized to placebo arm during the double-blind treatment in the parent studies received at least one dose of gantenerumab and were considered in the gantenerumab arm for safety evaluable set. Overall number analyzed is the number of participants with an ADA assay result from any post-baseline sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Participated in Graduate OLE | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 1 Participants |
| Placebo: No Participation in Graduate OLE | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 17 Participants |
| Gantenerumab: Participated in Graduate OLE | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 1 Participants |
| Gantenerumab: No Participation in Graduate OLE | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 14 Participants |