A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD)

Alzheimer's Disease Clinical Trial

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Official title:

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03114657
• Other study ID #: BN29553
• Secondary ID: 2016-003288-20
• Status: Terminated
• Phase: Phase 3
• Start date: March 29, 2017
• Est. completion date: June 11, 2019

Study information

• Verified date: June 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD. Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab or placebo every 4 weeks (Q4W) for 100 weeks. The primary efficacy assessment will be performed at 105 weeks. The participants who do not enter open-label extension will enter for a long term follow-up period for up to 52 weeks after the last crenezumab dose (Week 153).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 806
• Est. completion date: June 11, 2019
• Est. primary completion date: June 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Weight between 40 and 120 kilograms (Kg) inclusive

• Availability of a person (referred to as the "caregiver") who in the investigator's judgment:

• Has frequent and sufficient contact with the participant to be able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits (which require partner input for scale completion), signs the necessary consent form, and has sufficient cognitive capacity to accurately report upon the participant's behavior and cognitive and functional abilities

• Fluency in the language of the tests used at the study site

• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)

• Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid (CSF) amyloid beta 1-42 levels as measured on the Elecsys beta-amyloid(1-42) test system or amyloid PET scan by qualitative read by the core/central PET laboratory

• Demonstrated abnormal memory function at screening (up to 4 weeks before screening begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)

• Screening mini mental state examination (MMSE) score of greater than or equal to (>=) 22 points and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1.0

• Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment (MCI)

• If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening

• Participant must have completed at least 6 years of formal education after the age of 5 years

Exclusion Criteria:

• Any evidence of a condition other than AD that may affect cognition such as other dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or infections with neurological sequelae.

• History of major psychiatric illness such as schizophrenia or major depression (if not considered in remission)

• At risk of suicide in the opinion of the investigator

• Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical stroke, etc or inability to tolerate MRI procedures or contraindication to MRI

• Unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney or liver disease

• Uncontrolled hypertension

• Screening hemoglobin A1c (HbA1C) >8%

• Poor peripheral venous access

• History of cancer except:

If considered to be cured or If not being actively treated with anti-cancer therapy or radiotherapy

• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Crenezumab
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
• Placebo
Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

Locations

Country	Name	City	State
Argentina	Hospital Italiano	Buenos Aires
Argentina	Universidad Maimonides	Caba
Argentina	DAMIC	Cordoba
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Central Coast Neurosciences Research	Erina	New South Wales
Australia	Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care	Hornsby	New South Wales
Australia	The Queen Elizabeth Hospital; Neurology	Woodville	South Australia
Belgium	AZ Sint Jan	Brugge
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Hospital das Clinicas - UFMG	Belo Horizonte	MG
Brazil	CCBR - Brasilia	Brasilia	DF
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Centro Psiquiatria Sandra Ruschel Ltda	Rio de Janeiro	RJ
Brazil	Clínica Dr. Norton Sayeg LTDA - EPP	Sao Paulo	SP
Canada	Clinique Neuro Rive-Sud	Greenfield Park	Quebec
Canada	True North Clinical Research-Halifax	Halifax	Nova Scotia
Canada	OCT Research ULC	Kelowna	British Columbia
Canada	True North Clinical Research Kentville	Kentville	Nova Scotia
Canada	Providence Care; Mental Health Services	Kingston	Ontario
Canada	Parkwood Hospital; Geriatric Medicine	London	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	ALPHA Recherche Clinique	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Centre for Memory and Aging	Toronto	Ontario
Canada	Vancouver Island Health Authority	Victoria	British Columbia
Canada	Devonshire Clinical Research Inc.	Woodstock	Ontario
China	Beijing Union Hospital	Beijing
China	Tianjin Medical University General Hospital	Tianjin (??)
Denmark	Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken	Aarhus N
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
Estonia	Laane-Tallinna Keskhaigla	Tallinn
France	Hopital Pellegrin; Cmrr Aquitaine	Bordeaux
France	Hôpital de Jour du Centre pour Personnes Âgées; Louis Pasteur Neurologie	Colmar
France	Hopital Roger Salengro; Service de Neurologie	Lille
France	CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique	Limoges
France	CH Pitie Salpetriere; IM2A	Paris
France	Hopital Broca	Paris
France	Hôpital Maison Blanche	Reims
France	CHU Rennes - Hopital Pontchaillou	Rennes
France	CHU de Rouen Hopital; Service de Neurologie	Rouen
France	Hop Guillaume Et Rene Laennec; Cmrr St Herblain	St Herblain
France	Hopital des Charpennes	Villeurbanne
Germany	ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic	Berlin
Germany	Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik	Frankfurt
Germany	Universitätsklinikum Freiburg, Zentrum für Geriatrie und Gerontologie	Freiburg
Germany	Universitätsklinikum des Saarlandes Klinik f. Psychiatrie und Psychotherapie	Homburg/Saar
Germany	PANAKEIA - Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Pharmakologisches Studienzentrum	Mittweida
Germany	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München
Israel	Rambam Medical Center	Haifa
Israel	Sheba Medical Center; Psychiatry Department	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center; Department of Neurology	Tel Aviv
Italy	IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer	Brescia	Lombardia
Italy	Irccs Multimedica Santa Maria; Unita' Di Neurologia	Castellanza	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale Neurologico Besta; UO Neuropatologia	Milano	Lombardia
Italy	IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria	Milano	Lombardia
Italy	Ospedale S. Maria Nascente; Fondazione Don Gnocchi; Dip. Neurologia Riabilitativa	Milano	Lombardia
Italy	Ospedale Casati Passirana di Rho; Centro Regionale Alzheimer	Passirana	Lombardia
Italy	A.O. Universitaria Pisana; Neurologia	Pisa	Toscana
Italy	IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA	Pozzilli	Molise
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia	Roma	Lazio
Italy	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio
Italy	Umberto I Policlinico di Roma-Università di Roma La Sapienza	Roma	Lazio
Italy	AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria	Torino	Piemonte
Japan	National Center for Geriatrics and Gerontology	Aichi
Japan	Inage Neurology and Memory Clinic	Chiba
Japan	Fukuoka Mirai Hospital	Fukuoka
Japan	National Hospital Organization Hiroshima-Nishi Medical Center	Hiroshima
Japan	Tsukazaki Hospital	Hyogo
Japan	Iwate Medical University Hospital	Iwate
Japan	Kagawa Prefectural Central Hospital	Kagawa
Japan	Fujisawa City Hospital	Kanagawa
Japan	National Hospital Organization Sagamihara National Hospital	Kanagawa
Japan	Ijinkai Takeda General Hospital	Kyoto
Japan	Rakuwakai Otowarehabilitation Hospital	Kyoto
Japan	National Hospital Organization Matsumoto Medical Center	Nagano
Japan	Katayama Medical Clinic	Okayama
Japan	Asakayama General Hospital	Osaka
Japan	Osaka University Hospital	Osaka
Japan	NHO Shizuoka Institute of Epilepsy and Neurological Disorders	Shizuoka
Japan	Kanto Central Hospital	Tokyo
Japan	National Center of Neurology and Psychiatry	Tokyo
Japan	Shinjuku Research Park Clinic	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Tokyo Metropolitan Geriatric Hospital	Tokyo
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Borame Medical Center	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Norway	Akershus universitetssykehus HF; Nevroklinikken S203	Lørenskog
Norway	Oslo universitetssykehus HF Ullevål sykehus; Hukommelsesklinikken	Oslo
Peru	Clinica Internacional; Unidad De Investigacion	Lima
Peru	Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia	Lima
Poland	NZOZ Dom Sue Ryder	Bydgoszcz
Poland	Centrum Medyczne Euromedis Sp. z o.o.	Szczecin
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	NZOZ WCA	Wroclaw
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital Pedro Hispano; Servico de Neurologia	Matosinhos
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Russian Federation	State Healthcare Institution of Sverdlovsk Region Sverdlovsk Regional Clinical Psychiatric Hospita	Ekaterinburg	Sverdlovsk
Russian Federation	State Autonomous Healthcare Institution "Republican Clinical Neurological Center	Kazan
Russian Federation	State autonomous institution of healthcare Inter-regional clinical and diagnostic center	Kazan
Russian Federation	Institution of RAMS (Mental Health Research Center of RAMS)	Moscow
Russian Federation	City Clinical Psychiatry Hospital #1	Nizhny Novgorod
Russian Federation	LLC Baltic Medicine	Saint-Petersburg	Sankt Petersburg
Russian Federation	St Nicolas Psychiatric Hospital; Chair of Psychiatry and Narcology of St. Petersburg Medical Academy	St Petersburg
Russian Federation	Nebbiolo Center for Clinical Trials	Tomsk
Serbia	Clinic for Mental disorders Dr Laza Lazarevic	Belgrade
Serbia	Neurology clinic, Clinical Center of Serbia	Belgrade
Serbia	Clinic for neurology, Clinical Center Kragujevac	Kragujevac
South Africa	Private Practice; the Osteoporosis Clinic	Johannesburg
Spain	Hospital Perpetuo Socorro, Servicio de Geriatria	Albacete
Spain	CAE Oroitu	BaraKaldo	Vizcaya
Spain	Fundació ACE	BArcelon	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona
Spain	Hospital Universitario de Burgos. Servicio de Neurología	Burgos
Spain	Hospital la Magdalena; Servicio de Neurologia	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Neurologia	Cordoba
Spain	Policlínica Guipuzkoa; Servicio de Neurología	Donosti-San Sebastián	Guipuzcoa
Spain	Hospital General Universitario de Elche; Servicio de Neurología	Elche	Alicante
Spain	Hospital San Pedro; Servicio de Neurología	Logroño	LA Rioja
Spain	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Neurología	Pamplona	Navarra
Spain	Hospital Virgen del Puerto. Servicio de Neurología	Plasencia	Caceres
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría; CSM La Alamedilla	Salamanca
Spain	Hospital Santa Caterina, Unitat de Valoració de la memoria i les demencies	Salt	Girona
Spain	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Neurología	Santander	Cantabria
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Neurologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla
Spain	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Sweden	Skånes Universitetssjukhus Malmö, Minneskliniken	Malmö
Sweden	Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry	Mölndal
Taiwan	Changhua Christian Hospital; Neurology	Changhua County
Taiwan	Kaohsiung Medical University Hospital; Neurology	Kaohsiung
Taiwan	Taipei Medical University - Shuang Ho Hospital - Neurology	New Taipei City
Taiwan	National Taiwan University Hospital; Neurology	Taipei
Taiwan	Chang Gung Memorial Foundation - Linkou - Neurology	Taoyuan
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Istanbul University Istanbul School of Medicine; Neurology	Istanbul
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
United Kingdom	The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre	Cheltenham
United Kingdom	Surrey and Borders NHS Foundation Trust; Brain Science Research Unit	Chertsey
United Kingdom	Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit	Crowborough
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	NHS Lothian - Western General Hospital; NHS Lothian - Western General Hospital	Edinburgh
United Kingdom	Queen Elizabeth University Hospital; Clinical Research Facility	Glasgow
United Kingdom	Charing Cross Hospital; Imperial Memory Unit, Level 10 West	London
United Kingdom	RE:Cognition Health	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	University Southampton NHS Foundation Trust; Wessex Neurologica Centre	Southampton
United States	JEM Research LLC	Atlantis	Florida
United States	Senior Adults Specialty Research	Austin	Texas
United States	Gadolin Research, LLC	Beaumont	Texas
United States	Bradenton Research Center	Bradenton	Florida
United States	Behavioral Health Research	Charlotte	North Carolina
United States	University of Cincinnati; Department of Psychiatry and Behavioral Neuroscience	Cincinnati	Ohio
United States	MCB Clinical Research Centers	Colorado Springs	Colorado
United States	Columbus Memory Center	Columbus	Georgia
United States	Ohio State University; College of Medicine	Columbus	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	Kerwin Research Center, LLC	Dallas	Texas
United States	Texas Neurology PA	Dallas	Texas
United States	Dayton Center for Neuro Disorders	Dayton	Ohio
United States	Health Initiatives Research, PLLC	Fayetteville	Arkansas
United States	Precise Research Centers	Flowood	Mississippi
United States	Neuropsychiatric Research; Center of Southwest Florida	Fort Myers	Florida
United States	Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine	Houston	Texas
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	Clinical Trials Inc.	Little Rock	Arkansas
United States	Columbia University Medical Center	New York	New York
United States	Sentara Medical Group	Norfolk	Virginia
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	University of Nebraska Medical Center; Dept of Neurological Sciences	Omaha	Nebraska
United States	Bioclinica Research	Orlando	Florida
United States	Neuro-Therapeutics Inc.	Pasadena	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Northeastern Pennsylvania Memory	Plains	Pennsylvania
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	Wake Research Associates	Raleigh	North Carolina
United States	Desert Valley Medical Group	Rancho Mirage	California
United States	Anderson Clinical Research, Inc.	Redlands	California
United States	National Clinical Research Inc.-Richmond	Richmond	Virginia
United States	University of California, Davis; Alzheimers Disease Center, Department of Neurology	Sacramento	California
United States	Health Partners Institute for Education and Research	Saint Paul	Minnesota
United States	Clinical Trials of Texas, Inc	San Antonio	Texas
United States	UCSF - Memory and Aging Center	San Francisco	California
United States	Imaging End Points Clinical Research	Scottsdale	Arizona
United States	KI Health Partners, LLC; New England Institute for Clinical Research	Stamford	Connecticut
United States	The Cognitive and Research Center of New Jersey	Summit	New Jersey
United States	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Burke Rehabilitation Hospital	White Plains	New York
United States	Abington Neurological Associates	Willow Grove	Pennsylvania
United States	Alzheimers Disease Center; Neurology	Winchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Denmark,  Estonia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Norway,  Peru,  Poland,  Portugal,  Russian Federation,  Serbia,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score	The CDR-SB 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 no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline for this primary endpoint. Data after 29 January 2019 are censored for the primary and secondary efficacy analyses to avoid potential biases due to investigators, participants, raters, etc. being potentially influenced by early closure of the study due to lack of efficacy.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score	The ADAS-Cog-13 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 ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score	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 high scores representing severe dysfunction. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)	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. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)	The MMSE is a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target 6 areas: orientation, registration, attention, short-term recall, language and constructional praxis/visuospatial abilities. The scores on the MMSE range from 0 to 30, with higher scores indicating better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score	The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score	The ADCS-iADL (Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living) measures activities such as using the telephone, managing finances and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score	The Functional Activities Questionnaire (FAQ) is an instrument consisting of 10 items and assesses instrumental, social and cognitive functioning. The score range is from 0 to 30 with higher scores representing higher impairment. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score	The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score	The NPI-Q evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavioral disturbances and appetite/eating abnormalities. The severity of each neuropsychiatric symptom is rated on a 3-point scale (mild, moderate and marked). The total severity score range is from 0 to 36 with higher scores representing higher severity. Difference in mean change from Baseline to Week 53 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures adjusting for disease severity, APOEe4 status, geographic region and the use/non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 53
Secondary	Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score	The QoL-AD (Quality of Life - Alzheimer's Disease) scale assesses QoL in participants who have dementia. The QoL-AD consists of 13 items covering aspects of participants' relationships with friends and family, physical condition, mood, concerns about finances and overall assessment of QoL. Items are rated on 4-point Likert-type scales ranging from 1 [poor] to 4 [excellent]. The score range is from 13 to 52, with higher scores indicating a better QoL. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score	The ZCI-AD is a modified version of the Zarit Burden Interview, which was originally designed to reflect the stresses experienced by caregivers of people with dementia. This modified version includes slight modifications in item and title wording (e.g., removal of "your relative" to refer directly to the patient, removal of "burden" from title) and the use of 11-point numerical rating scales. The ZCI-AD scale consists of a total of 30 items. Total scores will be calculated with a total score range from 0 to 300 (higher scores indicate a higher burden on the caregiver). The difference in mean change from Baseline to Week 53 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 53
Secondary	European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants	The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers	The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 77
Secondary	Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)	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 16 weeks after the last dose of study drug (up to 117 weeks).
Secondary	Percentage of Participants With Anti-Crenezumab Antibodies	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 Crenezumab 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 to Week 105
Secondary	Serum Concentration of Crenezumab	Serum concentration data for Crenezumab will be tabulated and summarized. Descriptive summary statistics will include the arithmetic mean and SD. Since a sparse PK sampling design is being used, population (non-linear mixed-effects) modeling will be used to analyze the dose concentration-time data of crenezumab. Information from other clinical studies may be incorporated to establish the PK model. Please note that Post-dose samples were not collected at Weeks 5, 13, 37, 53 and 77.	Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (infusion length = as per the Pharmacy Manual)
Secondary	Plasma Amyloid Beta (Abeta) 40 Concentrations	Plasma Abeta 40 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.	Week 1 Day 1; Weeks 53
Secondary	Plasma Amyloid Beta (Abeta) 42 Concentrations	Plasma Abeta 42 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.	Week 1 Day 1; Weeks 53
Secondary	Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)	Percentage Change in Whole Brain Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 105
Secondary	Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)	Percentage Change in Ventricle Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 105
Secondary	Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)	Percentage Change in Hippocampal Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.	Baseline, Week 105