LECANEMAB for Mild cognitive impairment due to Alzheimer's disease | Alzheimer's disease dementia (mild)

Inclusion criteria

• {"criterion_text":"- Diagnosis; MCI due to AD–intermediate likelihood: Meet NIA-AA core clinical criteria for MCI due to AD–intermediate likelihood.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: BMI >17 and <35 at Screening.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: If receiving an approved AD treatment, such as AChEIs, or memantine, or both for AD, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naïve subjects for AD can be entered into the study. Unless otherwise stated, subjects must have been on stable doses of all other (ie, non-AD-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for Japanese subjects.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Have an identified study partner (defined as a person able to support the subject for the duration of the study and who spends at least 8 hours per week with the subject). The study partner must provide separate written informed consent. In addition, this person must be willing and able to provide follow-up information on the subject throughout the course of the study. This person must, in the opinion of the investigator, spend sufficient time with the subject on a regular basis such that the study partner can reliably fulfill the study requirements. A permanent study partner need not be living in the same residence with the subject. For such a study partner not residing with the subject, the investigator has to be satisfied that the subject can contact the study partner readily during the times when the study partner is not with the subject. If in doubt about whether a subject's care arrangements are suitable for inclusion, the investigator should discuss this with the medical monitor. Study partners need to participate in person for visits where clinical assessment of CDR (global and CDR-SB), EQ-5D-5L, QOL-AD, ADCS MCIADL and Zarit Burden Interview take place.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Provide written informed consent. If a subject lacks capacity to consent in the investigator's opinion, the subject'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 subjects who lack capacity to consent to participate in this study (eg Germany and Spain), they will not be enrolled.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Willing and able to comply with all aspects of the protocol.\n- Extension: See protocol for full details.\n- Diagnosis; MCI due to AD–intermediate likelihood: A global CDR score of 0.5 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline.\n- Diagnosis; MCI due to AD–intermediate likelihood: 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.\n- Diagnosis; Mild AD dementia: Meet NIA-AA core clinical criteria for probable AD dementia.\n- Diagnosis; Mild AD dementia: 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.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Objective impairment in episodic memory as indicated by at least 1 SD below age-adjusted mean in the WMS-IV LMII, as follows a. ≤15 for age 50-64 years b. ≤12 for age 65-69 years c. ≤11 for age 70-74 years d. ≤9 for age 75-79 years e. ≤7 for age 80-90 years\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Positive biomarker for brain amyloid pathology as indicated by at least 1 of the following: a. PET assessment of imaging agent uptake into brain. Note: amyloid PET screens will be performed according to local regulatory guidelines and thus may be restricted for those subjects who are not suitable for lumbar puncture (LP) to obtain CSF for testing of eligibility. b. CSF assessment of t-tau/Aβ[1-42] NOTE1: Subjects who are on anticoagulant therapy may not participate in CSF assessments. NOTE2: Subjects may consent to both the PET and CSF assessments, but to confirm eligibility, a positive amyloid result is needed in only 1 of the 2 procedures (ie, the subject will be eligible even if 1 of the 2 results does not meet its eligibility criterion). Subjects who consent to amyloid PET or CSF at Screening for the purposes of eligibility are not required to participate in the amyloid PET, tau PET, or CSF longitudinal substudies. Use of a historical amyloid positive PET (conducted within 12 months before the planned date of randomization) is acceptable for determination of eligibility provided the subject had not participated in any clinical studies involving anti-amyloid therapies subsequent to the PET assessment. Historical PET will not suffice for the baseline assessment if the subject wishes to consent to the amyloid PET longitudinal substudy. The historical imaging data must be made available to the sponsor to confirm amyloid positivity.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: Male or female subjects aged ≥50, ≤90 years, at the time of informed consent.\n- Diagnosis; Key Inclusion Criteria that must be met by all subjects: MMSE score greater than or equal to 22 at Screening and Baseline and less than or equal to 30 at Screening and Baseline."}

Exclusion criteria

• {"criterion_text":"- Females who are breastfeeding or pregnant at screening or Baseline.\n- Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment.\n- 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.\n- Subjects with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or INR >1.5 for subjects who are not on anticoagulant treatment. Subjects who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening. Subjects who are on anticoagulant therapy are not permitted to participate in CSF assessments.\n- Have TSH above normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator. This applies to all subjects whether or not they are taking thyroid supplements.\n- Abnormally low serum vitamin B12 levels for the testing laboratory.\n- Known to be HIV positive.\n- Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline which in the opinion of the investigator require further investigation.\n- Subjects with malignant neoplasms within 3 years of Screening.\n- Answer \"yes\" to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening.\n- Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Subjects who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if in the clinical opinion of the investigator, this is due to the subject taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse.\n- Females of childbearing potential who: a. Within 28 days before study entry, did not use a highly effective method of contraception b. Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation.\n- Any other medical conditions which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments.\n- Subjects who are taking prohibited medications.\n- 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 subject was randomized to placebo.\n- Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapies and any BACE inhibitor therapies) unless it can be documented that the subject only received placebo.\n- Subjects who have any known prior exposure to BAN2401.\n- Subjects 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 subject was in a placebo treatment arm.\n- Participated in any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the subject was in a placebo treatment arm.\n- Planned surgery which requires general anesthesia that would take place during the study.\n- Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately. Extension: See protocol for full details.\n- Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD.\n- History of transient ischemic attacks, stroke, or seizures within 12 months of Screening.\n- Any psychiatric diagnosis or symptoms that could interfere with study procedures in the subject.\n- GDS score greater than or equal to 8 at Screening.\n- Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants.\n- Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD.\n- Other significant pathological findings on brain MRI at Screening - see protocol for further details."}

Primary endpoints

• {"endpoint_text":"- Core - Change from baseline in the CDR-SB at 18 months.\n- Extension - Incidence of AEs and changes in vital signs, ECGs, laboratory safety tests, suicidality assessments, ADAs, and MRI safety parameters. - Change from Core Study baseline in CDR-SB","definition_or_measurement_approach":"Core: change from baseline in Clinical Dementia Rating–Sum of Boxes (CDR-SB) measured at 18 months. Extension: incidence of adverse events and clinical safety measures (vital signs, ECGs, laboratory safety tests, suicidality assessments, anti-drug antibodies (ADAs), MRI safety parameters) and change from Core Study baseline in CDR-SB."}

Secondary endpoints

• {"endpoint_text":"- The key secondary endpoints for this study are: - Change from baseline in amyloid PET using Centiloids at 18 months for brain amyloid levels - Change from baseline in ADAS-cog14 at 18 months - Change from baseline in ADCOMS at 18 months - Change from baseline in ADCS MCI-ADL at 18 months.","definition_or_measurement_approach":"Change from baseline measured by amyloid PET quantified in Centiloids at 18 months; cognitive scales ADAS-Cog14, ADCOMS, and ADCS MCI-ADL change from baseline at 18 months."}
• {"endpoint_text":"- OTHER SECONDARY ENDPOINTS: Refer to protocol.","definition_or_measurement_approach":"Refer to protocol."}
• {"endpoint_text":"- BM Endpoints: Refer to protocol.","definition_or_measurement_approach":"Refer to protocol."}

Spain

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

578

Number Of Sites

12

Number Of Participants

142

Germany

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

579

Number Of Sites

4

Number Of Participants

36

France

Earliest CTIS Part Ii Submission Date

02-07-2024

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

580

Number Of Sites

8

Number Of Participants

61

Italy

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

493

Number Of Sites

10

Number Of Participants

79

Sweden

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

577

Number Of Sites

4

Number Of Participants

30

Primary sponsor

Full Name

Eisai Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

WCT Worldwide Clinical Trials GER GmbH

Responsibilities

codes: 1,12,2,8,9

Name

IQVIA Limited

Responsibilities

code: 3

Name

Iqvia Laboratories Limited

Responsibilities

code: 4

Name

Bioclinica Inc.

Responsibilities

Medical image collection from sites, quality control, analysis/review of MRI and Amyloid PET; collection and quality control of Tau PET. Data and Image transfer to sponsor and vendor

Name

Clario

Responsibilities

ECG analysis/ review

Third parties

• {"country":"United States","full_name":"Scisafe Inc.","duties_or_roles":"Biomarker sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"PK Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Home nursing vendor","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image collection from sites, quality control, analysis/ review of MRI and Amyloid PET; collection and quality control of Tau PET. Data and Image transfer to sponsor and vendor","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Sampled (formerly Infinity Biologix)","duties_or_roles":"APOE4 genotyping","organisation_type":"Industry"}
• {"country":"United States","full_name":"QPS","duties_or_roles":"ADA/NAb samples","organisation_type":"Industry"}
• {"country":"United States","full_name":"Q2 Solutions, 2 Squared Solutions LLC","duties_or_roles":"Clinical Chemistry, Clinical haematology","organisation_type":"Industry"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Rater Training and Certification/Scale Management/Endpoint Reliability/eCOA.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clario","duties_or_roles":"ECG analysis/ review","organisation_type":"Industry"}
• {"country":"United States","full_name":"C2n Diagnostics LLC","duties_or_roles":"Specialty lab for CSF analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"WCT Worldwide Clinical Trials GER GmbH","duties_or_roles":"codes: 1,12,2,8,9","organisation_type":"Pharmaceutical company"}