Dementia with Lewy Bodies MedDRA version: 19.0 Level: PT Classification code 10067889 Term: Dementia with Lewy bodies System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: RVT-101
Product Code: RVT-101
Pharmaceutical Form: Tablet
INN or Proposed INN: 3-(Phenylsulfonyl)-8-(1-piperazinyl) quinoline
CAS Number: 607742-69-8
Current Sponsor code: RVT-101
Other
Sponsors
Axovant Sciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female subject with a clinical diagnosis of DLB established for a minimum of 2 months prior to Visit 1 and who currently meet consensus criteria as determined by the PI by having dementia and either a) or b) below: a) At least two of the following three Core Criteria: i) Fluctuating cognition, ii) Recurrent visual hallucinations, or iii) Spontaneous features of parkinsonism. b) One of the Core Criteria above and as least one of the following three Suggestive Criteria: i) REM Sleep Behavior Disorder, ii) Severe Neuroleptic Sensitivity, or iii) Low dopamine transporter uptake in basal ganglia on single photon emission computed tomography (SPECT) or positron emission tomography (PET) scan as determined by the investigator (SPECT or PET must have been performed in the 12 months prior to the Screening Visit otherwise it must be repeated prior to the Run-In Period). 2) Subject has an MMSE score of 14 to 26, inclusive, at Screening. In addition, the MMSE score at Baseline (V3) must not have declined by 4 points or more from the Visit 2 MMSE score. For subjects with an MMSE score at Baseline (V3) of 4 or more points lower than their Visit 2 MMSE score or an MMSE <14 at V3, the Run-In period may be extended for 1 to 10 days. If, after the first extension to the Run-In Period, the subject still does not meet the MMSE stability criterion, the Run-In period may again be extended for an additional 1 to 10 days. No more than 2 extensions to the Run-In Period will be allowed. If this MMSE stability requirement is not met after 2 extensions of the Run-In Period, the subject will be discontinued from the study. 3) If the subject is currently receiving any of the following medications, the treatment regimen has been stable (i.e., no changes in the type of drug, dose or frequency of dosing) for at least 30 days prior to the Screening Visit and there is no intent to change this treatment regimen for the duration of the study. Acetylcholinesterase inhibitors (i.e., donepezil, galantamine, rivastigmine, tacrine) Memantine Axona® (caprylidene) Antidepressants (other than MAO inhibitors) Thyroid hormones, Atypical antipsychotics (e.g., quetiapine),Benzodiazepines and other sedatives/hypnotics 4) Subject is 50 to 85 years of age, inclusive, at the time of the Screening Visit. 5) Female subjects 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 Screening. Female subjects of childbearing potential and who are sexually active are required to practice highly effective methods of birth control. Female subjects for whom menopausal status is in doubt, in the opinion of the investigator, will be required to use a highly form of birth control. Highly effective forms of birth control are defined as methods that have a failure rate of less than 1% per year when used correctly and consistently and include: ? combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal, or transdermal ? progestogen-only hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable ? intrauterine device (IUD) ? intrauterine hormone-releasing system ( IUS) ? bilateral tubal occlusion ? vasectomised
Exclusion criteria
Exclusion criteria: Other Causes for Dementia : 1) Parkinson?s disease dementia, vascular dementia, frontotemporal dementia, or Alzheimer?s disease dementia. 2) A CT or MRI scan performed within the past 12 months or at Screening could be interpreted as the primary cause of dementia (e.g., cerebrovascular disease [transient ischemic attack, stroke, hemorrhage]; structural or developmental abnormality; epilepsy; infectious, or degenerative or inflammatory/demyelinating CNS conditions) or any other history and/or evidence to suggest the same. 3) Current vitamin B12 deficiency, hypothyroidism, neurosyphilis, HIV dementia, or Korsakoff?s encephalopathy. 4) Focal findings on the neruological exam Confounding Medical Conditions: 5) History of schizophrenia, major depressive episode in the past 6 months bipolar affective disorder that in the opinion of the investigator would interfere with participation in the study or could affect performance on outcome measures. 6) Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, at Screening or at Baseline or; (2) suicidal behaviors within the past year or; (3) clinical assessment of significant suicidal risk during subject interview. 7) History of epilepsy, unexplained seizure or history of significant head trauma with loss of consciousness in the past 5 years. 8) History of malignancy during the 5 years before Screening. History of basal cell carcinoma and melanoma in situ are permitted. History of other cancers currently in a non-active state may be acceptable after review with the Medical Monitor. 9) Any clinically relevant concomitant disease including unregulated diabetes, progressive liver or kidney dysfunction, history of myocardial infarction or unstable angina within 6 months of Screening, history of more than one myocardial infarction within 5 years of Screening, history of clinically significant stroke, or any other medical or psychiatric condition, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study. 10) History of alcohol use disorder or other substance abuse disorder (excluding tobacco use). Concomintant Medications: 11) Participation in another investigational drug or device study during the 30 days prior to the Screening Visit (Visit 1), or within 5 half-lives of use of the investigational drug prior to the Screening Visit, whichever is longer. 12) Treatment with any concomitant medications : Butyrophenones, phenothiazines, and other ?conventional? antipsychotics, Barbiturates, MAO inhibitors, Any investigational drug, warfarin, phenytoin and (R)-acenocoumarol, ketoconazole, itraconazole, erythromycin, rifampicin, phenytoin and carbamazepine, itraconazole, ketoconazole, cyclosporin, diltiazem, verapamil, quinidine, and carvedilol. Unacceptable Tests/Laboratory values: 13) Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ?2.0 times upper limit of normal (ULN) at Screening. 14) Total bilirubin over 1.5 x ULN at Screening except due to documented Gilbert?s disease or evidence of Gilbert?s disease on Screening laboratory assessments. 15) Calculated creatinine clearance <40 mL/min (Cockroft-Gault formula) at Screening: 16) Positive hepatitis B surface antigen or hepatitis C antibody test at Screening. 17) Confirmed corrected QT interval (QTc) value greater than or equal to 450 msec for males or greater than or equal to 470 msec for females at Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To assess the effects of RVT-101 versus placebo on global function as measured by the Clinician?s Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) after 24 weeks of treatment ? To assess the effects of RVT-101 versus placebo on cognition as measured by the composite z-score of the 7 domains of the Cognitive Drug Research (CDR) computerized assessment system after 24 weeks of treatment (CDR domains include Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory, Speed of Memory, Cognitive Reaction Time and Reaction Time Variability);Secondary Objective: To assess the effects of RVT-101 versus placebo after 24 wks of treatment : 1.On attention, as measured by the z-score of the PoA domain of the CDR computerized assessment system 2.On instrumental activities of daily living as measured by the instrumental subscale of the ADCS-ADL scale 3.On cognition, including amnestic aspects of cognition, as measured by the ADAS-Cog-13 4. On working memory as a measure of executive func as assessed by the COWAT 5.On cognitive function as measured by a composite z-score combining the 7 domains for the CDR computerized assessment system and the COWAT 6.on hallucinations and delusions as measured by a 2-item subscore on the NPI which is the sum of the scores for the hallucinations and delusions domains 7.on visual hallucinations as measured by the NEVHI 8.On fluctuations in cognition using the CAF 9.On subject dependence using the DS 10.On an analysis of responders based on pre-specified efficacy evaluations 11. Assess the safety and tolerability;Primary end point(s): The primary efficacy endpoints will be an assessment of cognition and global function at Week 24. Change from baseline to Week 24 in cognition will be measured by a composite z-score of 7 domains of the CDR computerized assessment system (Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory, S | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: Instrumental activities of daily living will be measured by the instrumental subscale of the ADCS-ADL as a key secondary endpoint. Safety evaluation: Safety will be evaluated based on adverse events (AEs), physical examinations, vital signs (including measurements of orthostatic changes in blood pressure [BP] and heart rate [HR]), a questionnaire evaluating the occurrence of symptoms potentially associated with orthostasis, the Unified Parkinson's Disease Rating Scale - Part III (UPDRS-III) after 24 weeks of treatment, electrocardiograms (ECGs), the Columbia-Suicide Severity Rating Scale (C-SSRS) and routine clinical laboratory assessments.;Timepoint(s) of evaluation of this end point: The primary endpoints will be measured after 24 weeks of treatment. Study participation will last approximately 32 weeks: 0 to 4 weeks for Screening, a 2-week Single-Blind Run-In Period to evaluate baseline status, a 24-week randomized, double-blind, placebo-controlled Treatment Period and a 2-week Safety Follow-up Period for subjects who do not enter the extension study. There will be weekly clinical assessments for the first two weeks of double-blind treatment, bi-weekly assessments thereafter until 12 weeks post-randomization and every six weeks thereafter. For certain visits (Visits 5, 7 and 9), subjects may have the option of whether to have assessments performed at the clinical study site or by a trained, visiting nurse in their own home | — |
Countries
Canada, France, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Dept.
Axovant Sciences, Inc
Outcome results
None listed