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OnabotulinumtoxinA and Hydrogel admixture

Phase 3

Urinary Incontinence | Small molecule | Nephrology |AbbVie Inc.|Last Updated: Aug 13, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials4
Total Enrollment736
FDA Designations
No designations recorded
Clinical Trials (4)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01852058A Long-Term Extension Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor OveractivityPHASE3 COMPLETED 95Jan 11, 2014Oct 3, 2019May 12, 202030 United States, Belgium +6
NCT01852045Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Pediatric PatientsPHASE3 COMPLETED 114Jul 2, 2013Oct 11, 2018Nov 21, 201931 United States, Belgium +6
NCT01600716Safety and Efficacy Study of OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity (NDO) in Non-Catheterizing Patients With Multiple Sclerosis (MS)PHASE3 COMPLETED 144Jun 13, 2012Mar 27, 2015Apr 30, 201910 United States, Belgium +6
NCT03320850BOTOX® Intravesical Instillation in Participants With Overactive Bladder and Urinary IncontinencePHASE2 COMPLETED 383Oct 4, 2017Jul 21, 2020Aug 13, 202163 United States, Canada
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Study Endpoints
Primary Endpoints
Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1
Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle.

Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2
Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle.

Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3
Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle.

Change From Baseline in Daily Average Frequency of Daytime Urinary Incontinence Episodes
Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 2 consecutive days (normalized to a 12-hour daytime period) prior to the study visit. Daytime was defined as the time between waking up to start the day and first morning catheterization and going to bed to sleep for the night. The number of incontinence episodes were averaged daily during this period. A negative change from Baseline indicates improvement. Least squares estimates were based on an Analysis of Covariance (ANCOVA) model.

Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes
Baseline, Week 6

Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. The number of episodes of urinary incontinence is recorded over a 3-day period the week of the study visit. A negative number change from baseline indicates a reduction in incontinence episodes (improvement) and a positive number change indicates an increase in incontinence episodes (worsening).

Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day
Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12

The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses.

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period
Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks)

An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.

Secondary Endpoints
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)
First injection on Day 1 in Study 120 through completion of Study 121 (Up to 108 weeks)
Percentage of Participants With ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction From Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1
Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1
Percentage of Participants With ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction From Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2
Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
OnabotulinumtoxinA 50 UEXPERIMENTALFollowing treatment with onabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).
OnabotulinumtoxinA 100 UEXPERIMENTALFollowing treatment with onabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).
OnabotulinumtoxinA 200 UEXPERIMENTALFollowing treatment with onabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).
OnabotulinumtoxinAEXPERIMENTALOnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA 100 U injection.
Placebo (Normal Saline)OTHERPlacebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
100U cohort - BOTOX® plus Hydrogel admixtureEXPERIMENTAL100U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1
100U cohort - Placebo plus Hydrogel admixturePLACEBO_COMPARATORPlacebo and Hydrogel admixture administered as a single intravesical instillation on Day 1
300U cohort - BOTOX® plus Hydrogel admixtureEXPERIMENTAL300U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1
300U cohort - Placebo plus Hydrogel admixturePLACEBO_COMPARATORPlacebo and Hydrogel admixture administered as a single intravesical instillation on Day 1
400U cohort - BOTOX® plus Hydrogel admixtureEXPERIMENTAL400U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1
400U cohort - Placebo plus Hydrogel admixturePLACEBO_COMPARATORPlacebo and Hydrogel admixture administered as a single intravesical instillation on Day 1
500U cohort - BOTOX® plus Hydrogel admixtureEXPERIMENTAL500U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1
500U cohort - Placebo plus Hydrogel admixturePLACEBO_COMPARATORPlacebo and Hydrogel admixture administered as a single intravesical instillation on Day 1
Interventions
NameTypeDescription
OnabotulinumtoxinABIOLOGICALOnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.
Placebo (Normal Saline)DRUGPlacebo (normal saline) is administered into the detrusor at Day 1.
OnabotulinumtoxinA and Hydrogel admixtureDRUGBOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation
Placebo and Hydrogel admixtureDRUGPlacebo and Hydrogel admixture administered as a single intravesical instillation
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Eligibility Criteria
Age Range5 Years — 17 Years
SexALL
Healthy VolunteersNo
Study Sites30

Inclusion Criteria: * Successfully completed participation in Study 191622-120 * Aged ≥ 5 years to ≤ 17 years at the time of entry into Study 191622-120 * Regularly using clean intermittent catheterization to empty the bladder Exclusion Criteria: * Myasthenia gravis, Eaton-Lambert syndrome, or am...

Countries:United StatesBelgiumCanadaCzechiaFranceItalyPolandTurkey (Türkiye)PortugalRussia
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