Trial Outcomes & Findings for Clostridium Histolyticum Collagenase Injection for Urethral Disease (NCT NCT02948842)

Results Overview

Number of subjects with complication after treatment with clostridium histolyticum collagenase

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

84 days

Results posted on

2023-11-03

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	5
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Withdrawal by Subject	4

Baseline Characteristics

One subject withdrew consent before all baseline procedures were completed, data not available for that subject

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Group n=5 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized White · Hispanic	1 Participants n=5 Participants
Race/Ethnicity, Customized White · Non-Hispanic	4 Participants n=5 Participants
Height	70.8 inches STANDARD_DEVIATION 0.84 • n=5 Participants
Weight	200 lbs STANDARD_DEVIATION 19.0 • n=5 Participants
Stricture length	0.96 cm STANDARD_DEVIATION 0.37 • n=5 Participants
Post void residual urine	64 mL STANDARD_DEVIATION 63 • n=4 Participants • One subject withdrew consent before all baseline procedures were completed, data not available for that subject
Uroflowmetry	8 mL/s STANDARD_DEVIATION 2.9 • n=4 Participants • One subject withdrew consent before all baseline procedures were completed, data not available for that subject
Length of spongiofibrosis	0.51 cm STANDARD_DEVIATION 0.14 • n=4 Participants • One subject withdrew consent before all baseline procedures were completed, data not available for that subject
Urethral stricture grade 2	4 Participants n=4 Participants • One subject withdrew consent before all baseline procedures were completed, data not available for that subject
American Urological Association symptom score	16 scores on a scale STANDARD_DEVIATION 7.9 • n=5 Participants

PRIMARY outcome

Timeframe: 84 days

Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.

Number of subjects with complication after treatment with clostridium histolyticum collagenase

Outcome measures

Outcome measures
Measure	Treatment Group n=3 Participants 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
Number of Subjects With Complication After Treatment	0 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.

Further intervention - defined as any medical or surgical intervention for treatment of urethral stricture.

Outcome measures

Outcome measures
Measure	Treatment Group n=3 Participants 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
Number of Patients Needing Further Intervention for Treatment of Urethral Stricture	3 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.

Number of subjects with recurrence of urethral stricture

Outcome measures

Outcome measures
Measure	Treatment Group n=3 Participants 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
Number of Subjects With Recurrence of Urethral Stricture	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment Group n=2 Participants 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
Change From Baseline and 6 Weeks: American Urology Association Questionnaire Scores	-11.5 scores on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment Group n=2 Participants 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
Change From Baseline and 6 Months: American Urology Association Questionnaire Scores	-2.5 scores on a scale Standard Deviation 14.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment Group n=1 Participants 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
Change From Baseline and 9 Months: American Urology Association Questionnaire Scores	-17 scores on a scale

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment Group n=1 Participants 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
Change From Baseline and 12 Months: American Urology Association Questionnaire Scores	-19 scores on a scale

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment Group n=1 Participants 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
Change From Baseline and 2 Years: American Urology Association Questionnaire Scores	-24 scores on a scale

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Only 3 subjects were treated with study treatment. Two subjects withdrew prior to receiving study treatment.

Outcome measures

Outcome measures
Measure	Treatment Group n=3 Participants 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
Time to Additional Intervention for Urethral Stricture	6 months Interval 1.0 to 18.0

SECONDARY outcome

Timeframe: 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.