AzTrials
AzTrials

Alzheimer DiseasePhase 3NCT03443973

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

A Phase 3 study testing Gantenerumab in people with Alzheimer Disease, run by Hoffmann-La Roche at 155 sites in 19 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Read more about this study

Who is it for?
Ages 50 to 90 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Gantenerumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
975 participants
Where
155 sitesin 19 countries
Study dates
22 Aug 2018to 28 Nov 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

155 sites in 19 countries.

155 sites in 19 countries

United States47 sites

  • Emory University

    Atlanta, Georgia, 30329

  • American Health Network Institute, LLC

    Avon, Indiana, 46123

  • Missouri Memory Center

    Bolivar, Missouri, 65613

  • Brigham and Womens Hospital; Center for Alzheimer Research & Treatment

    Boston, Massachusetts, 02115

  • Accel Research Sites - CRU Tampa

    Bradenton, Florida, 34201

  • Neuro-Behavioral Clinical Research, Inc.

    Canton, Ohio, 44718

  • Behavioral Health Research

    Charlotte, North Carolina, 28211

  • Rush Alzheimer's Disease Cntr.

    Chicago, Illinois, 60612

  • Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health ? Neurological Institute

    Cleveland, Ohio, 44195

  • Texas Neurology PA

    Dallas, Texas, 75206

  • Kerwin Medical Center

    Dallas, Texas, 75231

  • Quest Research Institute

    Farmington Hills, Michigan, 48334

  • Health Initiatives Research, PLLC

    Fayetteville, Arkansas, 72703

  • Fullerton Neurology and Headache Center

    Fullerton, California, 92835

  • Neurology Center of North Orange County

    Fullerton, California, 92835

  • ActivMed Practices and Research

    Haverhill, Massachusetts, 01830

  • Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine

    Houston, Texas, 77030

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77054

  • Irvine Center for Clinical Research

    Irvine, California, 92614

  • Cleveland Clinic Lou Ruvo; Center for Brain Research

    Las Vegas, Nevada, 89106

  • ClinCloud, LLC

    Maitland, Florida, 32751

  • Alzheimer's Memory Center

    Matthews, North Carolina, 28105

  • Optimus U Corp

    Miami, Florida, 33125

  • Allied Biomedical Research Institute, Inc

    Miami, Florida, 33155

  • Yale University School Of Medicine

    New Haven, Connecticut, 06519

  • Boston Center for Memory

    Newton, Massachusetts, 02459

  • Renstar Medical Research

    Ocala, Florida, 34470

  • Lynn Health Science Institute

    Oklahoma City, Oklahoma, 73112

  • University of Nebraska Medical Center; Dept of Neurological Sciences

    Omaha, Nebraska, 68198-8440

  • Banner Alzheimer?s Institute

    Phoenix, Arizona, 85006

  • Barrow Neurological Institute

    Phoenix, Arizona, 85013

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Summit Research Network Inc.

    Portland, Oregon, 97210

  • Raleigh Neurology Associates

    Raleigh, North Carolina, 27607-6520

  • Desert Valley Research

    Redlands, California, 92374

  • AD-CARE, University of Rochester Medical Center

    Rochester, New York, 14620

  • Intercoastal Medical Group

    Sarasota, Florida, 34239

  • Southern California Research LLC

    Simi Valley, California, 93065

  • The Cognitive and Research Center of New Jersey

    Springfield, New Jersey, 07081

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Richmond Behavioral Associates

    Staten Island, New York, 10314

  • Banner Sun Health Research Insitute

    Sun City, Arizona, 85351

  • Infinity Clinical Research, LLC

    Sunrise, Florida, 33351

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Axiom Clinical Research of Florida

    Tampa, Florida, 33609

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

Japan16 sites

  • Yachiyo Hospital

    Aichi, 446-8510

  • Nagoya Ekisaikai Hospital

    Aichi, 454-8502

  • National Center for Geriatrics and Gerontology

    Aichi, 474-8511

  • Fukuoka University Hospital

    Fukuoka, 814-0180

  • National Hospital Organization Hiroshima-Nishi Medical Center

    Hiroshima, 739-0696

  • Hyogo Prefectural HarimaHimeji General Medical Center

    Hyōgo, 670-8560

  • Tsukazaki Hospital

    Hyōgo, 671-1227

  • Matsui Dietary and Dementia Clinic

    Hyōgo, 673-0891

  • Kagawa Prefectural Central Hospital

    Kagawa, 760-8557

  • Rakuwakai Otowa Hospital

    Kyoto, 607-8062

  • Uji Takeda Hospital

    Kyoto, 611-0021

  • Rijikai Medical Corporation Katayama Medical Clinic

    Okayama, 710-0813

  • Kishiwada Tokushukai Hospital

    Osaka, 596-0042

  • National Hospital Organization Hizen Psychiatric Medical Center

    Saga, 842-0192

  • Medical corporation Ichiekai Itsuki Hospital

    Tokushima, 770-0852

  • Tokushima Hospital

    Tokushima, 776-8585

Other trials in Japan

United Kingdom16 sites

  • Royal Cornhill Hospital; OAP Directorate

    Aberdeen, AB25 2ZH

  • The Rice Centre; Royal United Hospital

    Bath, BA1 3NG

  • Re-Cognition

    Birmingham, B16 8QQ

  • The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre

    Cheltenham, GL53 9DZ

  • Surrey and Borders NHS Foundation Trust; Brain Science Research Unit

    Chertsey, KT16 9AU

  • Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit

    Crowborough, TN6 1HB

  • Ninewells Hospital

    Dundee, DD12 9SY

  • Queen Elizabeth University Hospital; Clinical Research Facility

    Glasgow, G51 4TF

  • St George's Hospital

    London, SW17 0QT

  • RE:Cognition Health

    London, W1G 9RU

  • Charing Cross Hospital

    London, W6 8RF

  • Campus for Ageing and Vitality

    Newcastle, NE4 5PL

  • John Radcliffe Hospital

    Oxford, OX3 9DU

  • Royal Preston Hospital

    Preston, PR2 9HT

  • Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2JF

  • University Southampton NHS Foundation Trust; Wessex Neurologica Centre

    Southampton, SO166YD

Other trials in United Kingdom

Spain15 sites

  • Hospital del Mar; Servicio de Neurologia

    Barcelona, 08003

  • Fundación ACE; Servicio de Neurología

    Barcelona, 08028

  • Policlínica Guipuzcoa; Servicio de Neurología

    Donostia / San Sebastian, Guipuzcoa, 20014

  • Hospital General Universitario de Elche; Servicio de Neurología

    Elche, Alicante, 03203

  • CAE OROITU; Servicio de Neurología

    Getxo, Vizcaya, 48993

  • Hospital Universitario de Santa Maria; Servicio de Neurología

    Lleida, Lerida, 25198

  • Universitario de La Princesa; Servicio de Neurología

    Madrid, 28006

  • Clinica Universitaria de Navarra; Servicio de Neurología

    Pamplona, Navarre, 31008

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, 31008

  • Hospital Virgen del Puerto. Servicio de Neurología

    Plasencia, Caceres, 10600

  • Hospital Quiron de Madrid; Servicio de Neurologia

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Victoria Eugenia; Servico Neurología

    Seville

  • Hospital Mutua De Terrasa; Servicio de Neurologia

    Terrassa, Barcelona, 08222

  • Hospital Universitario la Fe; Servicio de Neurologia

    Valencia, 46026

  • Complejo Asistencial de Zamora; Servicio Psiquiatria

    Zamora, 49021

Other trials in Spain

South Korea12 sites

  • Dong-A University Hospital

    Busan, 49201

  • Myongji Hospital

    Gyeonggi-do, 10475

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Inha University Hospital

    Incheon, 22332

  • Seoul National University Bundang Hospital

    Seongnam-si, 463-707

  • Hanyang University Seoul Hospital

    Seoul, 04763

  • Konkuk University Medical Center

    Seoul, 05030

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • Seoul St Mary's Hospital

    Seoul, 06591

  • Ewha Womans University Hospital (Seoul)

    Seoul, 07804

  • Ewha Womans University Mokdong Hospital

    Seoul, 07985

Other trials in South Korea

Poland10 sites

  • O?rodek Badawczo-Naukowo-Dydaktyczny Chorób Ot?piennych w ?cinawie

    ?cinawa, 59-330

  • Podlaskie Centrum Psychogeriatrii

    Bia?ystok, 15-756

  • NZOZ Vitamed

    Bydgoszcz, 85-079

  • KO-MED Centra Kliniczne Lublin II

    Lublin, 20-362

  • Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych

    Plewiska, 62-064

  • NEURO-CARE Sp. z o.o. Sp. Komandytowa

    Siemianowice ?l?skie, 41-100

  • Senior Sp. Z O.O. Poradnia Psychogeriatryczna

    Sopot, 81-855

  • mMED Maciej Czarnecki

    Warsaw, 01-684

  • Pratia S.A.

    Warsaw, 01-868

  • NZOZ WCA

    Wroc?aw, 53-659

Other trials in Poland

Argentina7 sites

  • Hospital Italiano

    Buenos Aires, C1181ACH

  • Universidad Maimonides

    Caba, C1405BCK

  • Instituto Geriatrico Nuestra Señora de las Nieves

    Capital Federal, C1427CCP

  • Instituto Kremer

    Córdoba, X5004AOA

  • CEN Centro Especializado en Neurociencias

    Córdoba, X5004FJF

  • Instituto de Neurociencias San Agustín S.A.

    La Plata, B1902AVF

  • Fundacion Scherbovsky

    Mendoza, M5500AYB

Other trials in Argentina

Portugal5 sites

  • Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia

    Amadora, 2720-276

  • Hospital de Braga; Servico de Neurologia

    Braga, 4710-243

  • HUC; Servico de Neurologia

    Coimbra, 3000-075

  • Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia

    Guimarães

  • Hospital Geral de Santo Antonio; Servico de Neurologia

    Porto, 4099-001

Other trials in Portugal

Mexico4 sites

  • Hospital Angeles Culiacan; Neurociencias

    Culiacán, Sinaloa, 80020

  • Mexico Centre for Clinical Research

    Mexico City, Mexico CITY (federal District), 03100

  • Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta

    Monterrey, Nuevo León, 64460

  • AVIX Investigación Clínica S.C

    Monterrey, Nuevo León, 64710

Other trials in Mexico

Belgium3 sites

  • AZ Sint Blasius (Dendermonde)

    Dendermonde, 9200

  • UZ Gent

    Ghent, 9000

  • Jessa Zkh (Campus Virga Jesse)

    Hasselt, 3500

Other trials in Belgium

Chile3 sites

  • Psicomed Estudios Médicos

    Antofagasta, 1270244

  • Biomedica Research Group

    Santiago, 7500710

  • Especialidades Medicas LYS

    Santiago, 7560356

Other trials in Chile

Denmark3 sites

  • Aarhus Universitetshospital; Neurologisk Afd. F, Demensklinikken

    Aarhus N, 8200

  • Rigshospitalet, Hukommelsesklinikken

    København Ø, 2100

  • Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn

    Svendborg, 5700

Other trials in Denmark

Sweden3 sites

  • Skånes Universitetssjukhus Malmö, Minneskliniken

    Malmö, 211 46

  • Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry

    Mölndal, 431 41

  • KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54

    Stockholm, 141 86

Other trials in Sweden

Turkey (Türkiye)3 sites

  • Istanbul University Istanbul School of Medicine; Neurology

    Istanbul, 34093

  • Bezmialem Vakif Univ Medical

    Istanbul, 34286

  • Ondokuz Mayis Univ. Med. Fac.; Neurology

    Samsun, 55139

Other trials in Turkey (Türkiye)

Finland2 sites

  • Terveystalo Ruoholahti

    Helsinki, 00180

  • University of Eastern Finland

    Kuopio, 70210

Other trials in Finland

Puerto Rico2 sites

  • Santa Cruz Behavioral PSC

    Bayamón, 00961

  • University of Puerto Rico - Medical Science Campus; Internal Medicine

    San Juan, 00936

Other trials in Puerto Rico

Singapore2 sites

  • National University Hospital (NUH); Neuroscience

    Singapore, 117549

  • National Neuroscience Institute; Neurology

    Singapore, 308433

Other trials in Singapore

Croatia1 site

  • Clinical Hospital Centre Zagreb;Clinic for Neurology

    Zagreb, 10000

Other trials in Croatia

Netherlands1 site

  • Brain Research Center B.V

    Amsterdam, 1081 GN

Other trials in Netherlands

About this study

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

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.

Being tested
Gantenerumab, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GantenerumabDrug

    Also called RO4909832

    Gantenerumab will be administered as per the schedule specified in the respective arm.

  • PlaceboDrug

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

Study groups in NCT03443973
Study groupRoleWhat they receive
GantenerumabExperimentalGantenerumab will be administered as SC injections with gradual uptitration.
Receives: Drug: Gantenerumab
PlaceboPlacebo comparatorPlacebo will be administered as SC injections with gradual uptitration.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, Week 116

  2. 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.

    Measured: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)

  3. 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.

    Measured: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)

  4. 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.

    Measured: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)

  5. 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.

    Measured: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)

  6. 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.

    Measured: From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks)

Secondary outcomes (20)

  1. 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.

    Measured: Baseline, Week 116

  2. 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.

    Measured: Baseline, Week 116

  3. 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.

    Measured: Baseline, Week 116

  4. 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.

    Measured: Baseline, Week 116

  5. 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.

    Measured: Baseline, Week 116

  6. 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.

    Measured: Baseline, Week 116

  7. 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.

    Measured: Baseline, Week 116

  8. 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.

    Measured: Baseline, Week 116

  9. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  10. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  11. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  12. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  13. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  14. 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.

    Measured: From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks)

  15. 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.

    Measured: Baseline, Week 116

  16. 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.

    Measured: Baseline, Week 116

  17. 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.

    Measured: Baseline, Week 116

  18. DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin

    Measured: Baseline, Week 116

  19. 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.

    Measured: Baseline, Week 116

  20. 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.

    Measured: Baseline, Week 116

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2018
  2. Study start22 Aug 2018
  3. Primary completion23 Sep 2022
  4. Study completion28 Nov 2022

Why it stopped: Decision to terminate development of Gantenerumab for treatment of prodromal/mild/early stage Alzheimer's disease following results of a pre-planned analysis of the safety and efficacy of Gant in Graduate I\&II (WN29922/WN39658).

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
975 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03443973
Sponsor's protocol ID
WN39658
Other IDs
2017-001365-24, 2017
Status last verified
Dec 2023
First submitted
19 Feb 2018
Last updated
17 Jan 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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).

Publications

  • Tonietto M, Silvestri E, Belder CRS, Barkhof F, Fox NC, Smith J, Klein G. Volume change with gantenerumab: Impact of amyloid-related imaging abnormalities and amyloid removal. Alzheimers Dement. 2026 Aug;22(8):e71749. doi: 10.1002/alz.71749.

    PubMed 42598748

  • Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.

    PubMed 40603145

  • Asada T, Thanasopoulou A, Delmar P, Wojtowicz J, Smith J, Yoshiyama Y, Yokoi K, Watanabe C, Isozaki M, Ozaki R, Ishida T, Tatsuda H, Tamaoka A. Japanese participant data from three gantenerumab trials in early Alzheimer's disease. Alzheimers Dement. 2025 Apr;21(4):e70192. doi: 10.1002/alz.70192.

    PubMed 40302041

  • Bittner T, Tonietto M, Klein G, Belusov A, Illiano V, Voyle N, Delmar P, Scelsi MA, Gobbi S, Silvestri E, Barakovic M, Napolitano A, Galli C, Abaei M, Blennow K, Barkhof F. Biomarker treatment effects in two phase 3 trials of gantenerumab. Alzheimers Dement. 2025 Feb;21(2):e14414. doi: 10.1002/alz.14414. Epub 2025 Jan 30.

    PubMed 39887500

  • Salloway S, Wojtowicz J, Voyle N, Lane CA, Klein G, Lyons M, Rossomanno S, Mazzo F, Bullain S, Barkhof F, Bittner T, Schneider A, Grundman M, Aldea R, Boada M, Smith J, Doody R. Amyloid-Related Imaging Abnormalities (ARIA) in Clinical Trials of Gantenerumab in Early Alzheimer Disease. JAMA Neurol. 2025 Jan 1;82(1):19-29. doi: 10.1001/jamaneurol.2024.3937.

    PubMed 39556389

  • Bateman RJ, Smith J, Donohue MC, Delmar P, Abbas R, Salloway S, Wojtowicz J, Blennow K, Bittner T, Black SE, Klein G, Boada M, Grimmer T, Tamaoka A, Perry RJ, Turner RS, Watson D, Woodward M, Thanasopoulou A, Lane C, Baudler M, Fox NC, Cummings JL, Fontoura P, Doody RS; GRADUATE I and II Investigators and the Gantenerumab Study Group. Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease. N Engl J Med. 2023 Nov 16;389(20):1862-1876. doi: 10.1056/NEJMoa2304430.

    PubMed 37966285

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gantenerumab in people with Alzheimer Disease, run by Hoffmann-La Roche at 155 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 155 sites in United States, Japan, United Kingdom, Spain, South Korea and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB (time frame: Baseline, Week 116). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03443973, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.

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