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

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ClinicalTrials.gov Identifier: NCT03114657
Recruitment Status : Completed
First Posted : April 14, 2017
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 28, 2017
First Posted Date  ICMJE April 14, 2017
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE March 29, 2017
Actual Primary Completion Date May 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
Change from Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score [ Time Frame: Baseline, Week 105 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03114657 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Change from Baseline to Week 105 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) and Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Clinical Dementia Rating-Global Score (CDR-GS) and Mini Mental State Exam MMSE [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 on Function as assessed by (ADCS-ADL) Total Score and Its (ADCS-iADL) and by the Functional Activities Questionnaire (FAQ) total score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 on a Measure of Dependence Level Assessed from the ADCS-ADL Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score [ Time Frame: Baseline, Week 105 ]
  • Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  • Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  • European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores [ Time Frame: Baseline, Week 105 ]
  • Percentage of Participants with Adverse Event (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Baseline up to Week 105 ]
  • Percentage of Participants with Anti-Crenezumab Antibodies [ Time Frame: Baseline up to Week 105 ]
  • 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 5, 13, 37, 53, and 100 (infusion length = as per the Pharmacy Manual) ]
  • Plasma Amyloid Beta (Abeta) Concentrations [ Time Frame: Screening (Weeks -8 to -1) ; Day 1 Week 1; Weeks 5, 25, 53, and 100 ]
  • Change from Baseline to Week 105 in Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
  • Cerebrospinal Fluid (CSF) concentration of Crenezumab [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  • Brain Amyloid Load Over Time Measured by Amyloid-PET [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  • Brain Tau Load Over Time Measured by Tau-PET [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  • Cerebrospinal Fluid (CSF) Markers of Disease Over Time [ Time Frame: At pre-defined intervals from baseline through week 105 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
  • Change from Baseline to Week 105 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score [ Time Frame: Baseline, Week 105 ]
  • Time to Clinically Evident Decline [ Time Frame: Baseline up to Week 105 ]
    Clinically evident decline is defined by fulfilment of both of the following criteria: (1) a confirmed decline of greater than or equal to (>=) 2 points on the Mini Mental State Examination (MMSE) scale score; and (2) loss of >=1 point(s) on one or more basic Activity of Daily Living (ADL) subscale(s) score, or loss of >=2 points on one or more Instrumental Activity of Daily Living (iADL) scores. Time to clinically evident decline will be reported.
  • Change from Baseline to Week 105 in Clinical Dementia Rating-Global Score (CDR-GS) [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in MMSE Scale Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Alzheimer's Disease Assessment Scale-Cognition 12 (ADAS-Cog-12) Subscale Score [ Time Frame: Baseline, Week 105 ]
  • Time to an Increase of >=4 Points from Baseline at any Time Before or on Week 105 in the ADAS-Cog-13 Subscale Score [ Time Frame: Baseline up to Week 105 ]
  • Change from Baseline to Week 105 in Alzheimer's Disease Cooperative Study−Activities of Daily Living Inventory Instrumental Subscale (ADCS-iADL) Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Alzheimer's Disease Cooperative Study−Activities of Daily Living Inventory (ADCS-ADL) Total Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Dependence Level Assessed from the ADCS-ADL Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Functional Activities Questionnaire (FAQ) Total Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in Neuropsychiatric Inventory Questionnaire (NPI-Q) Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in the Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in the Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  • Change from Baseline to Week 105 in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores [ Time Frame: Baseline, Week 105 ]
  • Percentage of Participants with Adverse Event (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Baseline up to Week 105 ]
  • Percentage of Participants with Anti-Crenezumab Antibodies [ Time Frame: Baseline up to Week 105 ]
  • 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 5, 13, 37, 53, and 100 (infusion length = as per the Pharmacy Manual) ]
  • Plasma Amyloid Beta (Abeta) Concentrations [ Time Frame: Screening (Weeks -8 to -1) ; Day 1 Week 1; Weeks 5, 25, 53, and 100 ]
  • Change from Baseline to Week 105 in Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD)
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Crenezumab
    Crenezumab will be administered as IV infusion q4w for 100 weeks.
  • Drug: Placebo
    Placebo will be administered as IV infusion q4w for 100 weeks.
Study Arms  ICMJE
  • Experimental: Crenezumab
    Participants will receive IV infusion of crenezumab q4w for 100 weeks.
    Intervention: Drug: Crenezumab
  • Placebo Comparator: Placebo
    Participants will receive IV infusion of placebo q4w for 100 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2017)
750
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 31, 2019
Actual Primary Completion Date May 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 : (a) 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; (b) Is in sufficiently good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the study duration
  • 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 positron emission tomography (PET) scan by qualitative read by the core/central PET laboratory
  • Demonstrated abnormal memory function at early screening (up to 4 weeks before screening begins) or at screening
  • Evidence of retrospective decline confirmed by a diagnosis verification form
  • Mild symptomatology, as defined by a screening MMSE score of >=22 points and 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. If the participant is taking medical food supplements, these must also 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
  • For enrollment into the China Extension Phase, participants must have residence in mainland China, Hong Kong or Taiwan and be of Chinese ancestry

Exclusion Criteria:

  • Any evidence of a condition other than AD that may affect cognition, including but not limited to, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, Parkinson's disease, corticobasal degeneration, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, Huntington's disease, normal pressure hydrocephalus, seizure disorder, or hypoxia
  • Seizure history that, in the opinon of the investigator, is likely to results in cognitive impairment
  • History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
  • At risk of suicide in the opinion of the investigator
  • Presence of significant cerebral vascular pathology as assessed by MRI central reader
  • Unstable or clinically significant cardiovascular, kidney or liver disease
  • Uncontrolled hypertension
  • Screening hemoglobin A1c (HbA1C) greater than (>) 8 percent (%)
  • Clinical significant sleep apnea that may be contributing to cognitive impairment. Sleep apnea, which in the clinical judgement of the investigator is adequately treated is allowed
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   China,   Denmark,   Estonia,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Norway,   Peru,   Poland,   Portugal,   Russian Federation,   Serbia,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Guatemala,   Hungary
 
Administrative Information
NCT Number  ICMJE NCT03114657
Other Study ID Numbers  ICMJE BN29553
2016-003288-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP