Study of the safety and effectiveness of two doses of investigational study drug EVP-6124 in subjects with Alzheimer’s Disease

• Conditions: Mild to moderate Alzheimer's disease; MedDRA version: 16.1Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 16.1Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2013-002653-30-IT
• Lead Sponsor: EnVivo Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-30
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 790

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible to participate in the study:
1. Informed consent form (ICF) signed by the subject or legally acceptable representative before any study-specific procedures for the subject are performed and an ICF signed by the support person/caregiver before any study-specific procedures for the support person/caregiver are performed.
2. Male or female subjects of any race, aged =55 and =85 years
3. Clinical diagnosis of dementia due to probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer’s Disease Association (McKhann et al, 2011)
4. Clinical decline within 12 months before screening and onset of symptoms at least 12 months or longer before screening, which may include any documented cognition, functional, or other objective assessment or the clinical judgment of the investigator or the subject’s referring physician that the subject has experienced a clinical decline within the last 12 months
5. Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within 12 months before screening, with findings consistent with the diagnosis of dementia due to AD without any other clinically significant comorbid pathologies. If an MRI or CT scan is unavailable or occurred greater than 12 months before screening, this assessment should be completed and the findings confirmed before the subject enters the run-in period (Day -14) (copy of the report will be available at the study site)
6. Mini-Mental State Examination (MMSE) score =14 and =24 at screening and confirmed on Day 1 prior to randomization (fluctuations of ±2 points are acceptable on Day 1/baseline)
7. Clinical Dementia Rating Global score (CDR-GS) =1 (at least mild dementia) at screening and confirmed on Day 1 prior to randomization
8. Modified Hachinski Ischemic Scale (mHIS) score =4 at screening
9. Fertile, sexually active subjects (men and women) must use an effective method of contraception during the study. Female subjects and the female partner of male subjects must be surgically sterile (hysterectomy or bilateral tubal ligation), postmenopausal for at least 1-year, or willing to practice adequate methods of contraception if of childbearing potential (defined as consistent use of combined effective methods of contraception.
10. Reliable and capable support person/caregiver, who if not living in the same household, interacts with the subject approximately 4 times per week and will be available to attend clinic visits in person when possible.
11. Subject living at home, senior residential setting, or an institutional setting without the need for continuous (ie, 24-hour) nursing care.
12. General health status acceptable for participation in a 26-week study
13. Fluency (oral and written) in the language in which the standardized tests will be administered
14. Receiving a stable dose of an AChEI (donepezil, rivastigmine or galantamine) for at least 3 months (90 days) before screening and with continuous dosing for at least 6 months OR not presently receiving an AChEI (at least 30 days before screening), but with a history of previous AChEI treatment (subjects receiving donepezil 23 mg currently or within 3 months before screening are ineligible)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 79
F.1.3 Elderly (>=65 years) yes
F.1.

Exclusion Criteria

Subjects who meet any of the following exclusion criteria will be excluded from participating in the study:
Exclusion Criteria - General
1. Exposure to an experimental drug, experimental biologic or experimental medical device within 2 months (60 days) before screening
2. Prior participation in an amyloid vaccination clinical study at any time in the past or completion of a passive amyloid vaccination study within 6 months before screening
3. Inability to swallow a tablet
4. In the judgment of the investigator, inability of the subject or the support person/caregiver to complete a 26-week study
5. Inability to be =75% compliant with single-blind study drug
6. Inability to adequately cooperate or complete the cognitive testing procedures or any study assessment
7. Residence in a skilled nursing facility

Exclusion Criteria - Medical
8. Untreated vitamin B12 or folate deficiency (if treated, must be stably treated for at least 6 months before screening)
9. Clinically significant (in the judgment of the investigator) abnormal serum electrolytes (sodium, potassium, magnesium) after repeat testing
10. Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
11. Insufficiently controlled diabetes mellitus (in the judgment of the investigator) or requiring insulin
12. Renal insufficiency (serum creatinine >2.0 mg/dL)
13. Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or brachytherapy for localized prostate cancer)
14. Unstable medical condition that is clinically significant in the judgment of the investigator
15. Female subjects who are pregnant, nursing, or planning to become pregnant during the study
16. Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit of normal
Exclusion Criteria - Cardiovascular
17. History of myocardial infarction or unstable angina within 6 months before screening
18. History of more than 1 myocardial infarction within 5 years before screening
19. Clinically significant (in judgment of the investigator) cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (subjects with a pacemaker are acceptable)
20. Symptomatic hypotension or hypertension (supine diastolic blood pressure >95 mmHg) (in the judgment of the investigator)
21. Clinically significant abnormality on screening or baseline ECG, including but not necessarily limited to a confirmed QTc value =450 msec for males or =470 msec for females

Exclusion Criteria - Psychiatric
22. Diagnosis of severe major depressive disorder with psychotic features, delusions or hallucinations, which is either recurrent (Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision [DSM-IV-TR] 296.34) or single episode (DSM-IV-TR 296.24) within 5 years before screening (American Psychiatric Association, 2000)
23. Geriatric Depression Scale (GDS) score (15-item scale) >5 at screening or baseline
24. History or current diagnosis of psychosis (American Psychiatric Association, 2000)
25. History within 2 years before screening or current evidence of substance abuse as defined by the DSM-IV-TR
26. Significant suicide risk as defined by 1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified