A Phase 3 clinical study to investigate the effects of BAN2401 in patients with Early Alzheimer's Disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eisai Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Sep 2019 → ongoing

Decision date (initial)

2024-07-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eisai Limited.

External identifiers

EU CT number

2024-510887-22-00

EudraCT number

2018-004739-58

WHO UTN

U1111-1303-3866

ClinicalTrials.gov

NCT03887455

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

Core:
- To evaluate the efficacy of BAN2401 in subjects with early Alzheimer's disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR SB) at 18 months of treatment.

Extension Phase:
- To evaluate the long-term safety and tolerability of BAN2401 in subjects with EAD in the Extension Phase,
- To evaluate whether the long-term effects of BAN2401 as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.

Secondary objectives 4

1. Key Secondary Objective: To determine whether BAN2401 is superior to placebo in reducing brain amyloid levels as measured by amyloid positron emission tomography (PET) using Centiloids at 18 months.
2. Key Secondary Objective: To evaluate the efficacy of BAN2401 in subjects with early AD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the AD Assessment Scale–Cognitive Subscale14 (ADAS-cog14) at 18 months of treatment.
3. Key Secondary Objective: To evaluate the efficacy of BAN2401 in subjects with early AD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the AD composite score (ADCOMS) at 18 months of treatment
4. Key Secondary Objective: To evaluate the efficacy of BAN2401 in subjects with early AD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Alzheimer's Disease Cooperative Study- Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) at 18 months of treatment. For all other objectives see protocol.

Conditions and MedDRA coding

Mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia.

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Diagnosis; MCI due to AD–intermediate likelihood: Meet NIA-AA core clinical criteria for MCI due to AD–intermediate likelihood.
2. 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.
3. 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.
4. Diagnosis; Mild AD dementia: Meet NIA-AA core clinical criteria for probable AD dementia.
5. 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.
6. 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
7. 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.
8. 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.
9. 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.
10. Diagnosis; Key Inclusion Criteria that must be met by all subjects: BMI >17 and <35 at Screening.
11. 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.
12. 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.
13. 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.
14. Diagnosis; Key Inclusion Criteria that must be met by all subjects: Willing and able to comply with all aspects of the protocol.
15. Extension: See protocol for full details.

Exclusion criteria 28

1. Females who are breastfeeding or pregnant at screening or Baseline.
2. 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.
3. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD.
4. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening.
5. Any psychiatric diagnosis or symptoms that could interfere with study procedures in the subject.
6. GDS score greater than or equal to 8 at Screening.
7. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants.
8. Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD.
9. Other significant pathological findings on brain MRI at Screening - see protocol for further details.
10. Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment.
11. 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.
12. 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.
13. 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.
14. Abnormally low serum vitamin B12 levels for the testing laboratory.
15. Known to be HIV positive.
16. 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.
17. Subjects with malignant neoplasms within 3 years of Screening.
18. 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.
19. 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.
20. 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.
21. Subjects who are taking prohibited medications.
22. 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.
23. 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.
24. Subjects who have any known prior exposure to BAN2401.
25. 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.
26. 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.
27. Planned surgery which requires general anesthesia that would take place during the study.
28. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately. Extension: See protocol for full details.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Core - Change from baseline in the CDR-SB at 18 months.
2. 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

Secondary endpoints 3

1. 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.
2. OTHER SECONDARY ENDPOINTS: Refer to protocol.
3. BM Endpoints: Refer to protocol.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eisai Limited

Sponsor organisation

Eisai Limited

Address

European Knowledge Center, Mosquito Way Mosquito Way

City

Hatfield

Postcode

AL10 9SN

Country

United Kingdom

Scientific contact point

Organisation

Eisai Limited

Contact name

Medical Information

Public contact point

Organisation

Eisai Limited

Contact name

Medical Information

Third parties 13

Locations

5 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 74 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications