Dementia With Lewy Bodies
Conditions
Keywords
Dementia with Lewy bodies, Lewy bodies, intepirdine, RVT-101, dementia
Brief summary
This study seeks to evaluate the efficacy and safety of intepirdine (RVT-101) in patients with dementia with Lewy bodies.
Detailed description
The efficacy and safety of RVT-101 at doses of 70 mg and 35 mg daily will be evaluated over a 24-week double-blind treatment period in patients with dementia with Lewy bodies. The randomization ratio will be 1:1:1 (70 mg RVT-101: 35 mg RVT-101: placebo). Subjects completing this study will be eligible to enroll in an extension study of RVT-101 (Study RVT-101-2002).
Interventions
DRUGRVT-101 35 mg
once daily, oral, 35-mg tablets
DRUGRVT-101 70 mg
once daily, oral, 35-mg tablets
DRUGPlacebo
once daily, oral, matching tablets
Sponsors
Axovant Sciences Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subject with probable DLB * Mini Mental State Examination (MMSE) score of 14-26 inclusive at Screening and Baseline * Patient has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator * Patient has a reliable caregiver who is willing to report on the subject's status throughout the study * Patients currently receiving therapy for DLB are eligible for enrollment
Exclusion criteria
* Atypical clinical features or clinical course that would lead the investigator to conclude primary symptoms are more likely explained by an alternate dementia diagnosis. * Any clinically relevant concomitant disease that, in the opinion of the investigator, makes the patient unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24 | Change from Baseline at 24 weeks | The primary endpoint was to assess the effects of intepirdine versus placebo on the UPDRS Part III after 24 weeks of treatment. UPDRS Part III scores range from 0 to 108, with higher scores indicating worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24 | Change from Baseline at 24 weeks | The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment. |
| Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24 | Change from Baseline at 24 weeks | 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. CIBIC+ is recorded on a 7-point scale with a score of 4 indicating no change, scores above 4 indicating worsening, and scores below 4 indicating improvement. |
Countries
Canada, France, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
484 participants signed consent and were screened for participation. Of these, 306 entered a 2-week single-blind placebo run-in period with treatment with placebo qd. There was an overlap between the participants from the run-in period and the participants that were randomized during the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects dosed with two Placebo tablets
Placebo: once daily, oral, matching tablets | 91 |
| RVT-101 35 mg Subjects dosed with one Placebo tablet + 1 35 mg tablet of RVT-101
RVT-101 35 mg: once daily, oral, 35-mg tablets | 89 |
| RVT-101 70 mg Subjects dosed with two RVT-101 35 mg tablets
RVT-101 70 mg: once daily, oral, 35-mg tablets | 88 |
| Total | 268 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 7 | 10 |
| Overall Study | Death | 0 | 1 | 1 |
| Overall Study | Disease Progression | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 4 | 1 |
| Overall Study | Sponsor Termination | 1 | 0 | 1 |
| Overall Study | Withdrawal by Caregiver | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | RVT-101 35 mg | RVT-101 70 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 73.6 years | 73.0 years | 73.0 years | 73.0 years |
| Age, Customized < 65 years | 7 Participants | 9 Participants | 12 Participants | 28 Participants |
| Age, Customized >/=65 years | 84 Participants | 80 Participants | 76 Participants | 240 Participants |
| Age, Customized < 74 years | 45 Participants | 45 Participants | 45 Participants | 135 Participants |
| Age, Customized >/= 74 years | 46 Participants | 44 Participants | 43 Participants | 133 Participants |
| BMI | 26.59 kg/m^2 | 26.51 kg/m^2 | 26.81 kg/m^2 | 26.64 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 86 Participants | 83 Participants | 86 Participants | 255 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 90 Participants | 81 Participants | 85 Participants | 256 Participants |
| Sex: Female, Male Female | 20 Participants | 22 Participants | 15 Participants | 57 Participants |
| Sex: Female, Male Male | 71 Participants | 67 Participants | 73 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 91 | 1 / 89 | 2 / 88 |
| other Total, other adverse events | 66 / 91 | 69 / 89 | 59 / 88 |
| serious Total, serious adverse events | 11 / 91 | 11 / 89 | 13 / 88 |
Outcome results
Primary
Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24
The primary endpoint was to assess the effects of intepirdine versus placebo on the UPDRS Part III after 24 weeks of treatment. UPDRS Part III scores range from 0 to 108, with higher scores indicating worse outcome.
Time frame: Change from Baseline at 24 weeks
Population: UPDRS Primary Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24 | -0.55 units on a scale | Standard Error 1.039 |
| RVT-101 35 mg | Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24 | 1.45 units on a scale | Standard Error 1.025 |
| RVT-101 70 mg | Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) Change From Baseline at Week 24 | -1.29 units on a scale | Standard Error 1.056 |
p-value: 0.15895% CI: [-4.8, 0.79]Mixed Models Analysis
p-value: 0.606995% CI: [-2.08, 3.55]Mixed Models Analysis
Secondary
Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24
The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.
Time frame: Change from Baseline at 24 weeks
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24 | 1.68 units on a scale | Standard Error 0.774 |
| RVT-101 35 mg | Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24 | 2.15 units on a scale | Standard Error 0.769 |
| RVT-101 70 mg | Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Change From Baseline at Week 24 | 1.01 units on a scale | Standard Error 0.796 |
p-value: 0.653195% CI: [-2.55, 1.6]Mixed Models Analysis
p-value: 0.527495% CI: [-1.41, 2.75]Mixed Models Analysis
Secondary
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24
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. CIBIC+ is recorded on a 7-point scale with a score of 4 indicating no change, scores above 4 indicating worsening, and scores below 4 indicating improvement.
Time frame: Change from Baseline at 24 weeks
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24 | 4.42 units on a scale | Standard Error 0.127 |
| RVT-101 35 mg | Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24 | 4.27 units on a scale | Standard Error 0.128 |
| RVT-101 70 mg | Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Change From Baseline at Week 24 | 4.35 units on a scale | Standard Error 0.131 |
p-value: 0.395395% CI: [-0.2, 0.5]Mixed Models Analysis
p-value: 0.700895% CI: [-0.28, 0.42]Mixed Models Analysis