A Study of Gantenerumab in Participants With Mild Alzheimer Disease

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients

Part 1 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab in participants with mild Alzheimer disease. Participants will be randomized to receive either gantenerumab subcutaneously every 4 weeks or placebo subcutaneously every 4 weeks. Approved Alzheimer medication is allowed if on stable dose for 3 months prior to screening. Part 2 is an open-label extension (OLE).

A positron emission tomography (PET) imaging substudy will be conducted within the main study. Eligible participants who provide separate informed consent will undergo PET imaging scans using the radioligand florbetapir as a pharmacodynamic measure of changes in brain amyloid load over time.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Gantenerumab

• Study Type: Interventional
• Enrollment (Actual): 389
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1426ANZ
    • Instituto Neurologia Bs As
• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Memory Trials Centre
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital; Neurology
  • Victoria
    • Heidelberg West, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Foundation
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Bulgaria
  • Sofia, Bulgaria, 1113
    • Shat Np Sveti Naum; 3Rd Clinic of Neurology
  • Varna, Bulgaria, 9010
    • MBAL St. Marina; First Neurology Department
• Canada
  • Quebec, Canada, G3K 2P8
    • Alpha Recherche Clinique
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary; Heritage Medical Research Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • True North Clinical Research-Halifax
    • New Minas, Nova Scotia, Canada, B4N 3R7
      • True North Clinical Research
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • JBN Medical Diagnostic Services Inc.
    • London, Ontario, Canada, N6C 5J1
      • Parkwood Hospital; Geriatric Medicine
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Recherches Neuro-Hippocame
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • NeuroSearch Developpements inc
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital / McGill University
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Centre Hospitalier Affilie Universitaire de Quebec - Hopital de L'Enfant Jesus
    • Verdun, Quebec, Canada, H4H 1R3
      • McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
  • Koebenhavn Oe, Denmark, 2100
    • Rigshospitalet, Hukommelsesklinikken
• Finland
  • Kuopio, Finland, 70210
    • University of Eastern Finland
  • Turku, Finland, 20520
    • CRST Oy
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin; Cmrr Aquitaine
  • Bron, France, 69677
    • Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie
  • Limoges, France, 87042
    • CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
  • Marseille, France, 13005
    • CHU de la Timone - Hopital d Adultes; Service de Neurologie
  • Rennes, France, 35064
    • CHU Rennes - hopital Hotel Dieu; Consultation Memoire - Gerontologie
  • Strasbourg, France, 67098
    • Hopital Hautepierre; Centre dInvestigation Clinique
  • Toulouse, France, 31059
    • Hopital la Grave; Gerontopole - Centre de Recherche Clinique
• Germany
  • Berlin, Germany, 13125
    • ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
  • Leipzig, Germany, 04275
    • PANAKEIA - Arzneimittelforschung Leipzig GmbH
  • Mittweida, Germany, 09648
    • Pharmakologisches Studienzentrum
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar der TU München; Klinikapotheke
  • München, Germany, 80331
    • Neurologische Praxis Dr. Andrej Pauls
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
  • Westerstede, Germany, 26655
    • Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz
• 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, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia
    • Roma, Lazio, Italy, 00185
      • Umberto I Policlinico di Roma-Università di Roma La Sapienza
  • Lombardia
    • Brescia, Lombardia, Italy, 25125
      • IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
    • Castellanza, Lombardia, Italy, 21053
      • Irccs Multimedica Santa Maria; Unita' Di Neurologia
    • Monza, Lombardia, Italy, 20900
      • ASST DI MONZA; Neurologia
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • A.O. Universitaria Pisana; Neurologia
• Japan
  • Chiba, Japan, 260-8656
    • Medical Corporation Hakuyokai Kashiwado Hospital
  • Chiba, Japan, 260-8712
    • National Hospital Organization Chiba-east Hospital; Neurology
  • Chiba, Japan, 279-0021
    • Juntendo University Urayasu Hospital; Neurology
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital; Neurology and Health Care
  • Gunma, Japan, 371-0014
    • Maebashi Red Cross Hospital; Neurology
  • Hiroshima, Japan, 739-0696
    • National Hospital Organization Hiroshima-Nishi Medical Center
  • Hyogo, Japan, 670-0981
    • Hyogo Brain and Heart Center at Himeji; Department of Aging Brain and Cognitive Disorders
  • Kanagawa, Japan, 247-8533
    • Shonan Kamakura General Hospital; Neurology
  • Oita, Japan, 879-5593
    • Oita University Hospital; Neurology
  • Okayama, Japan, 710-0826
    • Kurashiki Heisei Hospital; Neurology
  • Shizuoka, Japan, 424-0911
    • Shizuoka City Shimizu Hospital; Neurology
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Dong-A University Medical Center
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital; Neurology Department
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital; Neurology Department
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 07804
    • Ewha Womans University Hospital (Seoul)
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center.
  • Seoul, Korea, Republic of, 158-710
    • Ewha Womans University Mokdong Hospital; Dept of Neurology
• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center B.V
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Mc - Locatie Centrum; Dept of Neurology
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Neurologia
• Russian Federation
  • Kazan, Russian Federation, 420021
    • State Autonomous Healthcare Institution "Republican Clinical Neurological Center
  • Kazan, Russian Federation, 420101
    • State autonomous institution of healthcare Inter-regional clinical and diagnostic center
  • Moscow, Russian Federation, 115522
    • Institution of RAMS (Mental Health Research Center of RAMS)
  • Moscow, Russian Federation, 119021
    • SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF
  • Saint Petersburg, Russian Federation, 190103
    • Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center
  • Saratov, Russian Federation, 410028
    • City Clinical Hospital # 2 n.a. V.I. Razumovsky
  • St. Petersburg, Russian Federation, 194044
    • Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Neurologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche; Servicio de Neurología
  • Barcelona
    • BArcelon, Barcelona, Spain, 08034
      • Fundacio ACE
  • Guipuzcoa
    • Donosti-San Sebastián, Guipuzcoa, Spain, 20014
      • Policlínica Guipuzkoa; Servicio de Neurología
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Neurologia
• Sweden
  • Malmö, Sweden, 211 46
    • Skånes Universitetssjukhus Malmö, Minneskliniken
  • Stockholm, Sweden, 141 86
    • KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
• Switzerland
  • Basel, Switzerland, 4002
    • Felix Platter-Spital Medizin Geriatrie
  • Lausanne, Switzerland, 1011
    • CHUV Lausanne Memory clinique
• Turkey
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul School of Medicine; Neurology
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Medicine Faculty; Noroloji Departmani
  • Samsun, Turkey, 55139
    • Ondokuz Mayis University School of Medicine; Neurology
• United Kingdom
  • Crowborough, United Kingdom, TN6 1HB
    • Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital; Dept of Neurosciences
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hosptial
  • Sheffield, United Kingdom, S35 8QS
    • Memory Service North
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Insitute
    • Tucson, Arizona, United States, 85704
      • Territory Neurology and Research Institute
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc
    • San Diego, California, United States, 92103
      • Pacific Research Network - PRN
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc
  • Florida
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research, Inc.
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research; Center of Southwest Florida
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems; Clinical Research
    • Orlando, Florida, United States, 32806
      • Accelerated Enrollment Solutions
    • Tampa, Florida, United States, 33613-4706
      • University of South Florida
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates
  • Michigan
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63132
      • Millennium Psychiatric Associates, LLC
  • New Jersey
    • Manchester, New Jersey, United States, 08759
      • Alzheimer's Research Corporation
    • Toms River, New Jersey, United States, 08775
      • Ocean Rheumatology
  • New York
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Institute
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Alzheimer's Memory Center
    • Raleigh, North Carolina, United States, 27609
      • Richard H Weisler, MD
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Plains, Pennsylvania, United States, 18705
      • Northeastern Pennsylvania Memory
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah, Center for Alzheimer's Care Imaging & Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of probable mild Alzheimer disease (AD) based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria or major NCD based whether or not receiving AD approved medication
• Cerebral spinal fluid (CSF) result consistent with the presence of amyloid pathology
• Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient contact with the participant, and is able to provide accurate information regarding the participant's cognitive and functional abilities
• Fluency in the language of the tests used at the study site
• Willingness and ability to complete all aspects of the study
• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
• If currently receiving approved medications for AD, the dosing regimen must have been stable for 3 months prior to screening
• Agreement not to participate in other research studies for the duration of this trial and its associated substudies

PART 2 - All participants who have been randomized and are actively participating in the study are eligible for Part 2

Exclusion Criteria:

• Dementia or neurocognitive disorder (NCD) due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia
• History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function
• History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months
• History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
• History of schizophrenia, schizoaffective disorder, or bipolar disorder
• Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years (nicotine use is allowed)
• History or presence of atrial fibrillation
• Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher)
• Uncontrolled hypertension
• Chronic kidney disease
• Impaired hepatic function

PET imaging substudy, in addition to above:

- Prior participation in other research study or clinical care within the last year such that the total radiation exposure would exceed the local or national annual limits

Part 2 Participants who have been discontinued from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Part 1 (Double Blind treatment): Placebo; Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study.	Drug: Placebo; Participants received Placebo SC injection Q4W.
EXPERIMENTAL: Part 1 (Double Blind treatment): Gantenerumab; Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
PLACEBO_COMPARATOR: Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg; Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Drug: Placebo; Participants received Placebo SC injection Q4W.
EXPERIMENTAL: Part 2 (OLE treatment): Gantenerumab up to 1200 mg; Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.	First dose up to 4 weeks after the last dose of study drug (up to 249 weeks)
Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)	Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for participants previously (in part 1) on Gantenerumab and Placebo. The prevalence of ADA at baseline was calculated as the percentage of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the percentage of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.	First dose up to last dose (Baseline up to until maximum 5 years)
Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment	Percentage of participants with adverse events leading to discontinuation from treatment were reported.	First dose up to 4 weeks after the last dose in OLE (Up to approximately 249 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percentage of Participants With AEs, SAEs	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A serious adverse event is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.	First dose up to last dose (Up to approximately 152 weeks)
Part 1: Percentage of Participants With Treatment Emergent ADAs	Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for participants previously (in part 1) on Gantenerumab and Placebo. The prevalence of ADA at baseline was calculated as the percentage of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the percentage of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.	First dose up to last dose (Up to approximately 152 weeks)
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints		Pre-dose: Weeks 4, 8, 12, 24, 48, 72 and Post dose: Day 4
Part 1: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment	Percentage of participants with adverse events leading to discontinuation from treatment were reported.	First dose up to last dose (Up to approximately 152 weeks)
Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104	Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analyzed at Week 104 using magnetic resonance imaging.	Baseline (Part 1 screening), Week 104
Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104	Change from baseline brain volume were analyzed at Week 104 using magnetic resonance imaging.	Baseline (Part 1 screening), Week 104
Part 2: Percent Change From Baseline in Cortical Thickness at Week 104	Change from baseline in cortical thickness were analyzed at Week 104 using magnetic resonance imaging.	Baseline (Part 1 screening), Week 104
Part 2: Ventricular Volume as Measured by MRI at Week 104	Ventricular volume were analyzed at Week 104 using magnetic resonance imaging.	Part 2: Week 104
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints		Pre-dose: Weeks 104, 116, 156, 208; Post-dose: Weeks 53, 101
Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants	Brain amyloid load over time was assessed using a Florbetapir [F18] injection, a positron emission tomography (PET) radioligand selective to amyloid. Analysis was conducted in a subset of participants who signed consent to participate in the PET substudy. 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 composite region was composed of the following six bilateral regions: frontal lobe, parietal lobe, temporal lobe, posterior cingulate cortex, anterior cingulate cortex. The reference region used to normalize the composite region was the cerebellar cortex. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to 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 scans.	Baseline, Week 156

Other Outcome Measures

Outcome Measure	Time Frame
Part 1: Mean Change From Baseline in Alzheimer's Disease Activity Scale-Cognitive Subscale 13 (ADAS-Cog13) Scores at Week 104	Baseline, Week 104
Part 1: Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Scores at Week 104	Baseline, Week 104
Part 1: Percentage Change From Baseline in Total Tau (T-tau) in CSF at Week 104	Baseline, Week 104
Part 1: Percentage Change From Baseline in Abeta 1-42 Levels in CSF at Week 104	Baseline, Week 104
Part 1: Percentage Change From Baseline in Phosphorylated Tau [P-tau] in CSF at Week 104	Baseline, Week 104
Part 1: Percent Change From Baseline in Hippocampal Volume at Week 104	Baseline, Week 104
Part 1: Percent Change From Baseline in Whole Brain Volume at Week 104	Baseline, Week 104
Part 1: Percent Change From Baseline in Cortical Thickness at Week 104	Baseline, Week 104
Part 1: Ventricular Volume as Measured by MRI at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104	Baseline, Week 104
Part 1: Change From Baseline in CDR Sum of Boxes (SB) at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104	Baseline, Week 104
Part 1: Change From Baseline in NPI Domain Score at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Dependence Scale (DS) at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Lite) Scale at Week 104	Baseline, Week 104
Part 1: Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104	Baseline, Week 104
Part 1: Time to Clinical Decline	Baseline up to Week 104
Part 1: Change From Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104	Baseline, Week 104
Part 1: Percentage of Participants With ADAS-Cog Response	Baseline up to Week 152

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Klein G, Delmar P, Voyle N, Rehal S, Hofmann C, Abi-Saab D, Andjelkovic M, Ristic S, Wang G, Bateman R, Kerchner GA, Baudler M, Fontoura P, Doody R. Gantenerumab reduces amyloid-beta plaques in patients with prodromal to moderate Alzheimer's disease: a PET substudy interim analysis. Alzheimers Res Ther. 2019 Dec 12;11(1):101. doi: 10.1186/s13195-019-0559-z.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 27, 2014
• Primary Completion (ACTUAL): April 16, 2021
• Study Completion (ACTUAL): April 16, 2021

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: January 30, 2014
• First Posted (ESTIMATE): January 31, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 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: WN28745; 2013-003390-95 (EUDRACT_NUMBER)

Drug and device information, study documents

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