Novel CCH Protocol for Peyronie's Disease

Recruiting in Orem (>99 mi)

Overseen By Landon Trost, MD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Charitable Union for the Research and Education of Peyronie's Disease

Disqualifiers: Prior penile surgery, Severe plaque calcification, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of administering CCH (Collagenase Clostridium Histolyticum) to men with Peyronie's Disease who did not respond well to previous treatments. Peyronie's Disease causes a bent penis due to scar tissue, making erections painful or difficult. The trial compares men who switch from no treatment to CCH injections with those who begin with CCH injections and then take a break. It targets men who have undergone at least six CCH treatments with minimal improvement and can still engage in sexual activity with or without medication. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you can continue using PDE5 inhibitors if needed for satisfactory erections.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you can participate if you can achieve an erection with or without PDE5 inhibitors, which suggests you may continue using them.

What is the safety track record for these treatments?

Research has shown that Collagenase Clostridium Histolyticum (CCH) is generally well-tolerated for treating Peyronie's Disease. Studies have found that CCH, already approved by the FDA for this condition, can reduce penile curvature by about 34%, indicating its effectiveness and relative safety.

In terms of safety, some patients may experience side effects like swelling or bruising at the injection site. However, these symptoms typically resolve on their own. Although the treatment is considered safe, individual reactions can vary, so discussing potential risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this trial?

Researchers are excited about the Novel CCH Protocol for Peyronie's Disease because it uses Collagenase Clostridium Histolyticum (CCH) to target and break down the collagen buildup causing the penile curvature, unlike traditional surgery or oral medications that may not directly address the collagen deposits. This treatment is distinctive due to its minimally invasive nature, as it involves a series of up to eight injections, potentially offering a less risky and more convenient option than surgical interventions. Additionally, the crossover protocol allows researchers to compare the effectiveness of CCH with no initial treatment, providing valuable insights into its long-term benefits and efficacy.

What evidence suggests that this trial's treatments could be effective for Peyronie's Disease?

Research has shown that a treatment called Collagenase Clostridium Histolyticum (CCH), which participants in this trial may receive, effectively treats Peyronie's Disease. Studies have found that CCH can reduce penile curvature by 27.4% to 37.4%. It also aids in increasing penis length and reducing pain. Some patients report enhanced sensitivity and improved erectile function. This treatment has a strong record of improving symptoms for many patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Landon Trost, MD

Principal Investigator

CURE PD

Are You a Good Fit for This Trial?

Men over 18 with Peyronie's Disease who've had little improvement from previous CCH treatments can join. They must have a significant curve in their penis (≥30 degrees), no past penile surgery except circumcision, and be able to get an erection suitable for sex. Severe plaque calcification or inability to complete the treatment disqualifies them.

Inclusion Criteria

I have completed 6-8 injections for my condition.

I am a man with Peyronie's Disease.

I can have an erection good enough for sex, with or without medication.

Exclusion Criteria

I have no health conditions that prevent me from receiving CCH treatment.

I have had surgery on my penis, not including circumcision.

Severe plaque calcification (i.e. >1 cm shadowing)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Men undergo baseline assessments followed by no treatment for 6 months

6 months

Baseline and final assessments

Treatment

Participants receive up to 8 injections of CCH or until curvature is <15 degrees

6 weeks

Interval assessments with each injection series

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Final assessments at 6 months

What Are the Treatments Tested in This Trial?

Interventions

• CCH administration
• RestoreX

Trial Overview The trial is testing a new way of giving CCH injections compared to the old method among men whose Peyronie's Disease didn't respond well before. It includes using a device called RestoreX after not responding to at least 6-8 prior CCH injections without this device.

How Is the Trial Designed?

Group I: Collagenase Clostridium Histolyticum Experimental Treatment 2 Interventions

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.

Group II: Control - Crossover to CCH Active Control 2 Interventions

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.

CCH administration is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Xiaflex for:

• Peyronie's disease
• Dupuytren's contracture

Approved in European Union as Xiaflex for:

• Dupuytren's contracture
• Peyronie's disease

Approved in Canada as Xiaflex for:

• Dupuytren's contracture
• Peyronie's disease

Who Is Running the Clinical Trial?

Charitable Union for the Research and Education of Peyronie's Disease

Lead Sponsor

Trials

6

Recruited

920+

Published Research Related to This Trial

Intralesional collagenase Clostridium histolyticum (CCH) significantly reduced penile curvature deformity and symptom bother in patients with Peyronie's disease across various subgroups, including those with different degrees of curvature and disease duration, indicating its efficacy as a treatment option.

While CCH treatment was generally associated with mild to moderate adverse events, serious complications like corporal rupture and penile hematoma were noted, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of collagenase Clostridium histolyticum in the treatment of Peyronie's disease by subgroup: results from two large, double-blind, randomized, placebo-controlled, phase III studies. Lipshultz, LI., Goldstein, I., Seftel, AD., et al.[2022]

The modified 'fan' injection technique for administering collagenase Clostridium histolyticum in Peyronie's disease significantly reduced the incidence of hematomas to 5.3% of patients and 0.6% of injections, indicating improved safety compared to previous protocols.

The introduction of a standardized hematoma classification system enhances the assessment of safety in treatment, as it allows for clearer reporting and understanding of adverse events, with no cases of corporal rupture reported in this study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A modified technique for intralesional injection of collagenase Clostridium histolyticum for Peyronie's disease results in reduced procedural morbidity using a standardized hematoma classification rubric. Amighi, A., Mills, SA., Eleswarapu, SV., et al.[2021]

In a study of 21 men with atypical Peyronie's disease, collagenase Clostridium histolyticum (CCH) treatment led to a significant average reduction in penile curvature of 19.2°, representing a 39% improvement, over a mean follow-up of 20.5 months.

The treatment was found to be safe, with 64% of patients with indentation or hourglass deformities reporting satisfaction and subjective improvement, alongside a notable decrease in symptom bother as measured by the Peyronie's Disease Questionnaire.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related Outcomes for Patients With Atypical Peyronie's Disease Using Xiaflex Injections. El-Khatib, FM., Osman, MM., Kopelevich, A., et al.[2022]

In a study of 53 patients with Peyronie's disease, a new modified treatment protocol using only three injections of collagenase clostridium histolyticum (CCH) resulted in a significant improvement in penile curvature, with 96.2% of patients showing an average reduction of 17.36° from a baseline curvature of 54° (P < 0.001).

The modified protocol was found to be safe and well-tolerated, with only mild and transient local side effects, and its efficacy was comparable to traditional protocols that required eight injections, making it a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie's disease using a new modified shortened protocol. Abdel Raheem, A., Capece, M., Kalejaiye, O., et al.[2018]

In a pooled analysis of 1,044 patients treated with collagenase Clostridium histolyticum (CCH) for Peyronie's disease, 85.8% reported at least one treatment-related adverse event (AE), with the most common being penile bruising, pain, and swelling.

While serious adverse events (SAEs) occurred in 0.9% of patients, primarily involving penile haematoma and corporal rupture, most AEs were mild to moderate, indicating that CCH treatment is generally safe but requires monitoring for potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD). Carson, CC., Sadeghi-Nejad, H., Tursi, JP., et al.[2015]

In a study of 51 patients with Peyronie's disease, treatment with collagenase Clostridium histolyticum (CCH) significantly improved penile curvature and circumference, but did not affect vascular parameters like peak systolic velocity or resistive index after four treatment cycles.

The lack of correlation between changes in curvature and vascular parameters suggests that CCH therapy primarily alters penile morphology rather than vascular function, supporting its safety profile as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of collagenase Clostridium histolyticum on penile vascular and morphological parameters in patients with Peyronie's disease. Diao, L., Anaissie, J., Nguyen, HMT., et al.[2022]

Collagenase clostridium histolyticum (CCH) therapy significantly improved penile curvature in men with Peyronie's disease over a 5-year period, with improvements of 20.9° in those with no calcification and similar results in those with stippled or interfering calcification.

No long-term safety issues were identified, indicating that CCH is a safe and effective nonsurgical treatment option for men with Peyronie's disease, even in cases of plaque calcification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Curvature Deformity Characterization in Men Previously Treated With Collagenase Clostridium Histolyticum for Peyronie's Disease, Subgrouped by Penile Plaque Calcification. Goldstein, I., McLane, MP., Xiang, Q., et al.[2022]

In a study involving 31 patients with Peyronie's disease, a modified treatment protocol using collagenase Clostridium histolyticum (CCH) resulted in an 80.6% improvement in curvature, with an average reduction of 20.65 degrees, demonstrating its efficacy.

The modified protocol was found to be safe, as no treatment-related adverse events were reported, suggesting it could be a viable alternative to the standard, more resource-intensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol. García Cruz, E., Mercader Barrull, C., Camacho Rovira, D., et al.[2021]

In a study of 67 patients with Peyronie's disease who experienced persistent issues after collagenase clostridium histolyticum (CCH) treatment, 49.3% required surgical intervention, particularly those with severe curvature (≥60°) and hinge effects, indicating that these factors are strong predictors for surgery.

Despite the presence of calcifications, which are typically a contraindication for CCH treatment, surgical outcomes were favorable with low complication rates, suggesting that surgery can be a safe option for patients with significant deformities after CCH treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes. Bajic, P., Wiggins, AB., Ziegelmann, MJ., et al.[2020]

In a long-term study of 280 men treated with collagenase clostridium histolyticum for Peyronie's disease, 73% completed the study, showing sustained improvements in penile curvature and quality of life over 5 years without additional treatment.

No long-term safety issues were identified, with only 17.5% of patients reporting adverse events, none of which were deemed treatment-related, indicating a favorable safety profile for collagenase clostridium histolyticum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Curvature Deformity Characterization in Patients Previously Treated with Collagenase clostridium Histolyticum for Peyronie's Disease. Goldstein, I., Lipshultz, LI., McLane, M., et al.[2020]

Collagenase clostridium histolyticum (CCH) is effective in treating ventral penile curvatures caused by Peyronie's Disease, with significant improvements observed in curvature after treatment, particularly for ventral (49% improvement) and lateral (38% improvement) curvatures compared to dorsal (25% improvement).

The treatment was found to have a similar safety profile across different curvature directions, with no urethral complications reported, indicating that CCH is a safe option for men with ventral Peyronie's Disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Collagenase Clostridium Histolyticum in Peyronie's Disease Men With Ventral Curvatures. Alom, M., Meng, Y., Sharma, KL., et al.[2020]

Surgical correction of residual curvature in Peyronie disease after treatment with intralesional collagenase is both safe and effective, with 80% of patients experiencing no residual curvature post-surgery.

It is recommended to wait at least 6 months after the last collagenase injection before performing surgery to minimize the risk of increased inflammation and surgical difficulty, as noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Residual Curvature in Peyronie Disease in Men Previously Treated With Intralesional Collagenase Clostridium Histolyticum. DeLay, K., Diao, L., Nguyen, HMT., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8451611/

Peyronie's disease – outcomes of collagenase clostridium ... In a small review of current data, it was determined that CCh was effective at reducing penile curvature (27.4–37.4%) while displaying no unique adverse ...

2. academic.oup.com academic.oup.com/smr/article/12/3/497/7655837

Efficacy of collagenase Clostridium histolyticum combination ... This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090429522008305

Improved Peyronie's Disease Curvature Outcomes Using a ... Results from the current study demonstrate significantly greater curvature and subjective improvements among men treated with a novel, more aggressive CCH ...

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.780956/full

Efficacy and Safety of Collagenase Clostridium ... The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: −318.77, p < 0.001) and PDSB (WMD: −1.20, ...

5. auajournals.org auajournals.org/doi/10.1097/01.JU.0001008872.42208.7a.13

MP28-13 EFFICACY OF A NOVEL COLLAGENASE ... 67% reported improved sensitivity (33% no change), while 60% reported improved or no change in erectile function, with 20% unsure, and 20% ...

6. peyronies-disease.xiaflex.com peyronies-disease.xiaflex.com/hcp/efficacy-safety/study-design/

Study Design XIAFLEX is the only FDA-approved treatment evaluated in 2 large multicenter studies of patients with Peyronie's disease (PD).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05777031?term=COLLAGENASE%20CLOSTRIDIUM%20HISTOLYTICUM&viewType=Table&rank=8

Safety and Efficacy of Collagenase Clostridium ... The purpose of this study is to learn about the safety and side effects of intralesional collagenase clostridium histolyticum (CCH) injected into the Peyronies ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25388099/

Clinical safety and effectiveness of collagenase clostridium ... Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study · Authors.