EN3835 for Plantar Fibromatosis

(STRIDE Trial)

Recruiting at 64 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Endo Pharmaceuticals

Disqualifiers: Non-PFI nodules, Neurological disorders, Bleeding disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

418 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a treatment called EN3835 (also known as Collagenase Clostridium Histolyticum or XIAFLEX) for individuals with plantar fibromatosis, or Ledderhose disease. This condition affects the feet and can cause pain due to fibrous nodules. Participants will receive either EN3835 or a placebo to determine if the treatment can reduce foot pain and improve comfort. It suits individuals diagnosed with plantar fibromatosis who experience foot pain from the condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to help potentially bring a new treatment to market.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot use any medication to treat PFI pain unless allowed by the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that EN3835 is likely to be safe for humans?

Research has shown that EN3835, a treatment under study for plantar fibromatosis, has undergone safety testing in earlier studies. Patients generally tolerated the treatment well in these studies. Common side effects included mild to moderate pain and swelling at the injection site, while serious side effects were rare. The studies did not identify any unexpected safety issues, suggesting the treatment is relatively safe. However, all treatments carry risks, so discussing these with a healthcare provider is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PFI?

EN3835 is unique because it offers a new approach to treating plantar fibromatosis by targeting collagen buildup in the feet, which is the primary cause of the condition. Unlike current treatments, which often involve surgery or corticosteroid injections to manage symptoms, EN3835 works as a collagenase enzyme that breaks down the excess collagen directly. Researchers are excited about EN3835 because it has the potential to provide a non-surgical, minimally invasive option that directly addresses the underlying problem, potentially leading to better outcomes and faster recovery for patients.

What evidence suggests that EN3835 might be an effective treatment for plantar fibromatosis?

Research has shown that EN3835, which contains an enzyme that breaks down proteins, may help treat plantar fibromatosis (PFI). In this trial, some participants will receive EN3835, while others will receive a placebo. Studies found that patients who received EN3835 experienced less foot pain and better foot function compared to those who received a placebo. Specifically, improvements appeared in the Foot Function Index, which measures pain and difficulty in moving the foot. These results suggest that EN3835 could work for PFI by breaking down the collagen buildup in foot lumps. Overall, previous patients demonstrated significant improvement, supporting the potential of EN3835 as a treatment for PFI. ^{1 4 6 7 8}

Who Is on the Research Team?

Luis Ortega

Principal Investigator

Endo Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Ledderhose disease, which causes painful foot lumps. Participants must be able to walk and give informed consent. Women must either not be able to have children or agree to use birth control during the study.

Inclusion Criteria

I agree not to take any prohibited medication during the study.

I have been diagnosed with primary fibromyalgia.

I have foot pain because of plantar fasciitis.

Exclusion Criteria

Is pregnant or plans to become pregnant

Is breastfeeding or is providing or plans to provide breast milk in any manner during the study

I have lumps on my foot not related to plantar fibromatosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either EN3835 or placebo to assess efficacy, safety, and tolerability in the treatment of Plantar Fibromatosis

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EN3835

Trial Overview

The trial is testing EN3835's effectiveness against a placebo in treating Ledderhose disease. It aims to see if EN3835 can reduce pain and improve condition without causing harm.

How Is the Trial Designed?

Group I: EN3835 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

EN3835 is already approved in United States for the following indications:

Approved in United States as XIAFLEX for:

• Dupuytren's contracture
• Peyronie's disease

Who Is Running the Clinical Trial?

Endo Pharmaceuticals

Lead 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 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]

In a study of 197 patients receiving collagenase clostridium histolyticum injections for Dupuytren contracture, 52% were on anticoagulation therapy, primarily aspirin, and the procedure showed no significant increase in complications compared to nonanticoagulated patients.

The study found that it is safe to perform collagenase injections in patients on anticoagulants, as there were no significant differences in complications like skin tears or tendon ruptures, indicating that anticoagulation does not adversely affect the safety of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Anticoagulation on the Treatment of Dupuytren Contracture with Collagenase. Noland, SS., Paul, AW., Pflibsen, LR., et al.[2022]

In a study of 788 patients treated with Xiapex® for Dupuytren's disease, 66.5% experienced a significant reduction in contracture, demonstrating the efficacy of the treatment.

The safety profile of Xiapex® was favorable, with no major complications reported and only minor adverse events, such as skin tears (26%), which resolved within 30 days; only 2% of patients required surgical intervention within a year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective observation of Clostridium histolyticum collagenase for the treatment of Dupuytren's disease in 788 patients: the Austrian register. Rohit, A., Peter, A., Paul, A., et al.[2020]

In a post-hoc analysis of 362 patients from two pivotal phase 3 trials, 82% of patients with Dupuytren's contracture and moderate disease achieved clinical success after treatment with collagenase clostridium histolyticum (CCH), indicating its efficacy in this specific population.

CCH was well tolerated, with mild to moderate adverse events reported and no discontinuations due to side effects, suggesting a favorable safety profile for patients with up to two joints affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of collagenase clostridium histolyticum in the treatment of patients with moderate Dupuytren's contracture. McGrouther, DA., Jenkins, A., Brown, S., et al.[2018]

In a study of 49 patients with Peyronie's disease, collagenase Clostridium histolyticum (CCh) treatment significantly reduced penile curvature by an average of 15.4 degrees (32.4%), improving the ability to perform intercourse by 29.1%.

While CCh showed promising results in reducing curvature and improving subjective symptoms, there were some safety concerns, including a 10.2% incidence of notable bleeding events, with one case resulting in a penile fracture.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peyronie's Disease and Injectable Collagenase Clostridium histolyticum: Safety, Efficacy, and Improvements in Subjective Symptoms. Yang, KK., Bennett, N.[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]

Collagenase clostridium histolyticum (CCH) is a safe and effective FDA-approved treatment for Dupuytren's contracture, with a low rate of serious adverse events (0.6% per 1,000 injections) reported in the first year after its approval.

The most common adverse events were minor, including local reactions like skin tears and peripheral edema, confirming the safety profile established in earlier clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsurgical treatment of Dupuytren's contracture: 1-year US post-marketing safety data for collagenase clostridium histolyticum. Peimer, CA., McGoldrick, CA., Fiore, GJ.[2021]

In a study involving 66 patients with Dupuytren's contracture, collagenase clostridium histolyticum (Xiaflex) was found to be significantly more effective than placebo, with 44.4% of treated cords achieving a reduction in contracture to 0° to 5° compared to only 4.8% in the placebo group.

Collagenase treatment resulted in a mean decrease in joint contracture of 70.5% and a significant increase in range of motion, demonstrating its efficacy as a well-tolerated, nonsurgical option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable collagenase Clostridium histolyticum: a new nonsurgical treatment for Dupuytren's disease. Gilpin, D., Coleman, S., Hall, S., et al.[2022]

Citations

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A Phase 2, Double-blind, Randomized, Placebo-Controlled ...

A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess Collagenase Clostridium Histolyticum vs Placebo in Patients With Plantar ...

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The first two presentations cover findings from Phase 1 and Phase 2 studies of collagenase clostridium histolyticum (CCH) in patients with PFA ...

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A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess Collagenase Clostridium Histolyticum vs Placebo in Patients With Plantar ...

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CCH treatment showed improvements across all effectiveness measures compared to placebo, though significance was not assessed. These results supported further ...

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The Phase I, open-label, randomized, dose-ranging study (EN3835–105) presented at APMA is the first trial to explore CCH for the treatment of plantar ...

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Endo Presents Plantar Fibromatosis and Plantar Fasciitis Data ...

The first two presentations cover findings from Phase 1 and Phase 2 studies of collagenase clostridium histolyticum (CCH) in patients with PFA ...