A Study of Gantenerumab in Participants With Mild Alzheimer Disease
- Registration Number
- NCT02051608
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 389
- 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
- Dementia or neurocognitive disorder (NCD) due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia
- History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function
- History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months
- History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
- History of schizophrenia, schizoaffective disorder, or bipolar disorder
- Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years (nicotine use is allowed)
- History or presence of atrial fibrillation
- Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher)
- Uncontrolled hypertension
- Chronic kidney disease
- Impaired hepatic function
PET imaging substudy, in addition to above:
- Prior participation in other research study or clinical care within the last year such that the total radiation exposure would exceed the local or national annual limits
Part 2 Participants who have been discontinued from the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 (Double Blind treatment): Placebo Placebo Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study. Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg Placebo 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. Part 1 (Double Blind treatment): Gantenerumab 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. Part 2 (OLE treatment): Gantenerumab up to 1200 mg Gantenerumab 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.
- Primary Outcome Measures
Name Time Method Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) First dose up to last dose (Baseline up to until maximum 5 years) 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.
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) First dose up to 4 weeks after the last dose of study drug (up to 249 weeks) 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.
Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment First dose up to 4 weeks after the last dose in OLE (Up to approximately 249 weeks) Percentage of participants with adverse events leading to discontinuation from treatment were reported.
- Secondary Outcome Measures
Name Time Method Part 2: Percent Change From Baseline in Cortical Thickness at Week 104 Baseline (Part 1 screening), Week 104 Change from baseline in cortical thickness were analyzed at Week 104 using magnetic resonance imaging.
Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104 Baseline (Part 1 screening), Week 104 Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analyzed at Week 104 using magnetic resonance imaging.
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) Percentage of participants with adverse events leading to discontinuation from treatment were reported.
Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104 Baseline (Part 1 screening), Week 104 Change from baseline brain volume were analyzed at Week 104 using magnetic resonance imaging.
Part 2: Ventricular Volume as Measured by MRI at Week 104 Part 2: Week 104 Ventricular volume were analyzed at Week 104 using magnetic resonance imaging.
Part 1: Percentage of Participants With Treatment Emergent ADAs First dose up to last dose (Up to approximately 152 weeks) 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.
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Pre-dose: Weeks 104, 116, 156, 208; Post-dose: Weeks 53, 101 Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants Baseline, Week 156 Brain amyloid load over time was assessed using a Florbetapir \[F18\] injection, a positron emission tomography (PET) radioligand selective to amyloid. Analysis was conducted in a subset of participants who signed consent to participate in the PET substudy. Amyloid PET burden was measured in a composite region of interest (ROI) by using standardized uptake value ratio (SUVR) mapped to the centiloid scale. The composite region was composed of the following six bilateral regions: frontal lobe, parietal lobe, temporal lobe, posterior cingulate cortex, anterior cingulate cortex. The reference region used to normalize the composite region was the cerebellar cortex. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans.
Part 1: Percentage of Participants With AEs, SAEs First dose up to last dose (Up to approximately 152 weeks) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A serious adverse event is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.
Trial Locations
- Locations (131)
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Banner Sun Health Research Insitute
🇺🇸Sun City, Arizona, United States
Territory Neurology and Research Institute
🇺🇸Tucson, Arizona, United States
Pennington Biomedical Research Center
🇺🇸Baton Rouge, Louisiana, United States
Alzheimer's Research Corporation
🇺🇸Manchester, New Jersey, United States
Ocean Rheumatology
🇺🇸Toms River, New Jersey, United States
Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
🇺🇸Kalamazoo, Michigan, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
Instituto Neurologia Bs As
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
🇦🇺Heidelberg West, Victoria, Australia
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Shat Np Sveti Naum; 3Rd Clinic of Neurology
🇧🇬Sofia, Bulgaria
True North Clinical Research
🇨🇦New Minas, Nova Scotia, Canada
MBAL St. Marina; First Neurology Department
🇧🇬Varna, Bulgaria
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
🇨🇦Quebec City, Quebec, Canada
McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
🇨🇦Verdun, Quebec, Canada
CRST Oy
🇫🇮Turku, Finland
Semmelweis University; Department of Neurology
ðŸ‡ðŸ‡ºBudapest, Hungary
Umberto I Policlinico di Roma-Università di Roma La Sapienza
🇮🇹Roma, Lazio, Italy
Medical Corporation Hakuyokai Kashiwado Hospital
🇯🇵Chiba, Japan
National Hospital Organization Chiba-east Hospital; Neurology
🇯🇵Chiba, Japan
Brain Research Center B.V
🇳🇱Amsterdam, Netherlands
Hospital de Santa Maria; Servico de Neurologia
🇵🇹Lisboa, Portugal
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
🇯🇵Hyogo, Japan
Shizuoka City Shimizu Hospital; Neurology
🇯🇵Shizuoka, Japan
SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF
🇷🇺Moscow, Russian Federation
Istanbul University Istanbul School of Medicine; Neurology
🇹🇷Istanbul, Turkey
CHU Rennes - hopital Hotel Dieu; Consultation Memoire - Gerontologie
🇫🇷Rennes, France
Erasmus Mc - Locatie Centrum; Dept of Neurology
🇳🇱Rotterdam, Netherlands
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Australian Alzheimer's Research Foundation
🇦🇺Nedlands, Western Australia, Australia
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Utah, Center for Alzheimer's Care Imaging & Research
🇺🇸Salt Lake City, Utah, United States
Pacific Research Network - PRN
🇺🇸San Diego, California, United States
Meridien Research
🇺🇸Brooksville, Florida, United States
California Neuroscience Research Medical Group, Inc
🇺🇸Sherman Oaks, California, United States
ATP Clinical Research, Inc
🇺🇸Costa Mesa, California, United States
Miami Jewish Health Systems; Clinical Research
🇺🇸Miami, Florida, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸Wellington, Florida, United States
Millennium Psychiatric Associates, LLC
🇺🇸Saint Louis, Missouri, United States
Nathan Kline Institute
🇺🇸Orangeburg, New York, United States
Central States Research
🇺🇸Tulsa, Oklahoma, United States
Northeastern Pennsylvania Memory
🇺🇸Plains, Pennsylvania, United States
Alzheimer's Memory Center
🇺🇸Matthews, North Carolina, United States
Richard H Weisler, MD
🇺🇸Raleigh, North Carolina, United States
Abington Neurological Associates
🇺🇸Abington, Pennsylvania, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
The Queen Elizabeth Hospital; Neurology
🇦🇺Woodville, South Australia, Australia
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
University of Calgary; Heritage Medical Research Clinic
🇨🇦Calgary, Alberta, Canada
True North Clinical Research-Halifax
🇨🇦Halifax, Nova Scotia, Canada
Jbn Medical Diagnostic Services Inc.
🇨🇦Burlington, Ontario, Canada
Kawartha Centre - Redefining Healthy Aging
🇨🇦Peterborough, Ontario, Canada
Parkwood Hospital; Geriatric Medicine
🇨🇦London, Ontario, Canada
Alpha Recherche Clinique
🇨🇦Quebec, Canada
Rigshospitalet, Hukommelsesklinikken
🇩🇰Koebenhavn Oe, Denmark
Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie
🇫🇷Bron, France
Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
🇩🇰Aarhus N, Denmark
University of Eastern Finland
🇫🇮Kuopio, Finland
Hopital Pellegrin; Cmrr Aquitaine
🇫🇷Bordeaux, France
CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
🇫🇷Limoges, France
CHU de la Timone - Hopital d Adultes; Service de Neurologie
🇫🇷Marseille, France
ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
🇩🇪Berlin, Germany
Hopital la Grave; Gerontopole - Centre de Recherche Clinique
🇫🇷Toulouse, France
Hopital Hautepierre; Centre dInvestigation Clinique
🇫🇷Strasbourg, France
PANAKEIA - Arzneimittelforschung Leipzig GmbH
🇩🇪Leipzig, Germany
Klinikum rechts der Isar der TU München; Klinikapotheke
🇩🇪Muenchen, Germany
Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz
🇩🇪Westerstede, Germany
Pharmakologisches Studienzentrum
🇩🇪Mittweida, Germany
Neurologische Praxis Dr. Andrej Pauls
🇩🇪München, Germany
Universitätsklinikum Ulm; Klinik für Neurologie
🇩🇪Ulm, Germany
Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze
🇮🇹Modena, Emilia-Romagna, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia
🇮🇹Roma, Lazio, Italy
Irccs Multimedica Santa Maria; Unita' Di Neurologia
🇮🇹Castellanza, Lombardia, Italy
IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
🇮🇹Brescia, Lombardia, Italy
A.O. Universitaria Pisana; Neurologia
🇮🇹Pisa, Toscana, Italy
ASST DI MONZA; Neurologia
🇮🇹Monza, Lombardia, Italy
Shonan Kamakura General Hospital; Neurology
🇯🇵Kanagawa, Japan
Oita University Hospital; Neurology
🇯🇵Oita, Japan
Kurashiki Heisei Hospital; Neurology
🇯🇵Okayama, Japan
Dong-A University Medical Center
🇰🇷Busan, Korea, Republic of
Seoul National University Bundang Hospital; Neurology Department
🇰🇷Gyeonggi-do, Korea, Republic of
Inha University Hospital; Neurology Department
🇰🇷Incheon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
🇵🇹Amadora, Portugal
State autonomous institution of healthcare Inter-regional clinical and diagnostic center
🇷🇺Kazan, Russian Federation
State Autonomous Healthcare Institution "Republican Clinical Neurological Center
🇷🇺Kazan, Russian Federation
Institution of RAMS (Mental Health Research Center of RAMS)
🇷🇺Moscow, Russian Federation
Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
🇷🇺St. Petersburg, Russian Federation
Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center
🇷🇺Saint Petersburg, Russian Federation
City Clinical Hospital # 2 n.a. V.I. Razumovsky
🇷🇺Saratov, Russian Federation
Hospital General Universitario de Elche; Servicio de NeurologÃa
🇪🇸Elche, Alicante, Spain
Fundació ACE
🇪🇸BArcelon, Barcelona, Spain
PoliclÃnica Guipuzkoa; Servicio de NeurologÃa
🇪🇸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
Skånes Universitetssjukhus Malmö, Minneskliniken
🇸🇪Malmö, Sweden
Hospital Universitario Virgen Macarena; Servicio de Neurologia
🇪🇸Sevilla, Spain
KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
🇸🇪Stockholm, Sweden
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Felix Platter-Spital Medizin Geriatrie
🇨ðŸ‡Basel, Switzerland
CHUV Lausanne Memory clinique
🇨ðŸ‡Lausanne, Switzerland
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Dokuz Eylul University Medicine Faculty; Noroloji Departmani
🇹🇷Izmir, Turkey
Ondokuz Mayis University School of Medicine; Neurology
🇹🇷Samsun, Turkey
Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
🇬🇧Crowborough, United Kingdom
Charing Cross Hospital; Dept of Neurosciences
🇬🇧London, United Kingdom
Royal Preston Hosptial
🇬🇧Preston, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Memory Service North
🇬🇧Sheffield, United Kingdom
Neuropsychiatric Research; Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Royal Adelaide Hospital; Memory Trials Centre
🇦🇺Adelaide, South Australia, Australia
Asan Medical Center.
🇰🇷Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Hospital (Seoul)
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital; Dept of Neurology
🇰🇷Seoul, Korea, Republic of
Accelerated Enrollment Solutions
🇺🇸Orlando, Florida, United States
Senior Adults Specialty Research
🇺🇸Austin, Texas, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Louisiana Research Associates
🇺🇸New Orleans, Louisiana, United States