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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02670083
• Date of registration: 28/01/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD). CREAD
• Scientific 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.
• Date of first enrolment: March 22, 2016
• Target sample size: 813
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02670083
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Costa Rica, Croatia, Czech Republic, Czechia, Denmark, Finland, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Poland, Portugal, Russian Federation, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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



Age minimum: 50 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alzheimer's Disease

Intervention(s)

Drug: Placebo

Drug: Crenezumab

Primary Outcome(s)

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

Secondary Outcome(s)

Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline, Week 105]

Plasma Amyloid Beta (Abeta) 42 Concentrations [Time Frame: Week 1 Day 1; Weeks 13, 25, 53, 77 and 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 13, 37 (Pre-dose), 53, 77 and 105 (infusion length = as per the Pharmacy Manual)]

Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q) [Time Frame: Baseline, Week 105]

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]

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) [Time Frame: Baseline, Week 105]

Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline, Week 105]

Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore [Time Frame: Baseline, Week 105]

Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score [Time Frame: Baseline, Week 105]

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) [Time Frame: Baseline, Week 105]

Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [Time Frame: Baseline up to Week 105]

EQ-5D Questionnaire Domain Score for Participants [Time Frame: Baseline up to Week 105]

Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline, Week 105]

Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score [Time Frame: Baseline, Week 105]

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).]

Plasma Amyloid Beta (Abeta) 40 Concentrations [Time Frame: Week 1 Day 1; Weeks 13, 25, 53, 77 and 105]

Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [Time Frame: Baseline up to Week 105]

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]

EQ-5D Questionnaire Domain Score for Caregivers [Time Frame: Baseline up to Week 105]

Percentage of Participants With Anti-Crenezumab Antibodies [Time Frame: Baseline up to Week 105]

Secondary ID(s)

BN29552

2015-003034-27

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02670083