A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD) (CREAD 2)

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

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).

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Crenezumab

• Study Type: Interventional
• Enrollment (Actual): 806
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Caba, Argentina, C1405BCK
    • Universidad Maimonides
  • Cordoba, Argentina, X500 3DCE
    • DAMIC
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Erina, New South Wales, Australia, 2250
      • Central Coast Neurosciences Research
    • Hornsby, New South Wales, Australia, 2077
      • Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital; Neurology
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • DF
    • Brasilia, DF, Brazil, 70200-730
      • CCBR - Brasilia
  • MG
    • Belo Horizonte, MG, Brazil, 31270-901
      • Hospital das Clinicas - UFMG
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22270-060
      • Centro Psiquiatria Sandra Ruschel Ltda
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 04534-011
      • Clínica Dr. Norton Sayeg LTDA - EPP
• Canada
  • Quebec, Canada, G3K 2P8
    • Alpha Recherche Clinique
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • OCT Research ULC
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1M7
      • True North Clinical Research-Halifax
    • Kentville, Nova Scotia, Canada, B4N 5E3
      • True North Clinical Research Kentville
  • Ontario
    • Kingston, Ontario, Canada, K7L 4X3
      • Providence Care; Mental Health Services
    • London, Ontario, Canada, N6C 5J1
      • Parkwood Hospital; Geriatric Medicine
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M4G 3E8
      • The Centre for Memory and Aging
    • Toronto, Ontario, Canada, M5B 1N9
      • St. Michael's Hospital
    • Woodstock, Ontario, Canada, N4S 5P5
      • Devonshire Clinical Research Inc.
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Clinique Neuro Rive-Sud
• China
  • Beijing, China, 100730
    • Beijing Union Hospital
  • Tianjin (天津), China, 300052
    • Tianjin Medical University General Hospital
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
  • København Ø, Denmark, 2100
    • Rigshospitalet, Hukommelsesklinikken
• Estonia
  • Tallinn, Estonia, 10617
    • Laane-Tallinna Keskhaigla
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin; Cmrr Aquitaine
  • Colmar, France, 68000
    • Hôpital de Jour du Centre pour Personnes Âgées; Louis Pasteur Neurologie
  • Lille, France
    • Hopital Roger Salengro; Service de Neurologie
  • Limoges, France, 87042
    • CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
  • Paris, France, 75013
    • Hôpital Broca
  • Paris, France, 75651
    • CH Pitie Salpetriere; IM2A
  • Reims, France, 51092
    • Hôpital Maison Blanche
  • Rennes, France, 35033
    • CHU Rennes - Hôpital Pontchaillou
  • Rouen, France, 76031
    • CHU de Rouen Hopital; Service de Neurologie
  • St Herblain, France, 44800
    • Hop Guillaume Et Rene Laennec; Cmrr St Herblain
  • Villeurbanne, France, 69100
    • Hôpital des charpennes
• Germany
  • Berlin, Germany, 13125
    • ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
  • Frankfurt, Germany, 60528
    • Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Zentrum für Geriatrie und Gerontologie
  • Homburg/Saar, Germany, 66421
    • Universitätsklinikum des Saarlandes Klinik f. Psychiatrie und Psychotherapie
  • Leipzig, Germany, 04275
    • PANAKEIA - Arzneimittelforschung Leipzig GmbH
  • Mittweida, Germany, 09648
    • Pharmakologisches Studienzentrum
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center; Psychiatry Department
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center; Department of Neurology
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia
    • Roma, Lazio, Italy, 00185
      • Umberto I Policlinico di Roma-Università di Roma La Sapienza
    • Roma, Lazio, Italy, 00186
      • Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
  • Lombardia
    • Brescia, Lombardia, Italy, 25125
      • IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
    • Castellanza, Lombardia, Italy, 21053
      • Irccs Multimedica Santa Maria; Unita' Di Neurologia
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria
    • Milano, Lombardia, Italy, 20148
      • Ospedale S. Maria Nascente; Fondazione Don Gnocchi; Dip. Neurologia Riabilitativa
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale Neurologico Besta; UO Neuropatologia
    • Passirana, Lombardia, Italy, 20017
      • Ospedale Casati Passirana di Rho; Centro Regionale Alzheimer
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • A.O. Universitaria Pisana; Neurologia
• Japan
  • Aichi, Japan, 474-8511
    • National Center for Geriatrics and Gerontology
  • Chiba, Japan, 263-0043
    • Inage Neurology and Memory Clinic
  • Fukuoka, Japan, 813-0017
    • Fukuoka Mirai Hospital
  • Hiroshima, Japan, 739-0696
    • National Hospital Organization Hiroshima-Nishi Medical Center
  • Hyogo, Japan, 671-1227
    • Tsukazaki Hospital
  • Iwate, Japan, 028-3695
    • Iwate Medical University Hospital
  • Kagawa, Japan, 760-8557
    • Kagawa Prefectural Central Hospital
  • Kanagawa, Japan, 252-0392
    • National Hospital Organization Sagamihara National Hospital
  • Kanagawa, Japan, 251-8550
    • Fujisawa City Hospital
  • Kyoto, Japan, 601-1495
    • Ijinkai Takeda General Hospital
  • Kyoto, Japan, 607-8113
    • Rakuwakai Otowarehabilitation Hospital
  • Nagano, Japan, 399-8701
    • National Hospital Organization Matsumoto Medical Center
  • Okayama, Japan, 710-0813
    • Katayama Medical Clinic
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 590-0018
    • Asakayama General Hospital
  • Shizuoka, Japan, 420-8688
    • NHO Shizuoka Institute of Epilepsy and Neurological Disorders
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Tokyo, Japan, 173-0015
    • Tokyo Metropolitan Geriatric Hospital
  • Tokyo, Japan, 158-8531
    • Kanto Central Hospital
  • Tokyo, Japan, 169-0073
    • Shinjuku Research Park Clinic
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-a University hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seongnam-si, Korea, Republic of, 13605
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 04763
    • Hanyang University Seoul Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 07061
    • Borame Medical Center
• Norway
  • Lørenskog, Norway, 1478
    • Akershus universitetssykehus HF; Nevroklinikken S203
  • Oslo, Norway, 0450
    • Oslo universitetssykehus HF Ullevål sykehus; Hukommelsesklinikken
• Peru
  • Lima, Peru, 15001
    • Clinica Internacional; Unidad De Investigacion
  • Lima, Peru, Lima 01
    • Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
• Poland
  • Bydgoszcz, Poland, 85-023
    • NZOZ Dom Sue Ryder
  • Szczecin, Poland, 70-111
    • Centrum Medyczne Euromedis Sp. z o.o.
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Wrocław, Poland, 53-659
    • NZOZ WCA
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Servico de Neurologia
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Neurologia
  • Matosinhos, Portugal, 4464-513
    • Hospital Pedro Hispano; Servico de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
• Russian Federation
  • Kazan, Russian Federation, 420021
    • State Autonomous Healthcare Institution "Republican Clinical Neurological Center
  • Kazan, Russian Federation, 420101
    • State autonomous institution of healthcare Inter-regional clinical and diagnostic center
  • Moscow, Russian Federation, 115522
    • Institution of RAMS (Mental Health Research Center of RAMS)
  • Nizhny Novgorod, Russian Federation, 603155
    • City Clinical Psychiatry Hospital #1
  • St Petersburg, Russian Federation, 190121
    • St Nicolas Psychiatric Hospital; Chair of Psychiatry and Narcology of St. Petersburg Medical Academy
  • Tomsk, Russian Federation, 634009
    • Nebbiolo Center for Clinical Trials
  • Sankt Petersburg
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, 194356
      • LLC Baltic Medicine
  • Sverdlovsk
    • Ekaterinburg, Sverdlovsk, Russian Federation, 620030
      • State Healthcare Institution of Sverdlovsk Region Sverdlovsk Regional Clinical Psychiatric Hospita
• Serbia
  • Belgrade, Serbia, 11000
    • Clinic for Mental disorders Dr Laza Lazarevic
  • Belgrade, Serbia, 11000
    • Neurology clinic, Clinical Center of Serbia
  • Kragujevac, Serbia, 34000
    • Clinic for neurology, Clinical Center Kragujevac
• South Africa
  • Johannesburg, South Africa, 2196
    • Private Practice; the Osteoporosis Clinic
• Spain
  • Albacete, Spain, 2006
    • Hospital Perpetuo Socorro, Servicio de Geriatria
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos. Servicio de Neurología
  • Castellon, Spain, 12004
    • Hospital la Magdalena; Servicio de Neurologia
  • Cordoba, Spain, 14011
    • Hospital Universitario Reina Sofia; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Salamanca, Spain, 37005
    • Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría; CSM La Alamedilla
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche; Servicio de Neurología
  • Barcelona
    • BArcelon, Barcelona, Spain, 08034
      • Fundacio ACE
    • Sant Cugat del Valles, Barcelona, Spain, 8195
      • Hospital General De Catalunya; Servicio de Neurologia
    • Terrassa, Barcelona, Spain, 08222
      • Hospital Mutua De Terrasa; Servicio de Neurologia
  • Caceres
    • Plasencia, Caceres, Spain, 10600
      • Hospital Virgen del Puerto. Servicio de Neurología
  • Cantabria
    • Santander, Cantabria, Spain
      • Hospital Universitario Marques de Valdecilla; Servicio de Neurología
  • Girona
    • Salt, Girona, Spain, 17090
      • Hospital Santa Caterina, Unitat de Valoració de la memoria i les demencies
  • Guipuzcoa
    • Donosti-San Sebastián, Guipuzcoa, Spain, 20014
      • Policlínica Guipuzkoa; Servicio de Neurología
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Neurologia
  • LA Rioja
    • Logroño, LA Rioja, Spain, 26006
      • Hospital San Pedro; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Neurología
  • Vizcaya
    • BaraKaldo, Vizcaya, Spain, 48903
      • CAE Oroitu
• Sweden
  • Malmö, Sweden, 211 46
    • Skånes Universitetssjukhus Malmö, Minneskliniken
  • Mölndal, Sweden, 431 41
    • Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
• Taiwan
  • Changhua County, Taiwan, 500
    • Changhua Christian Hospital; Neurology
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Hospital; Neurology
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University - Shuang Ho Hospital - Neurology
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital; Neurology
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Foundation - Linkou - Neurology
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Neurology
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul School of Medicine; Neurology
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
• United Kingdom
  • Cheltenham, United Kingdom, GL53 9DZ
    • The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre
  • Chertsey, United Kingdom, KT16 0AE
    • Surrey and Borders NHS Foundation Trust; Brain Science Research Unit
  • Crowborough, United Kingdom, TN6 1HB
    • Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
  • Dundee, United Kingdom, DD12 9SY
    • Ninewells Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • NHS Lothian - Western General Hospital; NHS Lothian - Western General Hospital
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital; Clinical Research Facility
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital; Imperial Memory Unit, Level 10 West
  • London, United Kingdom, W1G 9RU
    • RE:Cognition Health
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Southampton, United Kingdom, SO166YD
    • University Southampton NHS Foundation Trust; Wessex Neurologica Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Imaging End Points Clinical Research
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Health Initiatives Research, PLLC
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Inc.
  • California
    • Pasadena, California, United States, 91105
      • Neuro-Therapeutics Inc.
    • Rancho Mirage, California, United States, 92270
      • Desert Valley Medical Group
    • Redlands, California, United States, 92374
      • Anderson Clinical Research, Inc.
    • Sacramento, California, United States, 95817
      • University of California, Davis; Alzheimers Disease Center, Department of Neurology
    • San Francisco, California, United States, 94158
      • UCSF - Memory and Aging Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies, Inc.
    • Stamford, Connecticut, United States, 06905
      • KI Health Partners, LLC; New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Hospital
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research LLC
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research; Center of Southwest Florida
    • Lake Worth, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Lake Charles Clinical Trials, LLC
  • Massachusetts
    • Winchester, Massachusetts, United States, 01890
      • Alzheimers Disease Center; Neurology
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • Health Partners Institute for Education and Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Nebraska
    • Omaha, Nebraska, United States, 68198-8440
      • University of Nebraska Medical Center; Dept of Neurological Sciences
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New Jersey
    • Summit, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of NJ
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical center
    • White Plains, New York, United States, 10605
      • Burke Rehabilitation Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Behavioral Health Research
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati; Department of Psychiatry and Behavioral Neuroscience
    • Columbus, Ohio, United States, 43210
      • Ohio State University; College of Medicine
    • Dayton, Ohio, United States, 45459
      • Dayton Center for Neuro Disorders
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Plains, Pennsylvania, United States, 18705
      • Northeastern Pennsylvania Memory
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Beaumont, Texas, United States, 77702
      • Gadolin Research, LLC
    • Dallas, Texas, United States, 75231
      • Kerwin Research Center, LLC
    • Dallas, Texas, United States, 75214
      • Texas Neurology PA
    • Houston, Texas, United States, 77030
      • Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Medical Group
    • Richmond, Virginia, United States, 23294
      • National Clinical Research Inc.-Richmond

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.	Drug: Placebo; Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
EXPERIMENTAL: Crenezumab; Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.	Drug: Crenezumab; Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Ostrowitzki S, Bittner T, Sink KM, Mackey H, Rabe C, Honig LS, Cassetta E, Woodward M, Boada M, van Dyck CH, Grimmer T, Selkoe DJ, Schneider A, Blondeau K, Hu N, Quartino A, Clayton D, Dolton M, Dang Y, Ostaszewski B, Sanabria-Bohorquez SM, Rabbia M, Toth B, Eichenlaub U, Smith J, Honigberg LA, Doody RS. Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials. JAMA Neurol. 2022 Nov 1;79(11):1113-1121. doi: 10.1001/jamaneurol.2022.2909.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2017
• Primary Completion (ACTUAL): June 11, 2019
• Study Completion (ACTUAL): June 11, 2019

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (ACTUAL): April 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 16, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: June 1, 2020

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: BN29553; 2016-003288-20 (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