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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01224106

Collaborator

(none)

799

Enrollment

139

Locations

Arms

117.4

Actual Duration (Months)

5.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multi-center, randomized, double-blind, placebo-controlled parallel-group study will evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo. Participants who consent to be part of the sub study will undergo positron emission tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is 104 weeks in Part 1, with an option for an additional up to 2 years of treatment in Part 2, followed by an open-label extension (Part 3) until July 2020.

The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a low probability of meeting the primary outcome measure with the doses studied. The study has converted to open-label to investigate higher gantenerumab doses.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Gantenerumab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

799 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment

Actual Study Start Date :

Nov 30, 2010

Actual Primary Completion Date :

Sep 10, 2020

Actual Study Completion Date :

Sep 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo (Parts 1 and 2) Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Placebo Participants received Placebo SC injection Q4W.
Experimental: Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Gantenerumab Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Experimental: Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Gantenerumab Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Placebo Comparator: Placebo (Parts 1 and 2) switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Drug: Gantenerumab Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Experimental: Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Drug: Gantenerumab Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

Outcome Measures

Primary Outcome Measures

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) [Baseline up until a maximum of 5 years]
An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Secondary Outcome Measures

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) [Baseline, Week 156]
The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) [Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101]
The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) [Baseline, Week 104]
The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) [Baseline up until a maximum of 4.5 years]
An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) [Baseline up until a maximum of 4.5 years]
Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) [Baseline, Week 156]
The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) [Baseline, Week 156]
The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) [Baseline, Week 156]
The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.
Time to Onset of Dementia at Week 156 (OLE Phase) [Baseline, Week 156]
Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) [Baseline, Week 156]
FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) [Baseline, Week 156]
Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) [Baseline, Week 156]
The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) [Baseline, Week 152]
Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) [Baseline, Week 156]
The regions of the brain that were analyzed included cerebellum gray and composite reference.
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) [Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101]
The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) [Baseline, Week 156]
The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) [Baseline up until a maximum of 5 years]
Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult participants, 50-85 years of age
Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors
Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion
Has had sufficient education or work experience to exclude mental retardation
Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of
Screening Mini Mental State Exam (MMSE) score of 24 or above

Additional inclusion criteria for sub study:

Able and willing to travel to PET imaging center and complete the planned scanning sessions
Past and planned exposure to ionizing radiation not exceeding safe and permissible levels

Exclusion Criteria:

Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning
A history of stroke
A documented history of transient ischemic attack within the last 12 months
History of schizophrenia, schizoaffective or bipolar disorder
Currently meets criteria for major depression
Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)

Additional exclusion criteria for sub study:

Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months
Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203
Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
2	University of California, San Diego	La Jolla	California	United States	92037
3	Yale University ADRU	New Haven	Connecticut	United States	06510
4	Brain Matters Research, Inc.	Delray Beach	Florida	United States	33445
5	Infinity Clinical Research	Hollywood	Florida	United States	33024
6	Accelerated Enrollment Solutions	Orlando	Florida	United States	32806
7	Roskamp Institute, Inc.	Sarasota	Florida	United States	34243
8	Compass Research	The Villages	Florida	United States	32162
9	Premiere Research Institute	West Palm Beach	Florida	United States	33407
10	Indiana University	Indianapolis	Indiana	United States	46202
11	Boston Center for Memory	Newton	Massachusetts	United States	02459
12	Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research	Kalamazoo	Michigan	United States	49008
13	Neurological Research Center	Hattiesburg	Mississippi	United States	39401
14	Princeton Medical Institute	Princeton	New Jersey	United States	08540
15	Nathan Kline Institute	Orangeburg	New York	United States	10962
16	University of Rochester Medical Center; Monroe Community Hospital	Rochester	New York	United States	14627
17	Alzheimer's Memory Center	Matthews	North Carolina	United States	28105
18	Oregon Health and Science University, Layton Aging and Alzheimer's Disease Center	Portland	Oregon	United States	97239
19	Northeastern Pennsylvania Memory	Plains	Pennsylvania	United States	18705
20	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island	United States	02914
21	Butler Hospital	Providence	Rhode Island	United States	02906
22	Senior Adults Specialty Research	Austin	Texas	United States	78757
23	Texas Neurology PA	Dallas	Texas	United States	75206
24	Clinical Neuroscience Research Associates, Inc.	Bennington	Vermont	United States	05201
25	Hospital Italiano	Buenos Aires		Argentina	C1181ACH
26	IME - Instituto Médico Especializado; Ensayos Clínicos	Buenos Aires		Argentina	C1405BCH
27	ALPI-Inst. de Rehabilitacion Marcelo Fitte	Buenos Aires		Argentina	C1425BWO
28	CEMIC	Buenos Aires		Argentina	C1431FWO
29	Mulieris	Caba		Argentina	C1022AAO
30	Instituto De Neurología Cognitiva - INECO	Caba		Argentina	C1126AAB
31	FLENI	Caba		Argentina	C1428AQK
32	Instituto Kremer	Córdoba		Argentina	X5004AOA
33	CENPIA; Neurología - Psicología	La Plata		Argentina	B1902AJU
34	Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care	Hornsby	New South Wales	Australia	2077
35	Prince of Wales Hospital, Academic Department for Old Age Psychiatry	Randwick	New South Wales	Australia	2031
36	Royal Adelaide Hospital; Memory Trials Centre	Adelaide	South Australia	Australia	5000
37	The Queen Elizabeth Hospital; Neurology	Woodville	South Australia	Australia	5011
38	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria	Australia	3081
39	Australian Alzheimer's Research Foundation	Nedlands	Western Australia	Australia	6009
40	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
41	Hospital das Clinicas - UFPR; Ciencias da Saude	Curitiba	PR	Brazil	80060-900
42	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-903
43	Hospital Mae de Deus	Porto Alegre	RS	Brazil	90470-340
44	Hospital das Clinicas - FMUSP; Psiquiatria	Sao Paulo	SP	Brazil	05403-010
45	Universidade Federal de Sao Paulo - UNIFESPX; Neurologia	São Paulo	SP	Brazil	04024-002
46	True North Clinical Research	New Minas	Nova Scotia	Canada	B4N 3R7
47	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario	Canada	K9H 2P4
48	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7
49	Centre for Memory and Aging	Toronto	Ontario	Canada	M4G 3E8
50	NeuroSearch Developpements inc	Greenfield Park	Quebec	Canada	J4V 2J2
51	McGill University; Sir Mortimer B Davis Jewish General Hospital; Neurological and Psychiatric	Montreal	Quebec	Canada	H3T 1E2
52	CHAUQ - Hôpital Enfant-Jésus	Quebec City	Quebec	Canada	G1J 1Z4
53	Biomedica Research Group	Santiago		Chile	7500710
54	Especialidades Medicas LYS	Santiago		Chile	7560356
55	St. Anne´s University Hospital; Clinical Trials Department	Brno		Czechia	656 91
56	Vestra Clinics s.r.o.	Rychnov nad Kneznou		Czechia	516 01
57	Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken	Aarhus N		Denmark	8200
58	Rigshospitalet, Hukommelsesklinikken	Koebenhavn Oe		Denmark	2100
59	CRST Oy	Turku		Finland	20520
60	Hopital Avicenne; Neurologie	Bobigny		France	93009
61	Hopital Pellegrin; Cmrr Aquitaine	Bordeaux		France	33076
62	Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie	Bron		France	69677
63	CHU De Caen; Service De Neurologie Dejerine	Caen		France	14033
64	Hopital B Roger Salengro; Cmrr Lille	Lille		France	59037
65	Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere	Paris		France	75651
66	CHU de Rouen Hopital; Service de Neurologie	Rouen		France	76031
67	Hop Guillaume Et Rene Laennec; Cmrr St Herblain	St Herblain		France	44800
68	Hopital Hautepierre; Centre dInvestigation Clinique	Strasbourg		France	67098
69	Hopital de La Grave	Toulouse		France	31059
70	Univ Berlin; Klin fur Psychi & Psycho Charite	Berlin		Germany	12203
71	Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin	Bonn		Germany	53127
72	Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik	Frankfurt		Germany	60528
73	PANAKEIA - Arzneimittelforschung Leipzig GmbH	Leipzig		Germany	04275
74	Zentralinstitut für Seelische Gesundheit Abt.Gerontopsychiatrie	Mannheim		Germany	68159
75	Pharmakologisches Studienzentrum	Mittweida		Germany	09648
76	Neurologische Praxis Dr. Andrej Pauls	München		Germany	80331
77	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München		Germany	81675
78	Office of Dr Klaus Steinwachs Neurology & Psychiatry	Nürnberg		Germany	90402
79	Universitätsklinikum Rostock Zentrum für Nervenheilkunde	Rostock		Germany	18147
80	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm		Germany	89081
81	Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze	Modena	Emilia-Romagna	Italy	41126
82	Universita' Di Parma Istituto Neurologia	Parma	Emilia-Romagna	Italy	43126
83	Azienda Ospedaliera Spedali Civili; Scienze Neurologiche	Brescia	Lombardia	Italy	25100
84	IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer	Brescia	Lombardia	Italy	25125
85	Irccs Multimedica Santa Maria; Unita' Di Neurologia	Castellanza	Lombardia	Italy	21053
86	Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia	Milano	Lombardia	Italy	20132
87	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona	Torrette - Ancona	Marche	Italy	60100
88	Uni Di Firenze Dip. Scienze Neurol Psic Sod Neurologia 1	Firenze	Toscana	Italy	50134
89	Seoul National University Bundang Hospital; Neurology Department	Gyeonggi-do		Korea, Republic of	13620
90	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
91	Samsung Medical Center	Seoul		Korea, Republic of	06351
92	Seoul St Mary's Hospital	Seoul		Korea, Republic of	06591
93	Asan Medical Center.	Seoul		Korea, Republic of	138-736
94	Hospital Mexico Americano	Guadalajara	Mexico CITY (federal District)	Mexico	44610
95	Hospital Universitario; Dr. Jose E. Gonzalez	Monterrey	Nuevo LEON	Mexico	64460
96	Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC	Culiacan		Mexico	80020
97	Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia	Guadalajara		Mexico	44620
98	Estimulacion Magnetica Trnscraneal de Mexico SC.	Mexico City		Mexico	11000
99	Centro Medico San Francisco; Geriatrics	Monterrey		Mexico	64710
100	Hospital Universitario de Saltillo	Saltillo		Mexico	25000
101	Jeroen Bosch Ziekenhuis; Polikliniek Geriatrie	'S Hertogenbosch		Netherlands	5223 GZ
102	Brain Research Center B.V	Amsterdam		Netherlands	1081 GN
103	Podlaskie Centrum Psychogeriatrii	Białystok		Poland	15-756
104	PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER	Bydgoszcz		Poland	85-796
105	NEURO - KARD Ośrodek Badań Klinicznych	Poznań		Poland	61-853
106	Przychodnia Specjalistyczna PROSEN	Warszawa		Poland	01-231
107	mMED Maciej Czarnecki	Warszawa		Poland	01-684
108	Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia	Amadora		Portugal	2720-276
109	Hospital de Santa Maria; Servico de Neurologia	Lisboa		Portugal	1649-035
110	Sverdlovsk Regional Clinical Psychoneurological War Veteran Hospital	Ekaterinburg		Russian Federation	620036
111	State autonomous institution of healthcare Inter-regional clinical and diagnostic center	Kazan		Russian Federation	420101
112	Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center	Saint Petersburg		Russian Federation	190103
113	City Clinical Hospital # 2 n.a. V.I. Razumovsky	Saratov		Russian Federation	410028
114	Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department	St. Petersburg		Russian Federation	194044
115	Fundació ACE	BArcelon	Barcelona	Spain	08034
116	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona	Spain	08222
117	Hospital de Cruces; Servicio de Neurologia	Barakaldo	Vizcaya	Spain	48903
118	Hospital del Mar; Servicio de Neurologia	Barcelona		Spain	08003
119	Hospital Clinic i Provincial; Servicio de Neurologia	Barcelona		Spain	08036
120	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona		Spain	08041
121	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid		Spain	28034
122	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid		Spain	28041
123	Hospital Universitario La Paz; Servicio de Neurologia	Madrid		Spain	28046
124	Hospital Universitario Dr. Peset; Servicio de Neurologia	Valencia		Spain	46017
125	Skånes Universitetssjukhus Malmö, Minneskliniken	Malmö		Sweden	211 46
126	Felix Platter-Spital Medizin Geriatrie	Basel		Switzerland	4002
127	HUG; Département de santé mentale et de psychiatrie Unité de psychiatrie gériatrique	Chêne-Bourg		Switzerland	1225
128	Akdeniz University School of Medicine, Neurology Department	Antalya		Turkey	07058
129	Istanbul University Istanbul School of Medicine; Neurology	Istanbul		Turkey	34093
130	Ondokuz Mayis University School of Medicine; Neurology	Samsun		Turkey	55239
131	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
132	Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building	Cardiff		United Kingdom	CF64 2XX
133	St Margaret's Hospital	Epping		United Kingdom	CM16 6TN
134	Glasgow Memory Clinic	Glasgow		United Kingdom	G20 0XA
135	Charing Cross Hospital; Dept of Neurosciences	London		United Kingdom	W6 8RF
136	Campus for Ageing & Vitality; Clincal Ageing Research Unit	Newcastle		United Kingdom	NE4 5PL
137	Moorgreen Hospital; Memory Assessment & Rsch Ctr	Southampton		United Kingdom	SO30 3JB
138	Victoria Centre; Kingshill Research Centre	Swindon		United Kingdom	SN3 6BW
139	Hollins Park Hospital	Warrington		United Kingdom	WA2 8WA

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01224106

Other Study ID Numbers:

WN25203
2010-019895-66

First Posted:

Oct 19, 2010

Last Update Posted:

Dec 13, 2021

Last Verified:

Dec 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

Participant Flow

Recruitment Details

The study was conducted at 128 centers in 24 countries.

Pre-assignment Detail

A total of 799 participants were randomised in this study. Of these, a total of 797 participants were enrolled and received at least one dose of any study drug and represented the Safety population during the Double-Blind Treatment Phase (Parts 1 and 2 of the study). From the Double-Blind Treatment Phase, a total of 154 participants (at 53 sites) were enrolled into Open-Label Extension (OLE) Phase (Part 3 of the study).

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Period Title: Double-Blind Treatment Phase
STARTED	266	271	260	0	0
COMPLETED	187	185	180	0	0
NOT COMPLETED	79	86	80	0	0
Period Title: Double-Blind Treatment Phase
STARTED	0	0	0	49	105
COMPLETED	0	0	0	33	71
NOT COMPLETED	0	0	0	16	34

Baseline Characteristics

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])	Total
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Total of all reporting groups
Overall Participants	266	271	260	49	105	951
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.5 (7.5)	70.3 (7.0)	71.3 (7.1)	70.4 (7.2)
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.5 (5.8)	73.7 (7.3)	74.3 (6.9)
Sex: Female, Male (Count of Participants)
Female	149 56%	152 56.1%	152 58.5%	0 0%	0 0%	453 47.6%
Male	117 44%	119 43.9%	108 41.5%	0 0%	0 0%	344 36.2%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	27 55.1%	64 61%	91 9.6%
Male	0 0%	0 0%	0 0%	22 44.9%	41 39%	63 6.6%
Race/Ethnicity, Customized (Number) [Number]
Non-Hispanic	217 81.6%	221 81.5%	210 80.8%	648 1322.4%
Hispanic	41 15.4%	39 14.4%	47 18.1%	127 259.2%
American Indian or Alaska native	1 0.4%	6 2.2%	5 1.9%	12 24.5%
Asian	9 3.4%	4 1.5%	7 2.7%	20 40.8%
Black	1 0.4%	2 0.7%	2 0.8%	5 10.2%
White	239 89.8%	252 93%	239 91.9%	730 1489.8%
Not Available	24 9%	18 6.6%	10 3.8%	52 106.1%
Race/Ethnicity, Customized (Number) [Number]
Non-Hispanic	39 14.7%	88 32.5%	127 48.8%
Hispanic	10 3.8%	17 6.3%	27 10.4%
American Indian or Alaska native	0 0%	3 1.1%	3 1.2%
Asian	2 0.8%	0 0%	2 0.8%
White	42 15.8%	101 37.3%	143 55%
Unknown	5 1.9%	1 0.4%	6 2.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)
Description	The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	104	105	100
Mean (Standard Deviation) [Scores on a Scale]	1.19 (1.68)	1.41 (2.02)	1.47 (1.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6744
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	-0.044
	Confidence Interval	(2-Sided) 95% -0.248 to 0.161
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4494
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	-0.085
	Confidence Interval	(2-Sided) 95% -0.304 to 0.135
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)
Description	An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up until a maximum of 5 years

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	49	105
AEs	46 17.3%	100 36.9%
SAEs	18 6.8%	28 10.3%

3. Secondary Outcome

Title	Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)
Description	The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	105	104	100
Mean (Standard Deviation) [Scores on a Scale]	3.68 (6.64)	3.52 (6.28)	3.97 (6.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7458
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	0.035
	Confidence Interval	(2-Sided) 95% -0.179 to 0.250
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.723
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	0.042
	Confidence Interval	(2-Sided) 95% -0.191 to 0.275
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)
Description	Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	91	95	91
Median (95% Confidence Interval) [Days]	63.64	62.98	70.64

5. Secondary Outcome

Title	Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)
Description	The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	90	87	80	73
Mean (Standard Deviation) [Z-Score]	-1.72 (2.99)	-1.37 (2.74)	-1.4 (3.11)	-1.93 (3.08)

6. Secondary Outcome

Title	Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)
Description	FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by () 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words4. The minimum score is 0 (worse).
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	100	102	97	79
Mean (Standard Deviation) [Scores on a Scale]	-4.05 (8.73)	-4.11 (8.57)	-6.42 (8.45)	-4.05 (8.68)

7. Secondary Outcome

Title	Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)
Description	Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	105	104	99	84
Mean (Standard Deviation) [Scores on a Scale]	3.59 (4.93)	4.89 (6.2)	4.03 (5.75)	3.6 (4.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0825
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	-0.191
	Confidence Interval	(2-Sided) 95% -0.407 to 0.025
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7171
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Effect Size
	Estimated Value	0.043
	Confidence Interval	(2-Sided) 95% -0.19 to 0.276
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)
Description	The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	104	105	100	83
Mean (Standard Deviation) [Scores on a Scale]	0.1 (0.29)	0.18 (0.36)	0.14 (0.33)	0.1 (0.31)

9. Secondary Outcome

Title	Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)
Description	The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	103	105	99	82
Mean (Standard Deviation) [Scores on a Scale]	0.6 (3.22)	0.39 (2.57)	0.34 (2.84)	0.72 (3.35)

10. Secondary Outcome

Title	Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)
Description	CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	72	71	66	56
p-tau (Week 104)	2.77 (20.69)	-4.78 (11.9)	-7.34 (10.09)	2.84 (23.19)
t-tau (Week 104)	3.43 (19.95)	-1.36 (12.89)	-2.12 (11.01)	3.46 (22.32)
Abeta (Week 104)	4.87 (36.14)	2.45 (24.57)	15.2 (45.24)	4.3 (39.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments	Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9734
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments	Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0629
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments	Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0084
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments	Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
	Comments	Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0903
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
	Comments	Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0434
	Comments
	Method	Mixed Models Analysis
	Comments

11. Secondary Outcome

Title	Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)
Description	Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	131	124	119	107
HRV (Week 104)	-7.61 (4.03)	-7.52 (3.96)	-7.34 (3.84)	-7.7 (4.01)
HLV (Week 104)	-7.8 (4.28)	-7.76 (3.74)	-7.27 (3.78)	-8.12 (4.19)

12. Secondary Outcome

Title	Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)
Description	The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)	Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	6	4	10	4
Cerebellum gray (Week 156)	6.26 (9.1)	2.7 (10.59)	-8.36 (9.11)	5.95 (11.13)
Whole Cerebellum (Week 156)	5.41 (7.13)	2.07 (8.65)	-8.44 (8.06)	5.17 (8.66)
Composite White Matter (Week 156)	2.75 (3.18)	-0.87 (2.95)	-4.86 (6.35)	3.07 (2.07)
Subcortical White Matter (Week 156)	4.83 (4.95)	1.69 (4.45)	-0.42 (8.26)	4.59 (0.55)
Pons (Week 156)	1.72 (2.51)	-2.83 (3.39)	-6.99 (5.65)	2.1 (2.73)
Composite Reference (Week 156)	4.5 (3.48)	1.19 (5.63)	-6.75 (6.1)	4.46 (4.49)

13. Secondary Outcome

Title	Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)
Description	The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Time Frame	Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.

Arm/Group Title	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	239	227
Week 1 (Post-Dose)	3.56 (2.36)	7.4 (4.28)
Week 8 (Pre-Dose)	2.87 (1.84)	5.92 (3.16)
Week 20 (Pre-Dose)	3.7 (2.15)	7.66 (4.14)
Week 44 (Pre-Dose)	4.08 (2.44)	8.22 (4.51)
Week 53 (Post-Dose)	6.77 (3.94)	15 (9.34)
Week 68 (Pre-Dose)	3.95 (2.35)	8.91 (4.86)
Week 100 (Pre-Dose)	4.35 (2.34)	9.4 (4.69)
Week 101 (Post-Dose)	7.32 (3.53)	16.63 (7.96)

14. Secondary Outcome

Title	Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)
Description	The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Time Frame	Baseline, Week 104

Outcome Measure Data

Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	104	105	99
Mean (Standard Deviation) [Scores on a Scale]	-2.31 (3.23)	-2.46 (3.68)	-2.25 (3.31)

15. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)
Description	An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up until a maximum of 4.5 years

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	266	271	260
AEs	250 94%	241 88.9%	240 92.3%
SAEs	55 20.7%	48 17.7%	46 17.7%

16. Secondary Outcome

Title	Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)
Description	Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Time Frame	Baseline up until a maximum of 4.5 years

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2)	Gantenerumab 105 mg (Parts 1 and 2)	Gantenerumab 225 mg (Parts 1 and 2)
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Measure Participants	259	266	256
Baseline ADAs	5.8 2.2%	7.5 2.8%	5.5 2.1%
Treatment Emergent ADAs	5.0 1.9%	7.0 2.6%	6.4 2.5%

17. Secondary Outcome

Title	Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)
Description	The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	21	51
Mean (Standard Deviation) [Scores on a Scale]	5.8 (7.3)	8.9 (9.7)

18. Secondary Outcome

Title	Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)
Description	The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	21	52
Mean (Standard Deviation) [Scores on a Scale]	3.3 (2.4)	2.8 (3.0)

19. Secondary Outcome

Title	Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)
Description	The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	21	51
Mean (Standard Deviation) [Scores on a Scale]	8.0 (8.2)	10.4 (10.6)

20. Secondary Outcome

Title	Time to Onset of Dementia at Week 156 (OLE Phase)
Description	Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	3	14
Median (95% Confidence Interval) [Days]	38.18	50.82

21. Secondary Outcome

Title	Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)
Description	FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by () 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words4. The minimum score is 0 (worse).
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	22	51
Mean (Standard Deviation) [Scores on a Scale]	-7.7 (9.3)	-4.1 (8.3)

22. Secondary Outcome

Title	Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)
Description	Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	22	52
Mean (Standard Deviation) [Scores on a Scale]	8.1 (5.3)	6.8 (6.8)

23. Secondary Outcome

Title	Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)
Description	The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	21	52
Mean (Standard Deviation) [Scores on a Scale]	0.6 (0.6)	0.5 (0.6)

24. Secondary Outcome

Title	Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)
Description	Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.
Time Frame	Baseline, Week 152

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	18	51
HRV (Week 152)	16.7 (8.4)	16.1 (8.2)
HLV (Week 152)	16.2 (13.0)	18.0 (8.9)

25. Secondary Outcome

Title	Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)
Description	The regions of the brain that were analyzed included cerebellum gray and composite reference.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	2
Cerebellum gray (Week 156)	-0.2 (0.2)
Composite Reference (Week 156)	-41.4 (29.9)

26. Secondary Outcome

Title	Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)
Description	The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Time Frame	Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.

Arm/Group Title	Gantenerumab 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at a dose of 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	99
Week 64 (Pre-Dose)	33.0 (21.7)
Week 100 (Pre-Dose)	39.2 (22.7)
Week 101 (Post-Dose)	80.5 (37.8)
Week 104 (Pre-Dose)	40.5 (22.5)
Week 136 (Pre-Dose)	45.2 (22.4)
Week 156 (Pre-Dose)	39.6 (28.2)
Week 208 (Pre-Dose)	37.1 (29.2)

27. Secondary Outcome

Title	Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)
Description	The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Time Frame	Baseline, Week 156

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	22	53
Mean (Standard Deviation) [Scores on a Scale]	-4.3 (4.3)	-4.7 (4.6)

28. Secondary Outcome

Title	Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)
Description	Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Time Frame	Baseline up until a maximum of 5 years

Outcome Measure Data

Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Arm/Group Title	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Measure Participants	49	104
Baseline ADAs	2.0 0.8%	5.8 2.1%
Treatment Emergent ADAs	2.2 0.8%	2.9 1.1%

Adverse Events

	Placebo (Parts 1 and 2)		Gantenerumab 105 mg (Parts 1 and 2)		Gantenerumab 225 mg (Parts 1 and 2)		Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])		Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Time Frame	Baseline up until a maximum of 9.5 years
Adverse Event Reporting Description

Arm/Group Title	Placebo (Parts 1 and 2)		Gantenerumab 105 mg (Parts 1 and 2)		Gantenerumab 225 mg (Parts 1 and 2)		Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])		Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Arm/Group Description	Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.		Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.		Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.		Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.		Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/266 (2.3%)		0/271 (0%)		2/260 (0.8%)		1/49 (2%)		3/105 (2.9%)
Serious Adverse Events
	Placebo (Parts 1 and 2)		Gantenerumab 105 mg (Parts 1 and 2)		Gantenerumab 225 mg (Parts 1 and 2)		Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])		Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/266 (20.7%)		48/271 (17.7%)		46/260 (17.7%)		18/49 (36.7%)		28/105 (26.7%)
Blood and lymphatic system disorders
Anaemia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Iron deficiency anaemia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Arrhythmia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Atrial flutter	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Bradycardia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Cardiac failure	1/266 (0.4%)	1	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Mitral valve incompetence	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Myocardial infarction	2/266 (0.8%)	2	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Supraventricular tachycardia	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Acute coronary syndrome	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Angina pectoris	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Angina unstable	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Arteriosclerosis coronary artery	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Atrial fibrillation	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Atrial thrombosis	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Atrioventricular block second degree	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Cardiac ventricular thrombosis	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Coronary artery disease	0/266 (0%)	0	2/271 (0.7%)	2	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Myocardial rupture	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Sinus arrest	1/266 (0.4%)	1	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Ear and labyrinth disorders
Deafness unilateral	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Endocrine disorders
Diabetes insipidus	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Eye disorders
Retinal detachment	0/266 (0%)	0	2/271 (0.7%)	2	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Visual impairment	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Gastrointestinal disorders
Constipation	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Gastric haemorrhage	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Gastric ulcer	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Inguinal hernia	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Intestinal obstruction	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Abdominal distension	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Abdominal pain	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Diarrhoea	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Diverticulum intestinal haemorrhagic	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Gastritis	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Hiatus hernia	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Pancreatic mass	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Umbilical hernia	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
General disorders
Asthenia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Chest pain	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Gait disturbance	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Sudden death	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Device dislocation	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Malaise	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Pain	1/266 (0.4%)	1	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Pyrexia	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Cholelithiasis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Immune system disorders
Anaphylactic reaction	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Type I hypersensitivity	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Infections and infestations
Abdominal abscess	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Atypical pneumonia	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
COVID-19	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Diverticulitis	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Infection	0/266 (0%)	0	1/271 (0.4%)	2	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Lower respiratory tract infection	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Otitis media	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Pelvic abscess	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Respiratory tract infection	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Sepsis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Urinary tract infection	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Appendicitis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Bacterial sepsis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Cellulitis	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Cholecystitis infective	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Cystitis	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Erysipelas	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Gastroenteritis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Gastroenteritis viral	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Lyme disease	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Pleural infection bacterial	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Pneumonia	1/266 (0.4%)	1	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Post procedural infection	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Subcutaneous abscess	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Injury, poisoning and procedural complications
Fall	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	2/49 (4.1%)	2	4/105 (3.8%)	4
Femoral neck fracture	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Head injury	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Hip fracture	1/266 (0.4%)	1	1/271 (0.4%)	1	2/260 (0.8%)	2	1/49 (2%)	1	0/105 (0%)	0
Joint injury	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Lumbar vertebral fracture	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Muscle strain	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Pelvic fracture	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Post lumbar puncture syndrome	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Procedural pain	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Rib fracture	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Subdural haematoma	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	1/105 (1%)	1
Subdural haemorrhage	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Upper limb fracture	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Ankle fracture	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Femur fracture	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Humerus fracture	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Laceration	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Ligament rupture	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Lower limb fracture	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Meniscus injury	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Post procedural haematuria	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Radiation mucositis	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Radius fracture	2/266 (0.8%)	2	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Road traffic accident	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Spinal fracture	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Tibia fracture	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Urinary retention postoperative	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Investigations
Body temperature increased	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Blood pressure increased	0/266 (0%)	0	1/271 (0.4%)	4	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
C-reactive protein increased	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Diabetes mellitus	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Musculoskeletal and connective tissue disorders
Osteitis	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Osteoarthritis	1/266 (0.4%)	1	1/271 (0.4%)	1	1/260 (0.4%)	1	1/49 (2%)	1	0/105 (0%)	0
Pain in extremity	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Arthritis reactive	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Rotator cuff syndrome	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Spinal column stenosis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Biliary cancer metastatic	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Breast cancer	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Colon cancer	0/266 (0%)	0	1/271 (0.4%)	1	1/260 (0.4%)	1	1/49 (2%)	1	0/105 (0%)	0
Laryngeal squamous cell carcinoma	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Leukaemia	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Lung cancer metastatic	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Lung neoplasm malignant	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	1/105 (1%)	1
Metastases to bone	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Myelodysplastic syndrome	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Plasmacytoma	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Prostate cancer	2/266 (0.8%)	2	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Small cell carcinoma	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Basal cell carcinoma	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Benign ovarian tumour	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Bladder cancer	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Bladder transitional cell carcinoma	0/266 (0%)	0	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Bone sarcoma	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Breast cancer stage II	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Gastrointestinal tract adenoma	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Glioma	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Intestinal adenocarcinoma	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Intraductal proliferative breast lesion	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Pharyngeal neoplasm benign	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Rectal adenocarcinoma	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Renal cell carcinoma	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Renal oncocytoma	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Tongue neoplasm malignant stage unspecified	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Nervous system disorders
ARIA-E	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	2/105 (1.9%)	2
Balance disorder	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Cerebellar infarction	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Cerebral haematoma	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Cerebral haemorrhage	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	1/49 (2%)	1	0/105 (0%)	0
Dementia with Lewy bodies	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Epilepsy	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	2/105 (1.9%)	2
Generalised tonic-clonic seizure	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Headache	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Neuropathy peripheral	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Partial seizures	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Retrograde amnesia	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Seizure	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Speech disorder	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Subarachnoid haemorrhage	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Thalamic infarction	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Amyotrophic lateral sclerosis	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Ischaemic stroke	1/266 (0.4%)	1	0/271 (0%)	0	2/260 (0.8%)	2	0/49 (0%)	0	0/105 (0%)	0
Monoparesis	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Presyncope	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Radial nerve palsy	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Syncope	2/266 (0.8%)	2	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Transient global amnesia	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Transient ischaemic attack	1/266 (0.4%)	1	1/271 (0.4%)	1	2/260 (0.8%)	2	0/49 (0%)	0	0/105 (0%)	0
Dizziness	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Psychiatric disorders
Agitation	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Confusional state	1/266 (0.4%)	1	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	3/105 (2.9%)	3
Delusion	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Neuropsychiatric symptoms	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Suicidal behaviour	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	1/105 (1%)	1
Anxiety	1/266 (0.4%)	1	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Behavioral and psychological symptoms of dementia	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Depression	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Major depression	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Suicide attempt	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Renal and urinary disorders
Bladder obstruction	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Haematuria	0/266 (0%)	0	0/271 (0%)	0	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Reproductive system and breast disorders
Prostatomegaly	0/266 (0%)	0	0/271 (0%)	0	2/260 (0.8%)	2	0/49 (0%)	0	0/105 (0%)	0
Benign prostatic hyperplasia	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Cystocele	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Ovarian cyst	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Respiratory, thoracic and mediastinal disorders
Delirium	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Haemothorax	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Pulmonary embolism	1/266 (0.4%)	1	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Surgical and medical procedures
Rotator cuff repair	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Urethral caruncle removal	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Hip arthroplasty	0/266 (0%)	0	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Knee arthroplasty	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Spinal decompression	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Urethral dilation procedure	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Vascular disorders
Deep vein thrombosis	0/266 (0%)	0	1/271 (0.4%)	1	1/260 (0.4%)	1	0/49 (0%)	0	0/105 (0%)	0
Peripheral artery aneurysm	0/266 (0%)	0	1/271 (0.4%)	1	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Peripheral ischaemia	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	0/105 (0%)	0
Hypotension	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Malignant hypertension	1/266 (0.4%)	1	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	0/105 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo (Parts 1 and 2)		Gantenerumab 105 mg (Parts 1 and 2)		Gantenerumab 225 mg (Parts 1 and 2)		Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])		Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	163/266 (61.3%)		188/271 (69.4%)		189/260 (72.7%)		40/49 (81.6%)		87/105 (82.9%)
Eye disorders
Cataract	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	4/49 (8.2%)	5	2/105 (1.9%)	3
Gastrointestinal disorders
Diarrhoea	13/266 (4.9%)	18	15/271 (5.5%)	22	15/260 (5.8%)	18	3/49 (6.1%)	3	11/105 (10.5%)	14
Vomiting	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	5/49 (10.2%)	5	6/105 (5.7%)	9
General disorders
Injection site erythema	3/266 (1.1%)	3	29/271 (10.7%)	133	35/260 (13.5%)	114	17/49 (34.7%)	196	36/105 (34.3%)	359
Fatigue	8/266 (3%)	8	7/271 (2.6%)	7	15/260 (5.8%)	20	0/49 (0%)	0	0/105 (0%)	0
Infections and infestations
Bronchitis	10/266 (3.8%)	10	10/271 (3.7%)	12	14/260 (5.4%)	18	3/49 (6.1%)	3	7/105 (6.7%)	9
Herpes zoster	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	4/49 (8.2%)	4	1/105 (1%)	1
Influenza	13/266 (4.9%)	14	13/271 (4.8%)	18	15/260 (5.8%)	17	3/49 (6.1%)	4	7/105 (6.7%)	8
Nasopharyngitis	17/266 (6.4%)	34	30/271 (11.1%)	40	20/260 (7.7%)	35	7/49 (14.3%)	7	15/105 (14.3%)	23
Upper respiratory tract infection	11/266 (4.1%)	14	13/271 (4.8%)	15	18/260 (6.9%)	21	5/49 (10.2%)	5	10/105 (9.5%)	19
Urinary tract infection	25/266 (9.4%)	37	16/271 (5.9%)	25	22/260 (8.5%)	38	4/49 (8.2%)	6	15/105 (14.3%)	25
Injury, poisoning and procedural complications
Contusion	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	4/49 (8.2%)	4	5/105 (4.8%)	5
Fall	28/266 (10.5%)	42	23/271 (8.5%)	32	27/260 (10.4%)	38	13/49 (26.5%)	20	17/105 (16.2%)	29
Skin laceration	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	0/49 (0%)	0	7/105 (6.7%)	8
Investigations
Weight decreased	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	2/49 (4.1%)	2	6/105 (5.7%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	21/266 (7.9%)	29	12/271 (4.4%)	14	16/260 (6.2%)	17	2/49 (4.1%)	2	8/105 (7.6%)	8
Back pain	26/266 (9.8%)	33	16/271 (5.9%)	18	26/260 (10%)	32	2/49 (4.1%)	2	10/105 (9.5%)	10
Osteoporosis	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	3/49 (6.1%)	3	1/105 (1%)	1
Musculoskeletal pain	16/266 (6%)	18	6/271 (2.2%)	7	5/260 (1.9%)	5	0/49 (0%)	0	0/105 (0%)	0
Nervous system disorders
Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits	31/266 (11.7%)	51	58/271 (21.4%)	92	36/260 (13.8%)	64	7/49 (14.3%)	12	17/105 (16.2%)	44
Amyloid related imaging abnormality-oedema/effusion	2/266 (0.8%)	2	18/271 (6.6%)	20	34/260 (13.1%)	36	12/49 (24.5%)	21	29/105 (27.6%)	45
Dizziness	21/266 (7.9%)	21	21/271 (7.7%)	27	26/260 (10%)	35	4/49 (8.2%)	5	14/105 (13.3%)	18
Headache	36/266 (13.5%)	50	34/271 (12.5%)	47	25/260 (9.6%)	36	7/49 (14.3%)	11	12/105 (11.4%)	18
Psychiatric disorders
Agitation	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	3/49 (6.1%)	4	8/105 (7.6%)	10
Anxiety	18/266 (6.8%)	23	20/271 (7.4%)	20	16/260 (6.2%)	16	2/49 (4.1%)	2	7/105 (6.7%)	8
Confusional state	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	5/49 (10.2%)	5	8/105 (7.6%)	8
Irritability	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	1/49 (2%)	1	6/105 (5.7%)	9
Depression	13/266 (4.9%)	14	23/271 (8.5%)	23	25/260 (9.6%)	25	0/49 (0%)	0	0/105 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	13/266 (4.9%)	14	11/271 (4.1%)	13	13/260 (5%)	13	5/49 (10.2%)	5	8/105 (7.6%)	12
Productive cough	0/266 (0%)	0	0/271 (0%)	0	0/260 (0%)	0	3/49 (6.1%)	3	0/105 (0%)	0
Vascular disorders
Hypertension	18/266 (6.8%)	20	11/271 (4.1%)	11	20/260 (7.7%)	23	2/49 (4.1%)	2	8/105 (7.6%)	11

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800 821-8590
Email	genentech@druginfo.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01224106

Other Study ID Numbers:

WN25203
2010-019895-66

First Posted:

Oct 19, 2010

Last Update Posted:

Dec 13, 2021

Last Verified:

Dec 1, 2021

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

Study Details

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Brief Summary

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Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

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Inclusion Criteria:

Additional inclusion criteria for sub study:

Exclusion Criteria:

Additional exclusion criteria for sub study:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

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Study Results

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Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact