Phase 1 Study With OAB Assessing the Safety and Activity of hMaxi-K Gene Transfer
- Conditions
- Overactive Bladder
- Interventions
- Drug: Placebo (PBS-20% sucrose)
- Registration Number
- NCT01870037
- Lead Sponsor
- Urovant Sciences GmbH
- Brief Summary
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
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 \[ICIQ-SF\]).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 13
-
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
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Residual urine volume of ≤200 milliliters (ml)
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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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description hMaxi-K 24000 µg hMaxi-K Single treatment (24000 µg by 30 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo. Placebo (PBS-20% sucrose) Placebo (PBS-20% sucrose) 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. hMaxi-K 16000 µg hMaxi-K Single treatment (16000 µg by 20 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo.
- Primary Outcome Measures
Name Time Method Number of participants with any treatment-emergent adverse event 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 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 treatment-emergent adverse event during the Treatment Period 6 months (24 weeks) per participant 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
Name Time Method Change from Baseline in the Short Form-12 (SF-12) score Baseline; 6 months (24 weeks) per participant Change from Baseline in the number of micturitions per day 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 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 the International Consultation on Incontinence Questionnaire-Short Form score Baseline; 6 months (24 weeks) per participant
Trial Locations
- Locations (3)
AccuMed Research Associates
🇺🇸Garden City, New York, United States
NYU
🇺🇸New York, New York, United States
Premier Medical Group of the Hudson Valley, PC
🇺🇸Poughkeepsie, New York, United States