A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo 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: NCT02670083
• Other study ID #: BN29552
• Secondary ID: 2015-003034-27
• Status: Terminated
• Phase: Phase 3
• Start date: March 22, 2016
• Est. completion date: May 31, 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 final efficacy and safety assessment will be performed 52 weeks after the last crenezumab dose. Participants will then have the option to enter the Open Label Extension (OLE) study if eligible. Participants who do not enter the OLE study will have additional follow-up visits at 16 and 52 weeks after the last dose, primarily for safety and also for limited efficacy assessments.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 813
• Est. completion date: May 31, 2019
• Est. primary completion date: May 31, 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
Australia	Caulfield Hospital; Aged Psychiatry Research Unit	Caulfield	Victoria
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	Neurodegenerative Disorders Research; Neurology	West Perth	Western Australia
Australia	The Queen Elizabeth Hospital; Neurology	Woodville	South Australia
Austria	Konventhospital Barmherzige Brüder; Neurologie I	Linz
Belgium	UZ Gent	Gent
Bulgaria	ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine	Sofia
Bulgaria	Alexandrovska hospital; Neurology Department	Sofia
Canada	Parkwood Hospital; Geriatric Medicine	London	Ontario
Canada	Bruyere Continuing Care	Ottawa	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	CHA Hopital de I enfant-Jesus	Quebec City	Quebec
Canada	The Centre for Memory and Aging	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Vancouver Hospital - UBC Hospital Site	Vancouver	British Columbia
Canada	Vancouver Island Health Authority	Victoria	British Columbia
Canada	Devonshire Clinical Research Inc.	Woodstock	Ontario
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San Jose
Costa Rica	Hospital Clínica Biblica	San José
Croatia	Clinical Hospital Centre Zagreb;Clinic for Neurology	Zagreb
Czechia	Charles University, Medical faculty, Hradec Kralove ;Department of Neurology	Hradec Králové
Czechia	General Teaching Hospital, Departmetn of Neurology	Praha
Denmark	Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken	Aarhus N
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
Finland	Terveystalo Tampere	Tampere
Finland	CRST Oy	Turku
France	Hopital Avicenne; Neurologie	Bobigny
France	Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie	Bron
France	Hopital Gui de Chauliac; Neurologie	Montpellier
France	Hopital Lariboisiere	Paris
France	CHU Poitiers - Hopital La Miletrie	Poitiers
France	Hopital Hautepierre; Centre dInvestigation Clinique	Strasbourg
France	CHU Toulouse - La Grave	Toulouse
Germany	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München
Germany	Neurologische Praxis Dr. Andrej Pauls	München
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Steinwachs Klaus; Arztpraxis fur Neurologie u. Psychiatrie	Nürnberg
Germany	Universitätsklinikum Rostock Zentrum für Nervenheilkunde	Rostock
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Germany	Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz	Westerstede
Germany	Forschungszentrum Ruhr	Witten
Hong Kong	Prince of Wales Hospital; Dept. of Medicine & Therapeutics	Hong Kong
Hong Kong	Queen Mary Hospital, Division of Geriatric Medicine	Hong Kong
Hungary	Semmelweis University; Department of Neurology	Budapest
Hungary	Szabolcs-Szatmár-Bereg Megyei Kórházak - Jósa András Oktatókórház; Pszichiátria	Nyíregyháza
Hungary	University of Szeged; Department of Psychiatry	Szeged
Hungary	Szent Borbala Korhaz; Neurologiai es Stroke Osztaly	Tatabánya
Hungary	Jávorszky Ödön Kórház, Neurológia és stroke osztály	VAC
Italy	Ente Ospedaliero Ospedali Galliera; Ambulatorio di Neurologia	Genova	Liguria
Italy	Casa di Cura Policlinico; Dipartimento di Scienze Neuroriabilitative	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	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; S.C. Geriatria	Perugia	Umbria
Italy	Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica	Roma	Lazio
Italy	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio
Japan	Miyoshi Clinic of Neurology, Hananosato	Hiroshima
Japan	National Hospital Organization Hiroshima-Nishi Medical Center	Hiroshima
Japan	Rakuwakai Otowarehabilitation Hospital	Kyoto
Japan	Mie University Hospital	Mie
Japan	National Hospital Organization Matsumoto Medical Center	Nagano
Japan	Saigata Medical Center	Niigata
Japan	Katayama Medical Clinic	Okayama
Japan	National Center of Neurology and Psychiatry	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Tokyo Metropolitan Geriatric Hospital	Tokyo
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital; Dept of Neurology	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	KyungHee Medical Center	Seoul
Lithuania	Vilnius University Hospital Santariskiu Clinic	Vilnius
Mexico	Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC	Culiacan
Mexico	AVIX Investigación Clínica S.C	Monterrey
Mexico	Hospital Uni; Dr. Jose E. Gonzalez	Monterrey
Mexico	Hospital Universitario de Saltillo	Saltillo
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Poznan
Poland	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Siemianowice Slaskie
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	Optimum	Warszawa
Poland	Przychodnia Specjalistyczna PROSEN	Warszawa
Portugal	Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia	Amadora
Portugal	Hospital Beatriz Angelo; Servico de Neurologia	Loures
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	SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF	Moscow
Russian Federation	City Clinical Hospital # 2 n.a. V.I. Razumovsky	Saratov
Russian Federation	SHI City Psychoneurological Dispensary #7	St Petersburg
Russian Federation	Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department	St. Petersburg
Slovenia	University Medical Centre Maribor	Maribor
Spain	Hospital General Universitario de Albacete; Servicio de Neurología	Albacete
Spain	Fundació ACE	BArcelon	Barcelona
Spain	Hospital Vall d'Hebron; Servicio de Neurología	Barcelona
Spain	Hospital Universitario de Burgos. Servicio de Neurología	Burgos
Spain	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona
Spain	Clinica Ruber, 4 planta; Servicio de Neurologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Neurologia	Malaga
Spain	Hospital Sant Joan de Deu; Servicio de Neurología	Manresa	Barcelona
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Neurología	Murcia
Spain	Clinica Universitaria de Navarra; Servicio de Neurología	Pamplona	Navarra
Spain	Hospital Virgen del Puerto. Servicio de Neurología	Plasencia	Caceres
Spain	Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría	Salamaca	Salamanca
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	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Spain	Servicio de Neurología Hospital Viamed Montecanal.	Zaragoza
Sweden	Skånes Universitetssjukhus Malmö, Minneskliniken	Malmö
Sweden	Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry	Mölndal
Sweden	Karolinska Uni Hospital, Huddinge; Dept. of Geriatric Med	Stockholm
Switzerland	Universitäres Zentrum für Altersmedizin und Rehabilitation	Basel
Turkey	Hacettepe University School of Medicine; Neurology	Ankara
Turkey	Osmangazi University School of Medicine,Neurology Department	Eskisehir
Turkey	Istanbul University Istanbul School of Medicine; Neurology	Istanbul
Turkey	Ondokuz Mayis University School of Medicine; Neurology	Samsun
Ukraine	D.F.Chebotarev Institute of Gerontology NAMS;Depart of Age Physiology&Pathology of Nervous System	Kiev
Ukraine	National Medical Academy of Postgraduate Education named after P.L.Shupik; Neurology Department #1	Kiev
Ukraine	Regional mental hospital; Department of psychiatry, psychology and sexology	Lviv	KIEV Governorate
United Kingdom	Royal Preston Hospital	Blackburn
United Kingdom	Surrey and Borders NHS Foundation Trust; Brain Science Research Unit	Chertsey
United Kingdom	Coventry and Warwickshire Partnership NHS Trust	Coventry
United Kingdom	Charing Cross Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Campus for Ageing and Vitality	Newcastle Upon Tyne
United Kingdom	John Radcliffe Hospital	Oxford
United States	Albany Medical Faculty Physicians COmmunity Division. The Neurology Group	Albany	New York
United States	Neurological Associates of Albany, PC	Albany	New York
United States	Dent Neurological Institute	Amherst	New York
United States	Emory University	Atlanta	Georgia
United States	Maine Research Associates	Auburn	Maine
United States	Senior Adults Specialty Research	Austin	Texas
United States	Bradenton Research Center	Bradenton	Florida
United States	Valley Medical Primary Care	Centerville	Ohio
United States	Behavioral Health Research	Charlotte	North Carolina
United States	Kerwin Research Center, LLC	Dallas	Texas
United States	Associated Neurologists PC - Danbury	Danbury	Connecticut
United States	NeuroStudies.net, LLC	Decatur	Georgia
United States	Quantum Laboratories	Deerfield Beach	Florida
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Alexian Brothers Neurosci Inst	Elk Grove Village	Illinois
United States	Pharmacology Research Inst	Encino	California
United States	Precise Research Centers	Flowood	Mississippi
United States	University of North Texas Health Science Center; Fort Worth Patient Care Center	Fort Worth	Texas
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Galiz Research, LLC	Hialeah	Florida
United States	Indiana University	Indianapolis	Indiana
United States	Jacksonville Center For Clinical Research	Jacksonville	Florida
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Alliance for Wellness, dba Alliance for Research	Long Beach	California
United States	Collaborative Neuroscience Network Inc.	Long Beach	California
United States	Pharmacology Research Institute	Los Alamitos	California
United States	UCLA Medical Center, Department of Neurology	Los Angeles	California
United States	USC Keck School Of Medicine	Los Angeles	California
United States	Merritt - Island Medical Research	Merritt Island	Florida
United States	Miami Jewish Health Systems	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Pharmacology Research Inst	Newport Beach	California
United States	Shankle Clinic	Newport Beach	California
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	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Oklahoma Clinical Research	Oklahoma City	Oklahoma
United States	Bioclinica Research	Orlando	Florida
United States	Stanford Univ Medical Center	Palo Alto	California
United States	South Shore Neurologic Associates P.C.	Patchogue	New York
United States	Drexel Univ College of Med; Clinical Research Group	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	MidAmerica Neuroscience Institute	Prairie Village	Kansas
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	UCSF - Memory and Aging Center	San Francisco	California
United States	Neurological Research Inst	Santa Monica	California
United States	MMP Neurology	Scarborough	Maine
United States	North Bay Neuro Science Institute	Sebastopol	California
United States	Insight Clinical Trials LLC	Shaker Heights	Ohio
United States	Southern Illinois University, School of Medicine	Springfield	Illinois
United States	Springfield Neurology Associates	Springfield	Massachusetts
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute	Tampa	Florida
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Compass Research	The Villages	Florida
United States	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	Central States Research	Tulsa	Oklahoma
United States	Abington Neurological Associates	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Costa Rica,  Croatia,  Czechia,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Portugal,  Russian Federation,  Slovenia,  Spain,  Sweden,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) 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 105 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 105
Secondary	Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13)	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 105 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 105
Secondary	Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11)	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 105 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 105
Secondary	Change From Baseline to Week 105 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 105 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 105
Secondary	Change From Baseline to Week 105 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 105 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 105
Secondary	Change From Baseline to Week 105 on Function as Assessed by the 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 105 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 105
Secondary	Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore	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 105 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 105
Secondary	Change From Baseline to Week 105 on a Measure of Dependence Derived 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 105 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 105
Secondary	Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q)	The NPI-Q is an informant-based instrument that 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 and 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. The difference in mean change from Baseline to Week 105 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 105
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 105 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 up to Week 105
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 105 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 up to Week 105
Secondary	EQ-5D Questionnaire Domain Score 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 105 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 up to Week 105
Secondary	EQ-5D Questionnaire Domain Score 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 105 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 up to Week 105
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 37 and 105.	Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13, 37 (Pre-dose), 53, 77 and 105 (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 a Post-dose sample was only collected at Week 13.	Week 1 Day 1; Weeks 13, 25, 53, 77 and 105
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 a Post-dose sample was only collected at Week 13.	Week 1 Day 1; Weeks 13, 25, 53, 77 and 105
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