A Study of Gantenerumab in Participants With Mild Alzheimer Disease

NCT02051608 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: WN287452013-003390-95
• Study Type: interventional
• Target: 389
• Locations: 22 countries
• Sites: 131

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Part 1: Percentage of Participants With AEs, SAEs

  First dose up to last dose (Up to approximately 152 weeks)

• Part 1: Percentage of Participants With Treatment Emergent ADAs

  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

  First dose up to last dose (Up to approximately 152 weeks)

• Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104

  Baseline (Part 1 screening), Week 104

Other Outcomes (22)

• 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

Study Arms (4)

Part 1 (Double Blind treatment): Placebo

PLACEBO COMPARATOR

Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study.

Drug: Placebo

Part 1 (Double Blind treatment): Gantenerumab

EXPERIMENTAL

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

Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg

PLACEBO COMPARATOR

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

Part 2 (OLE treatment): Gantenerumab up to 1200 mg

EXPERIMENTAL

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

Interventions

Placebo DRUG

Participants received Placebo SC injection Q4W.

Part 1 (Double Blind treatment): Placebo; Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg

Gantenerumab DRUG

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

Part 1 (Double Blind treatment): Gantenerumab; Part 2 (OLE treatment): Gantenerumab up to 1200 mg

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (131)

Banner Sun Health Research Insitute

Sun City, Arizona, 85351, United States

Location

Territory Neurology and Research Institute

Tucson, Arizona, 85704, United States

Location

ATP Clinical Research, Inc

Costa Mesa, California, 92626, United States

Location

Pacific Research Network - PRN

San Diego, California, 92103, United States

Location

California Neuroscience Research Medical Group, Inc

Sherman Oaks, California, 91403, United States

Location

Meridien Research

Brooksville, Florida, 34601, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Miami Jewish Health Systems; Clinical Research

Miami, Florida, 33137, United States

Location

Accelerated Enrollment Solutions

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33613-4706, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Louisiana Research Associates

New Orleans, Louisiana, 70114, United States

Location

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

Kalamazoo, Michigan, 49008, United States

Location

Millennium Psychiatric Associates, LLC

St Louis, Missouri, 63132, United States

Location

Alzheimer's Research Corporation

Paterson, New Jersey, 08759, United States

Location

Ocean Rheumatology

Toms River, New Jersey, 08775, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Alzheimer's Memory Center

Matthews, North Carolina, 28105, United States

Location

Richard H Weisler, MD

Raleigh, North Carolina, 27609, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

Abington Neurological Associates

Abington, Pennsylvania, 19001, United States

Location

Northeastern Pennsylvania Memory

Plains, Pennsylvania, 18705, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Neurology Clinic PC

Cordova, Tennessee, 38018, United States

Location

Senior Adults Specialty Research

Austin, Texas, 78757, United States

Location

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

Salt Lake City, Utah, 84108, United States

Location

Instituto Neurologia Bs As

Ciudad Autonoma Buenos Aires, C1426ANZ, Argentina

Location

Royal Adelaide Hospital; Memory Trials Centre

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital; Neurology

Woodville, South Australia, 5011, Australia

Location

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, 3081, Australia

Location

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, 6009, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Shat Np Sveti Naum; 3Rd Clinic of Neurology

Sofia, 1113, Bulgaria

Location

MBAL St. Marina; First Neurology Department

Varna, 9010, Bulgaria

Location

University of Calgary; Heritage Medical Research Clinic

Calgary, Alberta, T2N 4Z6, Canada

Location

True North Clinical Research-Halifax

Halifax, Nova Scotia, B3S 1N2, Canada

Location

True North Clinical Research

New Minas, Nova Scotia, B4N 3R7, Canada

Location

Jbn Medical Diagnostic Services Inc.

Burlington, Ontario, L7M 4Y1, Canada

Location

Parkwood Hospital; Geriatric Medicine

London, Ontario, N6C 5J1, Canada

Location

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, K9H 2P4, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Recherches Neuro-Hippocame

Gatineau, Quebec, J8T 8J1, Canada

Location

NeuroSearch Developpements inc

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Jewish General Hospital / McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

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

Québec, Quebec, G1J 1Z4, Canada

Location

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

Verdun, Quebec, H4H 1R3, Canada

Location

Alpha Recherche Clinique

Québec, G3K 2P8, Canada

Location

Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken

Aarhus N, 8200, Denmark

Location

Rigshospitalet, Hukommelsesklinikken

Koebenhavn Oe, 2100, Denmark

Location

University of Eastern Finland

Kuopio, 70210, Finland

Location

CRST Oy

Turku, 20520, Finland

Location

Hopital Pellegrin; Cmrr Aquitaine

Bordeaux, 33076, France

Location

Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie

Bron, 69677, France

Location

CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique

Limoges, 87042, France

Location

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

Marseille, 13005, France

Location

CHU Rennes - hopital Hotel Dieu; Consultation Memoire - Gerontologie

Rennes, 35064, France

Location

Hopital Hautepierre; Centre dInvestigation Clinique

Strasbourg, 67098, France

Location

Hopital la Grave; Gerontopole - Centre de Recherche Clinique

Toulouse, 31059, France

Location

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

Berlin, 13125, Germany

Location

PANAKEIA - Arzneimittelforschung Leipzig GmbH

Leipzig, 04275, Germany

Location

Pharmakologisches Studienzentrum

Mittweida, 09648, Germany

Location

Neurologische Praxis Dr. Andrej Pauls

München, 80331, Germany

Location

Klinikum rechts der Isar der TU München; Klinikapotheke

München, 81675, Germany

Location

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, 89081, Germany

Location

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

Westerstede, 26655, Germany

Location

Semmelweis University; Department of Neurology

Budapest, 1083, Hungary

Location

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

Modena, Emilia-Romagna, 41126, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia

Rome, Lazio, 00133, Italy

Location

Umberto I Policlinico di Roma-Università di Roma La Sapienza

Rome, Lazio, 00185, Italy

Location

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

Brescia, Lombardy, 25125, Italy

Location

Irccs Multimedica Santa Maria; Unita' Di Neurologia

Castellanza, Lombardy, 21053, Italy

Location

ASST DI MONZA; Neurologia

Monza, Lombardy, 20900, Italy

Location

A.O. Universitaria Pisana; Neurologia

Pisa, Tuscany, 56126, Italy

Location

Medical Corporation Hakuyokai Kashiwado Hospital

Chiba, 260-8656, Japan

Location

National Hospital Organization Chiba-east Hospital; Neurology

Chiba, 260-8712, Japan

Location

Juntendo University Urayasu Hospital; Neurology

Chiba, 279-0021, Japan

Location

Fukuoka University Hospital; Neurology and Health Care

Fukuoka, 814-0180, Japan

Location

Maebashi Red Cross Hospital; Neurology

Gunma, 371-0014, Japan

Location

National Hospital Organization Hiroshima-Nishi Medical Center

Hiroshima, 739-0696, Japan

Location

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

Hyōgo, 670-0981, Japan

Location

Shonan Kamakura General Hospital; Neurology

Kanagawa, 247-8533, Japan

Location

Kurashiki Heisei Hospital; Neurology

Okayama, 710-0826, Japan

Location

Oita University Hospital; Neurology

Ōita, 879-5593, Japan

Location

Shizuoka City Shimizu Hospital; Neurology

Shizuoka, 424-0911, Japan

Location

Brain Research Center B.V

Amsterdam, 1081 GN, Netherlands

Location

Erasmus Mc - Locatie Centrum; Dept of Neurology

Rotterdam, 3015 GD, Netherlands

Location

Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia

Amadora, 2720-276, Portugal

Location

Hospital de Santa Maria; Servico de Neurologia

Lisbon, 1649-035, Portugal

Location

State Autonomous Healthcare Institution "Republican Clinical Neurological Center

Kazan', 420021, Russia

Location

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

Kazan', 420101, Russia

Location

Institution of RAMS (Mental Health Research Center of RAMS)

Moscow, 115522, Russia

Location

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

Moscow, 119021, Russia

Location

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

Saint Petersburg, 190103, Russia

Location

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

Saint Petersburg, 194044, Russia

Location

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

Saratov, 410028, Russia

Location

Dong-A University Medical Center

Busan, 602-715, South Korea

Location

Seoul National University Bundang Hospital; Neurology Department

Gyeonggi-do, 13620, South Korea

Location

Inha University Hospital; Neurology Department

Incheon, 22332, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Ewha Womans University Hospital (Seoul)

Seoul, 07804, South Korea

Location

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

Seoul, 137-701, South Korea

Location

Asan Medical Center.

Seoul, 138-736, South Korea

Location

Ewha Womans University Mokdong Hospital; Dept of Neurology

Seoul, 158-710, South Korea

Location

Hospital General Universitario de Elche; Servicio de Neurología

Elche, Alicante, 03203, Spain

Location

Fundació ACE

BArcelon, Barcelona, 08034, Spain

Location

Policlínica Guipuzkoa; Servicio de Neurología

Donosti-San Sebastián, Guipuzcoa, 20014, Spain

Location

Hospital de Cruces; Servicio de Neurologia

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital del Mar; Servicio de Neurologia

Barcelona, 08003, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, 41009, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Skånes Universitetssjukhus Malmö, Minneskliniken

Malmo, 211 46, Sweden

Location

KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54

Stockholm, 141 86, Sweden

Location

Felix Platter-Spital Medizin Geriatrie

Basel, 4002, Switzerland

Location

CHUV Lausanne Memory clinique

Lausanne, 1011, Switzerland

Location

Istanbul University Istanbul School of Medicine; Neurology

Istanbul, 34093, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty; Noroloji Departmani

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayis University School of Medicine; Neurology

Samsun, 55139, Turkey (Türkiye)

Location

Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit

Crowborough, TN6 1HB, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, G20 0XA, United Kingdom

Location

Charing Cross Hospital; Dept of Neurosciences

London, W6 8RF, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Royal Preston Hosptial

Preston, PR2 9HT, United Kingdom

Location

Memory Service North

Sheffield, S35 8QS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31831056 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

gantenerumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

As the participants transitioned early to OLE, most participants did not reach the primary analysis timepoint (Week 104). Hence, the efficacy endpoints for Part 1 became exploratory in nature.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2014
• First Posted: January 31, 2014
• Study Start: March 27, 2014
• Primary Completion: April 16, 2021
• Study Completion: April 16, 2021
• Last Updated: February 10, 2023
• Results First Posted: June 16, 2022

Record last verified: 2023-02

Locations

TU (3); FI (2); ES (8); BE (2); HU (1); AU (4); NL (2); SE (2); DE (7); BU (2); KR (9); AR (1); CH (2); GB (6); IT (7); CA (14); US (30); RU (7); FR (7); JP (11); PT (2); DK (2)