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

• ClinicalTrials.gov Identifier: NCT02670083
• Recruitment Status: Terminated
• First Posted: February 1, 2016
• Results First Posted: July 16, 2020
• Last Update Posted: July 16, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Crenezumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 813 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: March 22, 2016
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score [ Time Frame: Baseline, Week 105 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13) [ Time Frame: Baseline, Week 105 ]
   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.
2. Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11) [ Time Frame: Baseline, Week 105 ]
   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.
3. Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) [ Time Frame: Baseline, Week 105 ]
   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.
4. Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) [ Time Frame: Baseline, Week 105 ]
   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.
5. Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score [ Time Frame: Baseline, Week 105 ]
   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.
6. Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore [ Time Frame: Baseline, Week 105 ]
   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.
7. Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score [ Time Frame: Baseline, Week 105 ]
   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.
8. Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q) [ Time Frame: Baseline, Week 105 ]
   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.
9. Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [ Time Frame: Baseline up to Week 105 ]
   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.
10. Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [ Time Frame: Baseline up to Week 105 ]
    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.
11. EQ-5D Questionnaire Domain Score for Participants [ Time Frame: Baseline up to Week 105 ]
    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.
12. EQ-5D Questionnaire Domain Score for Caregivers [ Time Frame: Baseline up to Week 105 ]
    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.
13. Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks). ]
    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.
14. Percentage of Participants With Anti-Crenezumab Antibodies [ Time Frame: Baseline up to Week 105 ]
    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.
15. Serum Concentration of Crenezumab [ Time Frame: 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) ]
    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.
16. Plasma Amyloid Beta (Abeta) 40 Concentrations [ Time Frame: Week 1 Day 1; Weeks 13, 25, 53, 77 and 105 ]
    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.
17. Plasma Amyloid Beta (Abeta) 42 Concentrations [ Time Frame: Week 1 Day 1; Weeks 13, 25, 53, 77 and 105 ]
    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.
18. Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
    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.
19. Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
    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.
20. Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
    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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Banner Alzheimer's Institute

Phoenix, Arizona, United States, 85006

United States, California

Pharmacology Research Inst

Encino, California, United States, 91316

Collaborative Neuroscience Network Inc.

Long Beach, California, United States, 90502

Alliance for Wellness, dba Alliance for Research

Long Beach, California, United States, 90807

Pharmacology Research Institute

Los Alamitos, California, United States, 90720

USC Keck School Of Medicine

Los Angeles, California, United States, 90033

UCLA Medical Center, Department of Neurology

Los Angeles, California, United States, 90095

Pharmacology Research Inst

Newport Beach, California, United States, 92660

Shankle Clinic

Newport Beach, California, United States, 92663

Stanford Univ Medical Center

Palo Alto, California, United States, 94304

Anderson Clinical Research, Inc.

Redlands, California, United States, 92374

University of California, Davis; Alzheimers Disease Center, Department of Neurology

Sacramento, California, United States, 95817

UCSF - Memory and Aging Center

San Francisco, California, United States, 94158

Neurological Research Inst

Santa Monica, California, United States, 90404

North Bay Neuro Science Institute

Sebastopol, California, United States, 95472

United States, Connecticut

Associated Neurologists PC - Danbury

Danbury, Connecticut, United States, 06810

Institute for Neurodegenerative Disorders

New Haven, Connecticut, United States, 06510

Yale University School Of Medicine

New Haven, Connecticut, United States, 06510

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, United States, 06851

United States, Florida

Bradenton Research Center

Bradenton, Florida, United States, 34205

Quantum Laboratories

Deerfield Beach, Florida, United States, 33064

Brain Matters Research, Inc.

Delray Beach, Florida, United States, 33445

Galiz Research, LLC

Hialeah, Florida, United States, 33016

Jacksonville Center For Clinical Research

Jacksonville, Florida, United States, 32216

Alzheimer's Research and Treatment Center

Lake Worth, Florida, United States, 33414

Merritt - Island Medical Research

Merritt Island, Florida, United States, 32952

Miami Jewish Health Systems

Miami, Florida, United States, 33137

Renstar Medical Research

Ocala, Florida, United States, 34470

Bioclinica Research

Orlando, Florida, United States, 32806

Progressive Medical Research

Port Orange, Florida, United States, 32127

Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute

Tampa, Florida, United States, 33613

Stedman Clinical Trials, LLC

Tampa, Florida, United States, 33613

Compass Research

The Villages, Florida, United States, 32162

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30329

NeuroStudies.net, LLC

Decatur, Georgia, United States, 30033

United States, Illinois

Alexian Brothers Neurosci Inst

Elk Grove Village, Illinois, United States, 60007

Southern Illinois University, School of Medicine

Springfield, Illinois, United States, 62702

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Kansas

MidAmerica Neuroscience Institute

Prairie Village, Kansas, United States, 66206

United States, Maine

Maine Research Associates

Auburn, Maine, United States, 04210

MMP Neurology

Scarborough, Maine, United States, 04074

United States, Massachusetts

Springfield Neurology Associates

Springfield, Massachusetts, United States, 01104

United States, Mississippi

Precise Research Centers

Flowood, Mississippi, United States, 39232

United States, New Jersey

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, United States, 07081

Advanced Memory Research Institute of NJ

Toms River, New Jersey, United States, 08755

United States, New York

Albany Medical Faculty Physicians COmmunity Division. The Neurology Group

Albany, New York, United States, 12206

Neurological Associates of Albany, PC

Albany, New York, United States, 12208

Dent Neurological Institute

Amherst, New York, United States, 14226

Columbia University Medical Center

New York, New York, United States, 10032

South Shore Neurologic Associates P.C.

Patchogue, New York, United States, 11772

United States, North Carolina

Behavioral Health Research

Charlotte, North Carolina, United States, 28211

Guilford Neurologic Associates

Greensboro, North Carolina, United States, 27401

United States, Ohio

Valley Medical Primary Care

Centerville, Ohio, United States, 45459

Insight Clinical Trials LLC

Shaker Heights, Ohio, United States, 44122

United States, Oklahoma

Oklahoma Clinical Research

Oklahoma City, Oklahoma, United States, 73112

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States, 73116

Central States Research

Tulsa, Oklahoma, United States, 74136

United States, Oregon

Summit Research Network Inc.

Portland, Oregon, United States, 97210

United States, Pennsylvania

Drexel Univ College of Med; Clinical Research Group

Philadelphia, Pennsylvania, United States, 19102

Abington Neurological Associates

Willow Grove, Pennsylvania, United States, 19090

United States, Texas

Senior Adults Specialty Research

Austin, Texas, United States, 78757

Kerwin Research Center, LLC

Dallas, Texas, United States, 75231

University of North Texas Health Science Center; Fort Worth Patient Care Center

Fort Worth, Texas, United States, 76107

United States, Virginia

Sentara Medical Group

Norfolk, Virginia, United States, 23507

National Clinical Research Inc.-Richmond

Richmond, Virginia, United States, 23294

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Australia, South Australia

The Queen Elizabeth Hospital; Neurology

Woodville, South Australia, Australia, 5011

Australia, Victoria

Caulfield Hospital; Aged Psychiatry Research Unit

Caulfield, Victoria, Australia, 3162

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, Australia, 3081

Australia, Western Australia

Neurodegenerative Disorders Research; Neurology

West Perth, Western Australia, Australia, 6005

Austria

Konventhospital Barmherzige Brüder; Neurologie I

Linz, Austria, 4021

Belgium

UZ Gent

Gent, Belgium, 9000

Bulgaria

ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine

Sofia, Bulgaria, 1407

Alexandrovska hospital; Neurology Department

Sofia, Bulgaria, 1431

Canada, British Columbia

Vancouver Hospital - UBC Hospital Site

Vancouver, British Columbia, Canada, V6Z 1Y6

Vancouver Island Health Authority

Victoria, British Columbia, Canada, V8R 1J8

Canada, Ontario

Parkwood Hospital; Geriatric Medicine

London, Ontario, Canada, N6C 5J1

Bruyere Continuing Care

Ottawa, Ontario, Canada, K1N 5C8

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, Canada, K9H 2P4

The Centre for Memory and Aging

Toronto, Ontario, Canada, M4G 3E8

Toronto Western Hospital

Toronto, Ontario, Canada, M5T 2S8

Devonshire Clinical Research Inc.

Woodstock, Ontario, Canada, N4S 5P5

Canada, Quebec

CHA Hopital de I enfant-Jesus

Quebec City, Quebec, Canada, G1J 1Z4

Costa Rica

ICIMED Instituto de Investigación en Ciencias Médicas

San Jose, Costa Rica, 10108

Hospital Clínica Biblica

San José, Costa Rica, 10101

Croatia

Clinical Hospital Centre Zagreb;Clinic for Neurology

Zagreb, Croatia, 10000

Czechia

Charles University, Medical faculty, Hradec Kralove ;Department of Neurology

Hradec Králové, Czechia, 500 05

General Teaching Hospital, Departmetn of Neurology

Praha, Czechia, 110 00

Denmark

Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken

Aarhus N, Denmark, 8200

Rigshospitalet, Hukommelsesklinikken

København Ø, Denmark, 2100

Finland

Terveystalo Tampere

Tampere, Finland, 33100

CRST Oy

Turku, Finland, 20520

France

Hopital Avicenne; Neurologie

Bobigny, France, 93009

Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie

Bron, France, 69677

Hopital Gui de Chauliac; Neurologie

Montpellier, France, 34295

Hopital Lariboisiere

Paris, France, 75475

CHU Poitiers - Hopital La Miletrie

Poitiers, France, 86000

Hopital Hautepierre; Centre dInvestigation Clinique

Strasbourg, France, 67098

CHU Toulouse - La Grave

Toulouse, France, 31059

Germany

Neurologische Praxis Dr. Andrej Pauls

München, Germany, 80331

Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie

München, Germany, 81675

Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie

Münster, Germany, 48149

Steinwachs Klaus; Arztpraxis fur Neurologie u. Psychiatrie

Nürnberg, Germany, 90402

Universitätsklinikum Rostock Zentrum für Nervenheilkunde

Rostock, Germany, 18147

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, Germany, 89081

Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz

Westerstede, Germany, 26655

Forschungszentrum Ruhr

Witten, Germany, 58455

Hong Kong

Prince of Wales Hospital; Dept. of Medicine & Therapeutics

Hong Kong, Hong Kong

Queen Mary Hospital, Division of Geriatric Medicine

Hong Kong, Hong Kong

Hungary

Semmelweis University; Department of Neurology

Budapest, Hungary, 1083

Szabolcs-Szatmár-Bereg Megyei Kórházak - Jósa András Oktatókórház; Pszichiátria

Nyíregyháza, Hungary, 4400

University of Szeged; Department of Psychiatry

Szeged, Hungary, 6725

Szent Borbala Korhaz; Neurologiai es Stroke Osztaly

Tatabánya, Hungary, 2800

Jávorszky Ödön Kórház, Neurológia és stroke osztály

VAC, Hungary, 2600

Italy

Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica

Roma, Lazio, Italy, 00179

Ospedale San Giovanni Calibita Fatebenefratell;Neurologia

Roma, Lazio, Italy, 00186

Ente Ospedaliero Ospedali Galliera; Ambulatorio di Neurologia

Genova, Liguria, Italy, 16128

Casa di Cura Policlinico; Dipartimento di Scienze Neuroriabilitative

Milano, Lombardia, Italy, 20144

Ospedale S. Maria Nascente; Fondazione Don Gnocchi; Dip. Neurologia Riabilitativa

Milano, Lombardia, Italy, 20148

Ospedale Casati Passirana di Rho; Centro Regionale Alzheimer

Passirana, Lombardia, Italy, 20017

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; S.C. Geriatria

Perugia, Umbria, Italy, 06129

Japan

Miyoshi Clinic of Neurology, Hananosato

Hiroshima, Japan, 728-0013

National Hospital Organization Hiroshima-Nishi Medical Center

Hiroshima, Japan, 739-0696

Rakuwakai Otowarehabilitation Hospital

Kyoto, Japan, 607-8113

Mie University Hospital

Mie, Japan, 514-8507

National Hospital Organization Matsumoto Medical Center

Nagano, Japan, 399-8701

Saigata Medical Center

Niigata, Japan, 949-3193

Katayama Medical Clinic

Okayama, Japan, 710-0813

Tokyo Medical University Hospital

Tokyo, Japan, 160-0023

Tokyo Metropolitan Geriatric Hospital

Tokyo, Japan, 173-0015

National Center of Neurology and Psychiatry

Tokyo, Japan, 187-8551

Korea, Republic of

Chonnam National University Hospital

Gwangju, Korea, Republic of, 61469

Inha University Hospital

Incheon, Korea, Republic of, 22332

Konkuk University Medical Center

Seoul, Korea, Republic of, 05030

Asan Medical Center

Seoul, Korea, Republic of, 05505

KyungHee Medical Center

Seoul, Korea, Republic of, 130-702

Ewha Womans University Mokdong Hospital; Dept of Neurology

Seoul, Korea, Republic of, 158-710

Lithuania

Vilnius University Hospital Santariskiu Clinic

Vilnius, Lithuania, 08661

Mexico

Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC

Culiacan, Mexico, 80020

Hospital Uni; Dr. Jose E. Gonzalez

Monterrey, Mexico, 64460

AVIX Investigación Clínica S.C

Monterrey, Mexico, 64710

Hospital Universitario de Saltillo

Saltillo, Mexico, 25000

Poland

Podlaskie Centrum Psychogeriatrii

Białystok, Poland, 15-756

NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

Poznań, Poland, 61-853

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Siemianowice Śląskie, Poland, 41-100

Przychodnia Specjalistyczna PROSEN

Warszawa, Poland, 01-231

Centrum Medyczne NeuroProtect

Warszawa, Poland, 01-684

Optimum

Warszawa, Poland, 01-785

Portugal

Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia

Amadora, Portugal, 2720-276

Hospital Beatriz Angelo; Servico de Neurologia

Loures, Portugal, 2674-514

Russian Federation

State Autonomous Healthcare Institution "Republican Clinical Neurological Center

Kazan, Russian Federation, 420021

State autonomous institution of healthcare Inter-regional clinical and diagnostic center

Kazan, Russian Federation, 420101

Institution of RAMS (Mental Health Research Center of RAMS)

Moscow, Russian Federation, 115522

SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF

Moscow, Russian Federation, 119021

City Clinical Hospital # 2 n.a. V.I. Razumovsky

Saratov, Russian Federation, 410028

SHI City Psychoneurological Dispensary #7

St Petersburg, Russian Federation, 190005

Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department

St. Petersburg, Russian Federation, 194044

Slovenia

University Medical Centre Maribor

Maribor, Slovenia, 2000

Spain

Fundació ACE

BArcelon, Barcelona, Spain, 08034

Hospital Universitari de Bellvitge; Servicio de Neurologia

L'Hospitalet de Llobregat, Barcelona, Spain, 08907

Hospital Sant Joan de Deu; Servicio de Neurología

Manresa, Barcelona, Spain

Hospital General De Catalunya; Servicio de Neurologia

Sant Cugat del Valles, Barcelona, Spain, 8195

Hospital Mutua De Terrasa; Servicio de Neurologia

Terrassa, Barcelona, Spain, 08222

Hospital Virgen del Puerto. Servicio de Neurología

Plasencia, Caceres, Spain, 10600

Hospital Universitario Marques de Valdecilla; Servicio de Neurología

Santander, Cantabria, Spain

Clinica Universitaria de Navarra; Servicio de Neurología

Pamplona, Navarra, Spain, 31008

Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría

Salamaca, Salamanca, Spain, 37007

Hospital General Universitario de Albacete; Servicio de Neurología

Albacete, Spain

Hospital Vall d'Hebron; Servicio de Neurología

Barcelona, Spain, 08035

Hospital Universitario de Burgos. Servicio de Neurología

Burgos, Spain, 09006

Clinica Ruber, 4 planta; Servicio de Neurologia

Madrid, Spain, 28006

Universitario de La Princesa; Servicio de Neurología

Madrid, Spain, 28006

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, Spain, 28041

Hospital Regional Universitario Carlos Haya; Servicio de Neurologia

Malaga, Spain, 29010

Hospital Universitario Virgen de Arrixaca; Servicio de Neurología

Murcia, Spain

Hospital Universitario la Fe; Servicio de Neurologia

Valencia, Spain, 46026

Servicio de Neurología Hospital Viamed Montecanal.

Zaragoza, Spain, 50012

Sweden

Skånes Universitetssjukhus Malmö, Minneskliniken

Malmö, Sweden, 211 46

Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry

Mölndal, Sweden, 431 41

Karolinska Uni Hospital, Huddinge; Dept. of Geriatric Med

Stockholm, Sweden, 14186

Switzerland

Universitäres Zentrum für Altersmedizin und Rehabilitation

Basel, Switzerland, 4002

Turkey

Hacettepe University School of Medicine; Neurology

Ankara, Turkey, 06100

Osmangazi University School of Medicine,Neurology Department

Eskişehir, Turkey, 26480

Istanbul University Istanbul School of Medicine; Neurology

Istanbul, Turkey, 34093

Ondokuz Mayis University School of Medicine; Neurology

Samsun, Turkey, 55139

Ukraine

Regional mental hospital; Department of psychiatry, psychology and sexology

Lviv, KIEV Governorate, Ukraine, 79021

National Medical Academy of Postgraduate Education named after P.L.Shupik; Neurology Department #1

Kiev, Ukraine, 04112

D.F.Chebotarev Institute of Gerontology NAMS;Depart of Age Physiology&Pathology of Nervous System

Kiev, Ukraine, 04114

United Kingdom

Royal Preston Hospital

Blackburn, United Kingdom, PR2 9HT

Surrey and Borders NHS Foundation Trust; Brain Science Research Unit

Chertsey, United Kingdom, KT16 0AE

Coventry and Warwickshire Partnership NHS Trust

Coventry, United Kingdom, CV6 6NY

St George's Hospital

London, United Kingdom, SW17 0QT

Charing Cross Hospital

London, United Kingdom, W6 8RF

Manchester Royal Infirmary

Manchester, United Kingdom, M13 9WL

Campus for Ageing and Vitality

Newcastle Upon Tyne, United Kingdom, NE4 6BE

John Radcliffe Hospital

Oxford, United Kingdom, OX3 9DU

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol and Statistical Analysis Plan  [PDF] March 10, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02670083
• Other Study ID Numbers: BN29552; 2015-003034-27 ( EudraCT Number )
• First Posted: February 1, 2016
• Results First Posted: July 16, 2020
• Last Update Posted: July 16, 2020
• Last Verified: June 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders