Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

Alzheimer Disease Clinical Trial

Official title:

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03443973
• Other study ID #: WN39658
• Secondary ID: 2017-001365-24
• Status: Terminated
• Phase: Phase 3
• Start date: August 22, 2018
• Est. completion date: November 28, 2022

Study information

• Verified date: December 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 975
• Est. completion date: November 28, 2022
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

Key Inclusion criteria:

• Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment)
• Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid PET scan
• Demonstrated abnormal memory function
• MMSE score greater than or equal to 22 (= 22)
• Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0
• Availability of a reliable study partner who accepts to participate in study procedures throughout the 2 years duration of study
• If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening and until randomization
• For enrollment in the China extension, patients must have residence in mainland China, Hong Kong, or Taiwan and be of Chinese ancestry
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

Key Exclusion criteria:

• Any evidence of a condition other than AD that may affect cognition
• History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
• History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
• History or presence of clinically evident cerebrovascular disease
• History or presence of posterior reversible encephalopathy syndrome
• History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack
• History of severe, clinically significant CNS trauma
• History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
• History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
• At risk for suicide in the opinion of the investigator
• Alcohol and/or substance abuse or dependants in past 2 years
• Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
• Any contraindications to brain MRI
• Unstable or clinically significant cardiovascular, kidney or liver disease
• Uncontrolled hypertension
• Unstable or clinically significant cardiovascular disease
• Abnormal thyroid function
• Patients with evidence of folic acid deficiency

Exclusion for Open-Label Extension (OLE):

• Discontinued from study treatment during the double-blind treatment period
• Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment
• Participation in the OLE deemed inappropriate by the investigator
• Presence of ARIA-E findings at the Week 116 MRI scan

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Gantenerumab
Gantenerumab will be administered as per the schedule specified in the respective arm.
• Placebo
Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
Argentina	Hospital Italiano	Buenos Aires
Argentina	Universidad Maimonides	Caba
Argentina	Instituto Geriatrico Nuestra Señora de las Nieves	Capital Federal
Argentina	CEN Centro Especializado en Neurociencias	Cordoba
Argentina	Instituto Kremer	Córdoba
Argentina	Instituto de Neurociencias San Agustín S.A.	La Plata
Argentina	Fundacion Scherbovsky	Mendoza
Belgium	AZ Sint Blasius (Dendermonde)	Dendermonde
Belgium	UZ Gent	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Chile	Psicomed Estudios Médicos	Antofagasta
Chile	Biomedica Research Group	Santiago
Chile	Especialidades Medicas LYS	Santiago
Croatia	Clinical Hospital Centre Zagreb;Clinic for Neurology	Zagreb
Denmark	Aarhus Universitetshospital; Neurologisk Afd. F, Demensklinikken	Aarhus N
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
Denmark	Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn	Svendborg
Finland	Terveystalo Ruoholahti	Helsinki
Finland	University of Eastern Finland	Kuopio
Japan	Nagoya Ekisaikai Hospital	Aichi
Japan	National Center for Geriatrics and Gerontology	Aichi
Japan	Yachiyo Hospital	Aichi
Japan	Fukuoka University Hospital	Fukuoka
Japan	National Hospital Organization Hiroshima-Nishi Medical Center	Hiroshima
Japan	Hyogo Prefectural HarimaHimeji General Medical Center	Hyogo
Japan	Matsui Dietary and Dementia Clinic	Hyogo
Japan	Tsukazaki Hospital	Hyogo
Japan	Kagawa Prefectural Central Hospital	Kagawa
Japan	Rakuwakai Otowa Hospital	Kyoto
Japan	Uji Takeda Hospital	Kyoto
Japan	Rijikai Medical Corporation Katayama Medical Clinic	Okayama
Japan	Kishiwada Tokushukai Hospital	Osaka
Japan	National Hospital Organization Hizen Psychiatric Medical Center	Saga
Japan	Medical corporation Ichiekai Itsuki Hospital	Tokushima
Japan	Tokushima Hospital	Tokushima
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Myongji Hospital	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Hospital (Seoul)	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Mexico	Mexico Centre for Clinical Research	Ciudad de México	Mexico CITY (federal District)
Mexico	Hospital Angeles Culiacan; Neurociencias	Culiacán Rosales	Sinaloa
Mexico	AVIX Investigación Clínica S.C	Monterrey	Nuevo LEON
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta	Monterrey	Nuevo LEON
Netherlands	Brain Research Center B.V	Amsterdam
Poland	O?rodek Badawczo-Naukowo-Dydaktyczny Chorób Ot?piennych w ?cinawie	?cinawa
Poland	Podlaskie Centrum Psychogeriatrii	Bia?ystok
Poland	NZOZ Vitamed	Bydgoszcz
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych	Plewiska
Poland	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Siemianowice ?l?skie
Poland	Senior Sp. Z O.O. Poradnia Psychogeriatryczna	Sopot
Poland	mMED Maciej Czarnecki	Warszawa
Poland	Pratia S.A.	Warszawa
Poland	NZOZ WCA	Wroc?aw
Portugal	Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia	Amadora
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia	Guimarães
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Puerto Rico	Santa Cruz Behavioral PSC	Bayamon
Puerto Rico	University of Puerto Rico - Medical Science Campus; Internal Medicine	San Juan
Singapore	National Neuroscience Institute; Neurology	Singapore
Singapore	National University Hospital (NUH); Neuroscience	Singapore
Spain	Fundación ACE; Servicio de Neurología	Barcelona
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Policlínica Guipuzcoa; Servicio de Neurología	Donostia-san Sebastian	Guipuzcoa
Spain	Hospital General Universitario de Elche; Servicio de Neurología	Elche	Alicante
Spain	CAE OROITU; Servicio de Neurología	Getxo	Vizcaya
Spain	Hospital Universitario de Santa Maria; Servicio de Neurología	Lleida	Lerida
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Clinica Universitaria de Navarra; Servicio de Neurología	Pamplona	Navarra
Spain	Hospital Virgen del Puerto. Servicio de Neurología	Plasencia	Caceres
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Hospital Victoria Eugenia; Servico Neurología	Sevilla
Spain	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Spain	Complejo Asistencial de Zamora; Servicio Psiquiatria	Zamora
Sweden	Skånes Universitetssjukhus Malmö, Minneskliniken	Malmö
Sweden	Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry	Mölndal
Sweden	KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54	Stockholm
Turkey	Bezmialem Vakif Univ Medical	Istanbul
Turkey	Istanbul University Istanbul School of Medicine; Neurology	Istanbul
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
United Kingdom	Royal Cornhill Hospital; OAP Directorate	Aberdeen
United Kingdom	The Rice Centre; Royal United Hospital	Bath
United Kingdom	Re-Cognition	Birmingham
United Kingdom	The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre	Cheltenham
United Kingdom	Surrey and Borders NHS Foundation Trust; Brain Science Research Unit	Chertsey
United Kingdom	Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit	Crowborough
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Queen Elizabeth University Hospital; Clinical Research Facility	Glasgow
United Kingdom	Charing Cross Hospital	London
United Kingdom	RE:Cognition Health	London
United Kingdom	St George's Hospital	London
United Kingdom	Campus for Ageing and Vitality	Newcastle
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	University Southampton NHS Foundation Trust; Wessex Neurologica Centre	Southampton
United States	Emory University	Atlanta	Georgia
United States	American Health Network Institute, LLC	Avon	Indiana
United States	Missouri Memory Center	Bolivar	Missouri
United States	Brigham and Womens Hospital; Center for Alzheimer Research & Treatment	Boston	Massachusetts
United States	Accel Research Sites - CRU Tampa	Bradenton	Florida
United States	Neuro-Behavioral Clinical Research, Inc.	Canton	Ohio
United States	Behavioral Health Research	Charlotte	North Carolina
United States	Rush Alzheimer's Disease Cntr.	Chicago	Illinois
United States	Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health ? Neurological Institute	Cleveland	Ohio
United States	Kerwin Medical Center	Dallas	Texas
United States	Texas Neurology PA	Dallas	Texas
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Health Initiatives Research, PLLC	Fayetteville	Arkansas
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Neurology Center of North Orange County	Fullerton	California
United States	ActivMed Practices and Research	Haverhill	Massachusetts
United States	Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Irvine Center for Clinical Research	Irvine	California
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	ClinCloud, LLC	Maitland	Florida
United States	Alzheimer's Memory Center	Matthews	North Carolina
United States	Allied Biomedical Research Institute, Inc	Miami	Florida
United States	Optimus U Corp	Miami	Florida
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Boston Center for Memory	Newton	Massachusetts
United States	Renstar Medical Research	Ocala	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center; Dept of Neurological Sciences	Omaha	Nebraska
United States	Banner Alzheimer?s Institute	Phoenix	Arizona
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Desert Valley Research	Redlands	California
United States	AD-CARE, University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Intercoastal Medical Group	Sarasota	Florida
United States	Southern California Research LLC	Simi Valley	California
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Banner Sun Health Research Insitute	Sun City	Arizona
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Chile,  Croatia,  Denmark,  Finland,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Singapore,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma Concentration of Gantenerumab		Pre-dose on Days 1, Weeks 24, 52 and 76; Post-dose on Day 4, Weeks 41, 103, and 115
Primary	DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB	CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement.	Baseline, Week 116
Primary	OLE Period: Number of Participants With Adverse Events (AEs)	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.	From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
Primary	OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.	From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
Primary	OLE Period : Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD.	From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
Primary	OLE Period: Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces.	From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
Primary	OLE Period: Number of Participants With Injection-Site Reactions	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.	From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)
Secondary	DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score	The ADAS-Cog13 total score includes all of the items in the ADAS-Cog11 in addition to delayed word recall and the number cancellation. For the ADAS-cog 13 the range is 0-85 (score range for Delayed Word Recall [DWR] score is 0-10 and for Number Cancellation [NC] is 0-5, thus the score is ADAS-cog 11[0-70] plus the scores for DWR and NC). A higher score indicates worse performance. A negative change from baseline indicates improvement in cognitive function.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score	ADCS-ADL is a 23-item rater-administered, observer-reported outcome (ObsRO) that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score	FAQ is a rater-administered ObsRO (informant-based measure) that measures a participant's functional ability to perform complex higher-order activities. The observer provides performance ratings of the target person on ten complex higher-order activities. Total score that ranges from 0-30, with higher scores reflecting greater functional impairment. A negative change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score	MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. Total score ranges from 0-30, with lower scores indicating greater impairment. A positive change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score	The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. A negative change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score	VFT is a rater administered PerfO that measures speed and flexibility of verbal thought with a total score that ranges from 0-99 (lower scores indicating lower performance). A positive change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest	Coding, also called DSST is a rater administered PerfO that measures speed of processing and associative memory with a total score that ranges from 0-135 (lower scores indicating lower performance). The DSST was adapted from the Wechsler Adult Intelligence Scale. The 120-second version of the test was used in this study. Positive change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score	The ADCS-iADL measures activities such as using the telephone, shopping and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. Positive change from baseline indicates improvement.	Baseline, Week 116
Secondary	DBT Period: Number of Participants With AEs	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS	C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	DBT Period: Number of Participants With ARIA-E Confirmed by MRI	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	DBT Period: Number of Participants With ARIA-H Confirmed by MRI	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	DBT Period: Number of Participants With Injection-Site Reactions	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab	The number of participants with positive results for ADA against gantenerumab at any of the post-baseline assessment time-points were reported. Participant with an ADA assay result from at least one post-baseline sample was defined as a post-baseline evaluable participant. Treatment Emergent ADA = A participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)
Secondary	Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants	Brain amyloid load over time was assessed using [18F] florbetaben or [18F] flutemetamol tracers. These are PET radioligand selective to amyloid. Amyloid PET burden was measured in a composite region of interest (ROI) by using standardized uptake value ratio (SUVR) mapped to the centiloid scale. The weighted composite target region are composed of (both left and right side): frontal lobe, parietal lobe, temporal lobe lateral, cingulum posterior and anterior cingulate gyrus. The reference region used to normalize the composite region was the whole cerebellum. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan.	Baseline, Week 116
Secondary	Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants	Change in tau load= how much neurofibrillary tau pathology is present in brain assessed by PET Scan. Tau PET radioligand used was [18F] GTP1. Tau load was measured using SUVR in 4 composite target ROIs: Temporal target region included (both left & right)=anterior &posterior superior temporal gyrus, posterior temporal lobe, fusiform gyrus, &middle &inferior temporal gyrus; Medial temporal region excluding hippocampus included (both left & right): amygdala, parahippocampus & anterior medial & lateral temporal lobe; Frontal lobe (both left & right) & Parietal lobe (both left & right). Inferior cerebellar grey matter=reference region for calculating SUVRs for 4 target regions. Tau-PET-mITT analysis set=all participants in ITT analysis set who participated in Tau PET sub-study & had at least one Tau PET scan with valid quantitative measurement & who did not withdraw from Tau PET substudy before randomization. Overall number analyzed=number of participants with data available for analysis.	Baseline, Week 116
Secondary	DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)	NFL is a neuronal cytoplasmic protein highly expressed in large, myelinated axons. Its levels increase in CSF and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including AD.	Baseline, Week 116
Secondary	DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin		Baseline, Week 116
Secondary	DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Total Tau (tTau)	CSF biomarker tTau has been considered as a general marker of neurodegeneration. An elevation in levels of tau, as well as specific pTau species, is thought to be a marker for progressive cellular degeneration in AD.	Baseline, Week 116
Secondary	DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)	CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. CSF biomarker tTau has been considered as a general marker of neurodegeneration. An elevation in levels of pTau species, is thought to be a marker for progressive cellular degeneration in AD.	Baseline, Week 116