This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study.The efficacy and safety of investigated drug RVT-101 at a dose of 35 mg daily when used as an adjunct treatment to stable donepezil therapy will be evaluated over a 24-week treatment period for mild to moderate Alzheimer?s disease in patients on stable therapy with donepezil.
- Conditions
- Alzheimer?s DiseaseMedDRA version: 18.1Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2015-002957-37-ES
- Lead Sponsor
- Axovant Sciences Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1150
Subjects eligible for enrollment in the study must meet all of the following criteria:
-Male or female subject with a clinical diagnosis of AD in accordance the recommendations from the National Institute on Aging-Alzheimer?s Association workgroups on diagnostic guidelines for AD.
- Subject has a documented history of at least 4 months of ongoing donepezil therapy for AD, with stable dosing of 5 or 10 mg/day for at least the last 2 months and with no intent to change for the duration of the study.
- Subject has an MMSE score 12 to 24 inclusive at Screening and a Baseline MMSE score 10 to 26 inclusive. The difference between the Screening and Baseline MMSE score is less than or equal to 3 points. If a greater than 3-point difference between the Screening and Baseline MMSE score is in the opinion of the investigator due to recent changes in AD medication, Screening may be extended for an additional 3 weeks after discussion with the Medical Monitor, during which time MMSE stability, defined as less than or equal to 3-point change over 3 weeks, must be observed.
- Subject has a Hachinski Ischaemia score less than or equal to 4 at Screening.
- 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 pathologies. If an MRI (preferred) or CT scan is unavailable or was performed longer than 12 months prior to Screening, one must be performed during the Screening Period (prior to Run-In).
- Age greater than or equal to 50 years to less than or equal to 85 years at the time of Screening.
- If female, subject must be:
a. Of non-childbearing potential (i.e., any female who is post-menopausal [greater than 1 year without menstrual period in the absence of hormone replacement therapy]) or surgically sterile; or,
b. If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test and must not be lactating at the Screening and Baseline Visits. Female subjects of childbearing potential and who are sexually active are required to practice adequate methods of birth control. Female subjects for whom menopausal status is in doubt in the opinion of the investigator will be required to use an adequate form of birth control. Acceptable, adequate form of birth control is defined as consistent use of combined effective methods of contraception including at least 1 barrier method.
Male subjects who are sexually active will also be required to use an adequate form of birth control as described above.
- Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator.
- Subject must be able to ingest pills (in tablet form) whole.
- Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend visits, oversee the subject?s compliance with protocol-specified procedures and study medication, and report on subject?s status, and who has substantial contact with the subject. If the caregiver does not cohabitate with the subject, he/she ideally should have a minimum of 10 hours total and at least 3 days contact with the subject per week. Prior to randomization, study representatives will review eligibility of non-cohabitating caregivers. Every effort should be made to have the same caregiver throughout the study.
- Subject has provided full written informed consent prior to the performance of
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Other Causes for Dementia
- Diagnosis of possible, probable, or definite vascular dementia
- History and/or evidence of any other CNS disorder that could be interpreted as a cause of dementia
- Evidence of the following disorders where this is thought to be the cause of, or to contribute to the severity of, the subject?s dementia: current vitamin B12 deficiency, hypothyroidism, neurosyphilis, or Wernicke?s encephalopathy.
- Focal findings on the neurological exam that are inconsistent with a primary diagnosis of AD.
- History of existing negative amyloid positron emission tomography scan or similar brain amyloid imaging, or Screen Failure from research trial due to negative amyloid imaging within 5 years.
- Atypical clinical features or clinical course of dementia that conclude symptoms are more likely due to an alternate dementia diagnosis.
Confounding Medical Conditions
- History of significant psychiatric illness such as schizophrenia or bipolar affective disorder, or significant suicide risk. Current psychosis that in the opinion of the investigator would interfere with the subject?s ability to participate in this study. History of epilepsy or unexplained seizure in the past 5 years. History of alcohol use disorder or other substance abuse disorder in the past 10 years. History of Down syndrome or mental retardation.
- Any clinically relevant concomitant disease including progressive liver or kidney dysfunction, history of myocardial infarction or unstable angina within 6 months of Screening.
- Concomitant Medications: Participation in another investigational drug or device study in AD during the 60 days prior to the Screening Visit or Treatment with any concomitant medications as detailed in Table 1 of protocol.
Unacceptable Test/Laboratory Values such as:
-Postural hypotension at the time of screening.
- Persistent or recurrent liver enzyme elevations.
- Total bilirubin over 1.5 x ULN
- Calculated creatinine clearance less than 40 mL/min
- Positive hepatitis B surface antigen or hepatitis C antibody test.
- QT interval (QTc) value ?450 msec for males or ?470 msec for females
Other
Previous exposure to RVT-101 or SB742457.
Subject non-compliance in taking study medication as prescribed throughout the study
Subject or caregiver is an immediate family member or employee of the participating investigator, any of the participating site staff, or of the sponsor study staff.
Subject was prescribed cognitive tasks for cognitive rehabilitation performed under medical supervision in the 3 months prior to Screening and/or during the study.
Subject has participated in a program of neurostimulation in the past 3 months or plans to participate during the study.
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