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

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

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: Gantenerumab

• Study Type: Interventional
• Enrollment (Actual): 1053
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney; Neurology
    • Erina, New South Wales, Australia, 2250
      • Central Coast Neurosciences Research
    • Kogarah, New South Wales, Australia, 2217
      • Southern Neurology
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital; Neurology
  • Victoria
    • Heidelberg West, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
    • Noble Park, Victoria, Australia, 3174
      • Neuro Trials Victoria
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Foundation
• Brazil
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
    • Curitiba, PR, Brazil, 80810-040
      • Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia
    • Maringa, PR, Brazil, 87013-250
      • Clinica Clinilive ltda
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP_X; Neurologia
    • Sao Paulo, SP, Brazil, 04534-011
      • Clínica Dr. Norton Sayeg LTDA - EPP
• Canada
  • Quebec, Canada, G3K 2P8
    • ALPHA Recherche Clinique
  • British Columbia
    • Penticton, British Columbia, Canada, V1Y 1Z9
      • Medical Arts Health Research Group
    • Vancouver, British Columbia, Canada, V7T 2Z3
      • The Medical Arts Health Research Group - West Vancouver
  • Ontario
    • London, Ontario, Canada, N6C 5J1
      • Parkwood Hospital; Geriatric Medicine
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4G 3E8
      • Centre for Memory and Aging
    • Toronto, Ontario, Canada, M6A 2E1
      • Baycrest Health Sciences
    • Woodstock, Ontario, Canada, N4S 5P5
      • Devonshire Clinical Research
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Center for Diagnosis and Research on Alzheimer's disease
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Q & T Research Sherbrooke
• China
  • Beijing City, China, 100029
    • China-Japan Friendship Hospital
  • Beijing City, China, 100071
    • Beijing Tian Tan Hospital,Capital Medical University
  • Beijing City, China, 100032
    • Beijing Anding Hospital, Capital Medical University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Chongqing, China, 400016
    • The First Affiliated Hospital, Chongqing Medical University
  • Fuzhou City, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510180
    • Guangzhou First Municipal People's Hospital
  • Guangzhou, China, 510000
    • Sun Yat-sen Memorial Hospital; Neurology
  • Guangzhou City, China, 510180
    • Guangdong Provincial People's Hospital; Breast
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital, Zhejiang University
  • Hangzhou City, China, 310018
    • Sir Run Run Shaw Hospital
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Hefei, China, 230022
    • The First Affiliated Hospital of Anhui Medical University
  • Nanchang, China, 330006
    • The Second Affiliated Hospital to Nanchang University
  • Nanjing, China, 210009
    • Zhongda Hospital Affiliated to Southeast University
  • Nanjing City, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nanjing City, China, 210029
    • Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
  • Shanghai, China, 200080
    • Shanghai First People's Hospital
  • Shanghai, China, 200092
    • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai, China, 200030
    • Shanghai Mental Health Center
  • Shanghai, China, 200233
    • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai City, China, 200025
    • Ruijin Hospital Shanghai Jiaotong University School of Medicine
  • Shanghai City, China, 200040
    • Huashan Hospital Affiliated to Fudan University
  • Shenzhen City, China, 518053
    • The University of Hong Kong-Shenzhen Hospital; Local Ethic Committee
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical College
  • Yangzhou City, China, 225001
    • Northern Jangsu People's Hospital
  • Zhengzhou, China, 450003
    • Henan Provincial People's Hospital
• France
  • Amiens Cedex1, France, 80054
    • CHU Amiens Hopital Sud; Neurologie
  • Bobigny Cedex, France, 93009
    • Hôpital Avicenne; Centre de Recherche Clinique
  • Bron cedex, France, 69677
    • Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
  • Marseille, France, 13005
    • CHU de la Timone - Hopital d Adultes; Service de Neurologie
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Poitiers, France, 86000
    • CHU Poitiers - Hôpital la Milétrie
  • Strasbourg, France, 67098
    • CHU Strasbourg Hôpital Hautepierre
  • Toulouse, France, 31059
    • Gerontopole; Centre de Recherche clinique
  • Villeurbanne, France, 69100
    • Hôpital des Charpennes
• Germany
  • Berlin, Germany, 13125
    • ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
  • Berlin, Germany, 12200
    • Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
  • Bochum, Germany, 44791
    • St. Josef-Hospital, Klinik für Neurologie
  • Köln, Germany, 50937
    • Universitätsklinikum Köln; Klinik und Poliklinik für Psychiatrie und Psychotherapie
  • Leipzig, Germany, 04275
    • PANAKEIA - Arzneimittelforschung Leipzig GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin derJohannes Gutenberg-Universität Mainz;Klinik für Psychiatrie und Psychotherapi
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
  • Rostock, Germany, 18147
    • Universitätsklinikum Rostock Zentrum für Nervenheilkunde
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
  • Westerstede, Germany, 26655
    • Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
  • Witten, Germany, 58455
    • Forschungszentrum Ruhr
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University; Department of Neurology
• Italy
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41126
      • Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica ? Dipartimento di Neuroscienze
  • Lazio
    • Roma, Lazio, Italy, 00185
      • Umberto I Policlinico di Roma-Università di Roma La Sapienza
    • Roma, Lazio, Italy, 00186
      • Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
    • Roma, Lazio, Italy, 00179
      • Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica
  • Lombardia
    • Brescia, Lombardia, Italy, 25125
      • IRCCS ?Centro S. Giovanni di Dio? Fatebenefratelli -UO Alzheimer
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria
    • Monza, Lombardia, Italy, 20900
      • ASST DI MONZA; Neurologia
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Dipartimento delle Patologie Emergenti; Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
• Japan
  • Chiba, Japan, 260-8656
    • Medical Corporation Hakuyokai Kashiwado Hospital
  • Chiba, Japan, 263-0043
    • Inage Neurology and Memory Clinic
  • Chiba, Japan, 279-0021
    • Juntendo University Urayasu Hospital
  • Fukushima, Japan, 963-8052
    • Southern TOHOKU Medical Clinic
  • Kanagawa, Japan, 223-0059
    • Yuai Clinic
  • Kanagawa, Japan, 247-8533
    • Shonan Kamakura General Hospital
  • Niigata, Japan, 940-2302
    • Mishima Hospital
  • Shizuoka, Japan, 420-8688
    • NHO Shizuoka Institute of Epilepsy and Neurological Disorders
  • Shizuoka, Japan, 424-0911
    • Shizuoka City Shimizu Hospital
  • Tochigi, Japan, 329-0403
    • Jichiidai Station Brain Clinic
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 102-0084
    • Yotsuya Medical Cube
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
  • Tokyo, Japan, 181-0013
    • Nozomi Memory Clinic
  • Tokyo, Japan, 192-0071
    • P-One Clinic
  • Tokyo, Japan, 173-0015
    • Tokyo Metropolitan Geriatric Hospital
  • Yamagata, Japan, 990-0834
    • Yamagata Tokusyukai Hospital
• Lithuania
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinics; Neurology
• Peru
  • Bellavista, Peru, Callao 2
    • Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
  • Lima, Peru, 15001
    • Clinica Internacional; Unidad De Investigacion
  • Lima, Peru, 15003
    • Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
  • San Martin de Porres, Peru, 15102
    • Hospital Nacional Cayetano Heredia; Servicio de Neurologia
• Russian Federation
  • Saratov, Russian Federation, 410028
    • City Clinical Hospital # 2 n.a. V.I. Razumovsky
  • Tomsk, Russian Federation, 634009
    • Nebbiolo Center for Clinical Trials
  • Krasnojarsk
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660037
      • FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 121467
      • University ?linic of headaches
    • Moscow, Moskovskaja Oblast, Russian Federation, 125101
      • City Clin Hosp n.a. S.P.Botkin
    • Moskva, Moskovskaja Oblast, Russian Federation, 107150
      • Central Clinical Hospital #2 N.A. Semashko OAO RJHD
  • Sankt Petersburg
    • St Petersburg, Sankt Petersburg, Russian Federation, 194044
      • Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420047
      • Vertebronevrologiya LLC
    • Kazan, Tatarstan, Russian Federation, 420101
      • State autonomous institution of healthcare Inter-regional clinical and diagnostic center
• Spain
  • Albacete, Spain
    • Hospital General Universitario de Albacete; Servicio de Neurología
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial; Servicio de Neurologia
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron; Servicio de Neurología
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia; Servicio de Neurologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional; Servicio de Neurología
  • Salamanca, Spain, 37005
    • Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío; Servicio de Neurología
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset; Servicio de Neurologia
  • Zaragoza, Spain, 50012
    • Servicio de Neurología Hospital Viamed Montecanal.
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge; Servicio de Neurologia
    • Sant Cugat del Valles, Barcelona, Spain, 8195
      • Hospital General De Catalunya; Servicio de Neurologia
  • Cantabria
    • SANtander, Cantabria, Spain, 39011
      • Hospital Universitario Marques de Valdecilla; Servicio de Neurología
  • LA Rioja
    • Logroño, LA Rioja, Spain, 26006
      • Hospital San Pedro; Servicio de Neurología
  • Madrid
    • Móstoles, Madrid, Spain, 28938
      • HM Universitario Puerta del Sur CINAC (C.Integ.Neuroc);; Servicio de Psiquiatría
• Taiwan
  • Changhua County, Taiwan, 500
    • Changhua Christian Hospital; Neurology
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Hospital; Neurology
  • Niaosong Dist., Taiwan, 83301
    • Chang Gung Memorial Foundation - Kaohsiung - Neurology
  • North Dist., Taiwan, 40447
    • China Medical University Hospital; Neurology
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital; Neurology
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Foundation - Linkou - Neurology
• United States
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Center for Neurosciences
  • California
    • Irvine, California, United States, 92614
      • Global Clinical Trials; Irvine, CA
    • Sacramento, California, United States, 95816
      • Sutter Medical Group, Neurology
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies, Inc.
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research LLC
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research, Inc.
    • Wellington, Florida, United States, 33414
      • Alzheimer?s Research and Treatment Center
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University, School of Medicine
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Fort Wayne Neurological Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of NJ
  • New York
    • Lake Success, New York, United States, 11042
      • Neurological Associates of Long Island, PC
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University; College of Medicine
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University; College of Medicine
  • South Carolina
    • Port Royal, South Carolina, United States, 29935
      • Coastal Neurology
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Dallas, Texas, United States, 75243
      • Neurology Consultants of Dallas; Research Department
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
  • Virginia
    • Charlottesville, Virginia, United States, 22906
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Neurology Specialists
    • Richmond, Virginia, United States, 23294
      • National Clinical Research Inc.-Richmond
    • Richmond, Virginia, United States, 23229
      • Neurological Associates, Inc.
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • UW Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gantenerumab; Gantenerumab will be administered as SC injections with gradual uptitration.	Drug: Gantenerumab; Gantenerumab will be administered as per the schedule specified in the respective arm.; Other Names: RO4909832
Placebo Comparator: Placebo; Placebo will be administered as SC injections with gradual uptitration.	Drug: Placebo; Placebo will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
China Extension: 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin		Baseline, Week 116
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
DBT Period: Number of Participants With at Least One Adverse Event (AE)	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 131 weeks)
DBT 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 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)
DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding	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 131 weeks)
DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding	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 131 weeks)
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 131 weeks)
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 131 weeks)
DBT Period: 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
DBT Period: 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. [18F] GTP1 was the tau PET radioligand. Tau load was measured using SUVR in 4 composite target ROIs: Temporal composite target region (left & right)=anterior & posterior superior temporal gyrus, posterior temporal lobe, fusiform gyrus, & middle & inferior temporal gyrus; Medial temporal composite region excluding hippocampus (left & right): amygdala, parahippocampus & anterior medial & lateral temporal lobe; Frontal lobe (left & right) & Parietal lobe (left & right). Inferior cerebellar grey matter=reference region for calculating SUVRs for all 4 regions. Tau-PET-mITT analysis set=all participants in ITT analysis set who participated in Tau PET sub-study & who had at least one Tau PET scan with a 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
DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (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
DBT Period: Percent Change From Baseline to Week 116 in 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
China - DBT Period: Change From Baseline to Week 116 in 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
China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score	ADCS-ADL is a 23-item rater-administered, ObsRO that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement.	Baseline, Week 116
China - DBT Period: Change From Baseline to Week 116 in 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
China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score	MMSE is a rater-administered 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
China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score	The ADAS-Cog11 was designed to measure cognitive symptom change in participants with 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
China - DBT Period: Change From Baseline to Week 116 in 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
China - DBT Period: Change From Baseline to Week 116 in the Coding (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
China - DBT Period: Number of Participants With at Least One AE	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. Total number of participants with at least one event (AEs) have been reported here.	From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)
China - 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 124 weeks)
China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding	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 124 weeks)
China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding	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 124 weeks)
China - 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 124 weeks)
OLE Period: Number of Participants With at Least One AEs	An AE 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 68 weeks)
OLE 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 of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)
OLE Period: Number of Participants With at Least One ARIA-H MRI Finding	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 68 weeks)
OLE Period: Number of Participants With at Least One ARIA-E MRI Finding	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 68 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Gantenerumab Administered SC	Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis.	Baseline, Week 2, 24, 41, 52, 76, 103, 115, 128, 164 and at early termination and unscheduled visit, Week 1 and Week 24 (Open label extension)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Actual): December 28, 2022
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 19, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: WN29922; 2017-001364-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No