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

Trial Summary

What is the purpose of this trial?

Our team has previously demonstrated efficacy in performing a novel collagenase Clostridium histolyticum (CCH) injection protocol in men who previously failed to achieve a response to an initial 4 series of CCH. The objective of the current study is to evaluate a protocol that incorporates limited in-office modeling for up to 4 series, followed by up to 2 additional salvage series to determine safety and efficacy compared to historical data. Participants will receive up to 4 series of CCH injections using our previously published protocol, with mild in-office modeling. CCH injections are given on back-to back days, after which they are counseled to utilize Restorex and sildenafil daily, as instructed. Patients will undergo mild in-office modeling on day 2. The sexual partners of study participants will also be invited to enroll in the study and will complete non-validated questionnaires detailing their level of support for the patient's treatment.

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 data supports the effectiveness of the drug Collagenase Clostridium Histolyticum for Peyronie's Disease?

Research shows that Collagenase Clostridium Histolyticum is effective in treating Peyronie's Disease, as it is the only FDA-approved treatment for this condition. Studies have demonstrated its ability to improve penile curvature, and it is considered a safe and effective nonsurgical option. ^{1 2 3 4 5}

Is collagenase Clostridium histolyticum safe for treating Peyronie's disease?

Collagenase Clostridium histolyticum, also known as Xiaflex, is generally considered safe for treating Peyronie's disease, but it can cause side effects like bruising, swelling, and in rare cases, more serious issues like corporal rupture (a tear in the tissue of the penis). ^{3 6 7 8 9}

How is the drug Collagenase Clostridium Histolyticum unique for treating Peyronie's disease?

Collagenase Clostridium Histolyticum is unique because it is injected directly into the penile plaque, breaking down the collagen buildup that causes the curvature in Peyronie's disease. This approach is different from other treatments that may involve surgery or oral medications, offering a less invasive option with a modified protocol to reduce the number of injections and visits needed. ^{1 2 8 10 11}

Research Team

Landon Trost, MD

Principal Investigator

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

Eligibility Criteria

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

I am over 18 years old.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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]

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 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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Results of SMSNA Survey Regarding Complications Following Intralesional Injection Therapy With Collagenase Clostridium Histolyticum for Peyronie's Disease. [2018]

2. 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]

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

Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. [2022]

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

Intralesional Injection of Interferon-α2b Improves Penile Curvature in Men with Peyronie's Disease Independent of Plaque Location. [2018]

5. Netherlands 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. [2019]

6. Netherlands 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. [2022]

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

Restoration of Penile Function and Patient Satisfaction with Intralesional Collagenase Clostridium Histolyticum Injection for Peyronie's Disease. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. England 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. [2022]

11. 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]