A Phase 2 clinical study to investigate the effects of BAN2401 in patients with early Alzheimer's Disease
- Conditions
- Mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementiaTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2012-002843-11-NL
- Lead Sponsor
- Eisai Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 800
Mild Cognitive Impairment due to Alzheimer’s Disease – Intermediate Likelihood:
1. Subjects who meet the National Institute of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria for mild cognitive impairment due to Alzheimer’s disease
2. Subjects who have a CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline
3. Subjects who report a history of subjective memory decline with gradual onset and slow progression over the last one year before Screening; MUST be corroborated by an informant
4. Subjects with objective impairment in episodic memory as indicated by at least 1 standard deviations below age-adjusted mean in the WMS-IV LMII, as follows:
a) =15 for age 50 to 64 years
b) =12 for age 65 to 69 years
c) =11 for age 70 to 74 years
d) =9 for age 75 to 79 years
e) =7 for age 80 to 90 years
Mild Alzheimer’s Disease Dementia:
5. Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer’s disease dementia
6. Subjects who have a CDR score of 0.5 to 1.0 and a Memory Box score of 0.5 or greater at Screening and Baseline
Key Inclusion Criteria that must be met by ALL Subjects:
7. Positive amyloid load as indicated by PET assessment of imaging agent uptake into brain
8. Male or female subjects aged between 50 and 90 years, inclusive
9. MMSE score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline, except for the following countries, where MMSE score must be equal to or greater than 22 and equal to or less than 28 at Screening and Baseline: United Kingdom, Spain, Germany, Sweden, France, and the Netherlands.
10. Body Mass Index (BMI) < 35 at Screening
11. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin assay [ß-hCG]. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
12. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral
oophorectomy, all with surgery at least 1 month before dosing).
13. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 35 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 35 days after study drug discontinuation. Females who are using hormonal
contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 35 days after study drug discontinuation.
14. Subjects who are receiving an AChEIs or memantine for AD must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naïve subjects c
1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject’s AD
2. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
3. Any psychiatric diagnosis or symptoms, (e.g., hallucinations, major depression, or delusions) that could interfere with study procedures in the subject
4. GDS score = 8 at Screening
6. Evidence of other clinically significant lesions that could indicate a dementia diagnosis other than AD on brain MRI at Screening. All MRIs will be acquired using a standardized procedure that will be outlined in the Imaging Charter and Imaging Acquisition Guidelines (IAG) and will be read by an approved centralized reader.
7. Other significant pathological findings on brain MRI at Screening, including but not limited to: more than 4 micro-hemorrhages (defined as 10 mm or less at the greatest diameter); a single macro-hemorrhage greater than 10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, infective lesions, evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease or space occupying lesions (e.g., arachnoid cysts) or brain tumors (e.g., meningioma)
8. Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment
9. Any immunological disease which is not adequately controlled, or which requires treatment with biologic drugs during the study
10. Subjects with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or INR >1.5)
11. Subjects who have thyroid stimulating hormone (TSH) above normal range, or free triiodothyronine (T3) or free thyroxine (T4) outside of normal range. This applies to all subjects either taking or not taking thyroid supplements
12. Abnormally low serum Vitamin B12 levels for the testing laboratory (if subject is taking Vitamin B12 injections, level should be at or above the lower limit of normal [LLN] for the testing laboratory).
13. A prolonged QT/QTc interval (QTc > 450 ms) as demonstrated by a repeated electrocardiogram (ECG)
14. Known to be human immunodeficiency virus (HIV) positive
15. Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which in the opinion of the principal investigator (PI), require further investigation or treatment or which may interfere with study procedures or safety
16. Uncontrolled Type 1 or Type 2 diabetes mellitus. Evidence of uncontrolled diabetes mellitus includes hemoglobin A1c (HbA1c) > 9%
17. Uncontrolled hypertension with a history of blood pressure consistently above 165/100 mm Hg at Screening
18. History of uncontrolled cardiovascular disease within 6 months of Screening, including acute coronary syndrome, clinically significant valvular heart disease, uncompensated heart failure (New York Heart Association [NYHA] Class III and Class IV), or uncontrolled arrhythmia
19. Subjects with malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male subjects). Subjects who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need
not be excluded
20. Has a yes” answer to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method