Urethral Stricture
Conditions
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.
Interventions
DRUGClostridium 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.
OTHERSaline
0.08ml of injectable normal saline
Sponsors
University of South Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Complication After Treatment | 84 days | Number of subjects with complication after treatment with clostridium histolyticum collagenase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Recurrence of Urethral Stricture | 2 years | Number of subjects with recurrence of urethral stricture |
| 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 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 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. |
| 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 | — |
| 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 6 Months: Obstructive Voiding Dysfunction (Uroflow) | 6 months | Obstructive voiding dysfunction defined as change in uroflow |
| 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. |
| Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow) | 12 months | Obstructive voiding dysfunction defined as change in uroflow |
| 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 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 6 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | 6 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 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 2 Years: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | 2 years | Obstructive voiding dysfunction defined as change in post-void residual measurements |
| Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow) | 9 months | Obstructive voiding dysfunction defined as change in uroflow |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
Saline: 0.08ml of injectable normal saline | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| American Urological Association symptom score | 16 scores on a scale STANDARD_DEVIATION 7.9 |
| Height | 70.8 inches STANDARD_DEVIATION 0.84 |
| Length of spongiofibrosis | 0.51 cm STANDARD_DEVIATION 0.14 |
| Post void residual urine | 64 mL STANDARD_DEVIATION 63 |
| Race/Ethnicity, Customized White Hispanic | 1 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
| Stricture length | 0.96 cm STANDARD_DEVIATION 0.37 |
| Urethral stricture grade 2 | 4 Participants |
| Uroflowmetry | 8 mL/s STANDARD_DEVIATION 2.9 |
| Weight | 200 lbs STANDARD_DEVIATION 19 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Subjects With Complication After Treatment
Number of subjects with complication after treatment with clostridium histolyticum collagenase
Time frame: 84 days
Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects With Complication After Treatment | 0 Participants |
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.
Time frame: 12 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 12 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 12 Months: American Urology Association Questionnaire Scores | -19 scores on a scale |
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
Time frame: 12 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 12 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | 46 mL |
Secondary
Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 12 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 12 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 12 Months: Obstructive Voiding Dysfunction (Uroflow) | 5.8 mL/s |
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
Time frame: 18 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 18 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | -48 mL |
Secondary
Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 18 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 18 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 18 Months: Obstructive Voiding Dysfunction (Uroflow) | 19 mL/s |
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.
Time frame: 2 years
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 2 years follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 2 Years: American Urology Association Questionnaire Scores | -24 scores on a scale |
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
Time frame: 2 years
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 2 years follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | -15 mL |
Secondary
Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 2 years
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 2 years follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 2 Years: Obstructive Voiding Dysfunction (Uroflow) | 9.2 mL/s |
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.
Time frame: 6 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 months follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Months: American Urology Association Questionnaire Scores | -2.5 scores on a scale | Standard Deviation 14.8 |
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
Time frame: 6 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 months follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | 175.5 mL | Standard Deviation 224.1 |
Secondary
Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 6 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 months follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Months: Obstructive Voiding Dysfunction (Uroflow) | -5.5 mL/s | Standard Deviation 7.8 |
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.
Time frame: 6 weeks
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 weeks follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores | -11.5 scores on a scale | Standard Deviation 3.5 |
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
Time frame: 6 weeks
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 weeks follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | -41.5 mL | Standard Deviation 14.8 |
Secondary
Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 6 weeks
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 2 out of 3 treated subjects completed 6 weeks follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change From Baseline and 6 Weeks: Obstructive Voiding Dysfunction (Uroflow) | 1.5 mL/s | Standard Deviation 6.4 |
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.
Time frame: 9 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 9 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 9 Months: American Urology Association Questionnaire Scores | -17 scores on a scale |
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
Time frame: 9 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 9 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Post-void Residual Measurements) | 125 mL |
Secondary
Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow)
Obstructive voiding dysfunction defined as change in uroflow
Time frame: 9 months
Population: Two subjects withdrew prior to receiving study treatment. Only 3 subjects were treated with study treatment. Only 1 out of 3 treated subjects completed 9 months follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Change From Baseline and 9 Months: Obstructive Voiding Dysfunction (Uroflow) | 3.6 mL/s |
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.
Time frame: 2 years
Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Patients Needing Further Intervention for Treatment of Urethral Stricture | 3 Participants |
Secondary
Number of Subjects With Recurrence of Urethral Stricture
Number of subjects with recurrence of urethral stricture
Time frame: 2 years
Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects With Recurrence of Urethral Stricture | 0 Participants |
Secondary
Time to Additional Intervention for Urethral Stricture
Time frame: 2 years
Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Group | Time to Additional Intervention for Urethral Stricture | 6 months |
Secondary
Time to Urethral Stricture Recurrence
Time frame: 2 years
Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment. None of the treated subjects had recurrence of urethral stricture.