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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 : Recruiting
First Posted : April 14, 2017
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 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
Estimated Primary Completion Date : October 28, 2021
Estimated Study Completion Date : October 28, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Crenezumab
Participants will receive IV infusion of crenezumab q4w for 100 weeks.
Drug: Crenezumab
Crenezumab will be administered as IV infusion q4w for 100 weeks.

Placebo Comparator: Placebo
Participants will receive IV infusion of placebo q4w for 100 weeks.
Drug: Placebo
Placebo will be administered as IV infusion q4w for 100 weeks.




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

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Change from Baseline to Week 105 on a Measure of Dependence Level Assessed from the ADCS-ADL Score [ Time Frame: Baseline, Week 105 ]
  5. Change from Baseline to Week 105 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score [ Time Frame: Baseline, Week 105 ]
  6. Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  7. Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [ Time Frame: Baseline, Week 105 ]
  8. European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores [ Time Frame: Baseline, Week 105 ]
  9. Percentage of Participants with Adverse Event (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Baseline up to Week 105 ]
  10. Percentage of Participants with Anti-Crenezumab Antibodies [ Time Frame: Baseline up to Week 105 ]
  11. 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) ]
  12. Plasma Amyloid Beta (Abeta) Concentrations [ Time Frame: Screening (Weeks -8 to -1) ; Day 1 Week 1; Weeks 5, 25, 53, and 100 ]
  13. Change from Baseline to Week 105 in Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, Week 105 ]
  14. Cerebrospinal Fluid (CSF) concentration of Crenezumab [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  15. Brain Amyloid Load Over Time Measured by Amyloid-PET [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  16. Brain Tau Load Over Time Measured by Tau-PET [ Time Frame: At pre-defined intervals from baseline through week 105 ]
  17. Cerebrospinal Fluid (CSF) Markers of Disease Over Time [ Time Frame: At pre-defined intervals from baseline through week 105 ]


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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 : (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114657


Contacts
Contact: Reference Study ID Number: BN29553 www.roche.com/about_roche/ roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03114657     History of Changes
Other Study ID Numbers: BN29553
2016-003288-20 ( EudraCT Number )
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: June 2018

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