Clinical trial NCT01224106: A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease
Official title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-10-19
Enrollment: 799
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multi-center, randomized, double-blind, placebo-controlled parallel-group study will evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo. Participants who consent to be part of the sub study will undergo positron emission tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is 104 weeks in Part 1, with an option for an additional up to 2 years of treatment in Part 2, followed by an open-label extension (Part 3) until July 2020.

The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a low probability of meeting the primary outcome measure with the doses studied. The study has converted to open-label to investigate higher gantenerumab doses.


Eligibility criteria: Inclusion Criteria:

* Adult participants, 50-85 years of age
* Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors
* Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion
* Has had sufficient education or work experience to exclude mental retardation
* Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of
* Screening Mini Mental State Exam (MMSE) score of 24 or above

Additional inclusion criteria for sub study:

* Able and willing to travel to PET imaging center and complete the planned scanning sessions
* Past and planned exposure to ionizing radiation not exceeding safe and permissible levels

Exclusion Criteria:

* Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning
* A history of stroke
* A documented history of transient ischemic attack within the last 12 months
* History of schizophrenia, schizoaffective or bipolar disorder
* Currently meets criteria for major depression
* Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)

Additional exclusion criteria for sub study:

* Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months
* Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203
* Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits

Primary outcomes:
measure: Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)
timeFrame: Baseline up until a maximum of 5 years
Secondary outcomes:
measure: Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 156
measure: Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)
timeFrame: Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101
measure: Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)
timeFrame: Baseline, Week 104
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)
timeFrame: Baseline up until a maximum of 4.5 years
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)
timeFrame: Baseline up until a maximum of 4.5 years
measure: Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Time to Onset of Dementia at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)
timeFrame: Baseline, Week 152
measure: Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)
timeFrame: Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101
measure: Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)
timeFrame: Baseline, Week 156
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)
timeFrame: Baseline up until a maximum of 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: New Haven
country: United States
facility: Yale University ADRU
state: Connecticut
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research
state: Florida
city: Orlando
country: United States
facility: Accelerated Enrollment Solutions
state: Florida
city: Sarasota
country: United States
facility: Roskamp Institute, Inc.
state: Florida
city: The Villages
country: United States
facility: Compass Research
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Kalamazoo
country: United States
facility: Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
state: Michigan
city: Hattiesburg
country: United States
facility: Neurological Research Center
state: Mississippi
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center; Monroe Community Hospital
state: New York
city: Matthews
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University, Layton Aging and Alzheimer's Disease Center
state: Oregon
city: Plains
country: United States
facility: Northeastern Pennsylvania Memory
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Dallas
country: United States
facility: Texas Neurology PA
state: Texas
city: Bennington
country: United States
facility: Clinical Neuroscience Research Associates, Inc.
state: Vermont
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Buenos Aires
country: Argentina
facility: IME - Instituto Médico Especializado; Ensayos Clínicos
city: Buenos Aires
country: Argentina
facility: ALPI-Inst. de Rehabilitacion Marcelo Fitte
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Caba
country: Argentina
facility: Mulieris
city: Caba
country: Argentina
facility: Instituto De Neurología Cognitiva - INECO
city: Caba
country: Argentina
facility: FLENI
city: Córdoba
country: Argentina
facility: Instituto Kremer
city: La Plata
country: Argentina
facility: CENPIA; Neurología - Psicología
city: Hornsby
country: Australia
facility: Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital, Academic Department for Old Age Psychiatry
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital; Memory Trials Centre
state: South Australia
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital; Neurology
state: South Australia
city: Heidelberg West
country: Australia
facility: Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
state: Victoria
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Foundation
state: Western Australia
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Curitiba
country: Brazil
facility: Hospital das Clinicas - UFPR; Ciencias da Saude
state: PR
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus
state: RS
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas - FMUSP; Psiquiatria
state: SP
city: São Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFESPX; Neurologia
state: SP
city: New Minas
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: Centre for Memory and Aging
state: Ontario
city: Greenfield Park
country: Canada
facility: NeuroSearch Developpements inc
state: Quebec
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Neurological and Psychiatric
state: Quebec
city: Quebec City
country: Canada
facility: CHAUQ - Hôpital Enfant-Jésus
state: Quebec
city: Santiago
country: Chile
facility: Biomedica Research Group
city: Santiago
country: Chile
facility: Especialidades Medicas LYS
city: Brno
country: Czechia
facility: St. Anne´s University Hospital; Clinical Trials Department
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
city: Koebenhavn Oe
country: Denmark
facility: Rigshospitalet, Hukommelsesklinikken
city: Turku
country: Finland
facility: CRST Oy
city: Bobigny
country: France
facility: Hopital Avicenne; Neurologie
city: Bordeaux
country: France
facility: Hopital Pellegrin; Cmrr Aquitaine
city: Bron
country: France
facility: Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie
city: Caen
country: France
facility: CHU De Caen; Service De Neurologie Dejerine
city: Lille
country: France
facility: Hopital B Roger Salengro; Cmrr Lille
city: Paris
country: France
facility: Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere
city: Rouen
country: France
facility: CHU de Rouen Hopital; Service de Neurologie
city: St Herblain
country: France
facility: Hop Guillaume Et Rene Laennec; Cmrr St Herblain
city: Strasbourg
country: France
facility: Hopital Hautepierre; Centre dInvestigation Clinique
city: Toulouse
country: France
facility: Hopital de La Grave
city: Berlin
country: Germany
facility: Univ Berlin; Klin fur Psychi & Psycho Charite
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
city: Frankfurt
country: Germany
facility: Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik
city: Leipzig
country: Germany
facility: PANAKEIA - Arzneimittelforschung Leipzig GmbH
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit Abt.Gerontopsychiatrie
city: Mittweida
country: Germany
facility: Pharmakologisches Studienzentrum
city: München
country: Germany
facility: Neurologische Praxis Dr. Andrej Pauls
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
city: Nürnberg
country: Germany
facility: Office of Dr Klaus Steinwachs Neurology & Psychiatry
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock Zentrum für Nervenheilkunde
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Modena
country: Italy
facility: Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze
state: Emilia-Romagna
city: Parma
country: Italy
facility: Universita' Di Parma Istituto Neurologia
state: Emilia-Romagna
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili; Scienze Neurologiche
state: Lombardia
city: Brescia
country: Italy
facility: IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
state: Lombardia
city: Castellanza
country: Italy
facility: Irccs Multimedica Santa Maria; Unita' Di Neurologia
state: Lombardia
city: Milano
country: Italy
facility: Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
state: Lombardia
city: Torrette - Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona
state: Marche
city: Firenze
country: Italy
facility: Uni Di Firenze Dip. Scienze Neurol Psic Sod Neurologia 1
state: Toscana
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital; Neurology Department
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center.
city: Guadalajara
country: Mexico
facility: Hospital Mexico Americano
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario; Dr. Jose E. Gonzalez
state: Nuevo LEON
city: Culiacan
country: Mexico
facility: Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC
city: Guadalajara
country: Mexico
facility: Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
city: Mexico City
country: Mexico
facility: Estimulacion Magnetica Trnscraneal de Mexico SC.
city: Monterrey
country: Mexico
facility: Centro Medico San Francisco; Geriatrics
city: Saltillo
country: Mexico
facility: Hospital Universitario de Saltillo
city: 'S Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis; Polikliniek Geriatrie
city: Amsterdam
country: Netherlands
facility: Brain Research Center B.V
city: Białystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER
city: Poznań
country: Poland
facility: NEURO - KARD Ośrodek Badań Klinicznych
city: Warszawa
country: Poland
facility: Przychodnia Specjalistyczna PROSEN
city: Warszawa
country: Poland
facility: mMED Maciej Czarnecki
city: Amadora
country: Portugal
facility: Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Neurologia
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Psychoneurological War Veteran Hospital
city: Kazan
country: Russian Federation
facility: State autonomous institution of healthcare Inter-regional clinical and diagnostic center
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center
city: Saratov
country: Russian Federation
facility: City Clinical Hospital # 2 n.a. V.I. Razumovsky
city: St. Petersburg
country: Russian Federation
facility: Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
city: BArcelon
country: Spain
facility: Fundació ACE
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua De Terrasa; Servicio de Neurologia
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital de Cruces; Servicio de Neurologia
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial; Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset; Servicio de Neurologia
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus Malmö, Minneskliniken
city: Basel
country: Switzerland
facility: Felix Platter-Spital Medizin Geriatrie
city: Chêne-Bourg
country: Switzerland
facility: HUG; Département de santé mentale et de psychiatrie Unité de psychiatrie gériatrique
city: Antalya
country: Turkey
facility: Akdeniz University School of Medicine, Neurology Department
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul School of Medicine; Neurology
city: Samsun
country: Turkey
facility: Ondokuz Mayis University School of Medicine; Neurology
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building
city: Epping
country: United Kingdom
facility: St Margaret's Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic
city: London
country: United Kingdom
facility: Charing Cross Hospital; Dept of Neurosciences
city: Newcastle
country: United Kingdom
facility: Campus for Ageing & Vitality; Clincal Ageing Research Unit
city: Southampton
country: United Kingdom
facility: Moorgreen Hospital; Memory Assessment & Rsch Ctr
city: Swindon
country: United Kingdom
facility: Victoria Centre; Kingshill Research Centre
city: Warrington
country: United Kingdom
facility: Hollins Park Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, Ashford E, Retout S, Hofmann C, Delmar P, Klein G, Andjelkovic M, Dubois B, Boada M, Blennow K, Santarelli L, Fontoura P; SCarlet RoAD Investigators. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimers Res Ther. 2017 Dec 8;9(1):95. doi: 10.1186/s13195-017-0318-y.
citation: Delrieu J, Ousset PJ, Vellas B. Gantenerumab for the treatment of Alzheimer's disease. Expert Opin Biol Ther. 2012 Aug;12(8):1077-86. doi: 10.1517/14712598.2012.688022. Epub 2012 May 15.