Clostridium Histolyticum Collagenase Injection for Urethral Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of clostridium histolyticum collagenase (XIAFLEX®) in treating urethral strictures.

Detailed Description
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This is an open-label, pilot study to explore the efficacy of clostridium histolyticum collagenase (XIAFLEX®) in treating urethral strictures. Subjects will be followed for 2 years from the initial drug treatment.

Official Title
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Clostridium Histolyticum Collagenase Injection Treatment for Urethral Disease: a Prospective, Single-center, Open-label Study

Conditions
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Urethral Stricture

Intervention / Treatment
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* Drug: Clostridium Histolyticum Collagenase
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males Age ≥ 18 years Failed prior proven conservative measures, including DVIU or balloon dilation of the stricture will be included in this study Able and willing to undergo regular intervention as well as evaluation as described below will be included in the study With a single stricture <2cm in size that can be identified on retrograde urethrogram or voiding cystourethrogram will be included in the study. Must agree not to participate in a clinical study involving another investigational drug or device throughout the duration of this study Must be competent to understand the information given in IRB approved ICF and must sign the form prior to the initiation of any study procedure Exclusion Criteria: Has not yet undergone proven non-invasive measures, including DVIU or balloon dilation. Multiple strictures or a single stricture larger than 2cm in size, measured with retrograde urethrogram, voiding cystourethrogram, or urethral ultrasonography. Corporal spongiosum tissues < 5 mm in depth at proposed injection site Grade 5 spongiofibrosis Age <18 Females Prior urethroplasty Urethral fistula History of penile cancer, prostate cancer, or urinary tract malignancy (bladder, urethral, ureteral, or kidney). History of radiation (external or brachytherapy) to the pelvic organs, penis or groin. History of autoimmune or inflammatory bowel disease Contraindication to suprapubic tube placement Pre-procedure PVR >250mL Allergy or sensitivity to CHC Bleeding disorder or anticoagulant use other than aspirin up to 150mg/day Untreated urinary tract infection Inability to perform intermittent self-catheterization Participation in another clinical study or treatment with an investigational drug or device Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Patients will undergo instillation of local anesthesia (20 mL of 2% urethral lidocaine jelly), the patient will undergo cystoscopy, transurethral injection (via a 70 cm 4.8 Fr flexible cystoscopic needle with a 23 gauge needle tip manufactured by Laborie®, Ontario, Canada) of 0.08ml of XIAFLEX® (0.58 mg of XIAFLEX® mixed with 0.39 mL of sterile diluent) in a single location within the stricture, chased by an additional 0.25 mL of reconstituted XIAFLEX® to allow for clearance of the original 0.08 mL of reconstituted XIAFLEX® from the transurethral syringe into the urethral stricture. | Drug: Clostridium Histolyticum Collagenase<br>* 0.08ml of XIAFLEX® (0.58 mg of XIAFLEX® mixed with 0.39 mL of sterile diluent) in a single location within the stricture, chased by an additional 0.25 mL of reconstituted XIAFLEX® to allow for clearance of the original 0.08 mL of reconstituted XIAFLEX® from the transurethral syringe into the urethral stricture. This is based on 0.25 mL residual fluid that remains within the lumen of the injeTAK syringe. Thus, by adding the additional 0.25 mL of XIAFLEX® as a chase, we are expecting the original total of 0.08 mL of XIAFLEX® to be injected into the area of scarring.<br>* Other names: XIAFLEX®;Other: Saline<br>* 0.08ml of injectable normal saline<br>* Other names: Injectable normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Complication After Treatment | Number of subjects with complication after treatment with clostridium histolyticum collagenase | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Needing Further Intervention for Treatment of Urethral Stricture | Further intervention - defined as any medical or surgical intervention for treatment of urethral stricture. | 2 years | 
| Number of Subjects With Recurrence of Urethral Stricture | Number of subjects with recurrence of urethral stricture | 2 years | 
| Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores | The American Urology Association questionnaire score is totaled based on 7 questions. Each question asks the subject to rate their symptom on a 5-point scale from Not at All (0) to Almost Always (5). The total score is based on adding rating marked for each question. The total runs from 0 to 35 points with higher scores indicating more severe symptoms. | 6 weeks | 
| Change From Baseline and 6 Months: American Urology Association Questionnaire Scores | The American Urology Association questionnaire score is totaled based on 7 questions. Each question asks the subject to rate their symptom on a 5-point scale from Not at All (0) to Almost Always (5). The total score is based on adding rating marked for each question. The total runs from 0 to 35 points with higher scores indicating more severe symptoms. | 6 months | 
| Change From Baseline and 9 Months: American Urology Association Questionnaire Scores | The American Urology Association questionnaire score is totaled based on 7 questions. Each question asks the subject to rate their symptom on a 5-point scale from Not at All (0) to Almost Always (5). The total score is based on adding rating marked for each question. The total runs from 0 to 35 points with higher scores indicating more severe symptoms. | 9 months | 
| Change From Baseline and 12 Months: American Urology Association Questionnaire Scores | The American Urology Association questionnaire score is totaled based on 7 questions. Each question asks the subject to rate their symptom on a 5-point scale from Not at All (0) to Almost Always (5). The total score is based on adding rating marked for each question. The total runs from 0 to 35 points with higher scores indicating more severe symptoms. | 12 months | 
| Change From Baseline and 2 Years: American Urology Association Questionnaire Scores | The American Urology Association questionnaire score is totaled based on 7 questions. Each question asks the subject to rate their symptom on a 5-point scale from Not at All (0) to Almost Always (5). The total score is based on adding rating marked for each question. The total runs from 0 to 35 points with higher scores indicating more severe symptoms. | 2 years | 
| Time to Urethral Stricture Recurrence |  | 2 years | 
| Time to Additional Intervention for Urethral Stricture |  | 2 years | 
| Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 6 weeks | 
| Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 6 months | 
| Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 9 months | 
| Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 12 months | 
| Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 18 months | 
| Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow) | Obstructive voiding dysfunction defined as change in uroflow | 2 years | 
| Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 6 weeks | 
| Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 6 months | 
| Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 9 months | 
| Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 12 months | 
| Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 18 months | 
| Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | Obstructive voiding dysfunction defined as change in post-void residual measurements | 2 years |