A Phase 2b, double-blind, randomized, placebo-controlled study of RVT-101 in subjects with dementia with Lewy bodies (DLB).
- Conditions
- Dementia with Lewy Bodies. Dementia with Lewy bodies (DLB) is a type of dementia that shares symptoms with both Alzheimer's disease and Parkinson's disease.10057167
- Registration Number
- NL-OMON43126
- Lead Sponsor
- Axovant Sciences, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
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 (Visit 3) must not have declined by 4 points or more from the Visit 2 MMSE score. For subjects with an MMSE score at Baseline (Visit 3) of 4 or more points lower than their Visit 2 MMSE score, 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 (see also Section 8.1).
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 hor
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 phenprocoumon, (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) val
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy endpoint: The primary efficacy endpoints will be an assessment<br /><br>of cognition and global function at Week 24. Change from Baseline to Week 24 in<br /><br>cognition will be measured by a composite z-score of 7 domains of the CDR<br /><br>computerized assessment system (Power of Attention, Continuity of Attention,<br /><br>Quality of Working Memory, Quality of Episodic Memory, Speed of Memory,<br /><br>Cognitive Reaction Time and Reaction Time Variability). Global function at Week<br /><br>24 will be measured by the CIBIC+.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary efficacy endpoints: Instrumental activities of daily living will be<br /><br>measured by the instrumental subscale of the ADCS-ADL as a key secondary<br /><br>endpoint. Additional secondary endpoints are as described above in Objectives.</p><br>