Clostridium Histolyticum Collagenase Injection for Urethral Disease

Phase 2

Completed

Conditions: Urethral Stricture

Interventions: Drug: Clostridium Histolyticum Collagenase
Other: Saline

Registration Number: NCT02948842

Lead Sponsor: University of South Florida

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 5

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Group	Saline	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.
Treatment Group	Clostridium Histolyticum Collagenase	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Complication After Treatment	84 days	Number of subjects with complication after treatment with clostridium histolyticum collagenase

Secondary Outcome Measures

Name	Time	Method
Change From Baseline and 6 Months: American Urology Association Questionnaire Scores	6 months	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.
Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow)	6 months	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow)	9 months	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow)	12 months	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores	6 weeks	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.
Change From Baseline and 2 Years: American Urology Association Questionnaire Scores	2 years	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.
Time to Urethral Stricture Recurrence	2 years
Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow)	18 months	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow)	2 years	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	6 months	Obstructive voiding dysfunction defined as change in post-void residual measurements
Number of Patients Needing Further Intervention for Treatment of Urethral Stricture	2 years	Further intervention - defined as any medical or surgical intervention for treatment of urethral stricture.
Number of Subjects With Recurrence of Urethral Stricture	2 years	Number of subjects with recurrence of urethral stricture
Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	6 weeks	Obstructive voiding dysfunction defined as change in post-void residual measurements
Change From Baseline and 9 Months: American Urology Association Questionnaire Scores	9 months	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.
Change From Baseline and 12 Months: American Urology Association Questionnaire Scores	12 months	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.
Time to Additional Intervention for Urethral Stricture	2 years
Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow)	6 weeks	Obstructive voiding dysfunction defined as change in uroflow
Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	12 months	Obstructive voiding dysfunction defined as change in post-void residual measurements
Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	18 months	Obstructive voiding dysfunction defined as change in post-void residual measurements
Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	9 months	Obstructive voiding dysfunction defined as change in post-void residual measurements
Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Post-void Residual Measurements)	2 years	Obstructive voiding dysfunction defined as change in post-void residual measurements