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

Phase 4
Active, not recruiting
Conditions
Peyronie's Disease
Interventions
Drug: Control - Crossover to CCH
Drug: CCH administration
Device: RestoreX
Registration Number
NCT05108558
Lead Sponsor
Charitable Union for the Research and Education of Peyronie's Disease
Brief Summary

Compare key clinical outcomes between controls and men treated with a novel CCH administration protocol among men previously unresponsive to 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 Preliminary (unpublished - abstract submitted to SMSNA 2021) results from these men demonstrated a median \~60% curvature improvement.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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control - Crossover to CCHControl - Crossover to CCHMen 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.
Control - Crossover to CCHRestoreXMen 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.
Collagenase Clostridium HistolyticumCCH administrationMen 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.
Collagenase Clostridium HistolyticumRestoreXMen 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.
Primary Outcome Measures
NameTimeMethod
Penile Curvature6 months

Compare the change in degree of penile curvature from baseline (using a goniometer) between control and treatment groups at 6 months

Peyronie's Disease Questionnaire Outcomes6 months

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.

Secondary Outcome Measures
NameTimeMethod
International Index of Erectile Function Outcomes6 months

Compare International Index of Erectile Function Outcomes between control and treatment groups at 6 months

Penile Length Compared to Baseline12 months

Compare penile length changes in control men at baseline and 12 months (i.e. prior to and following cross-over to CCH)

Penile Curvature Compared to Baseline12 months

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

Compare Peyronie's Disease Questionnaire to Baseline12 months

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.

Compare International Index of Erectile Function to baseline12 months

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)

Penile Length Between Groups6 months

Compare penile length changes between control and treatment groups at 6 months

Adverse events - 6 months - pain, sensation, swelling6 months

Report adverse events at the 6-month time point

Adverse events - 12 months - pain, sensation, swelling12 months

Report adverse events at the 12-month time point

Change in penile curvature durability6 months

Report changes in penile curvature degree between the 6 and 12-month assessments for CCH men by goniometer.

Trial Locations

Locations (1)

The Male Fertility and Peyronie's Clinic

🇺🇸

Orem, Utah, United States

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