Clostridium Histolyticum Collagenase Injection for Urethral Disease

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

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

Study Overview

• Status: Completed
• Conditions: Urethral Stricture
• Intervention / Treatment: Drug: Clostridium Histolyticum Collagenase; Other: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Veronique Perry, MHA; Phone Number: 813-844-5972; Email: vperry@tgh.org
• Study Contact Backup: Name: Ray de la Morena Quirch, PhD; Phone Number: 83-844-8824; Email: rdelamorena@tgh.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida - South Tampa Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Group; 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; 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.; Other Names: XIAFLEX®; Other: Saline; 0.08ml of injectable normal saline; Other Names: Injectable normal saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of South Florida
• Investigators: Principal Investigator: Lucas R Wiegand, MD, University of South Florida

Publications and helpful links

General Publications

• Gelbard M, Goldstein I, Hellstrom WJ, McMahon CG, Smith T, Tursi J, Jones N, Kaufman GJ, Carson CC 3rd. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013 Jul;190(1):199-207. doi: 10.1016/j.juro.2013.01.087. Epub 2013 Jan 31.
• Santucci RA, Joyce GF, Wise M. Male urethral stricture disease. J Urol. 2007 May;177(5):1667-74. doi: 10.1016/j.juro.2007.01.041.
• Chenoweth CE, Saint S. Urinary tract infections. Infect Dis Clin North Am. 2011 Mar;25(1):103-15. doi: 10.1016/j.idc.2010.11.005. Epub 2010 Dec 18.
• Heyns CF, Steenkamp JW, De Kock ML, Whitaker P. Treatment of male urethral strictures: is repeated dilation or internal urethrotomy useful? J Urol. 1998 Aug;160(2):356-8. doi: 10.1016/s0022-5347(01)62894-5.
• Hussain M, Greenwell TJ, Shah J, Mundy A. Long-term results of a self-expanding wallstent in the treatment of urethral stricture. BJU Int. 2004 Nov;94(7):1037-9. doi: 10.1111/j.1464-410X.2004.05100.x.
• Zhang K, Qi E, Zhang Y, Sa Y, Fu Q. Efficacy and safety of local steroids for urethra strictures: a systematic review and meta-analysis. J Endourol. 2014 Aug;28(8):962-8. doi: 10.1089/end.2014.0090. Epub 2014 Jun 3.
• Peak TC, Mitchell GC, Yafi FA, Hellstrom WJ. Role of collagenase clostridium histolyticum in Peyronie's disease. Biologics. 2015 Sep 29;9:107-16. doi: 10.2147/BTT.S65619. eCollection 2015.
• Cavalcanti AG, Costa WS, Baskin LS, McAninch JA, Sampaio FJ. A morphometric analysis of bulbar urethral strictures. BJU Int. 2007 Aug;100(2):397-402. doi: 10.1111/j.1464-410X.2007.06904.x.
• Sangkum P, Yafi FA, Kim H, Bouljihad M, Ranjan M, Datta A, Mandava SH, Sikka SC, Abdel-Mageed AB, Moparty K, Hellstrom WJ. Collagenase Clostridium histolyticum (Xiaflex) for the Treatment of Urethral Stricture Disease in a Rat Model of Urethral Fibrosis. Urology. 2015 Sep;86(3):647.e1-6. doi: 10.1016/j.urology.2015.06.013. Epub 2015 Jun 27.

Helpful Links

• XIAFLEX® [package insert]

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Actual): March 4, 2023
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: October 26, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (Estimated): October 28, 2016

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urethral Obstruction; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urethral Stricture; Urethral Diseases
• Other Study ID Numbers: CHC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No