Clostridium Histolyticum Collagenase Injection for Urethral Disease

NCT02948842 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CHC
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Urethral Stricture

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Complication After Treatment

  Number of subjects with complication after treatment with clostridium histolyticum collagenase

  84 days

Secondary Outcomes (21)

• Number of Patients Needing Further Intervention for Treatment of Urethral Stricture

  2 years

• Number of Subjects With Recurrence of Urethral Stricture

  2 years

• Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores

  6 weeks

• Change From Baseline and 6 Months: American Urology Association Questionnaire Scores

  6 months

• Change From Baseline and 9 Months: American Urology Association Questionnaire Scores

  9 months

Study Arms (1)

Treatment Group

EXPERIMENTAL

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; Other: Saline

Interventions

Clostridium Histolyticum Collagenase DRUG

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.

Also known as: XIAFLEX®

Treatment Group

Saline OTHER

0.08ml of injectable normal saline

Also known as: Injectable normal saline

Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of South Florida: lead

Study Sites (1)

University of South Florida - South Tampa Campus

Tampa, Florida, 33606, United States

Location

Related Publications (9)

• 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.

  PMID: 17437780 RESULT

• 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.

  PMID: 21315996 RESULT

• 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.

  PMID: 9679876 RESULT

• 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.

  PMID: 15541123 RESULT

• 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.

  PMID: 24745607 RESULT

• 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.

  PMID: 26491251 RESULT

• 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.

  PMID: 23376148 RESULT

• 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.

  PMID: 17617144 RESULT

• 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.

  PMID: 26126692 RESULT

MeSH Terms

Conditions

Urethral Stricture

Interventions

Microbial Collagenase; Sodium Chloride

Condition Hierarchy (Ancestors)

Urethral Obstruction; Urethral Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

These are first-in-human cases with collagenase clostridium histolyticum (CCH) treatment for urethral stricture, although number of treated patients is low. Future directions will hopefully include increased sample size through multi-institutional participation and adjunctive procedures designed to augment the proposed beneficial effects of CCH therapy.

Results Point of Contact

• Title: Lucas Wiegand, MD
• Organization: University of South Florida

lwiegand@usf.edu

813-844-5972

Study Officials

• Lucas R Wiegand, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: October 28, 2016
• Study Start: May 22, 2020
• Primary Completion: March 4, 2023
• Study Completion: April 12, 2023
• Last Updated: November 3, 2023
• Results First Posted: November 3, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)