Long-Term Safety, Efficacy, and Durability of EN3835 in the Treatment and Retreatment of Plantar Fibromatosis

A Multi-Center, Open-Label, Extension Study to Evaluate the Long-Term Safety, Efficacy, and Durability of EN3835 in the Treatment and Retreatment of Plantar Fibromatosis

Assess the long-term safety and efficacy of EN3835 in participants who have participated in a parent placebo-controlled study of EN3835 (EN3835-222, NCT05152173) and assess the efficacy and safety of EN3835 in the treatment and retreatment of plantar fibromatosis.

Study Overview

• Status: Completed
• Conditions: Plantar Fibromatosis
• Intervention / Treatment: Biological: EN3835

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 19331
      • Endo Clinical Trial Site #12
    • Fresno, California, United States, 93710
      • Endo Clinical Trial Site #3
    • La Mesa, California, United States, 91942
      • Endo Clinical Trial Site #23
    • Tarzana, California, United States, 91356
      • Endo Clinical Trial Site #13
    • Vista, California, United States, 92083
      • Endo Clinical Trial Site #15
    • Whittier, California, United States, 90603
      • Endo Clinical Trial Site #18
  • Florida
    • Miami, Florida, United States, 33176
      • Endo Clinical Trial Site #24
    • Pinellas Park, Florida, United States, 33782
      • Endo Clinical Trial Site #8
    • Sweetwater, Florida, United States, 33172
      • Endo Clinical Trial Site #21
  • Georgia
    • Lawrenceville, Georgia, United States, 30043
      • Endo Clinical Trial Site #22
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Endo Clinical Trial Site #25
  • Illinois
    • Decatur, Illinois, United States, 62521
      • Endo Clinical Trial Site #19
    • O'Fallon, Illinois, United States, 62269
      • Endo Clinical Trial Site #2
    • Springfield, Illinois, United States, 62704
      • Endo Clinical Trial Site #14
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Endo Clinical Trial Site #6
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Endo Clinical Trial Site #16
  • Pennsylvania
    • York, Pennsylvania, United States, 17402
      • Endo Clinical Trial Site #9
  • Texas
    • Bedford, Texas, United States, 76021
      • Endo Clinical Trial Site #4
    • Dallas, Texas, United States, 75208
      • Endo Clinical Trial Site #17
    • Dallas, Texas, United States, 75251
      • Endo Clinical Trial Site #26
    • Fort Worth, Texas, United States, 76104
      • Endo Clinical Trial Site #5
    • Georgetown, Texas, United States, 78628
      • Endo Clinical Trial Site #27
    • Houston, Texas, United States, 77027
      • Endo Clinical Trial Site #7
    • Houston, Texas, United States, 77095
      • Endo Clinical Trial Site #10
    • McAllen, Texas, United States, 78501
      • Endo Clinical Trial Site #1
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Endo Clinical Trial Site #11
  • Virginia
    • Suffolk, Virginia, United States, 23434
      • Endo Clinical Trial Site #20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have been enrolled and completed a sponsored-clinical study of EN3835 (for the EN3835-222 study, participants who completed the study are those that completed the Day 57 visit, were assessed for safety and received at least 1 dose of study intervention).
2. Willing and able to comply with all protocol required visits and assessments.
3. Agree not to use opioids during the study period and has not used opioids 2 weeks prior to the Observational Day 1 Visit.
4. Agree to not initiate or change use of orthotics or inserts designed to relieve symptoms of plantar fibromatosis during the study period.
5. Willing and able to comply with all protocol required visits and assessments.
6. Be adequately informed and understand the nature and risks of the study and be able to provide consent
7. If female, be of non-childbearing potential (history of hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or postmenopausal with no history of menstrual flow in the 12 months prior to the Day 1 Visit), or, if of childbearing potential, be nonpregnant, non-lactating and agree to use effective contraception when with a male partner for the duration of the study and for 28 days after any active treatment period.
8. Have no significant medical history or examination findings related to the participant's plantar nodules, which in the investigator's opinion, would make the participant unsuitable for EN3835 administration.

Exclusion Criteria:

1. Has any musculoskeletal, neuromuscular, neurosensory, or other neurological or related disorder that affects the participant's use of his or her feet and/or would impair his/her completion of study assessments as determined by the investigator.
2. 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.
3. Received or plans to receive surgical or non-surgical treatments on the foot or nodules that were treated.
4. Has a known systemic allergy to collagenase or any other excipient of EN3835.
5. Has a known bleeding disorder that would make the participant unsuitable for treatment or retreatment in the study.
6. Has significant medical history or examination findings related to the participant's plantar nodules, which in the investigator's opinion, would make the participant unsuitable for EN3835 administration.
7. Has a known coagulation disorder or is taking any medications that would increase the risk of bleeding (except <150mg of aspirin daily, 7 days prior to first injection and for the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation Only Group
Experimental: Treated or Retreated Group	Biological: EN3835; Treatment or retreatment with EN3835

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants reporting adverse events (AE)	Proportion of participants reporting AE during the study assessed by incidence, severity and duration	Day 1 to Day 450

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on the Foot Function Index (FFI) total score in participants treated in the parent studies, and participants retreated in this study	Change from baseline on the FFI total score on a 5-point rating scale (0-4). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Observational Days 60, 120, 180, 270, 360, and 450
Change from baseline on the Foot Function Index (FFI) subscales in participants treated in the parent studies, and participants retreated in this study	Change from baseline on the FFI subscales (pain, difficulty, and activity limitation). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Observational Days 60, 120, 180, 270, 360, and 450
Change from baseline in the nodular hardness in participants treated in the parent studies, and participants retreated in this study	Change from baseline in the nodular hardness of the treated nodules measured by durometer	Observational Days 60, 120, 180, 270, 360, and 450
Change from baseline in the nodular consistency of the treated nodules by palpation in participants treated in the parent studies, and participants retreated in this study	Change from baseline in the nodular consistency of the treated nodules by palpation	Observational Days 60, 120, 180, 270, 360, and 450
Change from baseline on the Pain Intensity Numerical Rating Scale (NRS) in the parent studies, and participants retreated in this study	Change from baseline on the Pain Intensity NRS ranging from 0 (No Pain) to 10 (Worst Pain Imaginable)	Observational Days 60, 120, 180, 270, 360, and 450
Proportion of participants that meet Treatment Session 1 criteria in the parent studies, and participants retreated in this study	Proportion of participants that meet Treatment Session 1 criteria	Days 180 or 270
Proportion of participants on the Subject Satisfaction with Treatment Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting "Quiet Satisfied" (+1) and "Very Satisfied" (+2) on the Subject Satisfaction with Treatment Scale	Observational Days 60, 120, 180, 270, 360, and 450
Proportion of participants on the Clinician Global Impression of Change Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting "Minimally Improved" (+1), "Much Improved" (+2) or "Very Much Improved" (+3) on the Clinician Global Impression of Change Scale	Observational Days 60, 120, 180, 270, 360, and 450
Change from baseline (Retreatment) on the Foot Function Index (FFI) total score in the parent studies, and participants retreated in this study	Change from baseline (Retreatment Day 1) with EN3835 on the FFI total score on a 5-point rating scale (0-4). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Change from baseline (Retreatment Day 1) to Retreatment Days 15, 29,43, 57, 117, 197, and 237
Change from baseline (Retreatment) on the Foot Function Index (FFI) subscales (pain, difficulty, and activity limitation) in the parent studies, and participants retreated in this study	Change from baseline (Retreatment Day 1) with EN3835 on the FFI subscales (pain, difficulty, and activity limitation). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Change from baseline (Retreatment Day 1) to Retreatment Days 15, 29,43, 57, 117, 197, and 237
Change from baseline (Retreatment) in the nodular hardness of the treated nodules in the parent studies, and participants retreated in this study	Change from baseline (Retreatment Day 1) with EN3835 in the nodular hardness of the treated nodules measured by durometer	Change from baseline (Retreatment Day 1) to Retreatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Retreatment Day 1) in the nodular consistency of the treated nodules by palpation in the parent studies, and participants retreated in this study	Change from baseline (Retreatment Day 1) with EN3835 in the nodular consistency of the treated nodules by palpation	Change from baseline (Retreatment Day 1) to Retreatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Retreatment Day 1) on the Pain Intensity Numerical Rating Scale (NRS) in the parent studies, and participants retreated in this study	Change from baseline (Retreatment Day 1) with EN3835 on the Pain Intensity NRS ranging from 0 (No Pain) to 10 (Worst Pain Imaginable)	Change from baseline (Retreatment Day 1) to Retreatment Days 15, 29, 43, 57, 117, 197, and 237
Proportion of participants reporting on the Subject Satisfaction with Treatment Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting to be "Quiet Satisfied" (+1) and "Very Satisfied" (+2) on the Subject Satisfaction with Treatment Scale on Retreatment Days	Retreatment Days 15, 29, 43, 57, 117, 197, and 237
Proportion of participants reporting on the Clinician Global Impression of Change Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting "Minimally Improved" (+1), "Much Improved (+2)" or "Very Much Improved (+3) on the Clinician Global Impression of Change Scale on Retreatment Days	Retreatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Treatment Day 1) on the Foot Function Index (FFI) total score in the parent studies, and participants retreated in this study	Change from baseline (Treatment Day 1) with EN3835 on the FFI total score on a 5-point rating scale (0-4). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Change from baseline (Treatment 1) to Treatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Treatment Day 1) on the Foot Function Index (FFI) subscales in the parent studies, and participants retreated in this study	Change from baseline (Treatment Day 1) with EN3835 on the FFI subscales (pain, difficulty, and activity limitation). This score is comprised of activity limitation, difficulty, and pain subscales. Each subscale is scored on a 5-point rating scale, ranging from 0 to 4, with 0 being never, no difficulty, or none and 4 being always, a lot of difficulty, and extreme.	Change from Baseline (Treatment 1) to Treatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Treatment Day 1) in the nodular hardness of the treated nodules in the parent studies, and participants retreated in this study	Change from baseline (Treatment Day 1) with EN3835 in the nodular hardness of the treated nodules measured by durometer	Change from baseline (Treatment Day 1) to Treatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Treatment Day 1) in the nodular consistency of the treated nodules in the parent studies, and participants retreated in this study	Change from baseline (Treatment Day 1) with EN3835 in the nodular consistency of the treated nodules be palpation	Change from baseline (Treatment Day 1) to Treatment Days 15, 29, 43, 57, 117, 197, and 237
Change from baseline (Treatment Day 1) on the Pain Intensity Numerical Rating Scale (NRS) in the parent studies, and participants retreated in this study	Change from baseline (Treatment Day 1) with EN3835 on the Pain Intensity NRS ranging from 0 (No Pain) to 10 (Worst Pain Imaginable)	Change from baseline (Treatment Day 1) to Treatment Days 15, 29, 43, 57, 117, 197, and 237
Proportion of participants reporting on the Subject Satisfaction with Treatment Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting to be "Quite Satisfied" (+1) and "Very Satisfied" (+2) on the Subject Satisfaction with Treatment Scale	Treatment Days 15, 29, 43, 57, 117, 197, and 237
Proportion of participants reporting on the Clinician Global Impression of Change Scale in the parent studies, and participants retreated in this study	Proportion of participants reporting "Minimally Improved" (+1 ), "Much Improved" (+2) or "Very Much Improved" (+3) on the Clinician Global Impression of Change Scale	Treatment Days 15, 29, 43, 57, 117, 197, and 237
Presence of anti-AUX-I and anti-AUX-II antibody titer levels	Presence of anti-AUX-I and anti-AUX-II antibody titer levels in EN3835 treated and retreated participants	Retreatment/Treatment Day 57 and Day 450
Presence of neutralizing antibodies to AUX-I and AUX-II	Presence of neutralizing antibodies to AUX-I and AUX-II in EN3835 treated and retreated participants	Retreatment/ Treatment Day 57 and Day 450

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Nina Green, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): March 21, 2024
• Study Completion (Actual): March 21, 2024

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Connective Tissue Diseases; Neoplasms by Histologic Type; Skin Diseases; Foot Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Contracture; Fibromatosis, Plantar; Fibroma
• Other Study ID Numbers: EN3835-306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No