A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease (Scarlet Road)

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Gantenerumab

• Study Type: Interventional
• Enrollment (Actual): 799
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FWO
    • CEMIC
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Buenos Aires, Argentina, C1405BCH
    • IME - Instituto Médico Especializado; Ensayos Clínicos
  • Buenos Aires, Argentina, C1425BWO
    • ALPI-Inst. de Rehabilitacion Marcelo Fitte
  • Caba, Argentina, C1022AAO
    • Mulieris
  • Caba, Argentina, C1126AAB
    • Instituto De Neurología Cognitiva - INECO
  • Caba, Argentina, C1428AQK
    • FLENI
  • Córdoba, Argentina, X5004AOA
    • Instituto Kremer
  • La Plata, Argentina, B1902AJU
    • CENPIA; Neurología - Psicología
• Australia
  • New South Wales
    • Hornsby, New South Wales, Australia, 2077
      • Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital, Academic Department for Old Age Psychiatry
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Memory Trials Centre
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital; Neurology
  • Victoria
    • Heidelberg West, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Foundation
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • PR
    • Curitiba, PR, Brazil, 80060-900
      • Hospital das Clinicas - UFPR; Ciencias da Saude
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
    • Porto Alegre, RS, Brazil, 90470-340
      • Hospital Mae de Deus
  • SP
    • Sao Paulo, SP, Brazil, 05403-010
      • Hospital das Clinicas - FMUSP; Psiquiatria
    • São Paulo, SP, Brazil, 04024-002
      • Universidade Federal de Sao Paulo - UNIFESPX; Neurologia
• Canada
  • Nova Scotia
    • New Minas, Nova Scotia, Canada, B4N 3R7
      • True North Clinical Research
  • Ontario
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
    • Toronto, Ontario, Canada, M4G 3E8
      • Centre for Memory and Aging
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • NeuroSearch Developpements inc
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Neurological and Psychiatric
    • Quebec City, Quebec, Canada, G1J 1Z4
      • CHAUQ - Hôpital Enfant-Jésus
• Chile
  • Santiago, Chile, 7500710
    • BioMedica Research Group
  • Santiago, Chile, 7560356
    • Especialidades Medicas LYS
• Czechia
  • Brno, Czechia, 656 91
    • St. Anne´s University Hospital; Clinical Trials Department
  • Rychnov nad Kneznou, Czechia, 516 01
    • Vestra Clinics s.r.o.
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
  • Koebenhavn Oe, Denmark, 2100
    • Rigshospitalet, Hukommelsesklinikken
• Finland
  • Turku, Finland, 20520
    • CRST Oy
• France
  • Bobigny, France, 93009
    • Hopital Avicenne; Neurologie
  • Bordeaux, France, 33076
    • Hopital Pellegrin; Cmrr Aquitaine
  • Bron, France, 69677
    • Hopital Pierre Wertheimer; Laboratoire De Neuro Psychologie
  • Caen, France, 14033
    • CHU De Caen; Service De Neurologie Dejerine
  • Lille, France, 59037
    • Hopital B Roger Salengro; Cmrr Lille
  • Paris, France, 75651
    • Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere
  • Rouen, France, 76031
    • CHU de Rouen Hopital; Service de Neurologie
  • St Herblain, France, 44800
    • Hop Guillaume Et Rene Laennec; Cmrr St Herblain
  • Strasbourg, France, 67098
    • Hopital Hautepierre; Centre dInvestigation Clinique
  • Toulouse, France, 31059
    • Hopital de La Grave
• Germany
  • Berlin, Germany, 12203
    • Univ Berlin; Klin fur Psychi & Psycho Charite
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
  • Frankfurt, Germany, 60528
    • Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik
  • Leipzig, Germany, 04275
    • PANAKEIA - Arzneimittelforschung Leipzig GmbH
  • Mannheim, Germany, 68159
    • Zentralinstitut für Seelische Gesundheit Abt.Gerontopsychiatrie
  • Mittweida, Germany, 09648
    • Pharmakologisches Studienzentrum
  • München, Germany, 80331
    • Neurologische Praxis Dr. Andrej Pauls
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
  • Nürnberg, Germany, 90402
    • Office of Dr Klaus Steinwachs Neurology & Psychiatry
  • Rostock, Germany, 18147
    • Universitätsklinikum Rostock Zentrum für Nervenheilkunde
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
• Italy
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41126
      • Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica - Dipartimento di Neuroscienze
    • Parma, Emilia-Romagna, Italy, 43126
      • Universita' Di Parma Istituto Neurologia
  • Lombardia
    • Brescia, Lombardia, Italy, 25125
      • IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
    • Brescia, Lombardia, Italy, 25100
      • Azienda Ospedaliera Spedali Civili; Scienze Neurologiche
    • Castellanza, Lombardia, Italy, 21053
      • Irccs Multimedica Santa Maria; Unita' Di Neurologia
    • Milano, Lombardia, Italy, 20132
      • Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
  • Marche
    • Torrette - Ancona, Marche, Italy, 60100
      • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • Uni Di Firenze Dip. Scienze Neurol Psic Sod Neurologia 1
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital; Neurology Department
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center.
• Mexico
  • Culiacan, Mexico, 80020
    • Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC
  • Guadalajara, Mexico, 44620
    • Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
  • Mexico City, Mexico, 11000
    • Estimulacion Magnetica Trnscraneal de Mexico SC.
  • Monterrey, Mexico, 64710
    • Centro Medico San Francisco; Geriatrics
  • Saltillo, Mexico, 25000
    • Hospital Universitario de Saltillo
  • Mexico CITY (federal District)
    • Guadalajara, Mexico CITY (federal District), Mexico, 44610
      • Hospital Mexico Americano
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Hospital Universitario; Dr. Jose E. Gonzalez
• Netherlands
  • 'S Hertogenbosch, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis; Polikliniek Geriatrie
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center B.V
• Poland
  • Białystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Bydgoszcz, Poland, 85-796
    • PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER
  • Poznań, Poland, 61-853
    • NEURO - KARD Ośrodek Badań Klinicznych
  • Warszawa, Poland, 01-231
    • Przychodnia Specjalistyczna PROSEN
  • Warszawa, Poland, 01-684
    • mMED Maciej Czarnecki
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Neurologia
• Russian Federation
  • Ekaterinburg, Russian Federation, 620036
    • Sverdlovsk Regional Clinical Psychoneurological War Veteran Hospital
  • Kazan, Russian Federation, 420101
    • State autonomous institution of healthcare Inter-regional clinical and diagnostic center
  • Saint Petersburg, Russian Federation, 190103
    • Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center
  • Saratov, Russian Federation, 410028
    • City Clinical Hospital # 2 n.a. V.I. Razumovsky
  • St. Petersburg, Russian Federation, 194044
    • Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial; Servicio de Neurologia
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Neurologia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset; Servicio de Neurologia
  • Barcelona
    • BArcelon, Barcelona, Spain, 08034
      • Fundacio ACE
    • Terrassa, Barcelona, Spain, 08222
      • Hospital Mutua De Terrasa; Servicio de Neurologia
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Neurologia
• Sweden
  • Malmö, Sweden, 211 46
    • Skånes Universitetssjukhus Malmö, Minneskliniken
• Switzerland
  • Basel, Switzerland, 4002
    • Felix Platter-Spital Medizin Geriatrie
  • Chêne-Bourg, Switzerland, 1225
    • HUG; Département de santé mentale et de psychiatrie Unité de psychiatrie gériatrique
• Turkey
  • Antalya, Turkey, 07058
    • Akdeniz University School of Medicine, Neurology Department
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul School of Medicine; Neurology
  • Samsun, Turkey, 55239
    • Ondokuz Mayis University School of Medicine; Neurology
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF64 2XX
    • Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building
  • Epping, United Kingdom, CM16 6TN
    • St Margaret's Hospital
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital; Dept of Neurosciences
  • Newcastle, United Kingdom, NE4 5PL
    • Campus for Ageing & Vitality; Clincal Ageing Research Unit
  • Southampton, United Kingdom, SO30 3JB
    • Moorgreen Hospital; Memory Assessment & Rsch Ctr
  • Swindon, United Kingdom, SN3 6BW
    • Victoria Centre; Kingshill Research Centre
  • Warrington, United Kingdom, WA2 8WA
    • Hollins Park Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University ADRU
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research, Inc.
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research
    • Orlando, Florida, United States, 32806
      • Accelerated Enrollment Solutions
    • Sarasota, Florida, United States, 34243
      • Roskamp Institute, Inc.
    • The Villages, Florida, United States, 32162
      • Compass Research
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Michigan
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Neurological Research Center
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • New York
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Institute
    • Rochester, New York, United States, 14627
      • University of Rochester Medical Center; Monroe Community Hospital
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Alzheimer's Memory Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University, Layton Aging and Alzheimer's Disease Center
  • Pennsylvania
    • Plains, Pennsylvania, United States, 18705
      • Northeastern Pennsylvania Memory
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Dallas, Texas, United States, 75206
      • Texas Neurology PA
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Clinical Neuroscience Research Associates, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Parts 1 and 2); Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Placebo; Participants received Placebo SC injection Q4W.
Experimental: Gantenerumab 105 mg (Parts 1 and 2); Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Experimental: Gantenerumab 225 mg (Parts 1 and 2); Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Placebo Comparator: Placebo (Parts 1 and 2) switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]); Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Experimental: Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]); Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Drug: Gantenerumab; Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)	The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.	Baseline, Week 104
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)	An Adverse Event 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. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline up until a maximum of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)	The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.	Baseline, Week 104
Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)	Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.	Baseline, Week 104
Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)	The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.	Baseline, Week 104
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)	FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).	Baseline, Week 104
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)	Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.	Baseline, Week 104
Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)	The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.	Baseline, Week 104
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)	The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).	Baseline, Week 104
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)	CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.	Baseline, Week 104
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)	Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.	Baseline, Week 104
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)	The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.	Baseline, Week 156
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)	The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.	Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)	The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.	Baseline, Week 104
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)	An Adverse Event 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. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline up until a maximum of 4.5 years
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)	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 Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion 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 proportion 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.	Baseline up until a maximum of 4.5 years
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)	The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.	Baseline, Week 156
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)	The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.	Baseline, Week 156
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)	The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.	Baseline, Week 156
Time to Onset of Dementia at Week 156 (OLE Phase)	Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.	Baseline, Week 156
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)	FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).	Baseline, Week 156
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)	Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.	Baseline, Week 156
Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)	The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.	Baseline, Week 156
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)	Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.	Baseline, Week 152
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)	The regions of the brain that were analyzed included cerebellum gray and composite reference.	Baseline, Week 156
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)	The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.	Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)	The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.	Baseline, Week 156
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)	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. The prevalence of ADA at baseline was calculated as the proportion 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 proportion 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.	Baseline up until a maximum of 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Alzheimers Res Ther. 2018 Sep 27;10(1):99.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2010
• Primary Completion (Actual): September 10, 2020
• Study Completion (Actual): September 10, 2020

Study Registration Dates

• First Submitted: October 14, 2010
• First Submitted That Met QC Criteria: October 18, 2010
• First Posted (Estimate): October 19, 2010

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: WN25203; 2010-019895-66 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No