Safety and Efficacy 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: Gantenerumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 975
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Caba, Argentina, C1405BCK
    • Universidad Maimonides
  • Capital Federal, Argentina, C1427CCP
    • Instituto Geriatrico Nuestra Señora de las Nieves
  • Cordoba, Argentina, X5004FJF
    • CEN Centro Especializado en Neurociencias
  • Córdoba, Argentina, X5004AOA
    • Instituto Kremer
  • La Plata, Argentina, B1902AVF
    • Instituto de Neurociencias San Agustín S.A.
  • Mendoza, Argentina, M5500AYB
    • Fundacion Scherbovsky
• Belgium
  • Dendermonde, Belgium, 9200
    • AZ Sint Blasius (Dendermonde)
  • Gent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
• Chile
  • Antofagasta, Chile, 1270244
    • Psicomed Estudios Médicos
  • Santiago, Chile, 7500710
    • Biomedica Research Group
  • Santiago, Chile, 7560356
    • Especialidades Medicas LYS
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb;Clinic for Neurology
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Neurologisk Afd. F, Demensklinikken
  • København Ø, Denmark, 2100
    • Rigshospitalet, Hukommelsesklinikken
  • Svendborg, Denmark, 5700
    • Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn
• Finland
  • Helsinki, Finland, 00180
    • Terveystalo Ruoholahti
  • Kuopio, Finland, 70210
    • University of Eastern Finland
• Japan
  • Aichi, Japan, 446-8510
    • Yachiyo Hospital
  • Aichi, Japan, 454-8502
    • Nagoya Ekisaikai Hospital
  • Aichi, Japan, 474-8511
    • National Center for Geriatrics and Gerontology
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Hiroshima, Japan, 739-0696
    • National Hospital Organization Hiroshima-Nishi Medical Center
  • Hyogo, Japan, 670-8560
    • Hyogo Prefectural HarimaHimeji General Medical Center
  • Hyogo, Japan, 671-1227
    • Tsukazaki Hospital
  • Hyogo, Japan, 673-0891
    • Matsui Dietary and Dementia Clinic
  • Kagawa, Japan, 760-8557
    • Kagawa Prefectural Central Hospital
  • Kyoto, Japan, 607-8062
    • Rakuwakai Otowa Hospital
  • Kyoto, Japan, 611-0021
    • Uji Takeda Hospital
  • Okayama, Japan, 710-0813
    • Rijikai Medical Corporation Katayama Medical Clinic
  • Osaka, Japan, 596-0042
    • Kishiwada Tokushukai Hospital
  • Saga, Japan, 842-0192
    • National Hospital Organization Hizen Psychiatric Medical Center
  • Tokushima, Japan, 770-0852
    • Medical corporation Ichiekai Itsuki Hospital
  • Tokushima, Japan, 776-8585
    • Tokushima Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Gyeonggi-do, Korea, Republic of, 10475
    • Myongji Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 07985
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of, 04763
    • Hanyang University Seoul Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 07804
    • Ewha Womans University Hospital (Seoul)
• Mexico
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03100
      • Mexico Centre for Clinical Research
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64710
      • AVIX Investigación Clínica S.C
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta
  • Sinaloa
    • Culiacán Rosales, Sinaloa, Mexico, 80020
      • Hospital Angeles Culiacan; Neurociencias
• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center B.V
• Poland
  • ?cinawa, Poland, 59-330
    • O?rodek Badawczo-Naukowo-Dydaktyczny Chorób Ot?piennych w ?cinawie
  • Bia?ystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Bydgoszcz, Poland, 85-079
    • NZOZ Vitamed
  • Lublin, Poland, 20-362
    • KO-MED Centra Kliniczne Lublin II
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
  • Siemianowice ?l?skie, Poland, 41-100
    • NEURO-CARE Sp. z o.o. Sp. Komandytowa
  • Sopot, Poland, 81-855
    • Senior Sp. Z O.O. Poradnia Psychogeriatryczna
  • Warszawa, Poland, 01-684
    • mMED Maciej Czarnecki
  • Warszawa, Poland, 01-868
    • Pratia S.A.
  • Wroc?aw, Poland, 53-659
    • NZOZ WCA
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Servico de Neurologia
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Neurologia
  • Guimarães, Portugal
    • Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Santa Cruz Behavioral PSC
  • San Juan, Puerto Rico, 00936
    • University of Puerto Rico - Medical Science Campus; Internal Medicine
• Singapore
  • Singapore, Singapore, 117549
    • National University Hospital (NUH); Neuroscience
  • Singapore, Singapore, 308433
    • National Neuroscience Institute; Neurology
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Barcelona, Spain, 08028
    • Fundación ACE; Servicio de Neurología
  • Madrid, Spain, 28006
    • Universitario de La Princesa; Servicio de Neurología
  • Sevilla, Spain
    • Hospital Victoria Eugenia; Servico Neurología
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe; Servicio de Neurologia
  • Zamora, Spain, 49021
    • Complejo Asistencial de Zamora; Servicio Psiquiatria
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche; Servicio de Neurología
  • Barcelona
    • Terrassa, Barcelona, Spain, 08222
      • Hospital Mutua De Terrasa; Servicio de Neurologia
  • Caceres
    • Plasencia, Caceres, Spain, 10600
      • Hospital Virgen del Puerto. Servicio de Neurología
  • Guipuzcoa
    • Donostia-san Sebastian, Guipuzcoa, Spain, 20014
      • Policlínica Guipuzcoa; Servicio de Neurología
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitario de Santa Maria; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Neurología
  • Vizcaya
    • Getxo, Vizcaya, Spain, 48993
      • CAE OROITU; Servicio de Neurología
• Sweden
  • Malmö, Sweden, 211 46
    • Skånes Universitetssjukhus Malmö, Minneskliniken
  • Mölndal, Sweden, 431 41
    • Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
  • Stockholm, Sweden, 141 86
    • KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
• Turkey
  • Istanbul, Turkey, 34286
    • Bezmialem Vakif Univ Medical
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul School of Medicine; Neurology
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZH
    • Royal Cornhill Hospital; OAP Directorate
  • Bath, United Kingdom, BA1 3NG
    • The Rice Centre; Royal United Hospital
  • Birmingham, United Kingdom, B16 8QQ
    • Re-Cognition
  • Cheltenham, United Kingdom, GL53 9DZ
    • The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre
  • Chertsey, United Kingdom, KT16 9AU
    • Surrey and Borders NHS Foundation Trust; Brain Science Research Unit
  • Crowborough, United Kingdom, TN6 1HB
    • Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
  • Dundee, United Kingdom, DD12 9SY
    • Ninewells Hospital
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital; Clinical Research Facility
  • London, United Kingdom, SW17 0QT
    • St George's Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, W1G 9RU
    • Re:Cognition Health
  • Newcastle, United Kingdom, NE4 5PL
    • Campus for Ageing and Vitality
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
  • Southampton, United Kingdom, SO166YD
    • University Southampton NHS Foundation Trust; Wessex Neurologica Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer?s Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Insitute
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Health Initiatives Research, PLLC
  • California
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • Irvine, California, United States, 92614
      • Irvine Center for Clinical Research
    • Redlands, California, United States, 92374
      • Desert Valley Research
    • Simi Valley, California, United States, 93065
      • Southern California Research LLC
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School Of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Bradenton, Florida, United States, 34201
      • Accel Research Sites - CRU Tampa
    • Maitland, Florida, United States, 32751
      • ClinCloud, LLC
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute, Inc
    • Miami, Florida, United States, 33125
      • Optimus U Corp
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34239
      • Intercoastal Medical Group
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Alzheimer's Disease Cntr.
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network Institute, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
    • Haverhill, Massachusetts, United States, 01830
      • ActivMed Practices and Research
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Missouri Memory Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198-8440
      • University of Nebraska Medical Center; Dept of Neurological Sciences
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
  • New York
    • Rochester, New York, United States, 14620
      • AD-CARE, University of Rochester Medical Center
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Behavioral Health Research
    • Matthews, North Carolina, United States, 28105
      • Alzheimer's Memory Center
    • Raleigh, North Carolina, United States, 27607-6520
      • Raleigh Neurology Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research, Inc.
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health ? Neurological Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network Inc.
  • Texas
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center
    • Dallas, Texas, United States, 75206
      • Texas Neurology PA
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine

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 matching to gantenerumab 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
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)
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)
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)
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)
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 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: 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)
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)
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)
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)
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)
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)
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
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
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
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 - 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 - 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

Other Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of Gantenerumab	Pre-dose on Days 1, Weeks 24, 52 and 76; Post-dose on Day 4, Weeks 41, 103, and 115

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Actual): September 23, 2022
• Study Completion (Actual): November 28, 2022

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 17, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

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: WN39658; 2017-001365-24 (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