Alzheimer’s Disease MedDRA version: 19.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: RVT-101
Product Code: RVT-101
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: 607742-69-8
Sponsors
Axovant Sciences Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 with 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, the Run-in period 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 highly effective methods of birth control during the course of the study and until the completion of the follow-up visit. Male subjects who are sexually active will also be required to use an adequate form of birth control including at least 1 barrier method. - 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 w
Exclusion criteria
Exclusion criteria: 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 Intellectual Development Disorder. - 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 at screening - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of RVT-101 versus placebo as adjuncts to stable donepezil therapy: - on cognitive function as measured by the ADAS-Cog-11 after 24 weeks of treatment. - on activities of daily living as measured by ADCS-ADL scale after 24 weeks of treatment ; Secondary Objective: To assess the effects of RVT-101 versus placebo as adjuncts to stable donepezil therapy; - on cognition as measured by the ADAS-Cog-13 after 24 weeks of treatment - on global clinical assessment of change as measured by CIBIC+ after 24 weeks of treatment - on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) after 24 weeks of treatment - on an analysis of responders based on prespecified efficacy evaluations - on subject dependency as measured by the Dependence Scale (DS) To assess: - how baseline MMSE score affects efficacy outcome measures after 24 weeks of treatment - the safety and tolerability of RVT-101 as an adjunct therapy to stable donepezil treatment To measure RVT-101 plasma concentrations and donepezil plasma concentrations in study subjects To estimate the PK parameters of RVT-101 and explore relationships to efficacy or safety endpoints, as appropriate ; Primary end point(s): - ADAS-Cog-11 score change from baseline to Week 24 - ADCS-ADL score change from baseline to Week 24 ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ADAS-Cog-13 score change from baseline to Week 24 - CIBIC+ score at Week 24 - ADAS-Cog score change from baseline - ADCS-ADL score change from baseline; - CIBIC+ score; all assessed by MMSE baseline score - NPI score change from baseline to Week 24 - Analysis of responders defined as improvement of at least 3 points on ADAS-Cog-11 from baseline AND at least no worsening on ADCS-ADL from baseline AND no worsening on CIBIC+ at 24 weeks - DS score change from baseline to Week 24 - Measurement of concentrations of RVT-101 and donepezil in plasma - Steady state area under the concentration-time curve (AUCtss), peak concentration (Cmax-ss), and minimum concentration (Cmin-ss) of RVT-101 in plasma - Occurrence of adverse events (AEs) and changes in physical examinations, vital signs measurements, electrocardiograms (ECGs), routine laboratory assessments, and Columbia Suicide Severity Rating Scale (C-SSRS) ;Timepoint(s) of evaluation of this end point: Baseline to Week 24 | — |
Countries
Argentina, Australia, Bulgaria, Canada, Chile, Croatia, Czech Republic, France, Germany, Italy, Korea, Republic of, Malaysia, Poland, Serbia, Singapore, Slovakia, Spain, United Kingdom, United States
Contacts
Public ContactProject Management
Worldwide Clinical Trials
Outcome results
None listed