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

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]).

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