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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03887455




Registration number
NCT03887455
Ethics application status
Date submitted
21/03/2019
Date registered
25/03/2019

Titles & IDs
Public title
A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease
Scientific title
A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
Secondary ID [1] 0 0
2018-004739-58
Secondary ID [2] 0 0
BAN2401-G000-301
Universal Trial Number (UTN)
Trial acronym
Clarity AD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early 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 - Lecanemab
Treatment: Drugs - Placebo
Treatment: Drugs - Lecanemab
Treatment: Drugs - Lecanemab

Experimental: Core Study: Lecanemab 10 mg/kg biweekly -

Placebo comparator: Core Study: Placebo -

Experimental: Extension Phase: Lecanemab 10 mg/kg biweekly -

Experimental: Extension Phase: Lecanemab 720 mg Subcutaneous Injection Weekly - This will include approximately 40 de novo participants (those that did not participate in the core study) with early Alzheimer disease (AD).

Experimental: Extension Phase: Lecanemab 360 mg Subcutaneous Autoinjector Injection Weekly -


Treatment: Drugs: Lecanemab
10 milligram per kilogram (mg/kg) biweekly (once every 2 weeks) administered as i.v. infusion.

Treatment: Drugs: Placebo
Biweekly (once every 2 weeks) administered as i.v. infusion.

Treatment: Drugs: Lecanemab
720 milligram (mg) weekly administered as subcutaneous injection.

Treatment: Drugs: Lecanemab
360 mg weekly administered as subcutaneous injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Core Study: Change from Baseline in the CDR-SB at 18 Months
Timepoint [1] 0 0
Baseline, 18 months
Primary outcome [2] 0 0
Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
From first dose of study drug up to approximately 51 months (including 3 months follow up) for the extension phase
Primary outcome [3] 0 0
Extension Phase: Change from Core Study Baseline in CDR-SB
Timepoint [3] 0 0
Baseline up to Month 69
Secondary outcome [1] 0 0
Core Phase: Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at 18 Months
Timepoint [1] 0 0
Baseline, 18 months
Secondary outcome [2] 0 0
Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months
Timepoint [2] 0 0
Baseline, 18 months
Secondary outcome [3] 0 0
Core Phase: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months
Timepoint [3] 0 0
Baseline, 18 months
Secondary outcome [4] 0 0
Core Study: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) at 18 Months
Timepoint [4] 0 0
Baseline, 18 months

Eligibility
Key inclusion criteria
Core Study: Inclusion Criteria

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer's disease - intermediate likelihood:

* Meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to Alzheimer's disease - intermediate likelihood
* Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of 0.5 or greater at Screening and Baseline
* Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer's disease dementia:

* Meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
* Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline

Key Inclusion Criteria that must be met by all participants:

* Objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II (WMS-IV LMII)
* Positive biomarker for brain amyloid pathology
* Male or female participants aged greater than or equal to (>=) 50 and less than or equal to (<=) 90 years, at the time of informed consent
* Mini mental state examination (MMSE) score >=22 at Screening and Baseline and <=30 at Screening and Baseline
* Body mass index (BMI) greater than (>)17 and less than (<) 35 at Screening
* If receiving an approved Alzheimer's disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer's disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naive participants for Alzheimer's disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non-Alzheimer's disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for participants in Japan
* Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant)
* Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

Extension Phase:

* Participants who have completed the Core Study (except de novo participants)
* Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase
* Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled
* Participants entering the subcutaneous (vial) substudy at Extension Phase Week 1, must be willing to participate, or continue participating in the amyloid positron emission tomography (PET) substudy. All participants must have an amyloid PET scan within 4 weeks before starting subcutaneous BAN2401
* Participants enrolling into the subcutaneous autoinjector substudy must have had at least 6 months exposure to BAN2401 10 mg/kg intravenously biweekly or BAN2401 720 mg subcutaneously weekly.
* Participants enrolling into the subcutaneous 360 mg autoinjector substudy must have previously received BAN2401 by either intravenous administration and/or subcutaneous autoinjector administration and must have completed Visit 82 (Extension Week 79) at a minimum, regardless of previous route of administration
Minimum age
50 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease
* History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
* Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
* Geriatric Depression Scale (GDS) score >=8 at Screening
* Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example in skull and cardiac devices other than those approved as safe for use in MRI scanners)
* Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than Alzheimer's disease
* Other significant pathological findings on brain MRI at screening, including but not limited to: more than 4 microhemorrhages (defined as 10 millimeter [mm] or less at the greatest diameter); a single macrohemorrhage >10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and <1 centimeter [cm] at their greatest diameter need not be exclusionary)
* Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
* Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5 for participants who are not on anticoagulant treatment, example, warfarin). Participants who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening. Participants who are on anticoagulant therapy are not permitted to participate in cerebrospinal fluid (CSF) assessments
* Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
* Participation in a clinical study involving any therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months before screening unless it can be documented that the participant was randomized to placebo
* Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapies and any ß-site amyloid precursor protein cleaving enzyme [BACE] inhibitor therapies) unless it can be documented that the participant only received placebo
* Participants who have any known prior exposure to lecanemab
* Participants who were dosed in a clinical study involving any new chemical entities for AD within 6 months prior to screening unless it can be documented that the participant was in a placebo treatment arm

Extension Phase: Exclusion Criteria

* Participants who discontinued early from the Core Study
* Participants who develop the following conditions from the time of Screening for the Core Study to the start of the Extension Phase

* Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
* Any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
* Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners)
* Other significant pathological findings on brain MRI during the Core Study including but not limited to: cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors will be exclusionary if based on the opinion of the investigator, with consultation of medical monitor, these findings may interfere with the study procedures or safety
* Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment
* Any immunological disease which is not adequately controlled, or which requires chronic treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
* Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG, which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety
* Malignant neoplasms (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants) that are not stably and adequately controlled or which, based on the opinion of the investigator, may interfere with the participant's safety or participation in the study
* Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
* Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

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 administering the treatment/s
The people assessing the outcomes
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/09/2027
Actual
Sample size
Target
Accrual to date
Final
1906
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital - Translational Research Centre - Darlinghurst
Recruitment hospital [2] 0 0
KaRa Institute of Neurological Diseases - Macquarie Park
Recruitment hospital [3] 0 0
The Prince Charles Hospital/Internal Medicine & Dementia Research Unit - Chermside Brisbane
Recruitment hospital [4] 0 0
Central Adelaide Local Health Network, The Queen Elizabeth Hospital and the Royal Adelaide Hospital - Woodville South, Adelaid
Recruitment hospital [5] 0 0
Austin Health - Medical and Cognitive Research Unit - Ivanhoe
Recruitment hospital [6] 0 0
HammondCare Malvern Clinical Trials Unit - Malvern
Recruitment hospital [7] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2229 - Macquarie Park
Recruitment postcode(s) [3] 0 0
4032 - Chermside Brisbane
Recruitment postcode(s) [4] 0 0
5011 - Woodville South, Adelaid
Recruitment postcode(s) [5] 0 0
3081 - Ivanhoe
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Biogen
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03887455