Efficacy, Safety, and Tolerability, of EN3835 vs Placebo in the Treatment of Plantar Fibromatosis

Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of EN3835 vs Placebo in the Treatment of Plantar Fibromatosis

This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of up to 2 treatments of EN3835 vs placebo in participants with plantar fibromatosis.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Endo Clinical Trial Site #29
    • Tucson, Arizona, United States, 85712
      • Endo Clinical Trial Site #42
  • California
    • Bakersfield, California, United States, 93311
      • Endo Clinical Trial Site #15
    • Encinitas, California, United States, 92024
      • Endo Clinical Trial Site #41
    • Fresno, California, United States, 93710
      • Endo Clinical Trial Site #9
    • La Mesa, California, United States, 91942
      • Endo Clinical Trial Site #27
    • Los Angeles, California, United States, 90010
      • Endo Clinical Trial Site #30
    • Tarzana, California, United States, 91356
      • Endo Clinical Trial Site #12
    • Torrance, California, United States, 90502
      • Endo Clinical Trial Site #36
    • Vista, California, United States, 92083
      • Endo Clinical Trial Site #22
    • Whittier, California, United States, 90603
      • Endo Clinical Trial Site #13
  • Florida
    • Atlantis, Florida, United States, 33462
      • Endo Clinical Trial Site #16
    • Jacksonville, Florida, United States, 32209
      • Endo Clinical Trial Site #43
    • Miami, Florida, United States, 33176
      • Endo Clinical Trial Site #40
    • Pinellas Park, Florida, United States, 33782
      • Endo Clinical Trial Site #10
    • South Miami, Florida, United States, 33143
      • Endo Clinical Trial Site #3
    • Sweetwater, Florida, United States, 33172
      • Endo Clinical Trial Site #14
  • Georgia
    • Lawrenceville, Georgia, United States, 30043
      • Endo Clinical Trial Site #38
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Endo Clinical Trial Site #31
  • Illinois
    • Decatur, Illinois, United States, 62521
      • Endo Clinical Trial Site #32
    • O'Fallon, Illinois, United States, 62269
      • Endo Clinical Trial Site #19
    • Springfield, Illinois, United States, 62704
      • Endo Clinical Trial Site #33
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Endo Clinical Trial Site #23
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Endo Clinical Trial Site #28
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Endo Clinical Trial Site #20
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Endo Clinical Trial Site #34
  • Pennsylvania
    • York, Pennsylvania, United States, 17402
      • Endo Clinical Trial Site #4
  • Texas
    • Arlington, Texas, United States, 76015
      • Endo Clinical Trial Site #35
    • Bedford, Texas, United States, 76021
      • Endo Clinical Trial Site #5
    • Cedar Park, Texas, United States, 78613
      • Endo Clinical Trial Site #24
    • Dallas, Texas, United States, 75208
      • Endo Clinical Trial Site #17
    • Dallas, Texas, United States, 75251
      • Endo Clinical Trial Site #2
    • Fort Worth, Texas, United States, 76104
      • Endo Clinical Trial Site #7
    • Georgetown, Texas, United States, 78628
      • Endo Clinical Trial Site #39
    • Houston, Texas, United States, 77027
      • Endo Clinical Trial Site #25
    • Houston, Texas, United States, 77095
      • Endo Clinical Trial Site #8
    • McAllen, Texas, United States, 78501
      • Endo Clinical Trial Site #1
    • San Antonio, Texas, United States, 78211
      • Endo Clinical Trial Site #21
    • San Antonio, Texas, United States, 78229
      • Endo Clinical Trial Site #6
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Endo Clinical Trial Site #18
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Endo Clinical Trial Site #26
    • Midlothian, Virginia, United States, 23114
      • Endo Clinical Trial Site #37
    • Suffolk, Virginia, United States, 23434
      • Endo Clinical Trial Site #11

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a diagnosis of plantar fibromatosis AND have at least 1 measurable, hard or firm, palpable fibrous nodule on clinical examination.
2. Has no significant medical history or examination findings related to the participant's plantar nodule(s), which in the investigator's opinion, would make the participant unsuitable for study intervention administration.
3. Agree not to use opioids during the study period and has not used opioids 2 weeks before the Screening 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. 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 Screening Visit); or, if of childbearing potential, be non-pregnant, 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.
6. Willing and able to comply with all protocol required visits and assessments.
7. Be adequately informed and understand the nature and risks of the study and be able to provide consent.

Exclusion Criteria:

1. Has the presence of non-plantar fibromatosis-related nodules on the foot/feet (eg, neurofibroma, rhabdomyosarcoma, liposarcoma, neurilemmomas, rheumatoid nodules, desmoid tumors, or malignant soft tissue lesions of the foot or ankle).
2. Has any musculoskeletal, neuromuscular, neurosensory, 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.
3. Has a known allergy to collagenase or any other excipient of EN3835.
4. 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.
5. Has concurrent diseases that might interfere with the conduct of the study, confound the interpretation of the study results or endanger the participant's well-being. If there is a history of such disease and the condition has been stable for greater than one year and is judged by the investigator not to interfere, the participant may be included, with the documented approval of the Medical Monitor.
6. Is from a vulnerable population, as defined by the US Code of Federal Regulations (CFR) Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full-time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the IRB/IEC.
7. Has any other condition(s) that, in the investigator's opinion, might indicate the participants to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EN3835 Group; Participant will receive a maximum dose of up to 1.8mg of EN3835 injection	Biological: EN3835; Participant will receive a maximum dose of up to1.8mg of EN3835 injection
Placebo Comparator: Placebo Group; Participant will receive a matched Placebo injection	Other: Placebo; Participant will receive a matched Placebo injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 57 in the Foot Function Index (FFI) Pain Subscale Score	FFI pain subscale consisted of 9 items which were scored on a scale of 0 ("None") to 4 ("Extreme") with a total score ranging from 0 to 36. Lower scores indicated better foot function, while higher scores reflected greater impairment.	Baseline (Day 1), Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 57 in the FFI Total Combined (Pain and Difficulty) Score	The FFI pain subscale consisted of 9 items which were scored on a scale of 0 ("None") to 4 ("Extreme") with a total score ranging from 0 to 36. The FFI difficulty subscale consisted of 9 items which were scored on a scale of 0 ("No difficulty") to 4 ("A lot of difficulty") with a total score ranging from 0 to 36. The Total Combined score of pain and difficulty comprised scores of answered items in each subscale with a maximum total score range of 0 to 72. Lower scores indicated better foot function, while higher scores reflected greater impairment.	Baseline (Day 1), Day 57
Percentage of Participants With a Response of "Minimal Improvement", "Much Improvement" or "Very Much Improvement" (Responders) in the Clinician Global Impression of Change Scale	The responder (by foot/feet) was defined as a participant with a response of "Minimal Improvement", "Much Improvement" or "Very Much Improvement" in the CGIC Scale. All participants who withdrew early from the study were considered as non-responders. If participant was treated for both feet, then the assessment could be combined at participant level using worst case approach, if one foot response was recorded as 'Minimal Improvement' and 'Very Much Improvement' in another foot, then response was considered as 'Minimal Improvement'.	Day 57
Change From Baseline to Day 57 in the Nodular Hardness of the Treated Nodules by Durometer Measurement	A durometer was used to measure the hardness of treated nodules, on a scale ranging from 0 to 100. Higher scores indicated a greater hardness.	Baseline (Day 1), Day 57

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Luis Ortega, MD, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

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; Fibroma; Contracture; Skin and Connective Tissue Diseases; Fibromatosis, Plantar
• Other Study ID Numbers: EN3835-222

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