EN3835 for Plantar Fibroma

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

145 Participants Needed

Trial Summary

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).

What data supports the effectiveness of the drug EN3835 for treating plantar fibroma?

Research shows that the drug Collagenase Clostridium Histolyticum (CCH), also known as XIAFLEX, is effective in treating conditions like Dupuytren's disease and Peyronie's disease by breaking down excess collagen, which is a protein that can cause lumps or contractures. This suggests it might also help with plantar fibroma, which involves similar collagen buildup. ^{1 2 3 4 5}

Is EN3835 (Collagenase Clostridium Histolyticum) safe for humans?

Collagenase Clostridium Histolyticum, also known as EN3835 or XIAFLEX, has been studied for safety in conditions like Dupuytren's disease and Peyronie's disease. It is generally considered safe, but some studies have noted that it can cause side effects like swelling, bruising, and pain at the injection site. It has been used in many patients, and while it does not cause cell death (apoptosis), it can affect cell behavior temporarily. ^{1 6 7 8 9}

How is the drug EN3835 different from other treatments for plantar fibroma?

EN3835, also known as Collagenase Clostridium Histolyticum (CCH), is unique because it is an injectable treatment that breaks down collagen, offering a nonsurgical option for conditions like Dupuytren's disease. This approach could be novel for plantar fibroma, as it targets the collagen buildup directly, unlike traditional surgical methods. ^{1 2 5 10 11}

What is the purpose of this trial?

This trial is testing the safety and effectiveness of EN3835, a medication for treating Plantar Fibromatosis. The study focuses on people who have already participated in a previous trial of this medication. EN3835 works by breaking down the tough tissue that forms painful lumps on the bottom of the feet.

Research Team

Nina Green

Principal Investigator

Endo Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

References

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

In vitro study of novel collagenase (XIAFLEX®) on Dupuytren's disease fibroblasts displays unique drug related properties. [2022]

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

Improved Peyronie's Disease Curvature Outcomes Using a Novel Collagenase Administration Protocol. [2022]

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

Examining the efficacy and maintenance of contracture correction after collagenase clostridium histolyticum treatment for Dupuytren's disease. [2021]

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

Collagenase Clostridium histolyticum for the Treatment of Distal Interphalangeal Joint Contractures in Dupuytren Disease. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Injectable collagenase Clostridium histolyticum as a nonsurgical treatment for Dupuytren's disease. [2018]

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

Injectable collagenase Clostridium histolyticum: a new nonsurgical treatment for Dupuytren's disease. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Prospective observation of Clostridium histolyticum collagenase for the treatment of Dupuytren's disease in 788 patients: the Austrian register. [2020]

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

The Effect of Anticoagulation on the Treatment of Dupuytren Contracture with Collagenase. [2022]

9. 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]

10. Northern Ireland pubmed.ncbi.nlm.nih.gov

The use of Collagenase Clostridium Histolyticum in the management of Dupuytren's contracture-outcomes of a pilot study in a District General Hospital setting. [2022]

11. Spain pubmed.ncbi.nlm.nih.gov

[Treatment of Dupuytren's disease using collagenase from Clostridium histolyticum]. [2013]