A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease (Clarity AD)

• ClinicalTrials.gov Identifier: NCT03887455
• Recruitment Status: Active, not recruiting
• First Posted: March 25, 2019
• Last Update Posted: June 12, 2023
• Sponsor: Eisai Inc.
• Collaborator: Biogen
• Information provided by (Responsible Party): Eisai Inc.

Tracking Information

• First Submitted Date: March 21, 2019
• First Posted Date: March 25, 2019
• Last Update Posted Date: June 12, 2023
• Actual Study Start Date: March 27, 2019
• Estimated Primary Completion Date: September 15, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 13, 2022)

• Core Study: Change from Baseline in the CDR-SB at 18 Months [ Time Frame: Baseline, 18 months ]
• Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug up to approximately 51 months (including 3 months follow up) for the extension phase ]
  A TEAE is defined as an adverse event that emerges during treatment or within 30 days of the last dose of study drug, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the adverse event was continuous. Number of participants with TEAEs (serious and non-serious adverse events) were reported based on their regular measurement of vital signs, safety assessments of laboratory tests, antidrug antibody assessments, suicidality assessments, magnetic resonance imaging and electrocardiogram parameter values.
• Extension Phase: Change from Core Study Baseline in CDR-SB [ Time Frame: Baseline up to Month 69 ]

Original Primary Outcome Measures (submitted: March 21, 2019)

• Core Study: Change from Baseline in the CDR-SB at 18 Months [ Time Frame: Baseline, 18 months ]
• Extension Phase: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Month 45 ]
• Extension Phase: Change from Core Study Baseline in CDR-SB [ Time Frame: Baseline up to Month 45 ]
• Extension Phase: Change from Core Study Baseline in Cerebrospinal fluid (CSF) biomarkers (neurogranin, NFL, Aβ[1-42], t-tau, and p-tau) [ Time Frame: Baseline up to Month 45 ]

Current Secondary Outcome Measures (submitted: July 11, 2022)

• Core Phase: Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at 18 Months [ Time Frame: Baseline, 18 months ]
• Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months [ Time Frame: Baseline, 18 months ]
• Core Phase: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months [ Time Frame: Baseline, 18 months ]
• 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 [ Time Frame: Baseline, 18 months ]

Original Secondary Outcome Measures (submitted: March 21, 2019)

• Core Study: Change From Baseline in the Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) Composite [ Time Frame: Baseline, 18 months ]
• Core Study: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months [ Time Frame: Baseline, 18 months ]
• Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months [ Time Frame: Baseline, 18 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease
• Official 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
• Brief Summary: This study will be conducted to evaluate the efficacy of lecanemab in participants with early Alzheimer's disease (EAD) by determining the superiority of lecanemab compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of lecanemab in participants with EAD in the Extension Phase and whether the long-term effects of lecanemab as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.
• Detailed Description: All administrations of study drug will be administered in the clinic; However, home administrations of study drug will be allowed per sponsor approval according to country and local guidelines during the COVID-19 pandemic and following its resolution, where permitted.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Early Alzheimer's Disease

Intervention

• Drug: Lecanemab
  10 milligram per kilogram (mg/kg) biweekly (once every 2 weeks) administered as i.v. infusion.
  Other Name: BAN2401
• Drug: Placebo
  Biweekly (once every 2 weeks) administered as i.v. infusion.
• Drug: Lecanemab
  720 milligram (mg) weekly administered as subcutaneous injection.

Study Arms

• Experimental: Core Study: Lecanemab 10 mg/kg biweekly
  Intervention: Drug: Lecanemab
• Placebo Comparator: Core Study: Placebo
  Intervention: Drug: Placebo
• Experimental: Extension Phase: Lecanemab 10 mg/kg biweekly
  Intervention: Drug: Lecanemab
• 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).
  Intervention: Drug: Lecanemab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 15, 2022): 1906
• Original Estimated Enrollment (submitted: March 21, 2019): 1556
• Estimated Study Completion Date: September 15, 2027
• Estimated Primary Completion Date: September 15, 2027 (Final data collection date for primary outcome measure)

Eligibility 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: Inclusion Criteria:

• 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 (IV) biweekly or BAN2401 720 mg subcutaneously (SC) weekly.

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 β-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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Russian Federation, Singapore, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03887455
• Other Study ID Numbers: BAN2401-G000-301; 2018-004739-58 ( 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
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

• Current Responsible Party: Eisai Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Eisai Inc.
• Original Study Sponsor: Same as current
• Collaborators: Biogen
• Investigators: Not Provided
• PRS Account: Eisai Inc.
• Verification Date: June 2023