Stress Urinary Incontinence
Conditions
Keywords
Urinary Incontinence, Stress, Tissue Therapy (Cell Therapy), Transplantation, Autologous
Brief summary
This randomized, double-blind, placebo-controlled, multicenter, confirmatory study will evaluate the efficacy and safety of Cook MyoSite Incorporated Autologous Muscle-Derived Cells (generic name Iltamiocel) compared to a placebo (vehicle) control dose in the treatment of stress urinary incontinence (SUI) in adult female patients.
Detailed description
Study comparing intrasphincteric injection of iltamiocel with placebo. Subjects unblinded after 12 month visits, but followed for up to 2 years. Subjects randomized to placebo could elect to receive open-label iltamiocel after completing 12 month visit.
Interventions
OTHERPlacebo
Placebo control is the vehicle solution used for the study product.
BIOLOGICALIltamiocel
AMDC is the study product (autologous muscle-derived cells). The generic name is iltamiocel. Single intraurethral injection of 150 x 10\^6 cells.
Sponsors
Cook MyoSite
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patient has primary symptoms of SUI, as confirmed by patient medical history and clinical symptoms, including a focused incontinence evaluation.
Exclusion criteria
* Patient has symptoms of pure urge incontinence as confirmed by basic evaluation of etiology from a patient medical history, including a focused incontinence history. * Patient has symptoms of mixed urinary incontinence where urge incontinence is the predominant factor. * Patient has had stress urinary incontinence symptoms less than 6 months prior to signing the informed consent. * Patient has not previously attempted conservative treatment prior to signing the informed consent. (Examples of conservative treatment include behavior modifications, bladder exercises, biofeedback, etc.) * Patient has more than 2 episode of awakening to void during normal sleeping hours. * Patient cannot be maintained on a stable dose and/or frequency of medication (including diuretics) known to affect lower urinary tract function, including but not limited to, anticholinergics, tricyclic antidepressants or alpha-adrenergic blockers, for at least 2 weeks prior to screening or is likely to change during the course of the study. * Patient is pregnant, lactating, or plans to become pregnant during the course of the study. * Patient refuses to provide written informed consent. * Patient is not at least 18 years of age. * Patient is not available for the follow-up evaluations as required by the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Participants With ≥ 50% Reduction in Stress Incontinence Episode Frequency From Baseline to 12 Months Post-treatment; as Assessed by 3 Day Diary | Baseline and 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months | Baseline and 12 months |
| Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months | Baseline and 12 months |
| Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months | Baseline and 12 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Baseline and 12 months | Spearman's correlation used for analysis |
| Treatment Durability at 24 Months | Baseline, 12 months, and 24 months after injection with iltamiocel | Treatment durability defined as iltamiocel-treated participants with reduction in stress incontinence episode frequency (SIEF) at 12 months who maintained that response at 24 months |
Countries
Belgium, Germany, United States
Participant flow
Pre-assignment details
311 subjects were enrolled (underwent biopsy procedure) and 297 subjects underwent study treatment with iltamiocel (199 subjects) or placebo (98 subjects). Analysis population is based on 297 subjects that underwent study treatment. At randomization, participants stratified by presence or absence of prior incontinence surgery and by \< 10 or ≥10 stress incontinence episodes over 3 day diary at screening.
Participants by arm
| Arm | Count |
|---|---|
| Iltamiocel AMDC is the study product (autologous muscle-derived cells). The generic name is iltamiocel. Single intraurethral injection of 150 x 10\^6 cells. | 199 |
| Placebo Placebo control is the vehicle solution used for the study product. Single intraurethral injection of vehicle control. | 98 |
| Total | 297 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Period | Withdrawal by Subject | 1 | 1 |
| Open Label - Unblinded Period | Adverse Event | 1 | 0 |
| Open Label - Unblinded Period | Lack of Efficacy | 9 | 0 |
| Open Label - Unblinded Period | Lost to Follow-up | 4 | 3 |
| Open Label - Unblinded Period | Withdrawal by Subject | 18 | 7 |
Baseline characteristics
| Characteristic | Total | Placebo | Iltamiocel |
|---|---|---|---|
| 24 Hour Pad Test Weight | 45.2 grams STANDARD_DEVIATION 81.1 | 40.9 grams STANDARD_DEVIATION 52.8 | 47.6 grams STANDARD_DEVIATION 91.8 |
| 6-Item Urogenital Distress Inventory Score - Short Form (UDI-6) | 39.2 scores on scales STANDARD_DEVIATION 16.8 | 40.5 scores on scales STANDARD_DEVIATION 18.4 | 38.5 scores on scales STANDARD_DEVIATION 16 |
| 7-Item Incontinence Impact Questionnaire - Short Form (IIQ-7) | 44.2 scores on scales STANDARD_DEVIATION 21.2 | 43.7 scores on scales STANDARD_DEVIATION 21.8 | 44.4 scores on scales STANDARD_DEVIATION 20.9 |
| Age, Continuous | 54.4 years STANDARD_DEVIATION 10.8 | 55.0 years STANDARD_DEVIATION 10.7 | 54.1 years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 289 Participants | 93 Participants | 196 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Global Quality of Life Assessment (GQOL) | 5.7 scores on scales STANDARD_DEVIATION 1 | 5.6 scores on scales STANDARD_DEVIATION 1.1 | 5.7 scores on scales STANDARD_DEVIATION 1 |
| Incontinence Quality of Life (IQOL) Assessment -Total Score | 59.2 scores on scales STANDARD_DEVIATION 20 | 59.5 scores on scales STANDARD_DEVIATION 20.2 | 59.0 scores on scales STANDARD_DEVIATION 21 |
| Incontinence Severity Index (ISI) | 7.5 scores on scales STANDARD_DEVIATION 2.5 | 7.4 scores on scales STANDARD_DEVIATION 2.8 | 7.6 scores on scales STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 273 Participants | 89 Participants | 184 Participants |
| Region of Enrollment Belgium | 3 participants | 1 participants | 2 participants |
| Region of Enrollment Germany | 7 participants | 3 participants | 4 participants |
| Region of Enrollment United States | 287 participants | 94 participants | 193 participants |
| Sex: Female, Male Female | 297 Participants | 98 Participants | 199 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Stress Incontinence Episodes Over 3 Day Diary | 14.5 stress leaks STANDARD_DEVIATION 11.4 | 15 stress leaks STANDARD_DEVIATION 14.2 | 14.2 stress leaks STANDARD_DEVIATION 9.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 199 | 0 / 98 | 0 / 198 | 0 / 92 |
| other Total, other adverse events | 84 / 199 | 28 / 98 | 21 / 198 | 22 / 92 |
| serious Total, serious adverse events | 11 / 199 | 9 / 98 | 12 / 198 | 4 / 92 |
Outcome results
Primary
Participants With ≥ 50% Reduction in Stress Incontinence Episode Frequency From Baseline to 12 Months Post-treatment; as Assessed by 3 Day Diary
Time frame: Baseline and 12 months
Population: All participants with baseline and 12 month 3 day diary data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iltamiocel | Participants With ≥ 50% Reduction in Stress Incontinence Episode Frequency From Baseline to 12 Months Post-treatment; as Assessed by 3 Day Diary | 103 Participants |
| Placebo | Participants With ≥ 50% Reduction in Stress Incontinence Episode Frequency From Baseline to 12 Months Post-treatment; as Assessed by 3 Day Diary | 52 Participants |
Secondary
Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months
Time frame: Baseline and 12 months
Population: All participants with baseline and 12 month 3 day diary data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iltamiocel | Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months | -5.8 stress leaks | Standard Deviation 11 |
| Placebo | Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months | -4.9 stress leaks | Standard Deviation 13.5 |
Secondary
Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months
Time frame: Baseline and 12 months
Population: All participants with baseline and 12 month diary data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iltamiocel | Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months | 53 Participants |
| Placebo | Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months | 22 Participants |
Secondary
Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months
Time frame: Baseline and 12 months
Population: All participants with baseline and 12 month 3 day diary data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iltamiocel | Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months | 73 Participants |
| Placebo | Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months | 30 Participants |
Other Pre-specified
Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency
Spearman's correlation used for analysis
Time frame: Baseline and 12 months
Population: All participants with baseline and 12 month diary data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of IIQ-7 improvement with stress incontinence episode reduction at 12 months | 0.522 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of GQOL improvement with stress incontinence episode reduction at 12 months | 0.537 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of UDI-6 improvement with stress incontinence episode reduction at 12 months | 0.408 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of ISI improvement with stress incontinence episode reduction at 12 months | 0.529 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of IQOL improvement with stress incontinence episode reduction at 12 months | -0.556 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of ISI improvement with stress incontinence episode reduction at 12 months | 0.599 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of IQOL improvement with stress incontinence episode reduction at 12 months | -0.456 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of IIQ-7 improvement with stress incontinence episode reduction at 12 months | 0.442 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of UDI-6 improvement with stress incontinence episode reduction at 12 months | 0.433 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency | Association of GQOL improvement with stress incontinence episode reduction at 12 months | 0.422 correlation coefficient |
Post Hoc
Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only)
Spearman's correlation used for analysis
Time frame: Baseline and 12 months
Population: All participants with prior surgery and baseline and 12 month diary data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of IIQ-7 improvement with stress incontinence episode reduction at 12 months | 0.427 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of GQOL improvement with stress incontinence episode reduction at 12 months | 0.561 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of UDI-6 improvement with stress incontinence episode reduction at 12 months | 0.424 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of ISI improvement with stress incontinence episode reduction at 12 months | 0.426 correlation coefficient |
| Iltamiocel | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of IQOL improvement with stress incontinence episode reduction at 12 months | -0.489 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of ISI improvement with stress incontinence episode reduction at 12 months | 0.476 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of IQOL improvement with stress incontinence episode reduction at 12 months | -0.460 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of IIQ-7 improvement with stress incontinence episode reduction at 12 months | 0.542 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of UDI-6 improvement with stress incontinence episode reduction at 12 months | 0.604 correlation coefficient |
| Placebo | Association of Change in Quality of Life Scores With Change in Stress Incontinence Episode Frequency (Prior Surgery Participants Only) | Association of GQOL improvement with stress incontinence episode reduction at 12 months | 0.190 correlation coefficient |
Post Hoc
Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only)
Participants with a history of prior SUI surgery with baseline and 12 month diary data.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iltamiocel | Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only) | -6.7 stress leaks | Standard Deviation 14.5 |
| Placebo | Change in the Frequency of Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only) | -4.5 stress leaks | Standard Deviation 11.5 |
Post Hoc
Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months (Prior Surgery Participants Only)
Participants with a history of prior SUI surgery with baseline and 12 month diary data.
Time frame: Baseline and 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iltamiocel | Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months (Prior Surgery Participants Only) | 14 Participants |
| Placebo | Participants With 0 or 1 Stress Incontinence Episodes Based on 3 Day Diary Records at 12 Months (Prior Surgery Participants Only) | 3 Participants |
Post Hoc
Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only)
Participants with a history of prior SUI surgery with baseline and 12 month diary data.
Time frame: Baseline and 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Iltamiocel | Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only) | 20 Participants |
| Placebo | Participants With at ≥ 75% Reduction in Stress Incontinence Episodes From Baseline at 12 Months (Prior Surgery Participants Only) | 4 Participants |
Other Pre-specified
Treatment Durability at 24 Months
Treatment durability defined as iltamiocel-treated participants with reduction in stress incontinence episode frequency (SIEF) at 12 months who maintained that response at 24 months
Time frame: Baseline, 12 months, and 24 months after injection with iltamiocel
Population: All participants who received iltamiocel treatment during the double-blind period and with 12-month and 24-month stress incontinence episode frequency (SIEF) diary data. Participants who received placebo treatment in the double-blind period are not included due to receiving iltamiocel treatment in the open-label period after unblinding or were exited from the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Iltamiocel | Treatment Durability at 24 Months | Participants that had ≥ 50% reduction in stress incontinence episodes at Month 12 and Month 24 data | 80 Participants |
| Iltamiocel | Treatment Durability at 24 Months | Participants that had ≥ 75% reduction in stress incontinence episodes at Month 12 and Month 24 data | 50 Participants |
| Iltamiocel | Treatment Durability at 24 Months | Participants that had ≤1 stress incontinence episodes at Month 12 and Month 24 data | 36 Participants |
Post Hoc
Treatment Durability at 24 Months (Prior Surgery Participants)
Treatment durability defined as participants with reduction in stress incontinence episode frequency (SIEF) at 12 months who maintained response at 24 months
Time frame: Baseline, 12 months, and 24 months after injection with iltamiocel
Population: Prior surgery participants who received iltamiocel treatment during the double-blind period with 12-month and 24-month stress incontinence episode frequency (SIEF) diary data. Prior surgery participants who received placebo treatment in the double-blind period are not included due to receiving iltamiocel treatment in the open-label period after unblinding or were exited from the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Iltamiocel | Treatment Durability at 24 Months (Prior Surgery Participants) | Participants that had ≥ 50% reduction in stress incontinence episodes at Month 12 and Month 24 data | 19 Participants |
| Iltamiocel | Treatment Durability at 24 Months (Prior Surgery Participants) | Participants that had ≥ 75% reduction in stress incontinence episodes at Month 12 and Month 24 data | 12 Participants |
| Iltamiocel | Treatment Durability at 24 Months (Prior Surgery Participants) | Participants that had ≤1 stress incontinence episodes at Month 12 and Month 24 data | 11 Participants |