Phase 1 Study With OAB Assessing the Safety and Activity of hMaxi-K Gene Transfer

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety of a single treatment of hMaxi-K compared to placebo (PBS-20% sucrose) administered by direct bladder wall injections. Two dose levels (16000 µg and 24000 µg; 20 or 30 bladder wall injections, respectively) in females with moderate Overactive Bladder/Detrusor overactivity (OAB/DO) of ≥6 months duration will be evaluated. In each dose level, 6 participants will receive hMaxi-K and 3 will receive placebo.

Detailed Description
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This is a Phase 1 double-blind, placebo-controlled study assessing the safety and activity of 2 escalating doses of hMaxi-K gene transfer by direct injection into the bladder wall in female participants with OAB/DO. The safety parameters to be monitored include: adverse events, clinical laboratory tests, electrocardiograms, and physical examinations. The secondary objective is to evaluate the efficacy of multiple intramuscular injections of hMaxi-K compared to the control group. Efficacy parameters that will be evaluated are: number of micturitions per 24 hours, volume per micturition, incontinence episodes, pad weight measurement of accidental bladder leaks, uninhibited contractions during cystoscopy and other cystoscopic evaluations, and general and bladder-specific quality of life assessments (Kings Health Questionnaire, SF-12 Health Survey, and International Consultation on Incontinence Questionnaire [ICIQ-SF]).

Official Title
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Phase 1 Double Blind, Placebo Controlled Study Assessing Safety and Activity Of 2 Escalating Doses of hMaxi-K Gene Transfer By Direct Injection Into the Bladder Wall In Female Subjects With OAB

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Placebo (PBS-20% sucrose)
* Drug: hMaxi-K


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women of ≥18 years of age and non-childbearing potential Symptoms of overactive bladder for ≥6 months including at least one of the following: Frequent micturition ≥8 times per 24 hours Urinary urgency or nocturia Urge urinary incontinence five or more incontinence episodes per week Detrusor overactivity with ≥1 uncontrolled phasic contraction(s) of the detrusor of at least 5 centimeters/H20 pressure documented on cystometry at Screening Visit 1A Residual urine volume of ≤200 milliliters (ml) Non-response or poor tolerance to previous treatment for symptoms of OAB/urinary incontinence and do not wish to continue these treatments Have screening laboratory values and electrocardiogram that are within the normal range Able to understand study requirements (i.e., literate in English), give written informed consent, and comply with all study procedures and requirements. Exclusion Criteria: A woman with a positive serum (HCG) pregnancy test or who is lactating History of three or more culture-documented recurrent urinary tract infections per year Current history or previous diagnosis of painful bladder syndrome (interstitial cystitis) with pain in the region of the pelvis, perineum, or lower abdomen relieved by voiding Current history of neurological bladder dysfunction A life expectancy of less than 12 months Current history of Grade 2 or greater cystocele An indwelling urethral catheter or need for clean intermittent self-catheterization Recent heart attack Uncontrolled diabetes Latex allergy Stress urinary incontinence as determined by observation of the participant coughing while standing with a full bladder and/or response of 2 or 3 on the following Stress Urinary Incontinence question: Do you experience leakage when laughing, coughing, lifting heavy objects or other types of discreet, moderately intense activities? 0=NONE: No leakage. 1=MILD: Minimal leakage on rare occasions during these types of activities; easily tolerated; do not use pads for this. 2=MODERATE: Enough leakage that it requires occasional use of pads and may interfere with usual activity and tasks. 3=SEVERE: Extreme leakage and discomfort that stops all activity and tasks and requires the use of pads on all occasions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: sequential, dose escalation
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (PBS-20% sucrose)<br>PBS-20% sucrose administered during two single-treatment dose levels (16000 micrograms [µg] and 24000 µg) by direct bladder wall intramuscular injections, 20 to 30 injections depending on active dose comparator. | Drug: Placebo (PBS-20% sucrose)<br> <br> * Other names: Placebo;|
| Experimental: hMaxi-K 16000 µg<br>Single treatment (16000 µg by 20 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo. | Drug: hMaxi-K<br>* Single treatment/2 escalating dose levels (16000 µg and 24000 µg by intramuscular injection)<br>* Other names: URO-902;|
| Experimental: hMaxi-K 24000 µg<br>Single treatment (24000 µg by 30 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo. | Drug: hMaxi-K<br>* Single treatment/2 escalating dose levels (16000 µg and 24000 µg by intramuscular injection)<br>* Other names: URO-902;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with any treatment-emergent adverse event during the Treatment Period |  | 6 months (24 weeks) per participant | 
| Number of participants with any treatment-emergent adverse event during the Safety Follow-up Period |  | 18 months | 
| Number of participants with any clinically significant clinical laboratory test value during the Treatment Period |  | 6 months (24 weeks) per participant | 
| Number of participants with any clinically significant clinical laboratory test value during the Safety Follow-up Period |  | 18 months | 
| Number of participants with any clinically significant electrocardiogram finding during the Treatment Period |  | 6 months (24 weeks) per participant | 
| Number of participants with any clinically significant electrocardiogram finding during the Safety Follow-up Period |  | 18 months | 
| Number of participants with any clinically significant physical examination finding during the Treatment Period |  | 6 months (24 weeks) per participant | 
| Number of participants with any clinically significant physical examination finding during the Safety Follow-up Period |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the number of micturitions per day |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in the volume of micturitions |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in incontinence episodes |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in pad weight |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in uninhibited contractions during cystoscopy |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in the participant rating of the Kings Health Questionnaire (KHQ) score |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in the International Consultation on Incontinence Questionnaire-Short Form score |  | Baseline; 6 months (24 weeks) per participant | 
| Change from Baseline in the Short Form-12 (SF-12) score |  | Baseline; 6 months (24 weeks) per participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overactive Bladder, OAB, gene therapy