Delayed Dose Collagenase Clostridium Histolyticum (CCH) Protocol for Men With Peyronie's Disease

Efficacy of a Step-wise Protocol in Optimizing CCH Outcomes in Men With Peyronie's Disease

Our team has previously demonstrated efficacy in performing a novel collagenase Clostridium histolyticum (CCH) injection protocol in men who previously failed to achieve a response to an initial 4 series of CCH.

The objective of the current study is to evaluate a protocol that incorporates limited in-office modeling for up to 4 series, followed by up to 2 additional salvage series to determine safety and efficacy compared to historical data.

Participants will receive up to 4 series of CCH injections using our previously published protocol, with mild in-office modeling. CCH injections are given on back-to back days, after which they are counseled to utilize Restorex and sildenafil daily, as instructed. Patients will undergo mild in-office modeling on day 2.

The sexual partners of study participants will also be invited to enroll in the study and will complete non-validated questionnaires detailing their level of support for the patient's treatment.

Study Overview

• Status: Recruiting
• Conditions: Peyronie Disease
• Intervention / Treatment: Drug: Collagenase Clostridium Histolyticum; Device: RestoreX; Drug: Sildenafil

Detailed Description

The current study would prospectively follow 40 men through the following treatment protocol:

• Men would receive 4 series of CCH injections according to the protocol below, which represents a modified version of our most recently published technique.13

  • Medication administered on back-to-back days
  • Total of 0.9 mg administered with each series, diluted to 0.8 mL
  • Mild in-office modeling performed on treatment day 2 of each series
  • Wraps performed ranging from 2-4 full-time and 2-4 part-time days to minimize bruising
  • Sildenafil 25 mg nightly beginning treatment day 2 until 6 weeks after final injection of the final series.
  • Restorex initiated beginning on post-injection day 3 or as soon as tolerated - 30 min daily, continuing until 6 weeks after final injection of the final series.
• Note that men may stop sooner if they are satisfied before completing the 4 series.

• If the patient is not satisfied with outcomes by the end of the 4th series, they would be permitted to enter the 'salvage' phase of the treatment protocol.

  • This would be performed 9-12 months after the 4th series of injections.
  • The technique would be similar to the one noted above with the exception of more aggressive in-office modeling as described in our prior publication and per our ongoing randomized trial.
  • The men would receive up to two additional series per this protocol for a maximum number of cycles being 6 in total.

At the time of initial enrollment, partners of study participants will be invited to enroll in the study and will be administered non-validated questionnaires designed to assess the partner's overall support for the ongoing treatment protocol.

Assessments and study questionnaires will be administered at baseline, with the 1st injection of each series, 6 weeks after completing the 4th series of CCH injections, and 1 year after completion of the final series of CCH injections.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Landon Trost, MD; Phone Number: 801-655-0015; Email: email@mfp.clinic
• Study Contact Backup: Name: Holli Burgon; Phone Number: 801-691-4714; Email: burgon.holli@menshealthstudies.com

Study Locations

• United States
  • Utah
    • Orem, Utah, United States, 84057
      • Recruiting
      • Male Fertility and Peyronie's Clinic
      • Contact: Landon Trost, MD; Phone Number: 801-655-0015; Email: email@mfp.clinic
      • Contact: Jesse Labbe, PhD; Phone Number: 801-655-0015; Email: labbe.jesse@menshealthstudies.com
      • Principal Investigator: Landon Trost, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men with Peyronie's Disease
• Older than 18 years old
• Curvature ≥30 degrees
• Ability to achieve an erection satisfactory for intercourse with or without phosphodiesterase-5 (PDE5) inhibitors
• The patient exhibits a palpable plaque consistent with Peyronie's Disease
• For partners, the only inclusion criteria is being willing to complete a questionnaire

Exclusion Criteria:

• Prior surgical treatment on the penis (other than circumcision)
• Prior treatment with CCH injections
• Any contraindications to CCH - as determined by the PI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Primary Cohort; Men would receive 4 series of CCH injections: Administered on back-to-back days; 0.9 mg administered with each series, diluted to 0.8 mL; Mild in-office modeling performed on treatment day 2 of each series; Wraps applied 2-4 full-time and 2-4 part-time days; Sildenafil 25 mg nightly and Restorex beginning treatment day 2 (sildenafil) or 3 (Restorex - 30 min/day) until 6 weeks after final injection of the final series. Note that men may stop sooner if they are satisfied before completing the 4 series. If the patient is not satisfied with outcomes by the end of the 4th series, they would be permitted to enter the 'salvage' phase of the treatment protocol.; Performed 9-12 months after the 4th series of injections.; The technique would incorporate more aggressive, in-office modeling.; Men would receive up to two additional series per this protocol.

Drug: Collagenase Clostridium Histolyticum; 4 Series given to each participant, 6 weeks apart. Medication administered on back-to-back days. If failing to achieve an adequate response, men may receive up to 2 additional series 9-12 months after the 4th series. Total of 0.9 mg administered with each series, diluted to 0.8 mL; Other Names: Xiaflex; CCH; Device: RestoreX; Restorex initiated beginning on post-injection day 3 or as soon as tolerated - 30 min daily, continuing until 6 weeks after final injection of the final CCH series.; Drug: Sildenafil; Men will be prescribed sildenafil 25 mg nightly beginning treatment day 2 until 6 weeks after final injection of the final series.; Other Names: Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penile Curvature	Compare penile curvature between baseline and post-treatment in men 1 year after completing the final injection series. A goniometer (protractor) will be used to measure from the penile angulation during a full erection in two planes (dorsal/ventral and lateral). Measurements will be in degrees.	1 year
Penile Length	Compare penile length between baseline and post-treatment in men 1 year after completing the final injection series. Measurements will be performed using a ruler, with measurements obtained from the pubic symphysis to the corona of the glans penis (measured in cm).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penile curvature compared to more aggressive technique	Compare curvature outcomes to our historical series of men treated up-front with the more aggressive technique. This will be done using a goniometer (protractor) with a full erection and measured in two planes (dorsal/ventral and lateral). The curvature will be measured using degrees.	1 year
Penile curvature compared to our current salvage approach for CCH	Compare curvature changes to those in our ongoing randomized, controlled trial (NCT05108558) evaluating the salvage approach in men who previously failed 6-8 CCH injections. This will be done using a goniometer (protractor) with a full erection and measured in two planes (dorsal/ventral and lateral). The curvature will be measured using degrees.	1 year
Adverse Events	Report subjectively noted adverse events (AE) at 1 year following the final injection series. Patients will be able to write-in specific adverse events, and absolute occurrences of each of the written responses will be summed and reported.	1 year
Partner Support	Evaluate partner support as a predictor of whether the patient continues with treatment. Support will be assessed using a non-validated question, "How supportive are you of your partner's decision to undergo Xiaflex treatments?" This will be measured using the selectable options: Very Supportive, Somewhat Supportive, Neutral, Somewhat Unsupportive, and Very Unsupportive.	1 year
Compliance with Therapy - Penile Curvature	Evaluate compliance with therapy as a predictor of penile curvature improvements during the study. A daily diary will be maintained by the patient to track actual device utilization. Patients will record how many minutes that they used the device daily. This information will be used to try to correlate penile curvature outcomes with actual device utilization.	1 year
Satisfaction with therapy	Report patient-outcome measures related to satisfaction with therapy. This measure will be evaluated using a non-standardized question, "How would you rate your overall satisfaction with Xiaflex?" Patients will be able to select from the following responses: Very Satisfied, Somewhat Satisfied, Neither Satisfied nor Dissatisfied, Somewhat Dissatisfied, Very Dissatisfied.	1 year
Penile length compared to more aggressive technique	Compare penile length changes to our historical series of men treated up-front with the more aggressive technique. Measurements will be performed using a ruler, with measurements obtained from the pubic symphysis to the corona of the glans penis (measured in cm).	1 year
Penile length compared to our current salvage approach for CCH	Compare penile length changes to our ongoing randomized, controlled trial (NCT05108558) evaluating the salvage approach in men who previously failed 6-8 CCH injections. Measurements will be performed using a ruler, with measurements obtained from the pubic symphysis to the corona of the glans penis (measured in cm).	1 year
Compliance with Therapy - Penile Length	Evaluate compliance with therapy as a predictor of penile length changes during the study. A daily diary will be maintained by the patient to track actual device utilization. Patients will record how many minutes that they used the device daily. This information will be used to try to correlate penile length outcomes with actual device utilization.	1 year

Collaborators and Investigators

• Sponsor: Charitable Union for the Research and Education of Peyronie's Disease
• Collaborators: Endo Pharmaceuticals
• Investigators: Principal Investigator: Landon Trost, MD, Charitable Union for the Research and Education of Peyronie's Disease

Publications and helpful links

General Publications

• Nguyen HMT, Anaissie J, DeLay KJ, Yafi FA, Sikka SC, Hellstrom WJG. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie's Disease. J Sex Med. 2017 Oct;14(10):1220-1225. doi: 10.1016/j.jsxm.2017.08.008. Epub 2017 Sep 2.
• Larson H, Warner J, Savage J, Kohler T, Ziegelmann M, Trost L. Changes in Point of Maximal Curvature During Collagenase Clostridium Histolyticum Injections for Peyronie's Disease. Urology. 2024 Feb;184:122-127. doi: 10.1016/j.urology.2023.11.024. Epub 2023 Dec 6.
• Gelbard M, Lipshultz LI, Tursi J, Smith T, Kaufman G, Levine LA. Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. J Urol. 2012 Jun;187(6):2268-74. doi: 10.1016/j.juro.2012.01.032. Epub 2012 Apr 13. Erratum In: J Urol. 2012 Aug;188(2):678.
• Alom M, Sharma KL, Toussi A, Kohler T, Trost L. Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie's Disease. J Sex Med. 2019 Jun;16(6):891-900. doi: 10.1016/j.jsxm.2019.03.007. Epub 2019 Apr 5.
• Ziegelmann MJ, Viers BR, Montgomery BD, Westerman ME, Savage JB, Trost LW. Self-reported Clinical Meaningfulness Early in the Treatment Course Predicts Objective Outcomes in Men Undergoing Collagenase Clostridium histolyticum Injections for Peyronie Disease. Urology. 2017 Aug;106:107-112. doi: 10.1016/j.urology.2017.04.045. Epub 2017 May 5.
• Ziegelmann MJ, Viers BR, McAlvany KL, Bailey GC, Savage JB, Trost LW. Restoration of Penile Function and Patient Satisfaction with Intralesional Collagenase Clostridium Histolyticum Injection for Peyronie's Disease. J Urol. 2016 Apr;195(4 Pt 1):1051-6. doi: 10.1016/j.juro.2015.10.065. Epub 2015 Oct 23.
• Alom M, Meng Y, Sharma KL, Savage J, Kohler T, Trost L. Safety and Efficacy of Collagenase Clostridium Histolyticum in Peyronie's Disease Men With Ventral Curvatures. Urology. 2019 Jul;129:119-125. doi: 10.1016/j.urology.2019.01.055. Epub 2019 Mar 22.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: October 12, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: traction; collagenase clostridium histolyticum; salvage; curvature; Xiaflex; Restorex
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Connective Tissue Diseases; Penile Diseases; Penile Induration; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Vasodilator Agents; Urological Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: CUREPD120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes