Safety and Efficacy of EN3835 in Participants With Frozen Shoulder
Condition: Adhesive Capsulitis; Frozen Shoulder
MeSH terms: Bursitis
Intervention: EN3835; Placebo
Intervention description: Collagenase clostridium histolyticum; Placebo comparator
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety and efficacy of EN3835 for the treatment of adhesive
      capsulitis of the shoulder (frozen shoulder).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have idiopathic unilateral adhesive capsulitis (also known as frozen shoulder).

          2. Have unaffected range of motion in the contralateral shoulder as determined by the
             investigator.

          3. Be willing to undergo x-ray and magnetic resonance imaging (MRI) of both affected and
             unaffected shoulder.

          4. Agree to participate in supervised, in-office physical therapy sessions and to
             complete home exercises at designated time points during the study.

          5. Agree to avoid general lifting and carrying during the study as instructed.

          6. Be able to read, understand, and independently complete participant reported outcome
             instruments in English.

          7. If female, be of non-childbearing potential (history of hysterectomy,
             bilateraloophorectomy, 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 for participant who early terminate). Acceptable forms of
             contraception include hormonal measures (oral contraceptive pills, contraceptive
             patch, contraceptive ring, and 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.

          8. If male with reproductive potential, agree to use effective contraception (abstinence,
             surgical sterilization [vasectomy], or condom with spermicide) with a female partner
             of child-bearing potential for the duration of the study (and for 28 days after any
             active treatment period for participant who early terminate).

          9. Be willing and able to cooperate with the requirements of the study.

         10. Be adequately informed and understand the nature and risks of the study and be able to
             provide consent .

        Exclusion Criteria:

          1. Has a known allergy to collagenase or any other excipient of EN3835 or any other
             procedural medication (including local anesthetics).

          2. Has received treatment for adhesive capsulitis (in the timeframes outlined below) or
             is planning to receive any treatment (other than study treatment) for adhesive
             capsulitis at any time during the study in the affected shoulder, including but not
             limited to:

               -  Physical therapy or acupuncture within 2 weeks before the first injection of
                  study treatment.

               -  Intra-articular or intrabursal injection(s) of lidocaine, suprascapular nerve
                  blocks, or electroanalgesic and/or thermoanalgesic modalities within 1 month
                  before the Screening Visit.

               -  Intra-articular or intrabursal injection(s) of corticosteroids within 8 weeks
                  before the Screening Visit.

               -  Intra-articular or intrabursal injection(s) of sodium hyaluronate and/or
                  glenohumeral distension arthrography within 3 months before the Screening Visit.

               -  Manipulation under anaesthesia at any time prior to the study.

               -  Surgery (including arthroscopic or open capsular release, capsulectomy, or
                  capsulotomy) at any time prior to the study.

          3. Has any abnormalities/conditions in the affected shoulder that would be potentially
             confounding as determined by the central MRI review committee grading criteria.

          4. Has a prosthesis or replacement of right or left shoulder, elbow, wrist, and/or hand.

          5. Has systemic conditions (malignancy, hypertension, diabetes, thyroid disease,
             thrombosis, physical impairment, infection, significant medical condition) that
             restricts study participation.

          6. Has any contraindications for MRI (implant containing metal, internal metallic object,
             permanent cosmetics/make-up/tattoos, claustrophobia, anemia, uncontrolled
             hypertension, epilepsy, asthma, sickle cell disease) as determined by the
             technologist, the radiologist, and/or investigator performing the imaging, with
             exemption of the area to be treated/reviewed.

          7. Has a known coagulation disorder or is taking any medications that would increase the
             risk of bleeding (except <150 milligrams of aspirin daily), 7 days prior to first
             injection and for the duration of the study.

          8. Has received oral or parenteral steroids for any reason within 3 weeks before the
             Screening Visit.

          9. Has, at any time, received collagenase for the treatment of adhesive capsulitis
             (including participant who received treatment in Study AUX-CC-870 or AUX-CC-871).

         10. Has received treatment with an investigational product within 30 days (or 5 half
             lives, whichever is longer) of the screening visit.

         11. Has received collagenase treatments (for example, Santyl® ointment and/or
             XIAFLEX/XIAPEX®) for any other indication within 30 days prior to study treatment
             administration, or is planning to be treated with collagenase (other than study
             treatment) at any time during the study.

         12. Has donated blood within 30 days prior to the Screening Visit or has plans to donate
             blood during the study.

         13. Has a corrected QT interval (QTc) of ≥ 450 milliseconds (ms) for male participant or
             ≥470 ms for female participant on the screening electrocardiogram (ECG).

         14. 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 Institutional Review Board (IRB)/Independent
             Ethics Committee (IEC).

         15. 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,
             (for example, evidence of any significant hematological, endocrine, cardiovascular,
             respiratory, neurological, renal, hepatic, or gastrointestinal disease). If there is a
             history of such disease but the condition has been stable for more than 5 year(s) and
             is judged by the investigator not to interfere with the participant's participation in
             the study, the participant may be included, with the documented approval of the
             Medical Monitor.

         16. Has any other condition(s) that, in the investigator's opinion, might indicate the
             participant to be unsuitable for the study.