Collagenase Injections for Peyronie's Disease

Overseen By Holli Burgon

Age: 18+

Sex: Any

Trial Phase: Phase 4

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

Must be taking: Sildenafil, Restorex

Disqualifiers: Prior penile surgery, Prior CCH, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks per series

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 using collagenase Clostridium histolyticum (CCH) injections for men with Peyronie's Disease who did not benefit from initial treatment. The study aims to determine if adding gentle in-office modeling and up to two additional series of injections can enhance safety and effectiveness compared to past data. Men with a noticeable penile curve of 30 degrees or more, who can achieve an erection for intercourse, and have a detectable lump (plaque) are suitable candidates. Partners of participants can also join by completing a support questionnaire. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, participants are instructed to use sildenafil daily, so it seems you may continue with medications that do not interfere with this treatment.

What is the safety track record for Collagenase Clostridium Histolyticum?

Research has shown that collagenase Clostridium histolyticum (CCH) has been studied for its safety in treating Peyronie's disease, which affects the penis. In large studies, this treatment has proven effective. It is the only FDA-approved treatment for this condition, indicating a strong safety record for its use in people.

In one study, 70.89% of patients completed their CCH treatment without stopping due to side effects, meaning most patients finished their treatment. Common side effects include swelling, bruising, and pain at the injection site, but these are usually mild and temporary.

Another study focused on individuals in the early stages of Peyronie's disease and found that the safety of CCH was consistent with earlier research.

Overall, evidence suggests that CCH is generally well-tolerated. Anyone considering joining a trial should discuss any concerns or questions about the treatment with their doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Collagenase Clostridium Histolyticum is unique because it specifically targets the buildup of collagen that causes Peyronie's disease, unlike traditional options like oral medications or surgery that focus on symptom relief or physical correction. Researchers are excited about this treatment because it involves a less invasive, injection-based approach that directly breaks down the problematic collagen, potentially reducing curvature and restoring function more effectively. Additionally, the combination with mild in-office modeling and structured use of devices like Restorex enhances its effectiveness, providing a comprehensive, non-surgical treatment pathway.

What is the effectiveness track record for Collagenase Clostridium Histolyticum in treating Peyronie's Disease?

Research shows that collagenase Clostridium histolyticum (CCH) effectively treats Peyronie's disease, which causes bent erections. Studies have found that CCH can reduce the bend by 34%, with an average decrease of about 17 degrees. The FDA has approved this as the only treatment for the condition, highlighting its proven effectiveness. Reviews of multiple studies have also noted improvements in penis length and overall satisfaction. In this trial, participants will receive a series of CCH injections. More intensive CCH treatment plans can lead to even better results in reducing curvature and increasing patient satisfaction. ^{2 6 7 8 9}

Who Is on the Research Team?

Landon Trost, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for men with Peyronie's Disease who didn't respond to initial treatments. They'll receive up to 4 series of CCH injections, followed by possible additional treatments. Partners can join the study too and will fill out questionnaires.

Inclusion Criteria

Curvature ≥30 degrees

I am over 18 years old.

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

Exclusion Criteria

Any contraindications to CCH - as determined by the PI

I have received CCH injections before.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 4 series of CCH injections with mild in-office modeling and additional treatments like sildenafil and Restorex

6 weeks per series

Multiple visits for each series

Salvage Treatment

Participants not satisfied with initial treatment may receive up to 2 additional series with more aggressive in-office modeling

9-12 months after the 4th series

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Collagenase Clostridium Histolyticum

Trial Overview The trial tests a new protocol using Collagenase Clostridium Histolyticum (CCH) injections combined with in-office modeling, RestoreX device use, and daily Sildenafil. It aims to see if this approach is safe and works better than past methods.

How Is the Trial Designed?

Group I: Primary Cohort Experimental Treatment 3 Interventions

Men would receive 4 series of CCH injections: * Administered on back-to-back days * 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 applied 2-4 full-time and 2-4 part-time days * Sildenafil 25 mg nightly and Restorex beginning treatment day 2 (sildenafil) or 3 (Restorex - 30 min/day) 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. * Performed 9-12 months after the 4th series of injections. * The technique would incorporate more aggressive, in-office modeling. * Men would receive up to two additional series per this protocol.

Collagenase Clostridium Histolyticum is already approved in United States, European Union for the following indications:

Approved in United States as Xiaflex for:

• Peyronie's disease
• Dupuytren's contracture

Approved in European Union as Xiaflex for:

• Peyronie's disease
• Dupuytren's contracture

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

6

Recruited

920+

Endo Pharmaceuticals

Industry Sponsor

Trials

136

Recruited

33,700+

Matthew Davis

Endo Pharmaceuticals

Chief Medical Officer since 2016

MD

Scott Hirsch

Endo Pharmaceuticals

Chief Executive Officer

BA in Economics from Princeton University

Published Research Related to This Trial

In a study of 69 patients with Peyronie's disease, collagenase clostridium histolyticum injections significantly improved penile curvature, with a mean improvement of 23 degrees (38%) after up to 4 treatment series, indicating its efficacy as a non-surgical option.

A majority of patients (57%) reported that the treatment eliminated the need for surgery, and 52% experienced restoration of penetration, with 81% considering the treatment meaningful and 88% noting subjective improvements after 4 injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoration of Penile Function and Patient Satisfaction with Intralesional Collagenase Clostridium Histolyticum Injection for Peyronie's Disease. Ziegelmann, MJ., Viers, BR., McAlvany, KL., 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 phase 2b study involving 147 subjects, collagenase Clostridium histolyticum significantly improved penile curvature by 29.7% compared to 11.0% in the placebo group, indicating its efficacy as a treatment for Peyronie disease.

The treatment was well tolerated with mostly mild to moderate adverse events occurring at the injection site, and no serious treatment-related adverse events were reported, suggesting it is a safe nonsurgical option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. Gelbard, M., Lipshultz, LI., Tursi, J., et al.[2022]

Intralesional interferon-α2b treatment for Peyronie's disease resulted in a positive response (greater than 20% reduction in curvature) in 91% of the 131 men studied, regardless of whether they had ventral or dorsal/lateral plaques.

The study found no significant differences in treatment response rates or changes in curvature between men with ventral plaques and those with dorsal/lateral plaques, indicating that the effectiveness of interferon-α2b is consistent across different plaque locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intralesional Injection of Interferon-α2b Improves Penile Curvature in Men with Peyronie's Disease Independent of Plaque Location. Stewart, CA., Yafi, FA., Knoedler, M., et al.[2018]

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 of 135 men with stable Peyronie's disease, a modified treatment protocol using Collagenase Clostridium histolyticum (CCH) injections significantly improved penile curvature by an average of 19.07 degrees and enhanced sexual function for both patients and their partners.

The treatment resulted in a high global satisfaction rate of 89.6%, indicating that CCH injections not only benefited the patients but also positively impacted their partners' sexual function, although the study had limitations such as the lack of a placebo group and long-term follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Factors of Patients' and Their Partners' Sexual Function Improvement After Collagenase Clostridium Histolyticum Injection for Peyronie's Disease: Results From a Multi-Center Single-Arm Study. Cocci, A., Russo, GI., Salonia, A., et al.[2019]

A survey of 100 Sexual Medicine Society of North America members revealed that 34% encountered corporal ruptures after administering collagenase clostridium histolyticum (CCH) for Peyronie's disease, with most ruptures occurring within 5 days of injection.

There is significant variability in how prescribers manage complications from CCH, with no clear advantage in patient outcomes between surgical intervention and conservative management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of SMSNA Survey Regarding Complications Following Intralesional Injection Therapy With Collagenase Clostridium Histolyticum for Peyronie's Disease. Yafi, FA., Anaissie, J., Zurawin, J., 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 phase 3 study involving 189 men, treatment with Collagenase Clostridium histolyticum (CCH) resulted in a significant 36.3% reduction in penile curvature deformity and a 2.4-point decrease in symptom bother after 36 weeks, demonstrating its efficacy for Peyronie's disease.

The treatment not only improved the men's symptoms but also positively affected their female partners, with a decrease in reported sexual dysfunction from 75% to 33.3%, indicating potential benefits for both partners involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the Effects of Peyronie's Disease After Treatment With Collagenase Clostridium histolyticum: Male Patients and Their Female Partners. Goldstein, I., Knoll, LD., Lipshultz, LI., et al.[2022]

Collagenase Clostridium histolyticum (CCH), known as Xiaflex, is an effective non-surgical treatment for Peyronie's disease, but it can lead to rare complications such as lateral herniation of the tunica albuginea, as demonstrated in a case involving a 58-year-old male.

The patient experienced a painless swelling on the left side of the penis after CCH injections, indicating a potential herniation rather than a rupture, highlighting the need for awareness of this rare side effect during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateral herniation during treatment with collagenase Clostridium histolyticum (Xiaflex) for Peyronie's disease. Gannon, MK., Pearlman, AM.[2021]

In a phase 3 study involving 347 men with Peyronie's disease, collagenase clostridium histolyticum (CCH) demonstrated a significant mean improvement of 34.4% in penile curvature deformity and a reduction of 3.3 points in the PD symptom bother score after 36 weeks of treatment.

CCH was generally well tolerated, with most adverse events being mild or moderate, and only three serious treatment-related adverse events were reported, all of which resolved with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study. Levine, LA., Cuzin, B., Mark, S., et al.[2022]

Citations

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

Peyronie's disease – outcomes of collagenase clostridium ... The capstone CCh study was the IMPRESS trial thatshowed a 34% reduction in curvature with a mean (SD) – 17.0 (14.8)° reduction with IL CCh,while men in the ...

2. 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).

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

Efficacy of collagenase Clostridium histolyticum combination ... In meta-analyses of CCH combined treatment for PD disease, results consistently showed significant improvements in penile length, PDQ-SB, and ...

4. 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 ...

5. auajournals.org auajournals.org/doi/10.1097/JU.0000000000003634

Comparison of Collagenase Clostridium histolyticum to ... Secondary outcomes demonstrated statistically greater improvements in curve improvement among Surgery men (65° vs 32.5°, P = .02) and better ...

6. 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.

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

Efficacy and Safety of Collagenase Clostridium ... Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial.

8. academic.oup.com academic.oup.com/jsm/article/22/5/794/8113152

Are patients undergoing intralesional collagenase Clostridium ... Overall compliance rate for CCH injection therapy was 70.89%. Greater curvature reduction was demonstrated in compliant patients.

9. tandfonline.com tandfonline.com/doi/full/10.1080/2090598X.2021.1957411

Peyronie's disease – outcomes of collagenase clostridium ... Safety and efficacy of collagenase clostridium histolyticum in the treatment of acute phase Peyronie's disease: a multi-institutional analysis. Urology ...