A Study of Gantenerumab in Participants With Mild Alzheimer Disease

NCT ID: NCT02051608

Last Updated: 2023-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 389 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-27
• Study Completion Date: 2021-04-16

Brief Summary

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants received Placebo SC injection Q4W.

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.

Group Type: EXPERIMENTAL

Gantenerumab

Intervention Type: DRUG

Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants received Placebo SC injection Q4W.

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.

Group Type: EXPERIMENTAL

Gantenerumab

Intervention Type: DRUG

Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

Interventions

Placebo

Participants received Placebo SC injection Q4W.

Intervention Type: DRUG

Gantenerumab

Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Banner Sun Health Research Insitute

Sun City, Arizona, United States

Territory Neurology and Research Institute

Tucson, Arizona, United States

ATP Clinical Research, Inc

Costa Mesa, California, United States

Pacific Research Network - PRN

San Diego, California, United States

California Neuroscience Research Medical Group, Inc

Sherman Oaks, California, United States

Meridien Research

Brooksville, Florida, United States

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, United States

Miami Jewish Health Systems; Clinical Research

Miami, Florida, United States

Accelerated Enrollment Solutions

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Alzheimer's Research and Treatment Center

Wellington, Florida, United States

Indiana University

Indianapolis, Indiana, United States

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Louisiana Research Associates

New Orleans, Louisiana, United States

Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research

Kalamazoo, Michigan, United States

Millennium Psychiatric Associates, LLC

St Louis, Missouri, United States

Alzheimer's Research Corporation

Paterson, New Jersey, United States

Ocean Rheumatology

Toms River, New Jersey, United States

Nathan Kline Institute

Orangeburg, New York, United States

Richmond Behavioral Associates

Staten Island, New York, United States

Alzheimer's Memory Center

Matthews, North Carolina, United States

Richard H Weisler, MD

Raleigh, North Carolina, United States

Central States Research

Tulsa, Oklahoma, United States

Abington Neurological Associates

Abington, Pennsylvania, United States

Northeastern Pennsylvania Memory

Plains, Pennsylvania, United States

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States

Neurology Clinic PC

Cordova, Tennessee, United States

Senior Adults Specialty Research

Austin, Texas, United States

University of Utah, Center for Alzheimer's Care Imaging & Research

Salt Lake City, Utah, United States

Instituto Neurologia Bs As

Ciudad Autonoma Buenos Aires, , Argentina

Royal Adelaide Hospital; Memory Trials Centre

Adelaide, South Australia, Australia

The Queen Elizabeth Hospital; Neurology

Woodville, South Australia, Australia

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, Australia

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, Australia

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Shat Np Sveti Naum; 3Rd Clinic of Neurology

Sofia, , Bulgaria

MBAL St. Marina; First Neurology Department

Varna, , Bulgaria

University of Calgary; Heritage Medical Research Clinic

Calgary, Alberta, Canada

True North Clinical Research-Halifax

Halifax, Nova Scotia, Canada

True North Clinical Research

New Minas, Nova Scotia, Canada

Jbn Medical Diagnostic Services Inc.

Burlington, Ontario, Canada

Parkwood Hospital; Geriatric Medicine

London, Ontario, Canada

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, Canada

Toronto Memory Program

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Recherches Neuro-Hippocame

Gatineau, Quebec, Canada

NeuroSearch Developpements inc

Greenfield Park, Quebec, Canada

Jewish General Hospital / McGill University

Montreal, Quebec, Canada

Centre Hospitalier Affilie Universitaire de Quebec - Hopital de L'Enfant Jesus

Québec, Quebec, Canada

McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric

Verdun, Quebec, Canada

Alpha Recherche Clinique

Québec, , Canada

Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken

Aarhus N, , Denmark

Rigshospitalet, Hukommelsesklinikken

Koebenhavn Oe, , Denmark

University of Eastern Finland

Kuopio, , Finland

CRST Oy

Turku, , Finland

Hopital Pellegrin; Cmrr Aquitaine

Bordeaux, , France

Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie

Bron, , France

CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique

Limoges, , France

CHU de la Timone - Hopital d Adultes; Service de Neurologie

Marseille, , France

CHU Rennes - hopital Hotel Dieu; Consultation Memoire - Gerontologie

Rennes, , France

Hopital Hautepierre; Centre dInvestigation Clinique

Strasbourg, , France

Hopital la Grave; Gerontopole - Centre de Recherche Clinique

Toulouse, , France

ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic

Berlin, , Germany

PANAKEIA - Arzneimittelforschung Leipzig GmbH

Leipzig, , Germany

Pharmakologisches Studienzentrum

Mittweida, , Germany

Neurologische Praxis Dr. Andrej Pauls

München, , Germany

Klinikum rechts der Isar der TU München; Klinikapotheke

München, , Germany

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, , Germany

Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz

Westerstede, , Germany

Semmelweis University; Department of Neurology

Budapest, , Hungary

Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze

Modena, Emilia-Romagna, Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia

Rome, Lazio, Italy

Umberto I Policlinico di Roma-Università di Roma La Sapienza

Rome, Lazio, Italy

IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer

Brescia, Lombardy, Italy

Irccs Multimedica Santa Maria; Unita' Di Neurologia

Castellanza, Lombardy, Italy

ASST DI MONZA; Neurologia

Monza, Lombardy, Italy

A.O. Universitaria Pisana; Neurologia

Pisa, Tuscany, Italy

Medical Corporation Hakuyokai Kashiwado Hospital

Chiba, , Japan

National Hospital Organization Chiba-east Hospital; Neurology

Chiba, , Japan

Juntendo University Urayasu Hospital; Neurology

Chiba, , Japan

Fukuoka University Hospital; Neurology and Health Care

Fukuoka, , Japan

Maebashi Red Cross Hospital; Neurology

Gunma, , Japan

National Hospital Organization Hiroshima-Nishi Medical Center

Hiroshima, , Japan

Hyogo Brain and Heart Center at Himeji; Department of Aging Brain and Cognitive Disorders

Hyōgo, , Japan

Shonan Kamakura General Hospital; Neurology

Kanagawa, , Japan

Kurashiki Heisei Hospital; Neurology

Okayama, , Japan

Oita University Hospital; Neurology

Ōita, , Japan

Shizuoka City Shimizu Hospital; Neurology

Shizuoka, , Japan

Brain Research Center B.V

Amsterdam, , Netherlands

Erasmus Mc - Locatie Centrum; Dept of Neurology

Rotterdam, , Netherlands

Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia

Amadora, , Portugal

Hospital de Santa Maria; Servico de Neurologia

Lisbon, , Portugal

State Autonomous Healthcare Institution "Republican Clinical Neurological Center

Kazan', , Russia

State autonomous institution of healthcare Inter-regional clinical and diagnostic center

Kazan', , Russia

Institution of RAMS (Mental Health Research Center of RAMS)

Moscow, , Russia

SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF

Moscow, , Russia

Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center

Saint Petersburg, , Russia

Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department

Saint Petersburg, , Russia

City Clinical Hospital # 2 n.a. V.I. Razumovsky

Saratov, , Russia

Dong-A University Medical Center

Busan, , South Korea

Seoul National University Bundang Hospital; Neurology Department

Gyeonggi-do, , South Korea

Inha University Hospital; Neurology Department

Incheon, , South Korea

Konkuk University Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Ewha Womans University Hospital (Seoul)

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Asan Medical Center.

Seoul, , South Korea

Ewha Womans University Mokdong Hospital; Dept of Neurology

Seoul, , South Korea

Hospital General Universitario de Elche; Servicio de Neurología

Elche, Alicante, Spain

Fundació ACE

BArcelon, Barcelona, Spain

Policlínica Guipuzkoa; Servicio de Neurología

Donosti-San Sebastián, Guipuzcoa, Spain

Hospital de Cruces; Servicio de Neurologia

Barakaldo, Vizcaya, Spain

Hospital del Mar; Servicio de Neurologia

Barcelona, , Spain

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, , Spain

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Skånes Universitetssjukhus Malmö, Minneskliniken

Malmo, , Sweden

KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54

Stockholm, , Sweden

Felix Platter-Spital Medizin Geriatrie

Basel, , Switzerland

CHUV Lausanne Memory clinique

Lausanne, , Switzerland

Istanbul University Istanbul School of Medicine; Neurology

Istanbul, , Turkey (Türkiye)

Dokuz Eylul University Medicine Faculty; Noroloji Departmani

Izmir, , Turkey (Türkiye)

Ondokuz Mayis University School of Medicine; Neurology

Samsun, , Turkey (Türkiye)

Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit

Crowborough, , United Kingdom

Glasgow Memory Clinic

Glasgow, , United Kingdom

Charing Cross Hospital; Dept of Neurosciences

London, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Royal Preston Hosptial

Preston, , United Kingdom

Memory Service North

Sheffield, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Bulgaria; Canada; Denmark; Finland; France; Germany; Hungary; Italy; Japan; Netherlands; Portugal; Russia; South Korea; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31831056 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-003390-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WN28745

Identifier Type: -

Identifier Source: org_study_id