Novel CCH Protocol for Peyronie's Disease

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

Trial Summary

What is the purpose of this trial?

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

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 data supports the idea that Novel CCH Protocol for Peyronie's Disease is an effective treatment?

The available research shows that the Novel CCH Protocol, which involves using a drug called collagenase Clostridium histolyticum, is effective for treating Peyronie's Disease. Studies have shown that this treatment can help reduce the curvature of the penis, which is a common problem in this condition. For example, one study found that men treated with this drug experienced improvements in their condition over a long period, up to five years. Another study highlighted that even in cases with different types of penile deformities, the treatment was effective and safe. However, it's important to note that some patients may not respond to the treatment and might need surgery. Overall, the data supports that this drug is a beneficial option for many patients with Peyronie's Disease. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment for Peyronie's Disease?

Research shows that collagenase Clostridium histolyticum (CCH) is effective in treating Peyronie's disease by reducing penile curvature and improving symptoms in many patients, with studies demonstrating its long-term safety and efficacy. ^{1 2 3 4 5}

What safety data is available for CCH treatment in Peyronie's disease?

Safety data for CCH treatment in Peyronie's disease comes from multiple clinical studies. A pooled safety analysis of six studies showed that patients receiving CCH injections experienced adverse events such as bruising, swelling, hematoma, and corporal rupture in over 50% of cases. However, modified injection techniques and protocols have been proposed to reduce these adverse events. The safety and efficacy of CCH, marketed as Xiaflex, have been demonstrated in clinical trials, and new protocols aim to improve safety by reducing the number of injections and standardizing safety assessments. ^{5 6 7 8 9}

Is the treatment with collagenase Clostridium histolyticum (CCH) safe for humans?

Clinical studies show that collagenase Clostridium histolyticum (CCH) is generally safe for treating Peyronie's disease, but side effects like bruising, swelling, and hematoma (a collection of blood outside of blood vessels) are common, occurring in over 50% of cases. Modified injection techniques are being developed to reduce these side effects. ^{5 6 7 8 9}

Is the drug CCH a promising treatment for Peyronie's Disease?

Yes, CCH is a promising treatment for Peyronie's Disease. It has been shown to effectively reduce penile curvature and improve the condition in patients. Studies have demonstrated its success in treating different types of curvature and its long-term safety. ^{1 3 10 11 12}

How is the drug Collagenase Clostridium Histolyticum (CCH) unique for treating Peyronie's Disease?

Collagenase Clostridium Histolyticum (CCH) is unique because it is injected directly into the scar tissue in the penis, where it breaks down the collagen buildup that causes the curvature, unlike other treatments that may involve surgery or oral medications. ^{1 3 10 11 12}

Research Team

Landon Trost, MD

Principal Investigator

CURE PD

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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 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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Collagenase Clostridium Histolyticum in Peyronie's Disease Men With Ventral Curvatures. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes. [2020]

3. England 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. [2022]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment-related Outcomes for Patients With Atypical Peyronie's Disease Using Xiaflex Injections. [2022]

6. England 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). [2015]

7. Germany 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. [2021]

8. England 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. [2018]

9. Spain pubmed.ncbi.nlm.nih.gov

Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Curvature Deformity Characterization in Patients Previously Treated with Collagenase clostridium Histolyticum for Peyronie's Disease. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Successful Treatment of Residual Curvature in Peyronie Disease in Men Previously Treated With Intralesional Collagenase Clostridium Histolyticum. [2018]

12. China pubmed.ncbi.nlm.nih.gov

Effect of collagenase Clostridium histolyticum on penile vascular and morphological parameters in patients with Peyronie's disease. [2022]