Clinical trial NCT01870037: Phase 1 Study With OAB Assessing the Safety and Activity of hMaxi-K Gene Transfer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overactive Bladder
Keywords: Overactive Bladder
OAB
gene therapy
Lead sponsor: Urovant Sciences GmbH
Sponsor class: INDUSTRY
Collaborators: name: Ion Channel Innovations
First posted: 2013-06-05
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: sequential, dose escalation
Primary purpose: OTHER

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 \[ICIQ-SF\]).

Eligibility criteria: Inclusion Criteria:

1. Healthy women of ≥18 years of age and non-childbearing potential
2. Symptoms of overactive bladder for ≥6 months including at least one of the following:

   1. Frequent micturition ≥8 times per 24 hours
   2. Urinary urgency or nocturia
   3. Urge urinary incontinence five or more incontinence episodes per week
3. 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
4. Residual urine volume of ≤200 milliliters (ml)
5. Non-response or poor tolerance to previous treatment for symptoms of OAB/urinary incontinence and do not wish to continue these treatments
6. Have screening laboratory values and electrocardiogram that are within the normal range
7. 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

Primary outcomes:
measure: Number of participants with any treatment-emergent adverse event during the Treatment Period
timeFrame: 6 months (24 weeks) per participant
measure: Number of participants with any treatment-emergent adverse event during the Safety Follow-up Period
timeFrame: 18 months
measure: Number of participants with any clinically significant clinical laboratory test value during the Treatment Period
timeFrame: 6 months (24 weeks) per participant
measure: Number of participants with any clinically significant clinical laboratory test value during the Safety Follow-up Period
timeFrame: 18 months
measure: Number of participants with any clinically significant electrocardiogram finding during the Treatment Period
timeFrame: 6 months (24 weeks) per participant
measure: Number of participants with any clinically significant electrocardiogram finding during the Safety Follow-up Period
timeFrame: 18 months
measure: Number of participants with any clinically significant physical examination finding during the Treatment Period
timeFrame: 6 months (24 weeks) per participant
measure: Number of participants with any clinically significant physical examination finding during the Safety Follow-up Period
timeFrame: 18 months
Secondary outcomes:
measure: Change from Baseline in the number of micturitions per day
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in the volume of micturitions
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in incontinence episodes
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in pad weight
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in uninhibited contractions during cystoscopy
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in the participant rating of the Kings Health Questionnaire (KHQ) score
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in the International Consultation on Incontinence Questionnaire-Short Form score
timeFrame: Baseline; 6 months (24 weeks) per participant
measure: Change from Baseline in the Short Form-12 (SF-12) score
timeFrame: Baseline; 6 months (24 weeks) per participant
Other outcomes:
Locations:
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: New York
country: United States
facility: NYU
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley, PC
state: New York
Study officials:
References: