Clostridium Histolyticum Collagenase Injection for Urethral Disease

Urethral Stricture Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02948842
• Other study ID #: CHC
• Status: Completed
• Phase: Phase 2
• Start date: May 22, 2020
• Est. completion date: April 12, 2023

Study information

• Verified date: October 2023
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: April 12, 2023
• Est. primary completion date: March 4, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urethral Diseases
• Urethral Stricture

Intervention

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:
• Saline
0.08ml of injectable normal saline

Locations

Country	Name	City	State
United States	University of South Florida - South Tampa Campus	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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, rando — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Complication After Treatment	Number of subjects with complication after treatment with clostridium histolyticum collagenase	84 days
Secondary	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
Secondary	Number of Subjects With Recurrence of Urethral Stricture	Number of subjects with recurrence of urethral stricture	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to Urethral Stricture Recurrence		2 years
Secondary	Time to Additional Intervention for Urethral Stricture		2 years
Secondary	Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	6 weeks
Secondary	Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	6 months
Secondary	Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	9 months
Secondary	Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	12 months
Secondary	Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	18 months
Secondary	Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow)	Obstructive voiding dysfunction defined as change in uroflow	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   XIAFLEX® [package insert]