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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03443973
Recruitment Status : Active, not recruiting
First Posted : February 23, 2018
Last Update Posted : June 16, 2021
Information provided by (Responsible Party):
Hoffmann-La Roche

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

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Gantenerumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 981 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
Actual Study Start Date : August 22, 2018
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : November 3, 2023

Resource links provided by the National Library of Medicine

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 Name: 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.

Primary Outcome Measures :
  1. Change From Baseline to Week 116 in Global Outcome, as Measured by Clinical Dementia Rating-Sum of Boxes (CDR-SOB) [ Time Frame: Baseline up to Week 116 ]

Secondary Outcome Measures :
  1. Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: Baseline up to Week 116 ]
  2. Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [ Time Frame: Baseline up to Week 116 ]
  3. Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [ Time Frame: Baseline up to Week 116 ]
  4. Change From Baseline to Week 116 in Verbal Fluency Task Score [ Time Frame: Baseline up to Week 116 ]
  5. Change From Baseline to Week 116 in Coding [ Time Frame: Change from baseline to Week 116 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest. ]
  6. Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline to Week 116 ]
  7. Change From Baseline to Week 116 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [ Time Frame: Baseline up to Week 116 ]
  8. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  9. Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline up to Week 116 or Week 24 in Open label extension ]
  10. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  11. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  12. Percentage of Participants with Injection-Site Reactions [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  13. Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  14. Plasma Concentration of Gantenerumab [ Time Frame: 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) ]
  15. Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  16. Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  17. Change From Baseline in Cerebral Spinal Fluid (CSF) Marker of Disease in a Subset of Patients - Amyloid-beta 1-42 (Aβ1-42) up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  18. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  19. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  20. Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI) up to Week 116 [ Time Frame: Baseline up to Week 116 ]
    MRI will be used to assess the effect of treatment on volume of whole brain, ventricles, hippocampus, or other structures.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 104 MRI scan

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03443973

Hide Hide 157 study locations
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United States, Arizona
Banner Alzheimer's Institute
Phoenix, Arizona, United States, 85006
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
Banner Sun Health Research Insitute
Sun City, Arizona, United States, 85351
United States, Arkansas
Health Initiatives Research, PLLC
Fayetteville, Arkansas, United States, 72703
United States, California
Fullerton Neurology and Headache Center
Fullerton, California, United States, 92835
Neurology Center of North Orange County
Fullerton, California, United States, 92835
Irvine Center for Clinical Research
Irvine, California, United States, 92614
Desert Valley Research
Redlands, California, United States, 92374
Southern California Research LLC
Simi Valley, California, United States, 93065
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Accel Research Sites - CRU Tampa
Bradenton, Florida, United States, 34201
ClinCloud, LLC
Maitland, Florida, United States, 32751
Optimus U Corp
Miami, Florida, United States, 33125
Allied Biomedical Research Institute, Inc
Miami, Florida, United States, 33155
Renstar Medical Research
Ocala, Florida, United States, 34470
Progressive Medical Research
Port Orange, Florida, United States, 32127
Intercoastal Medical Group
Sarasota, Florida, United States, 34232
Infinity Clinical Research, LLC
Sunrise, Florida, United States, 33351
Axiom Clinical Research of Florida
Tampa, Florida, United States, 33609
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
United States, Illinois
Rush Alzheimer's Disease Cntr.
Chicago, Illinois, United States, 60612
United States, Indiana
American Health Network Institute, LLC
Avon, Indiana, United States, 46123
United States, Massachusetts
Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
Boston, Massachusetts, United States, 02115
ActivMed Practices and Research
Haverhill, Massachusetts, United States, 01830
Boston Center for Memory
Newton, Massachusetts, United States, 02459
United States, Michigan
Quest Research Institute
Farmington Hills, Michigan, United States, 48334
United States, Missouri
Missouri Memory Center
Bolivar, Missouri, United States, 65613
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center; Dept of Neurological Sciences
Omaha, Nebraska, United States, 68198-8440
United States, Nevada
Cleveland Clinic Lou Ruvo; Center for Brain Research
Las Vegas, Nevada, United States, 89106
United States, New Jersey
The Cognitive and Research Center of New Jersey
Springfield, New Jersey, United States, 07081
United States, New York
UNiversity of Rochester
Rochester, New York, United States, 14620
Richmond Behavioral Associates
Staten Island, New York, United States, 10312
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Behavioral Health Research
Charlotte, North Carolina, United States, 28211
Alzheimer's Memory Center
Matthews, North Carolina, United States, 28105
Raleigh Neurology Associates
Raleigh, North Carolina, United States, 27607-6520
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Neuro-Behavioral Clinical Research, Inc.
Canton, Ohio, United States, 44718
Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health - Neurological Institute
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Lynn Health Science Institute
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
Summit Research Network Inc.
Portland, Oregon, United States, 97210
United States, Texas
Texas Neurology PA
Dallas, Texas, United States, 75206
Kerwin Medical Center
Dallas, Texas, United States, 75231
Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
Houston, Texas, United States, 77030
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77054
Hospital Italiano
Buenos Aires, Argentina, C1181ACH
Universidad Maimonides
Caba, Argentina, C1405BCK
Instituto Geriatrico Nuestra Señora de las Nieves
Capital Federal, Argentina, C1427
CEN Centro Especializado en Neurociencias
Cordoba, Argentina, X5004FJF
Instituto Kremer
Córdoba, Argentina, X5004AOA
Instituto de Neurociencias San Agustín S.A.
La Plata, Argentina, 1900
Fundación Scherbovsky
Mendoza, Argentina, 5500
AZ Sint Blasius (Dendermonde)
Dendermonde, Belgium, 9200
UZ Gent
Gent, Belgium, 9000
Jessa Zkh (Campus Virga Jesse)
Hasselt, Belgium, 3500
Psicomed Estudios Médicos
Antofagasta, Chile, 1270244
Biomedica Research Group
Santiago, Chile, 7500710
Especialidades Medicas LYS
Santiago, Chile, 7560356
Clinical Hospital Centre Zagreb;Clinic for Neurology
Zagreb, Croatia, 10000
Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
Aarhus N, Denmark, 8200
Rigshospitalet, Hukommelsesklinikken
Koebenhavn Oe, Denmark, 2100
Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn
Svendborg, Denmark, 5700
Terveystalo Ruoholahti
Helsinki, Finland, 00180
University of Eastern Finland
Kuopio, Finland, 70210
Yachiyo Hospital
Aichi, Japan, 446-8510
Nagoya Ekisaikai Hospital
Aichi, Japan, 454-8502
National Center for Geriatrics and Gerontology
Aichi, Japan, 474-8511
Fukuoka University Hospital
Fukuoka, Japan, 814-0180
National Hospital Organization Hiroshima-Nishi Medical Center
Hiroshima, Japan, 739-0696
Kobe University Hospital
Hyogo, Japan, 650-0017
Hyogo Brain and Heart Center at Himeji
Hyogo, Japan, 670-0981
Tsukazaki Hospital
Hyogo, Japan, 671-1227
Matsui Dietary and Dementia Clinic
Hyogo, Japan, 673-0891
Kagawa Prefectural Central Hospital
Kagawa, Japan, 760-8557
Rakuwakai Otowa Hospital
Kyoto, Japan, 607-8062
Uji Takeda Hospital
Kyoto, Japan, 611-0021
Okayama Kyokuto Hospital
Okayama, Japan, 703-8265
Rijikai Medical Corporation Katayama Medical Clinic
Okayama, Japan, 710-0813
MI Clinic
Osaka, Japan, 560-0004
Kishiwada Tokushukai Hospital
Osaka, Japan, 596-0042
National Hospital Organization Hizen Psychiatric Medical Center
Saga, Japan, 842-0192
Medical corporation Ichiekai Itsuki Hospital
Tokushima, Japan, 770-0852
Tokushima Hospital
Tokushima, Japan, 776-8585
Korea, Republic of
Dong-A University Hospital
Busan, Korea, Republic of, 49201
Myongji Hospital
Gyeonggi-do, Korea, Republic of, 10475
Gachon University Gil Medical Center
Incheon, Korea, Republic of, 21565
Inha University Hospital
Incheon, Korea, Republic of, 22332
Seoul National University Bundang Hospital
Seongnam-si, Korea, Republic of, 13605
Hanyang University Seoul Hospital
Seoul, Korea, Republic of, 04763
Konkuk University Medical Center
Seoul, Korea, Republic of, 05030
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06531
Seoul St Mary's Hospital
Seoul, Korea, Republic of, 06591
Ewha Womans University Hospital (Seoul)
Seoul, Korea, Republic of, 07804
Ewha Womans University Mokdong Hospital
Seoul, Korea, Republic of, 07985
Mexico Centre for Clinical Research
Ciudad de México, Mexico CITY (federal District), Mexico, 03100
Hospital Angeles Culiacan; Neurociencias
Culiacan, Mexico, 80020
Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; NeurologíaPta.BajaConsulta
Monterrey, Mexico, 64460
AVIX Investigación Clínica S.C
Monterrey, Mexico, 64710
Brain Research Center B.V
Amsterdam, Netherlands, 1081 GN
Podlaskie Centrum Psychogeriatrii
Białystok, Poland, 15-756
NZOZ Vitamed
Bydgoszcz, Poland, 85-079
KO-MED Centra Kliniczne Lublin II
Lublin, Poland, 20-362
Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
Plewiska, Poland, 62-064
NEURO-CARE Sp. z o.o. Sp. Komandytowa
Siemianowice Śląskie, Poland, 41-100
Senior Sp. Z O.O. Poradnia Psychogeriatryczna
Sopot, Poland, 81-855
mMED Maciej Czarnecki
Warszawa, Poland, 01-684
Pratia S.A.
Warszawa, Poland, 01-868
Wrocław, Poland, 53-659
Ośrodek Badawczo-Naukowo-Dydaktyczny Chorób Otępiennych w Ścinawie
Ścinawa, Poland, 59-330
Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
Amadora, Portugal, 2720-276
Hospital de Braga; Servico de Neurologia
Braga, Portugal, 4710-243
HUC; Servico de Neurologia
Coimbra, Portugal, 3000-075
Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia
Guimarães, Portugal
Hospital Geral de Santo Antonio; Servico de Neurologia
Porto, Portugal, 4099-001
Puerto Rico
Santa Cruz Behavioral PSC
Bayamon, Puerto Rico, 00961
University of Puerto Rico - Medical Science Campus; Internal Medicine
San Juan, Puerto Rico, 00936
National University Hospital (NUH); Neuroscience
Singapore, Singapore, 117549
National Neuroscience Institute; Neurology
Singapore, Singapore, 308433
Hospital General Universitario de Elche; Servicio de Neurología
Elche, Alicante, Spain, 03203
Hospital Mutua De Terrasa; Servicio de Neurologia
Terrassa, Barcelona, Spain, 08222
Hospital Virgen del Puerto. Servicio de Neurología
Plasencia, Caceres, Spain, 10600
Policlínica Guipuzcoa; Servicio de Neurología
Donostia-san Sebastian, Guipuzcoa, Spain, 20014
Hospital Universitario de Santa Maria; Servicio de Neurología
Lleida, Lerida, Spain, 25198
Hospital Quiron de Madrid; Servicio de Neurologia
Pozuelo de Alarcon, Madrid, Spain, 28223
Clinica Universitaria de Navarra; Servicio de Neurología
Pamplona, Navarra, Spain, 31008
CAE OROITU; Servicio de Neurología
Getxo, Vizcaya, Spain, 48993
Hospital del Mar; Servicio de Neurologia
Barcelona, Spain, 08003
Fundación ACE; Servicio de Neurología
Barcelona, Spain, 08028
Universitario de La Princesa; Servicio de Neurología
Madrid, Spain, 28006
Clinica Universitaria Navarra; Servicio Neurologia
Madrid, Spain, 28027
Hospital Victoria Eugenia; Servico Neurología
Sevilla, Spain
Hospital Universitario la Fe; Servicio de Neurologia
Valencia, Spain, 46026
Complejo Asistencial de Zamora; Servicio Psiquiatria
Zamora, Spain, 49021
Skånes Universitetssjukhus Malmö, Minneskliniken
Malmö, Sweden, 211 46
Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
Mölndal, Sweden, 431 41
KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
Stockholm, Sweden, 141 86
Istanbul University Istanbul School of Medicine; Neurology
Istanbul, Turkey, 34093
Bezmialem Vakif Univ Medical
Istanbul, Turkey, 34286
Ondokuz Mayis Univ. Med. Fac.; Neurology
Samsun, Turkey, 55139
United Kingdom
The Rice Centre; Royal United Hospital
Bath, United Kingdom, BA1 3NG
Birmingham, United Kingdom, B16 8QQ
The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre
Cheltenham, United Kingdom, GL53 9DZ
Surrey and Borders NHS Foundation Trust; Brain Science Research Unit
Chertsey, United Kingdom, KT16 0AE
Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
Crowborough, United Kingdom, TN6 1HB
Ninewells Hospital
Dundee, United Kingdom, DD12 9SY
Queen Elizabeth University Hospital; Clinical Research Facility
Glasgow, United Kingdom, G51 4TF
St George's Hospital
London, United Kingdom, SW17 0QT
RE:Cognition Health
London, United Kingdom, W1G 9RU
Charing Cross Hospital
London, United Kingdom, W6 8RF
Campus for Ageing and Vitality
Newcastle, United Kingdom, NE4 5PL
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Royal Preston Hospital
Preston, United Kingdom, PR2 9HT
Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom, S10 2JF
University Southampton NHS Foundation Trust; Wessex Neurologica Centre
Southampton, United Kingdom, SO166YD
Sponsors and Collaborators
Hoffmann-La Roche
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Study Director: Clinical Trials Hoffmann-La Roche
Additional Information:
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Responsible Party: Hoffmann-La Roche Identifier: NCT03443973    
Other Study ID Numbers: WN39658
2017-001365-24 ( EudraCT Number )
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform ( Further details on Roche's criteria for eligible studies are available here ( 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 (

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders