Clinical trial NCT04496167: Safety and Efficacy of EN3835 in Participants With Frozen Shoulder
Official title: A Phase 2, Randomized, Double Blind, Placebo Controlled Study of the Safety and Efficacy of EN3835 for the Treatment of Adhesive Capsulitis of the Shoulder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adhesive Capsulitis
Frozen Shoulder
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-03
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95
timeFrame: Baseline, Day 95
Secondary outcomes:
measure: Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Internal Rotation in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for External Rotation in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Abduction in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Internal Rotation in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for External Rotation in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Abduction in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
timeFrame: Baseline, Days 22, 43, 64, and 95
measure: Change From Baseline in the Adapted ASES Composite Score
timeFrame: Baseline, Day 22, 43, and 64
measure: Change From Baseline in the Adapted ASES Function Subscale Score
timeFrame: Baseline, Day 22, 43, 64, and 95
measure: Change From Baseline in the Adapted ASES Pain Subscale Score
timeFrame: Baseline, Day 22, 43, 64, and 95
measure: Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder
timeFrame: Baseline, Days 64 and 95
measure: Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale
timeFrame: Baseline, Day 22, 43, 64, and 95
measure: Patient-reported Change in Severity of Adhesive Capsulitis Scale
timeFrame: Days 22, 43, 64 and 95
measure: Number of Responders Assessed With Investigator Assessment of Improvement
timeFrame: Days 64 and 95
measure: Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment
timeFrame: Days 64 and 95
measure: Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies
timeFrame: Day 95
measure: Number of Participants Positive for Neutralizing Antibodies
timeFrame: Day 95
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Endo Clinical Trial Site #38
state: Alabama
city: Birmingham
country: United States
facility: Endo Clinical Trial Site #24
state: Alabama
city: Mobile
country: United States
facility: Endo Clinical Trial Site #9
state: Alabama
city: Tucson
country: United States
facility: Endo Clinical Trial Site #29
state: Arizona
city: Encinitas
country: United States
facility: Endo Clinical Trial Site #12
state: California
city: Huntington Beach
country: United States
facility: Endo Clinical Trial Site #16
state: California
city: La Mesa
country: United States
facility: Endo Clinical Trial Site #18
state: California
city: Pasadena
country: United States
facility: Endo Clinical Trial Site #14
state: California
city: Denver
country: United States
facility: Endo Clinical Trial Site #37
state: Colorado
city: Bradenton
country: United States
facility: Endo Clinical Trial Site #33
state: Florida
city: Clearwater
country: United States
facility: Endo Clinical Trial Site #3
state: Florida
city: Clermont
country: United States
facility: Endo Clinical Trial Site #32
state: Florida
city: DeLand
country: United States
facility: Endo Clinical Trial Site #13
state: Florida
city: Fort Lauderdale
country: United States
facility: Endo Clinical Trial Site #1
state: Florida
city: Tampa
country: United States
facility: Endo Clinical Trial Site #2
state: Florida
city: Winter Park
country: United States
facility: Endo Clinical Trial Site #20
state: Florida
city: Dalton
country: United States
facility: Endo Clinical Trial Site #34
state: Georgia
city: Lawrenceville
country: United States
facility: Endo Clinical Trial Site #26
state: Georgia
city: Newnan
country: United States
facility: Endo Clinical Trial Site #30
state: Georgia
city: Stockbridge
country: United States
facility: Endo Clinical Trial Site #28
state: Georgia
city: Oak Brook
country: United States
facility: Endo Clinical Trial Site #31
state: Illinois
city: New Orleans
country: United States
facility: Endo Clinical Trial Site #35
state: Louisiana
city: Lincoln
country: United States
facility: Endo Clinical Trial Site #8
state: Nebraska
city: Stony Brook
country: United States
facility: Endo Clinical Trial Site #10
state: New York
city: Durham
country: United States
facility: Endo Clinical Trial Site #21
state: North Carolina
city: Mooresville
country: United States
facility: Endo Clinical Trial Site #36
state: North Carolina
city: Dayton
country: United States
facility: Endo Clinical Trial Site #6
state: Ohio
city: Altoona
country: United States
facility: Endo Clinical Trial Site #11
state: Pennsylvania
city: Indiana
country: United States
facility: Endo Clinical Trial Site #7
state: Pennsylvania
city: State College
country: United States
facility: Endo Clinical Trial Site #5
state: Pennsylvania
city: Bedford
country: United States
facility: Endo Clinical Trial Site #17
state: Texas
city: Bellaire
country: United States
facility: Endo Clinical Trial Site #19
state: Texas
city: Fort Worth
country: United States
facility: Endo Clinical Trial Site #15
state: Texas
city: Georgetown
country: United States
facility: Endo Clinical Trial Site #27
state: Texas
city: Laredo
country: United States
facility: Endo Clinical Trial Site #25
state: Texas
city: Plano
country: United States
facility: Endo Clinical Trial Site #23
state: Texas
city: Plano
country: United States
facility: Endo Clinical Trial Site #22
state: Texas
city: Danville
country: United States
facility: Endo Clinical Trial Site #4
state: Virginia
Study officials:
affiliation: Endo Pharmaceuticals
name: Luis Ortega, MD
role: STUDY_DIRECTOR
References: