EN3835 for Plantar Fibroma

No longer recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Endo Pharmaceuticals

Must not be taking: Opioids, Anticoagulants

Disqualifiers: Neurological disorders, Bleeding disorders, others

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

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: 61

Duration: 34 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EN3835 (also known as Collagenase Clostridium Histolyticum or XIAFLEX) to evaluate its effectiveness and safety for individuals with plantar fibromatosis, a condition that causes painful lumps in the feet. Participants will either receive the treatment or join an observation group for comparison. The trial is open to those who have participated in a previous EN3835 study and completed all required visits. Individuals with plantar fibromatosis who have finished a prior EN3835 study may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the validation of a promising treatment.

Will I have to stop taking my current medications?

The trial requires that you do not use opioids during the study and have not used them for 2 weeks before starting. You should also not take medications that increase the risk of bleeding, except for a small dose of aspirin (less than 150mg daily).

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

Research shows that EN3835 is generally safe for people. In studies, patients who received collagenase Clostridium histolyticum, the main ingredient in EN3835, reported it as safe. The FDA has already approved this treatment for other conditions, like Dupuytren's contracture and Peyronie's disease, suggesting a good safety record.

Some people have reported mild side effects, such as swelling and bruising at the injection site. These effects are common with injections and are usually not serious. More serious side effects are rare but can occur, as with any medical treatment. Overall, the safety information appears promising for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for plantar fibroma, which often involve surgery or corticosteroid injections, EN3835 is unique because it uses a novel enzyme to target and break down the collagen in fibromas. This enzymatic approach could potentially reduce the size of fibromas without the need for invasive procedures. Researchers are excited about EN3835 because it offers a less invasive alternative with the possibility of fewer side effects and a quicker recovery time compared to traditional surgical options.

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

Research has shown that EN3835, which includes a special enzyme, may help treat plantar fibromatosis. In earlier studies, up to 72% of patients experienced lasting improvement with this treatment. Specifically, patients reported less foot pain and better movement, indicating an enhanced quality of life. Additionally, the size of the lumps under the skin decreased. In this trial, participants in the "Treated or Retreated Group" will receive EN3835, while those in the "Observation Only Group" will not receive any intervention. These findings suggest that EN3835 could be a helpful option for people with plantar fibromatosis. ^{1 2 6 7 8}

Who Is on the Research Team?

Nina Green

Principal Investigator

Endo Pharmaceuticals

Are You a Good Fit for This Trial?

Participants who completed a previous EN3835 study for plantar fibromatosis, haven't used opioids in the last 2 weeks, and won't change orthotics use during the trial. Women must be non-childbearing or using contraception. Excludes those with disorders affecting feet function, known allergies to collagenase or excipients of EN3835, bleeding disorders, or conditions making them unsuitable for treatment.

Inclusion Criteria

I will not start or change my use of inserts for foot lump symptoms during the study.

Agree not to use opioids during the study period and has not used opioids 2 weeks prior to the Observational Day 1 Visit

I am a woman not able to have children or will use birth control during the study.

Exclusion Criteria

Any other significant medical condition or had an SAE in the parent study which in the investigator's opinion, would make the participant unsuitable for enrollment in the study

I have a bleeding disorder that may affect my treatment.

My foot nodules may not be suitable for EN3835 treatment according to my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EN3835 for the treatment and retreatment of plantar fibromatosis

34 weeks

Visits on Treatment Days 1, 15, 29, 43, 57, 117, 197, and 237

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 weeks

Observational Days 60, 120, 180, 270, 360, and 450

Open-label extension

Participants continue to receive EN3835 to assess long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• EN3835

Trial Overview The trial is testing the long-term safety and effectiveness of a drug called EN3835 on individuals with plantar fibromatosis who have previously received it. It will evaluate how well it works over time and if re-treatment is safe and effective.

How Is the Trial Designed?

Group I: Treated or Retreated Group Experimental Treatment 1 Intervention

Group II: Observation Only Group Active Control 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10590045/

Ultrasound-Guided Collagenase Injection Therapy of ... Lauritzson et al demonstrated that clinical improvement after treatment with collagenase Clostridium histolyticum was maintained in 72% of the ...

2. investor.endo.com investor.endo.com/2021-07-29-Endo-Presents-New-Investigational-Collagenase-Clostridium-Histolyticum-Data-at-the-American-Podiatric-Medical-Association-Annual-Scientific-Meeting

Endo Presents New Investigational Collagenase ... 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 ...

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/2473011424S00116?icid=int.sj-abstract.similar-articles.7

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 ...

4. mallinckrodt.gcs-web.com mallinckrodt.gcs-web.com/news-releases/news-release-details/endo-presents-plantar-fibromatosis-and-plantar-fasciitis-data

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 ...

5. consultant360.com consultant360.com/exclusive/collagenase-clostridium-histolyticum-shows-efficacy-subgroup-patients-plantar

Collagenase Clostridium Histolyticum Shows Efficacy in ... Key findings included greater improvement in Foot Function Index (FFI) Total Pain scores, combined FFI Pain and Difficulty scores, nodule ...

6. journals.sagepub.com journals.sagepub.com/doi/10.1177/2473011423S00210

Tolerability and Safety of Collagenase Clostridium ... Plantar fibromatosis (PFi) is a functionally disabling disorder characterized by fibrous collagen-containing nodules along the plantar fascia.

7. withpower.com withpower.com/trial/phase-3-plantar-fibromatosis-1-2022-d57bc

EN3835 for Plantar Fibroma · Info for Participants This trial is testing the safety and effectiveness of EN3835, a medication for treating Plantar Fibromatosis. The study focuses on people who have already ...

8. aetna.com aetna.com/cpb/medical/data/1000_1099/1061.html

Collagenase Clostridium Histolyticum (Xiaflex) Xiaflex is an intralesional injection that has been FDA-approved for treatment of Dupuytren's contracture and Peyronie's disease.