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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03114657




Registration number
NCT03114657
Ethics application status
Date submitted
28/03/2017
Date registered
14/04/2017
Date last updated
16/07/2020

Titles & IDs
Public title
A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD)
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
Secondary ID [1] 0 0
2016-003288-20
Secondary ID [2] 0 0
BN29553
Universal Trial Number (UTN)
Trial acronym
CREAD 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Crenezumab
Treatment: Drugs - Placebo

Placebo comparator: Placebo - Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.

Experimental: Crenezumab - Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.


Treatment: Drugs: Crenezumab
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

Treatment: Drugs: Placebo
Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score
Timepoint [1] 0 0
Baseline, Week 77
Secondary outcome [1] 0 0
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score
Timepoint [1] 0 0
Baseline, Week 77
Secondary outcome [2] 0 0
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score
Timepoint [2] 0 0
Baseline, Week 77
Secondary outcome [3] 0 0
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)
Timepoint [3] 0 0
Baseline, Week 77
Secondary outcome [4] 0 0
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)
Timepoint [4] 0 0
Baseline, Week 77
Secondary outcome [5] 0 0
Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score
Timepoint [5] 0 0
Baseline, Week 77
Secondary outcome [6] 0 0
Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score
Timepoint [6] 0 0
Baseline, Week 77
Secondary outcome [7] 0 0
Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score
Timepoint [7] 0 0
Baseline, Week 77
Secondary outcome [8] 0 0
Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score
Timepoint [8] 0 0
Baseline, Week 77
Secondary outcome [9] 0 0
Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score
Timepoint [9] 0 0
Baseline, Week 53
Secondary outcome [10] 0 0
Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score
Timepoint [10] 0 0
Baseline, Week 77
Secondary outcome [11] 0 0
Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score
Timepoint [11] 0 0
Baseline, Week 53
Secondary outcome [12] 0 0
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants
Timepoint [12] 0 0
Baseline, Week 77
Secondary outcome [13] 0 0
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers
Timepoint [13] 0 0
Baseline, Week 77
Secondary outcome [14] 0 0
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)
Timepoint [14] 0 0
Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
Secondary outcome [15] 0 0
Percentage of Participants With Anti-Crenezumab Antibodies
Timepoint [15] 0 0
Baseline up to Week 105
Secondary outcome [16] 0 0
Serum Concentration of Crenezumab
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Plasma Amyloid Beta (Abeta) 40 Concentrations
Timepoint [17] 0 0
Week 1 Day 1; Weeks 53
Secondary outcome [18] 0 0
Plasma Amyloid Beta (Abeta) 42 Concentrations
Timepoint [18] 0 0
Week 1 Day 1; Weeks 53
Secondary outcome [19] 0 0
Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [19] 0 0
Baseline, Week 105
Secondary outcome [20] 0 0
Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [20] 0 0
Baseline, Week 105
Secondary outcome [21] 0 0
Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)
Timepoint [21] 0 0
Baseline, Week 105

Eligibility
Key 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
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/06/2019
Sample size
Target
Accrual to date
Final
806
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [3] 0 0
Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care - Hornsby
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2250 - Erina
Recruitment postcode(s) [3] 0 0
2077 - Hornsby
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment outside Australia
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United States of America
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Sevilla
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Malmö
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Sweden
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Mölndal
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Taiwan
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Changhua County
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Taiwan
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Kaohsiung
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Taiwan
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New Taipei City
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Samsun
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United Kingdom
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Cheltenham
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Chertsey
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Crowborough
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Dundee
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Edinburgh
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Glasgow
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London
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Manchester
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Oxford
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT03114657
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03114657