Urinary Urgency Incontinence
Conditions
Keywords
UUI
Brief summary
Prospective, multi-center, single-arm, seamless phase-pivotal study conducted in participants diagnosed with UUI who have failed or could not tolerate more conservative treatment. The trial will be conducted in two phases. Objective of Phase I: To assess the utilization of the system during the Sacral Nerve Stimulation (SNS) trial period and to help inform the length of hours of daily stimulation to be used in Phase II of the trial. Objective of Phase II: To assess the safety and efficacy of the Neuspera SNS System at 6-months for the primary efficacy endpoint and at 12 months for secondary safety and efficacy endpoints.
Detailed description
Neuspera's Implantable Sacral Nerve Stimulation (SNS) System is indicated to treat participants with UUI who have failed or could not tolerate more conservative treatments. The study will be conducted in two phases: Phase I of the study will be conducted at up to 9 clinical study sites in the US and Europe. Phase II of the study will be conducted in up to 35 clinical sites in the US and Europe, inclusive of the Phase I centers. Prospective, multi-center, single-arm, seamless phase-pivotal study. Objective of Phase I: To assess the utilization of the system during the Sacral Nerve Stimulation (SNS) trial period and to help inform the length of hours of daily stimulation to be used in Phase II of the trial. Objective of Phase II: To assess the safety and efficacy of the Neuspera SNS System at 6-months for the primary efficacy endpoint and at 12 months for secondary safety and efficacy endpoints. All participants will receive the same length of device stimulation as determined in Phase I testing. Phase I will enroll up to 55 participants. Phase II will enroll up to 255 participants.
Interventions
DEVICENeuspera Implantable Sacral Nerve Stimulation System
Stimulation of the Sacral Nerve.
Sponsors
Neuspera Medical, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, seamless two-phased pivotal study design. Phase I is designed to assess the initial feasibility of Neuspera's Implantable SNS System and to determine optimal daily stimulation parameters for Phase II. The data from Phase I informed the duration of daily stimulation and was applied in Phase II, which aims to evaluate the safety and efficacy of the system. Phase I and Phase II involve distinct patient populations with no overlap. Phase I enrolled 89 subjects and Phase II enrolled 242 subjects.
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has a Body Mass Index (BMI) between 18 and 40. 2. Has a diagnosis of UUI for greater than or equal to 6 months prior to the screening baseline visit date. 3. Has failed or was not a candidate for more conservative treatment (e.g. pelvic floor training, biofeedback, behavioral modification). 4. Has failed or could not tolerate (stopped taking medication due to lack of efficacy or intolerable side effects) or not a good candidate for (as determined by treating physician) at least one (1) antimuscarinic or β3 adrenoceptor agonist medication. 5. Has a diagnosis of UUI with at least 4 UUI episodes on a 72-hour diary, and minimum of one (1) UUI episode per 24-hour period.
Exclusion criteria
1. Has a hemoglobin A1c of greater than 8 percent, or has diabetes mellitus with glucosuria. 2. Has diabetic neuropathy. 3. Has interstitial cystitis or bladder pain syndrome as defined by either American Urological Association (AUA) or European Association of Urology (EAU) guidelines, chronic pelvic pain or recurrent symptomatic urinary tract infections. 4. Has neurogenic bladder dysfunction such as traumatic or atraumatic myelopathy, multiple sclerosis, Parkinsonism, or history of cerebrovascular accident. 5. Has documented urinary retention within 6 months prior to the screening baseline visit date. 6. Has clinically significant bladder outlet obstruction. 7. Is a subject with a mechanical obstruction such as benign prostatic hypertrophy, urethral stricture or cancer. 8. Has primary stress incontinence or mixed incontinence where the stress component predominates or has been treated surgically for stress urinary incontinence within 6 months prior to the screening baseline visit date. 9. Has received tibial nerve stimulation (TNS) in the past 3 months for the treatment of overactive bladder or unwilling to stay off TNS therapy for 12-month period following implant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint: Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence Episodes. | 6 months | Change in Urinary Urgency Incontinence episodes at six months, relative to the number of Urinary Urgency Incontinence episodes at baseline. |
| Primary Safety Endpoint: Defined as the Proportion of Subjects Experiencing a Device-related Serious Adverse Events. | 6 months | The analysis of the endpoint is the proportion of subjects experiencing a device-related SAE through the 6-month post-implant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II Urgent Voids Per Day | 6 and 12 months | Change in urgent voids per day from baseline to 6-months and 12 months. Calculated across all diary episodes with at least mild urgency. |
| Phase II Change in Average Number of Daily Voids | 6 and 12 months | Change in average number of daily voids from baseline in subjects with at least 8 voids at baseline. |
| Phase II Comprehensive Summary of All Adverse Events | 6 and 12 months | The incidence of adverse events will be reported. |
| Phase II Device Parameter Information Collected | 6 and 12 months | Device amplitude will be collected in volts. |
| Phase II Physician and Subject User Experience Questionnaire | 6 and 12 months | Physician and subject satisfaction will be obtained by answering questions on the use of the device using a five point scale:strongly agree, agree, neither agree nor disagree, disagree, strongly disagree. Answers towards strongly agree indicate a better outcome. |
| Phase II Change in Quality of Life: Measured From Baseline as Measured and Assessed by the Total and Subset International Consultation on Incontinence Questionnaire Overactive Bladder Quality of Life Score. | 6 and 12 months | Change from baseline in qualify of life. Total score (25 min,160 max) with higher score indicating increase impact on quality of life. |
| Phase II Safety Endpoint: Defined as the Incidence of Device-related Serious Adverse Events in the Post-trial Period Follow-up. | 12 months | The number of serious adverse events related to the device. |
| Phase II Urinary Output | 6 and 12 months | Total urinary output as measured by 72-hour bladder diary. |
| Phase II Fecal Incontinence Measured by Wexner Scale | 6 months | Wexner scale total points 0-20, higher the score the worse the outcome. Fecal incontinence as measured by the Wexner Scale compared to baseline. |
| Phase II Patient Global Impression of Improvement | 6 and 12 months | Patient Global Impression of Improvement measured after implant during follow-up. Single question answered on a seven point scale: very much better, much better, a little better, no change, a little worse, much worse, very much worse. Selection of very much better is the best outcome. |
| Phase II Urinary Tract Symptoms Questionnaire: International Consultation on Incontinence Questionnaire Female & Male Lower Urinary Tract Symptoms Modules | 6 and 12 months | Change in female lower urinary tract symptoms questionnaire. Male questionnaire score ranges from 0-52 and female questionnaire score ranges from 0-48. Higher number indicates worse outcome. |
| Phase II Efficacy Endpoint: Defined as the Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence. | 12 months | Change in Urinary Urgency Incontinence episodes at 12 months post-completion of the trial phase, relative to the number of Urinary Urgency Incontinence episodes at baseline prior to the trial phase. |
Countries
Belgium, Netherlands, United States
Participant flow
Pre-assignment details
Ph I Study: Of 89 subjects consented, 39 subjects had implant attempted, 34 were successfully implanted. 35 subjects were screen failures, 11 withdrew consent, 1 withdrawn by investigator, 2 LTF, and 1 other withdrawal reason. Ph II Study: Of 242 subjects consented, 130 subjects had implant attempted and 128 were successfully implanted. 80 subjects were screen failure,16 withdrew consent, 3 withdrawn by investigator, 5 LTF, 4 due to site termination by sponsor, and 4 other withdrawal reasons.
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Neuspera Implantable Sacral Nerve Stimulation System Implantation of the simulator. Neuspera Implantable Sacral Nerve Stimulation System: Stimulation of the Sacral Nerve. | 39 |
| Phase II: Neuspera Implantable Sacral Nerve Stimulation System Implantation of the simulator. Neuspera Implantable Sacral Nerve Stimulation System: Stimulation of the Sacral Nerve. | 130 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Implant attempted but not completed | 5 | 2 |
| Overall Study | Missed Visit | 0 | 2 |
| Overall Study | Not satisfied with therapy outcome | 0 | 8 |
| Overall Study | Other reason | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Phase I: Neuspera Implantable Sacral Nerve Stimulation System | Phase II: Neuspera Implantable Sacral Nerve Stimulation System | Total |
|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 12.6 | 60.4 Years STANDARD_DEVIATION 10.2 | 60.2 Years STANDARD_DEVIATION 10.8 |
| Body Mass Index (BMI) | 30 kg/m2 STANDARD_DEVIATION 5.4 | 29.5 kg/m2 STANDARD_DEVIATION 5.1 | 29.6 kg/m2 STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 10 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 120 Participants | 158 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 38 Participants | 124 Participants | 162 Participants |
| Sex: Female, Male Female | 37 Participants | 128 Participants | 165 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 130 |
| other Total, other adverse events | 10 / 39 | 0 / 130 |
| serious Total, serious adverse events | 1 / 39 | 16 / 130 |
Outcome results
Primary
Primary Efficacy Endpoint: Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence Episodes.
Change in Urinary Urgency Incontinence episodes at six months, relative to the number of Urinary Urgency Incontinence episodes at baseline.
Time frame: 6 months
Population: Completers data: number of subjects with completed assessments for primary endpoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I, Neuspera Implantable Sacral Nerve Stimulation System | Primary Efficacy Endpoint: Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence Episodes. | 93.3 percentage of participants |
| Phase II, Neuspera Implantable Sacral Nerve Stimulation System | Primary Efficacy Endpoint: Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence Episodes. | 95.5 percentage of participants |
Primary
Primary Safety Endpoint: Defined as the Proportion of Subjects Experiencing a Device-related Serious Adverse Events.
The analysis of the endpoint is the proportion of subjects experiencing a device-related SAE through the 6-month post-implant.
Time frame: 6 months
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I, Neuspera Implantable Sacral Nerve Stimulation System | Primary Safety Endpoint: Defined as the Proportion of Subjects Experiencing a Device-related Serious Adverse Events. | 0 Participants |
| Phase II, Neuspera Implantable Sacral Nerve Stimulation System | Primary Safety Endpoint: Defined as the Proportion of Subjects Experiencing a Device-related Serious Adverse Events. | 0 Participants |
Secondary
Phase II Change in Average Number of Daily Voids
Change in average number of daily voids from baseline in subjects with at least 8 voids at baseline.
Time frame: 6 and 12 months
Secondary
Phase II Change in Quality of Life: Measured From Baseline as Measured and Assessed by the Total and Subset International Consultation on Incontinence Questionnaire Overactive Bladder Quality of Life Score.
Change from baseline in qualify of life. Total score (25 min,160 max) with higher score indicating increase impact on quality of life.
Time frame: 6 and 12 months
Secondary
Phase II Comprehensive Summary of All Adverse Events
The incidence of adverse events will be reported.
Time frame: 6 and 12 months
Secondary
Phase II Device Parameter Information Collected
Device amplitude will be collected in volts.
Time frame: 6 and 12 months
Secondary
Phase II Efficacy Endpoint: Defined as the Percentage of Participants Who Experience a 50 Percent or More Change in Urinary Urgency Incontinence.
Change in Urinary Urgency Incontinence episodes at 12 months post-completion of the trial phase, relative to the number of Urinary Urgency Incontinence episodes at baseline prior to the trial phase.
Time frame: 12 months
Secondary
Phase II Fecal Incontinence Measured by Wexner Scale
Wexner scale total points 0-20, higher the score the worse the outcome. Fecal incontinence as measured by the Wexner Scale compared to baseline.
Time frame: 6 months
Secondary
Phase II Patient Global Impression of Improvement
Patient Global Impression of Improvement measured after implant during follow-up. Single question answered on a seven point scale: very much better, much better, a little better, no change, a little worse, much worse, very much worse. Selection of very much better is the best outcome.
Time frame: 6 and 12 months
Secondary
Phase II Physician and Subject User Experience Questionnaire
Physician and subject satisfaction will be obtained by answering questions on the use of the device using a five point scale:strongly agree, agree, neither agree nor disagree, disagree, strongly disagree. Answers towards strongly agree indicate a better outcome.
Time frame: 6 and 12 months
Secondary
Phase II Safety Endpoint: Defined as the Incidence of Device-related Serious Adverse Events in the Post-trial Period Follow-up.
The number of serious adverse events related to the device.
Time frame: 12 months
Secondary
Phase II Urgent Voids Per Day
Change in urgent voids per day from baseline to 6-months and 12 months. Calculated across all diary episodes with at least mild urgency.
Time frame: 6 and 12 months
Secondary
Phase II Urinary Output
Total urinary output as measured by 72-hour bladder diary.
Time frame: 6 and 12 months
Secondary
Phase II Urinary Tract Symptoms Questionnaire: International Consultation on Incontinence Questionnaire Female & Male Lower Urinary Tract Symptoms Modules
Change in female lower urinary tract symptoms questionnaire. Male questionnaire score ranges from 0-52 and female questionnaire score ranges from 0-48. Higher number indicates worse outcome.
Time frame: 6 and 12 months