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

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

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.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Placebo (PBS-20% sucrose); Drug: hMaxi-K

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]).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • New York, New York, United States, 10016
      • NYU
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 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.	Drug: Placebo (PBS-20% sucrose); Other Names: Placebo
EXPERIMENTAL: hMaxi-K 16000 µg; 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; Single treatment/2 escalating dose levels (16000 µg and 24000 µg by intramuscular injection); Other Names: URO-902
EXPERIMENTAL: hMaxi-K 24000 µg; 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; Single treatment/2 escalating dose levels (16000 µg and 24000 µg by intramuscular injection); Other Names: URO-902

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Urovant Sciences GmbH
• Collaborators: Ion Channel Innovations

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2013
• Primary Completion (ACTUAL): June 1, 2017
• Study Completion (ACTUAL): February 17, 2018

Study Registration Dates

• First Submitted: June 3, 2013
• First Submitted That Met QC Criteria: June 3, 2013
• First Posted (ESTIMATE): June 5, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 8, 2019
• Last Update Submitted That Met QC Criteria: May 7, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: gene therapy; Overactive Bladder; OAB
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive
• Other Study ID Numbers: ION 03-OAB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: individual participant data will not be shared