Clinical trial NCT06649539: Delayed Dose Collagenase Clostridium Histolyticum (CCH) Protocol for Men With Peyronie's Disease
Official title: Efficacy of a Step-wise Protocol in Optimizing CCH Outcomes in Men With Peyronie's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Peyronie Disease
Keywords: collagenase clostridium histolyticum
curvature
Restorex
Xiaflex
traction
salvage
Lead sponsor: Charitable Union for the Research and Education of Peyronie's Disease
Sponsor class: OTHER
Collaborators: name: Endo Pharmaceuticals
First posted: 2024-10-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: prospective, single-blinded clinical trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Penile Curvature
timeFrame: 1 year
measure: Penile Length
timeFrame: 1 year
Secondary outcomes:
measure: Penile curvature compared to more aggressive technique
timeFrame: 1 year
measure: Penile curvature compared to our current salvage approach for CCH
timeFrame: 1 year
measure: Adverse Events
timeFrame: 1 year
measure: Partner Support
timeFrame: 1 year
measure: Compliance with Therapy - Penile Curvature
timeFrame: 1 year
measure: Satisfaction with therapy
timeFrame: 1 year
measure: Penile length compared to more aggressive technique
timeFrame: 1 year
measure: Penile length compared to our current salvage approach for CCH
timeFrame: 1 year
measure: Compliance with Therapy - Penile Length
timeFrame: 1 year
Other outcomes:
Locations:
city: Orem
country: United States
facility: Male Fertility and Peyronie's Clinic
state: Utah
Study officials:
affiliation: Charitable Union for the Research and Education of Peyronie's Disease
name: Landon Trost, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.