Clinical trial NCT02948842: Clostridium Histolyticum Collagenase Injection for Urethral Disease
Official title: Clostridium Histolyticum Collagenase Injection Treatment for Urethral Disease: a Prospective, Single-center, Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urethral Stricture
Lead sponsor: University of South Florida
Sponsor class: OTHER
First posted: 2016-10-28
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects With Complication After Treatment
timeFrame: 84 days
Secondary outcomes:
measure: Number of Patients Needing Further Intervention for Treatment of Urethral Stricture
timeFrame: 2 years
measure: Number of Subjects With Recurrence of Urethral Stricture
timeFrame: 2 years
measure: Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores
timeFrame: 6 weeks
measure: Change From Baseline and 6 Months: American Urology Association Questionnaire Scores
timeFrame: 6 months
measure: Change From Baseline and 9 Months: American Urology Association Questionnaire Scores
timeFrame: 9 months
measure: Change From Baseline and 12 Months: American Urology Association Questionnaire Scores
timeFrame: 12 months
measure: Change From Baseline and 2 Years: American Urology Association Questionnaire Scores
timeFrame: 2 years
measure: Time to Urethral Stricture Recurrence
timeFrame: 2 years
measure: Time to Additional Intervention for Urethral Stricture
timeFrame: 2 years
measure: Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 6 weeks
measure: Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 6 months
measure: Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 9 months
measure: Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 12 months
measure: Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 18 months
measure: Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow)
timeFrame: 2 years
measure: Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 6 weeks
measure: Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 6 months
measure: Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 9 months
measure: Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 12 months
measure: Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 18 months
measure: Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Post-void Residual Measurements)
timeFrame: 2 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: University of South Florida - South Tampa Campus
state: Florida
Study officials:
affiliation: University of South Florida
name: Lucas R Wiegand, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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, 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.
citation: 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.
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. Urology. 2015 Sep;86(3):647.e1-6. doi: 10.1016/j.urology.2015.06.013. Epub 2015 Jun 27.