Age and Sex
1. Be an ambulatory male or female ≥18 years of age.
Disease Characteristics
2. Have a diagnosis of plantar fibromatosis AND at least 1 “Hard” or “Firm Throughout” palpable
fibrous nodule on clinical examination and measurable by caliper.
3. Have unilateral plantar fibromatosis with ≤ 2 nodules in the foot to be treated.
4. Have current foot pain due to plantar fibromatosis.
Type of Participant
5. Be willing and able to comply with all protocol required visits, procedures, and assessments.
6. Be able to read and understand the patient reported assessments in English, Spanish, or the local
language of the respective participating country and is adequately informed and understand the
nature and risks of the study.
7. Agree not to use opioids (eg, codeine, heroin, hydrocodone, hydromorphone, morphine,
oxycodone) during the study period and has not used opioids 30 days before the Screening
Visit.

8. Agree not to use drugs (eg, marijuana, cocaine) and/or use of prescription drugs for the purposes
of inducing psychoactive effects during the study and has not used these products in the 30 days
prior to the Screening Visit.
9. Agree not to use prohibited medication, throughout the study, and not use any medication to
treat pain due to plantar fibromatosis except as permitted per the protocol.
10. 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. Acceptable forms of contraception include
hormonal measures (oral contraceptive pills, contraceptive patch, contraceptive ring, injections),
intrauterine devices, double barrier method (condom plus diaphragm, condom or diaphragm
plus spermicidal gel or foam, surgical sterilization of the male partner), and abstinence.
Informed Consent
11. Be capable of providing consent, are adequately informed, and understand the nature and risks
of the study.
Key Exclusion Criteria:
A participant is ineligible for study participation if the participant meets any of the following criteria:
Medical Conditions
1. Has the presence of non-plantar fibromatosis-related nodules on the affected foot
(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 foot and/or would impair his/her completion of
study assessments as determined by the investigator.
3. Has any 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 or required assessments and evaluations.
4. Has any nodule > 40.0 mm.
5. Has a known systemic allergy to collagenase or any excipient of EN3835 or placebo.
6. History of intolerance or hypersensitivity to acetaminophen/paracetamol or any of its excipients
or existence of a medical condition for which the use of acetaminophen/paracetamol is
contraindicated (refer to product labeling).
7. Has a known bleeding disorder which would make the participant unsuitable for enrollment in
the study (see Exclusion Criterion #15).
8. Has a clinically significant laboratory abnormality or any laboratory test results meeting any of
the following criteria:
• alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN)
• total bilirubin (TBL) ≥ 2 × ULN (> 35% direct bilirubin)
• aspartate aminotransferase (AST) ≥ 3 × ULN
• international normalized ratio (INR) >1.5

9. Has concurrent diseases that might interfere with the conduct of the study, confound the
interpretation of the study results, endanger the participant’s well-being (eg, evidence or history
of malignancy other than excised basal-cell carcinoma), or any significant hematological,
endocrine, cardiovascular, respiratory, renal, hepatic, or gastrointestinal disease. If there is a
history of such disease but the condition has been stable (defined as not requiring significant
change in therapy or hospitalization for worsening disease) for more than 1 year and is judged
by the investigator not to interfere with participation in the study, the participant may be
included, with the documented approval of the medical monitor.
10. Any other significant medical condition(s), which in the investigator’s opinion would make the
participant unsuitable for enrollment in the study.
11. Is pregnant or plans to become pregnant.
12. Is breastfeeding or is providing or plans to provide breast milk in any manner during the study.
Prior/Concomitant Therapy
13. Has received any surgical or non-surgical treatment(s) (eg, steroid injection, transdermal/
intralesional verapamil, radiation therapy, extracorporeal shock wave therapy) on the foot or
nodule(s) to be treated within 3 months before administration of study intervention.
14. Has received any collagenase treatment (eg, Santyl® ointment, XIAFLEX, EN3835, or CCH)
within 30 days prior to Day 1.
15. Is currently receiving, has received (within 7 days of the first treatment of study intervention),
or plans to receive any anticoagulant or antiplatelet medication (except for ≤ 150 mg aspirin
daily) that would increase the risk of bleeding during the study.
Prior/Concurrent Clinical Study Experience
16. Participation in other studies involving an investigational drug within 30 days before treatment
with study intervention and/or concurrent study participation.
17. Has previously participated in clinical studies of EN3835 in plantar fibromatosis or plantar
fasciitis.
Other Considerations
18. 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.