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

• ClinicalTrials.gov Identifier: NCT03114657
• Recruitment Status: Terminated
• First Posted: April 14, 2017
• 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 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).

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 806 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 29, 2017
• Actual Primary Completion Date: June 11, 2019
• Actual Study Completion Date: June 11, 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 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score [ Time Frame: Baseline, Week 77 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score [ Time Frame: Baseline, Week 77 ]
   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.
2. Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score [ Time Frame: Baseline, Week 77 ]
   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.
3. Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) [ Time Frame: Baseline, Week 77 ]
   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.
4. Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) [ Time Frame: Baseline, Week 77 ]
   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.
5. Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score [ Time Frame: Baseline, Week 77 ]
   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.
6. Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score [ Time Frame: Baseline, Week 77 ]
   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.
7. Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score [ Time Frame: Baseline, Week 77 ]
   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.
8. Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score [ Time Frame: Baseline, Week 77 ]
   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.
9. Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score [ Time Frame: Baseline, Week 53 ]
   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.
10. Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [ Time Frame: Baseline, Week 77 ]
    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.
11. Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [ Time Frame: Baseline, Week 53 ]
    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.
12. European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants [ Time Frame: Baseline, Week 77 ]
    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.
13. European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers [ Time Frame: Baseline, Week 77 ]
    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.
14. 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.
15. 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.
16. 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 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (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 5, 13, 37, 53 and 77.
17. Plasma Amyloid Beta (Abeta) 40 Concentrations [ Time Frame: Week 1 Day 1; Weeks 53 ]
    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.
18. Plasma Amyloid Beta (Abeta) 42 Concentrations [ Time Frame: Week 1 Day 1; Weeks 53 ]
    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.
19. 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.
20. 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.
21. 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

Imaging End Points Clinical Research

Scottsdale, Arizona, United States, 85258

United States, Arkansas

Health Initiatives Research, PLLC

Fayetteville, Arkansas, United States, 72703

Clinical Trials Inc.

Little Rock, Arkansas, United States, 72205

United States, California

Neuro-Therapeutics Inc.

Pasadena, California, United States, 91105

Desert Valley Medical Group

Rancho Mirage, California, United States, 92270

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

United States, Colorado

MCB Clinical Research Centers

Colorado Springs, Colorado, United States, 80910

United States, Connecticut

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, United States, 06851

KI Health Partners, LLC; New England Institute for Clinical Research

Stamford, Connecticut, United States, 06905

United States, District of Columbia

Georgetown University Hospital

Washington, District of Columbia, United States, 20057

United States, Florida

JEM Research LLC

Atlantis, Florida, United States, 33462

Bradenton Research Center

Bradenton, Florida, United States, 34205

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, United States, 33912

Alzheimer's Research and Treatment Center

Lake Worth, Florida, United States, 33414

Renstar Medical Research

Ocala, Florida, United States, 34470

Bioclinica Research

Orlando, Florida, United States, 32806

Progressive Medical Research

Port Orange, Florida, United States, 32127

United States, Georgia

Columbus Memory Center

Columbus, Georgia, United States, 31909

United States, Louisiana

Lake Charles Clinical Trials, LLC

Lake Charles, Louisiana, United States, 70601

United States, Massachusetts

Alzheimers Disease Center; Neurology

Winchester, Massachusetts, United States, 01890

United States, Minnesota

Health Partners Institute for Education and Research

Saint Paul, Minnesota, United States, 55130

United States, Mississippi

Precise Research Centers

Flowood, Mississippi, United States, 39232

United States, Nebraska

University of Nebraska Medical Center; Dept of Neurological Sciences

Omaha, Nebraska, United States, 68198-8440

United States, Nevada

Cleveland Clinic Lou Ruvo; Center for Brain Research

Las Vegas, Nevada, United States, 89106

United States, New Jersey

The Cognitive and Research Center of New Jersey

Summit, New Jersey, United States, 07081

Advanced Memory Research Institute of NJ

Toms River, New Jersey, United States, 08755

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Burke Rehabilitation Hospital

White Plains, New York, United States, 10605

United States, North Carolina

Behavioral Health Research

Charlotte, North Carolina, United States, 28211

Wake Research Associates

Raleigh, North Carolina, United States, 27612

United States, Ohio

University of Cincinnati; Department of Psychiatry and Behavioral Neuroscience

Cincinnati, Ohio, United States, 45219

Ohio State University; College of Medicine

Columbus, Ohio, United States, 43210

Dayton Center for Neuro Disorders

Dayton, Ohio, United States, 45459

United States, Oregon

Summit Research Network Inc.

Portland, Oregon, United States, 97210

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Northeastern Pennsylvania Memory

Plains, Pennsylvania, United States, 18705

Abington Neurological Associates

Willow Grove, Pennsylvania, United States, 19090

United States, Tennessee

Neurology Clinic PC

Cordova, Tennessee, United States, 38018

United States, Texas

Senior Adults Specialty Research

Austin, Texas, United States, 78757

Gadolin Research, LLC

Beaumont, Texas, United States, 77702

Texas Neurology PA

Dallas, Texas, United States, 75214

Kerwin Research Center, LLC

Dallas, Texas, United States, 75231

Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine

Houston, Texas, United States, 77030

Clinical Trials of Texas, Inc

San Antonio, Texas, United States, 78229

United States, Virginia

Sentara Medical Group

Norfolk, Virginia, United States, 23507

National Clinical Research Inc.-Richmond

Richmond, Virginia, United States, 23294

Argentina

Hospital Italiano

Buenos Aires, Argentina, C1181ACH

Universidad Maimonides

Caba, Argentina, C1405BCK

DAMIC

Cordoba, Argentina, X500 3DCE

Australia, New South Wales

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia, 2010

Central Coast Neurosciences Research

Erina, New South Wales, Australia, 2250

Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care

Hornsby, New South Wales, Australia, 2077

Australia, South Australia

The Queen Elizabeth Hospital; Neurology

Woodville, South Australia, Australia, 5011

Belgium

AZ Sint Jan

Brugge, Belgium, 8000

AZ Groeninge

Kortrijk, Belgium, 8500

UZ Leuven Gasthuisberg

Leuven, Belgium, 3000

Brazil

CCBR - Brasilia

Brasilia, DF, Brazil, 70200-730

Hospital das Clinicas - UFMG

Belo Horizonte, MG, Brazil, 31270-901

Instituto de Neurologia de Curitiba

Curitiba, PR, Brazil, 81210-310

Centro Psiquiatria Sandra Ruschel Ltda

Rio de Janeiro, RJ, Brazil, 22270-060

Hospital das Clinicas - UFRGS

Porto Alegre, RS, Brazil

Clínica Dr. Norton Sayeg LTDA - EPP

Sao Paulo, SP, Brazil, 04534-011

Canada, British Columbia

OCT Research ULC

Kelowna, British Columbia, Canada, V1Y 1Z9

Vancouver Island Health Authority

Victoria, British Columbia, Canada, V8R 1J8

Canada, Nova Scotia

True North Clinical Research-Halifax

Halifax, Nova Scotia, Canada, B3S 1M7

True North Clinical Research Kentville

Kentville, Nova Scotia, Canada, B4N 5E3

Canada, Ontario

Providence Care; Mental Health Services

Kingston, Ontario, Canada, K7L 4X3

Parkwood Hospital; Geriatric Medicine

London, Ontario, Canada, N6C 5J1

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, Canada, K9H 2P4

The Centre for Memory and Aging

Toronto, Ontario, Canada, M4G 3E8

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1N9

Devonshire Clinical Research Inc.

Woodstock, Ontario, Canada, N4S 5P5

Canada, Quebec

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, Canada, J4V 2J2

Canada

ALPHA Recherche Clinique

Quebec, Canada, G3K 2P8

China

Beijing Union Hospital

Beijing, China, 100730

Tianjin Medical University General Hospital

Tianjin (天津), China, 300052

Denmark

Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken

Aarhus N, Denmark, 8200

Rigshospitalet, Hukommelsesklinikken

København Ø, Denmark, 2100

Estonia

Laane-Tallinna Keskhaigla

Tallinn, Estonia, 10617

France

Hopital Pellegrin; Cmrr Aquitaine

Bordeaux, France, 33076

Hôpital de Jour du Centre pour Personnes Âgées; Louis Pasteur Neurologie

Colmar, France, 68000

Hopital Roger Salengro; Service de Neurologie

Lille, France

CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique

Limoges, France, 87042

Hopital Broca

Paris, France, 75013

CH Pitie Salpetriere; IM2A

Paris, France, 75651

Hôpital Maison Blanche

Reims, France, 51092

CHU Rennes - Hopital Pontchaillou

Rennes, France, 35033

CHU de Rouen Hopital; Service de Neurologie

Rouen, France, 76031

Hop Guillaume Et Rene Laennec; Cmrr St Herblain

St Herblain, France, 44800

Hopital des Charpennes

Villeurbanne, France, 69100

Germany

ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic

Berlin, Germany, 13125

Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik

Frankfurt, Germany, 60528

Universitätsklinikum Freiburg, Zentrum für Geriatrie und Gerontologie

Freiburg, Germany, 79106

Universitätsklinikum des Saarlandes Klinik f. Psychiatrie und Psychotherapie

Homburg/Saar, Germany, 66421

PANAKEIA - Arzneimittelforschung Leipzig GmbH

Leipzig, Germany, 04275

Pharmakologisches Studienzentrum

Mittweida, Germany, 09648

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

München, Germany, 81675

Israel

Rambam Medical Center

Haifa, Israel, 3109601

Sheba Medical Center; Psychiatry Department

Ramat Gan, Israel, 5262100

Tel Aviv Sourasky Medical Center; Department of Neurology

Tel Aviv, Israel, 6423906

Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia

Roma, Lazio, Italy, 00133

Umberto I Policlinico di Roma-Università di Roma La Sapienza

Roma, Lazio, Italy, 00185

Ospedale San Giovanni Calibita Fatebenefratell;Neurologia

Roma, Lazio, Italy, 00186

IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer

Brescia, Lombardia, Italy, 25125

Irccs Multimedica Santa Maria; Unita' Di Neurologia

Castellanza, Lombardia, Italy, 21053

IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria

Milano, Lombardia, Italy, 20132

Fondazione IRCCS Istituto Nazionale Neurologico Besta; UO Neuropatologia

Milano, Lombardia, Italy, 20133

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

IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA

Pozzilli, Molise, Italy, 86077

AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria

Torino, Piemonte, Italy, 10126

A.O. Universitaria Pisana; Neurologia

Pisa, Toscana, Italy, 56126

Japan

National Center for Geriatrics and Gerontology

Aichi, Japan, 474-8511

Inage Neurology and Memory Clinic

Chiba, Japan, 263-0043

Fukuoka Mirai Hospital

Fukuoka, Japan, 813-0017

National Hospital Organization Hiroshima-Nishi Medical Center

Hiroshima, Japan, 739-0696

Tsukazaki Hospital

Hyogo, Japan, 671-1227

Iwate Medical University Hospital

Iwate, Japan, 028-3695

Kagawa Prefectural Central Hospital

Kagawa, Japan, 760-8557

Fujisawa City Hospital

Kanagawa, Japan, 251-8550

National Hospital Organization Sagamihara National Hospital

Kanagawa, Japan, 252-0392

Ijinkai Takeda General Hospital

Kyoto, Japan, 601-1495

Rakuwakai Otowarehabilitation Hospital

Kyoto, Japan, 607-8113

National Hospital Organization Matsumoto Medical Center

Nagano, Japan, 399-8701

Katayama Medical Clinic

Okayama, Japan, 710-0813

Osaka University Hospital

Osaka, Japan, 565-0871

Asakayama General Hospital

Osaka, Japan, 590-0018

NHO Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Japan, 420-8688

Kanto Central Hospital

Tokyo, Japan, 158-8531

Tokyo Medical University Hospital

Tokyo, Japan, 160-0023

Shinjuku Research Park Clinic

Tokyo, Japan, 169-0073

Tokyo Metropolitan Geriatric Hospital

Tokyo, Japan, 173-0015

National Center of Neurology and Psychiatry

Tokyo, Japan, 187-8551

Tokyo Medical University Hachioji Medical Center

Tokyo, Japan, 193-0998

Korea, Republic of

Dong-A University Hospital

Busan, Korea, Republic of, 49201

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 21565

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 13605

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Hanyang University Seoul Hospital

Seoul, Korea, Republic of, 04763

Konkuk University Medical Center

Seoul, Korea, Republic of, 05030

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Seoul St Mary's Hospital

Seoul, Korea, Republic of, 06591

Borame Medical Center

Seoul, Korea, Republic of, 07061

Norway

Akershus universitetssykehus HF; Nevroklinikken S203

Lørenskog, Norway, 1478

Oslo universitetssykehus HF Ullevål sykehus; Hukommelsesklinikken

Oslo, Norway, 0450

Peru

Clinica Internacional; Unidad De Investigacion

Lima, Peru, 15001

Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia

Lima, Peru, Lima 01

Poland

NZOZ Dom Sue Ryder

Bydgoszcz, Poland, 85-023

Centrum Medyczne Euromedis Sp. z o.o.

Szczecin, Poland, 70-111

Centrum Medyczne NeuroProtect

Warszawa, Poland, 01-684

NZOZ WCA

Wrocław, Poland, 53-659

Portugal

Hospital de Braga; Servico de Neurologia

Braga, Portugal, 4710-243

HUC; Servico de Neurologia

Coimbra, Portugal, 3000-075

Hospital Pedro Hispano; Servico de Neurologia

Matosinhos, Portugal, 4464-513

Hospital Geral de Santo Antonio; Servico de Neurologia

Porto, Portugal, 4099-001

Russian Federation

LLC Baltic Medicine

Saint-Petersburg, Sankt Petersburg, Russian Federation, 194356

State Healthcare Institution of Sverdlovsk Region Sverdlovsk Regional Clinical Psychiatric Hospita

Ekaterinburg, Sverdlovsk, Russian Federation, 620030

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

City Clinical Psychiatry Hospital #1

Nizhny Novgorod, Russian Federation, 603155

St Nicolas Psychiatric Hospital; Chair of Psychiatry and Narcology of St. Petersburg Medical Academy

St Petersburg, Russian Federation, 190121

Nebbiolo Center for Clinical Trials

Tomsk, Russian Federation, 634009

Serbia

Clinic for Mental disorders Dr Laza Lazarevic

Belgrade, Serbia, 11000

Neurology clinic, Clinical Center of Serbia

Belgrade, Serbia, 11000

Clinic for neurology, Clinical Center Kragujevac

Kragujevac, Serbia, 34000

South Africa

Private Practice; the Osteoporosis Clinic

Johannesburg, South Africa, 2196

Spain

Hospital General Universitario de Elche; Servicio de Neurología

Elche, Alicante, Spain, 03203

Fundació ACE

BArcelon, Barcelona, Spain, 08034

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

Hospital Santa Caterina, Unitat de Valoració de la memoria i les demencies

Salt, Girona, Spain, 17090

Policlínica Guipuzkoa; Servicio de Neurología

Donosti-San Sebastián, Guipuzcoa, Spain, 20014

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Neurologia

Santiago de Compostela, LA Coruña, Spain, 15706

Hospital San Pedro; Servicio de Neurología

Logroño, LA Rioja, Spain, 26006

Hospital Quiron de Madrid; Servicio de Neurologia

Pozuelo de Alarcon, Madrid, Spain, 28223

Clinica Universitaria de Navarra; Servicio de Neurología

Pamplona, Navarra, Spain, 31008

CAE Oroitu

BaraKaldo, Vizcaya, Spain, 48903

Hospital Perpetuo Socorro, Servicio de Geriatria

Albacete, Spain, 2006

Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia

Barcelona, Spain, 08025

Hospital Universitario de Burgos. Servicio de Neurología

Burgos, Spain, 09006

Hospital la Magdalena; Servicio de Neurologia

Castellon, Spain, 12004

Hospital Universitario Reina Sofia; Servicio de Neurologia

Cordoba, Spain, 14011

Hospital Ramon y Cajal; Servicio de Neurologia

Madrid, Spain, 28034

Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría; CSM La Alamedilla

Salamanca, Spain, 37005

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Sevilla, Spain, 41009

Sweden

Skånes Universitetssjukhus Malmö, Minneskliniken

Malmö, Sweden, 211 46

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

Mölndal, Sweden, 431 41

Taiwan

Changhua Christian Hospital; Neurology

Changhua County, Taiwan, 500

Kaohsiung Medical University Hospital; Neurology

Kaohsiung, Taiwan, 807

Taipei Medical University - Shuang Ho Hospital - Neurology

New Taipei City, Taiwan, 23561

National Taiwan University Hospital; Neurology

Taipei, Taiwan, 100

Chang Gung Memorial Foundation - Linkou - Neurology

Taoyuan, Taiwan, 333

Turkey

Hacettepe University Medical Faculty; Neurology

Ankara, Turkey, 06100

Istanbul University Istanbul School of Medicine; Neurology

Istanbul, Turkey, 34093

Ondokuz Mayis Univ. Med. Fac.; Neurology

Samsun, Turkey, 55139

United Kingdom

The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre

Cheltenham, United Kingdom, GL53 9DZ

Surrey and Borders NHS Foundation Trust; Brain Science Research Unit

Chertsey, United Kingdom, KT16 0AE

Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit

Crowborough, United Kingdom, TN6 1HB

Ninewells Hospital

Dundee, United Kingdom, DD12 9SY

NHS Lothian - Western General Hospital; NHS Lothian - Western General Hospital

Edinburgh, United Kingdom, EH4 2XU

Queen Elizabeth University Hospital; Clinical Research Facility

Glasgow, United Kingdom, G51 4TF

RE:Cognition Health

London, United Kingdom, W1G 9RU

Charing Cross Hospital; Imperial Memory Unit, Level 10 West

London, United Kingdom, W6 8RF

Manchester Royal Infirmary

Manchester, United Kingdom, M13 9WL

John Radcliffe Hospital

Oxford, United Kingdom, OX3 9DU

University Southampton NHS Foundation Trust; Wessex Neurologica Centre

Southampton, United Kingdom, SO166YD

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 14, 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: NCT03114657
• Other Study ID Numbers: BN29553; 2016-003288-20 ( EudraCT Number )
• First Posted: April 14, 2017
• 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