Efficacy of a Novel CCH Protocol for PD Among Prior Non-responders

Efficacy of a Novel Collagenase Clostridium Histolyticum Protocol for Peyronie's Disease Among Prior Non-responders: A Randomized, Controlled, Single-Blinded Study

Compare key clinical outcomes between controls and men treated with a novel CCH administration protocol among men previously unresponsive to CCH administration.

Study Overview

• Status: Recruiting
• Conditions: Peyronie's Disease
• Intervention / Treatment: Drug: Control - Crossover to CCH; Device: RestoreX; Drug: CCH administration

Detailed Description

Beginning approximately 3 years ago, the investigators' team sought to achieve further improvements with CCH through the addition of more aggressive modeling therapies. Results from a comparison of CCH alone vs CCH and traction with RestoreX demonstrated a mean 33.8 degree (49%) curvature improvement with combined therapy compared to 19-20 degrees (30-31%) with CCH alone or CCH and other traction devices). These results currently represent the greatest improvements with CCH in published literature and further build upon phase IIb results which demonstrated that mechanical traction (via manual modeling in the phase IIb trial) represents a critical factor in achieving improvements with CCH.

The investigators' team additionally published a survey of men who had experienced suspected penile fractures with CCH and demonstrated greater curvature improvements without any loss / worsening of erectile function. This critical study highlighted that conservative management of suspected fractures should not only be considered a standard of care in managing suspected fractures, but also that these men achieved better final outcomes (again highlighting the importance of the combination of mechanical curvature correction in addition to CCH management).

Based on the above findings, the investigators' team began performing a more aggressive manual modeling protocol. This novel protocol included several notable innovations: dilution of the 0.9 mg of CCH in 0.7 ml of diluent, injection to the erect penis to assure accurate injection, repeat curvature assessments with each series (due to changing of the point of maximal curvature), incorporation of RestoreX traction therapy post injection, and 'aggressive' manual modeling (equivalent of 10-15 lbs of force) to achieve curvature correction. Preliminary (unpublished - abstract submitted to SMSNA 2021) results from these men demonstrated a median ~60% curvature improvement. Importantly, several of the patients had previously undergone 8 CCH injections with outside providers and were able to similarly achieve a median 60% improvement with the investigators' injection / modeling protocol.

These preliminary findings have several important ramifications for the treatment of PD:

1. Men who have previously not achieved adequate curvature correction with 4 series of CCH injections may benefit from additional injections using a more aggressive traction protocol.
2. A more aggressive traction protocol would benefit patients to achieve greater outcomes than with previously reported protocols.

1.2 Investigational Treatments

The current study would randomize men 1:3 into one of two treatment cohorts: 1. Observation followed by CCH or 2. CCH followed by observation. This study design offers the benefits of a randomized, controlled trial (highest level of evidence). RCTs are particularly important in PD, where the disease changes over time in a percentage of men as a function of its natural history. This would also allow blinding of measurements using photographs (single-blinded assessments), which provides further study rigor.

1. No treatment (control) followed by CCH. Men in this cohort would undergo baseline assessments followed by no treatment for 6 months and then repeat assessments. Men would then cross-over to CCH treatment and undergo up to 8 injections (or until curvature is <15 degrees). Interval assessments would be performed with the 1st injection of each series, and final assessments would then be performed 6 weeks following the final injection.
2. CCH followed by no treatment. Men in this cohort would undergo baseline assessments followed by up to 8 injections of CCH (or until curvature is <15 degrees). Interval assessments would be performed with the 1st injection of each series and 6 weeks following completion of treatment. Men then would not undergo any additional treatments for 6 months, after which final assessments would then performed.

• 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 Locations

• United States
  • Utah
    • Orem, Utah, United States, 84057
      • Recruiting
      • The Male Fertility and Peyronie's Clinic
      • Contact: Landon Trost, MD; Phone Number: 888-655-0015; Email: trost.landon@mfp.clinic
      • Sub-Investigator: Benjamin D. Green, Economics/MA
      • Sub-Investigator: Holli Burgon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men with Peyronie's Disease
• >18 years old
• Curvature ≥30 degrees
• Previously completed 6-8 CCH injections
• Prior minimal (<20% and/or <10 degrees) responsiveness to CCH administration
• Prior CCH injections must have been performed without use of a Restorex traction device and used the IMPRESS protocol
• Ability to achieve an erection satisfactory for intercourse with or without PDE5 inhibitors
• The patient exhibits a palpable plaque consistent with Peyronie's Disease

Exclusion Criteria:

• Prior surgical treatment on the penis (other than circumcision)
• Any contraindications to CCH - as determined by the PI
• Inability to complete 8 additional CCH injections
• Severe plaque calcification (i.e. >1 cm shadowing)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control - Crossover to CCH; Men in this cohort would undergo baseline assessments followed by no treatment for 6 months and then repeat assessments. Men would then cross-over to CCH treatment and undergo up to 8 injections (or until curvature is <15 degrees). Final assessments would then be performed 6 weeks following the final injection.	Drug: Control - Crossover to CCH; Patients will be randomized 1:3 into the control arm. After undergoing baseline assessments, control men will not undergo treatments for 6 months. They will then have repeat assessments and receive up to 8 CCH injections. They will then have final assessments performed 6 weeks after treatment.; Other Names: Collagenase Clostridium Histolyticum; Device: RestoreX; Both treatment arms will incorporate the use of RestoreX for 30-60 minutes daily during CCH administration and continued until 6 weeks after final injection administration.
Experimental: Collagenase Clostridium Histolyticum; Men in this cohort would undergo baseline assessments followed by up to 8 injections of CCH (or until curvature is <15 degrees). Men would then undergo assessments 6 weeks later, followed by a 6-month no treatment phase and then final assessments.	Device: RestoreX; Both treatment arms will incorporate the use of RestoreX for 30-60 minutes daily during CCH administration and continued until 6 weeks after final injection administration.; Drug: CCH administration; Patients will be randomized 3:1 into the CCH administration arm. After undergoing baseline assessments, this arm will receive up to 8 CCH injections, followed by final assessments 6 weeks later.; Other Names: Collagenase Clostridium Histolyticum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Penile Curvature	Compare the change in degree of penile curvature from baseline (using a goniometer) between control and treatment groups at 6 months	6 months
Peyronie's Disease Questionnaire Outcomes	Compare Peyronie's Disease Questionnaire outcomes between control and treatment groups at 6 months using the Peyronie's Disease Questionnaire (15 items; subdomains - psychological and physical (Q1-6, 0-24), penile pain (Q7-9; 0-30), symptom bother (Q10-15; 0-16); 12 and 14 (Y/N q's); lower is better.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Index of Erectile Function Outcomes	Compare International Index of Erectile Function Outcomes between control and treatment groups at 6 months	6 months
Penile Curvature Compared to Baseline	Compare penile curvature changes (degrees) in control men at baseline and 12 months (i.e. prior to and following cross-over to CCH) - using goniometer	12 months
Penile Length Compared to Baseline	Compare penile length changes in control men at baseline and 12 months (i.e. prior to and following cross-over to CCH)	12 months
Compare Peyronie's Disease Questionnaire to Baseline	Compare PDQ changes in control men at baseline and 12 months (i.e. prior to and following cross-over to CCH) using the Peyronie's Disease Questionnaire (15 items; subdomains - psychological and physical (Q1-6, 0-24), penile pain (Q7-9; 0-30), symptom bother (Q10-15; 0-16); 12 and 14 (Y/N q's); lower is better.	12 months
Compare International Index of Erectile Function to baseline	Compare International Index of Erectile Function changes in control men at baseline and 12 months (i.e. prior to and following cross-over to CCH)	12 months
Penile Length Between Groups	Compare penile length changes between control and treatment groups at 6 months	6 months
Adverse events - 6 months - pain, sensation, swelling	Report adverse events at the 6-month time point	6 months
Adverse events - 12 months - pain, sensation, swelling	Report adverse events at the 12-month time point	12 months
Change in penile curvature durability	Report changes in penile curvature degree between the 6 and 12-month assessments for CCH men by goniometer.	6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Estimated): December 20, 2025
• Study Completion (Estimated): September 20, 2028

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Penile Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Penile Induration
• Other Study ID Numbers: CUREPD 103

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