Adhesive CapsulitisPhase 2NCT04496167
Safety and Efficacy of EN3835 in Participants With Frozen Shoulder
A Phase 2 study testing EN3835 in people with Adhesive Capsulitis and Frozen Shoulder, run by Endo USA Inc., a Keenova Therapeutics Company at 38 sites in United States.
Trial summary
This study will evaluate the safety and efficacy of EN3835 for the treatment of adhesive capsulitis of the shoulder (frozen shoulder). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adhesive Capsulitis, Frozen Shoulder
- What is being tested?
- EN3835
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 198 participants
- Where
- 38 sitesUnited States
- Study dates
- 29 Jul 2020to 14 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have idiopathic unilateral adhesive capsulitis (also known as frozen shoulder).
- Have unaffected range of motion in the contralateral shoulder as determined by the investigator.
- Be willing to undergo x-ray and magnetic resonance imaging (MRI) of both affected and unaffected shoulder.
- Agree to participate in supervised, in-office physical therapy sessions and to complete home exercises at designated time points during the study.
- Agree to avoid general lifting and carrying during the study as instructed.
- Be able to read, understand, and independently complete participant reported outcome instruments in English.
Show all 10Show fewer
- 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.
- 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).
- Be willing and able to cooperate with the requirements of the study.
- Be adequately informed and understand the nature and risks of the study and be able to provide consent .
Who cannot join
- Has a known allergy to collagenase or any other excipient of EN3835 or any other procedural medication (including local anesthetics).
- 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.
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- 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.
- Has any abnormalities/conditions in the affected shoulder that would be potentially confounding as determined by the central MRI review committee grading criteria.
- Has a prosthesis or replacement of right or left shoulder, elbow, wrist, and/or hand.
- Has systemic conditions (malignancy, hypertension, diabetes, thyroid disease, thrombosis, physical impairment, infection, significant medical condition) that restricts study participation.
- 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.
- 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.
- Has received oral or parenteral steroids for any reason within 3 weeks before the Screening Visit.
- 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).
- Has received treatment with an investigational product within 30 days (or 5 half lives, whichever is longer) of the screening visit.
- 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.
- Has donated blood within 30 days prior to the Screening Visit or has plans to donate blood during the study.
- Has a corrected QT interval (QTc) of ≥ 450 milliseconds (ms) for male participant or ≥470 ms for female participant on the screening electrocardiogram (ECG).
- 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).
- 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.
- Has any other condition(s) that, in the investigator's opinion, might indicate the participant to be unsuitable for the study.
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
United States38 sites
Endo Clinical Trial Site #11
Altoona, Pennsylvania, 16602
Endo Clinical Trial Site #17
Bedford, Texas, 76021
Endo Clinical Trial Site #19
Bellaire, Texas, 77401
Endo Clinical Trial Site #38
Birmingham, Alabama, 32505
Endo Clinical Trial Site #24
Birmingham, Alabama, 35243
Endo Clinical Trial Site #33
Bradenton, Florida, 34209
Endo Clinical Trial Site #3
Clearwater, Florida, 33765
Endo Clinical Trial Site #32
Clermont, Florida, 34711
Endo Clinical Trial Site #34
Dalton, Georgia, 30720
Endo Clinical Trial Site #4
Danville, Virginia, 24541
Endo Clinical Trial Site #6
Dayton, Ohio, 45432
Endo Clinical Trial Site #13
DeLand, Florida, 32720
Endo Clinical Trial Site #37
Denver, Colorado, 80209
Endo Clinical Trial Site #21
Durham, North Carolina, 27704
Endo Clinical Trial Site #12
Encinitas, California, 92024
Endo Clinical Trial Site #1
Fort Lauderdale, Florida, 33316
Endo Clinical Trial Site #15
Fort Worth, Texas, 76104
Endo Clinical Trial Site #27
Georgetown, Texas, 78628
Endo Clinical Trial Site #16
Huntington Beach, California, 92647
Endo Clinical Trial Site #7
Indiana, Pennsylvania, 15701
Endo Clinical Trial Site #18
La Mesa, California, 91942
Endo Clinical Trial Site #25
Laredo, Texas, 78041
Endo Clinical Trial Site #26
Lawrenceville, Georgia, 30043
Endo Clinical Trial Site #8
Lincoln, Nebraska, 68510
Endo Clinical Trial Site #9
Mobile, Alabama, 36609
Endo Clinical Trial Site #36
Mooresville, North Carolina, 28117
Endo Clinical Trial Site #35
New Orleans, Louisiana, 70121
Endo Clinical Trial Site #30
Newnan, Georgia, 30265
Endo Clinical Trial Site #31
Oak Brook, Illinois, 60523
Endo Clinical Trial Site #14
Pasadena, California, 91105
Endo Clinical Trial Site #23
Plano, Texas, 75075
Endo Clinical Trial Site #22
Plano, Texas, 75093
Endo Clinical Trial Site #5
State College, Pennsylvania, 16801
Endo Clinical Trial Site #28
Stockbridge, Georgia, 30281
Endo Clinical Trial Site #10
Stony Brook, New York, 11794
Endo Clinical Trial Site #2
Tampa, Florida, 33606
Endo Clinical Trial Site #29
Tucson, Arizona, 85712
Endo Clinical Trial Site #20
Winter Park, Florida, 32789
About this study
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
This study will evaluate the safety and efficacy of EN3835 for the treatment of adhesive capsulitis of the shoulder (frozen shoulder).
- Conditions
- Adhesive Capsulitis, Frozen Shoulder
- Being tested
- EN3835, Placebo
- Medical subject headings
- Bursitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EN3835Drug
Collagenase clostridium histolyticum
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| EN3835 | Experimental | EN3835 up to 1.74 mg Receives: Drug: EN3835 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95
Adapted ASES is a self-administered participant reported outcome measure, divided into 2 sections: pain and function. Pain subscale is a single item, 11-point numeric rating scale, ranging from 0 (no pain at all) to 10 (worst pain), calculated as 10 - pain raw score and multiplying by 5, score ranging from 0 (worst pain) to 50 (no pain). Function subscale consists of 10 activities, 4-point ordinal scale about their ability to do the activity with the affected arm, ranging from 0 (unable to do) to 3 (not difficult), calculated by multiplying total score for 10 items by 5 and then dividing it by 3, score range of 0 (no function) to 50 (full function).
Adapted ASES composite score is the sum of the pain subscale score (50% of the composite score) and function subscale score (50% of the composite score), score range of 0 (worst pain) to 100 (least pain). Positive change from Baseline score means an improvement in pain and/or shoulder function.
Measured: Baseline, Day 95
Secondary outcomes (30)
Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder
PROM for forward flexion was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Internal Rotation in the Affected Shoulder
PROM for internal rotation was measured using a goniometer and a spinal level. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for External Rotation in the Affected Shoulder
PROM for external rotation was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Abduction in the Affected Shoulder
PROM for abduction was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder
PROM for shoulder extension was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
PROM for forward flexion was measured using a goniometer. PROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. PROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
PROM for internal rotation was measured using a goniometer and a spinal level. PROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. PROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
PROM for external rotation was measured using a goniometer PROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. PROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
PROM for abduction was measured using a goniometer. PROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. PROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
PROM for shoulder extension was measured using a goniometer. PROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. PROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder
AROM for forward flexion was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Internal Rotation in the Affected Shoulder
AROM for internal rotation was measured using a goniometer and a spinal level. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for External Rotation in the Affected Shoulder
AROM for external rotation was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Abduction in the Affected Shoulder
AROM for abduction was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder
AROM for shoulder extension was measured using a goniometer. Positive change from Baseline means an improvement.
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
AROM for forward flexion was measured using a goniometer. AROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. AROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
AROM for internal rotation was measured using a goniometer and a spinal level. AROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. AROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
AROM for external rotation was measured using a goniometer. AROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. AROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
AROM for abduction was measured using a goniometer. AROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. AROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
AROM for shoulder extension was measured using a goniometer. AROM measurements for the contralateral (unaffected) shoulder were taken at Baseline. AROM measurements of the affected shoulder were take at Baseline, Days 22, 43, 64, and 95.
Baseline Value = Measurement at Baseline in Affected Shoulder- Measurement at Baseline Contralateral Unaffected Shoulder
Change from baseline was calculated as:
(Measurement at Visit in Affected Shoulder - Measurement at Baseline Contralateral Shoulder) - Baseline Value
Measured: Baseline, Days 22, 43, 64, and 95
Change From Baseline in the Adapted ASES Composite Score
The adapted ASES is a self-administered participant reported outcome measure, divided into 2 sections: pain and function. Pain subscale is a single item, 11-point numeric rating scale, ranging from (no pain at all) to 10 (worst pain), calculated as 10 - pain raw score and multiplying by 5, score ranging from 0 (worst pain) to 50 (no pain). Function subscale consists of 10 activities, 4-point ordinal scale about their ability to do the activity with the affected arm, ranging from 0 (unable to do) to 3 (not difficult), calculated by multiplying the total score for 10 items by 5 and then dividing it by 3, score ranging from 0 (no function) to 50 (full function).
The adapted ASES composite score is the sum of the pain subscale score (50% of the composite score) and function subscale score (50% of the composite score). The range for composite score is 0 (worst pain) to 100 (least pain). Positive change from Baseline score means an improvement in pain and/or shoulder function.
Measured: Baseline, Day 22, 43, and 64
Change From Baseline in the Adapted ASES Function Subscale Score
The adapted ASES function subscale consists of 10 activities, 4-point ordinal scale about their ability to do the activity with the affected arm, ranging from 0 (unable to do) to 3 (not difficult), calculated by multiplying the total score for 10 items by 5 and then dividing it by 3, score ranging from 0 (worst no function) to 50 (full function).
Positive change from Baseline score means an improvement in shoulder function.
Measured: Baseline, Day 22, 43, 64, and 95
Change From Baseline in the Adapted ASES Pain Subscale Score
The adapted ASES pain subscale is a single item, 11-point numeric rating scale, ranging from (no pain at all) to 10 (worst pain), calculated as 10 - pain raw score and multiplying by 5, score ranging from 0 (worst pain) to 50 (no pain). Positive change from Baseline score means an improvement in shoulder pain.
Measured: Baseline, Day 22, 43, 64, and 95
Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder
The PUM scale is a single item 11-point numerical rating scale of pain in the affected shoulder after AROM forward flexion, internal rotation, external rotation, abduction, and shoulder extension on a scale from 0 (no pain at all) to 10 (pain as bad as it can be). A decrease from Baseline indicates improvement.
Measured: Baseline, Days 64 and 95
Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale
The Patient-reported Global Severity of Adhesive Capsulitis is a single item, 11-point numerical rating scale that asks participants to rate the overall severity of their adhesive capsulitis symptoms on a scale from 0 (no severity) to 10 (severe as can be). A decrease from Baseline indicates improvement.
Measured: Baseline, Day 22, 43, 64, and 95
Patient-reported Change in Severity of Adhesive Capsulitis Scale
The Patient-reported Change in Severity of Adhesive Capsulitis is a questionnaire that asks participants if their adhesive capsulitis symptoms are "Better, About the Same, or Worse" since the last time the questionnaire was administered. Participants who reported that their symptoms are better or worse are then asked to rate the change in their symptoms on a 7-point ordinal scale for worse and better severity. An overall severity of worse was rated from 0 (almost the same, hardly worse at all) to -6 (a very great deal worse). An overall severity of better was rated from 0 (almost the same, hardly better at all) to 6 (a very great deal better).
Only participants with a response of 'Worse' or 'Better' were analyzed. Participants with an overall severity response of 'About the same' were excluded from the summary table below. For overall worse severity, a lower score indicated a worse outcome. For overall better severity, a higher score indicated a better outcome.
Measured: Days 22, 43, 64 and 95
Number of Responders Assessed With Investigator Assessment of Improvement
Investigator assessment of improvement with treatment in the severity of the participant's treated shoulder using a 7-point Likert scale from very much worse (-3) to very much improved (3). A responder was defined as a response of "very much improved", "much improved" or "minimally improved" in the investigator assessment of improvement with treatment.
Measured: Days 64 and 95
Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment
Participants rated their satisfaction with treatment on a 7-point Likert scale from very dissatisfied (-3) to very satisfied (3) at specified times for relief of pain in treated shoulder, relief of stiffness in treated shoulder, relief of pain in treated shoulder compared to better shoulder, and relief of stiffness in treated shoulder compared to better shoulder. A responder was defined as a participant with a response of "very satisfied", "satisfied" or "somewhat satisfied" in the satisfaction with treatment.
Measured: Days 64 and 95
Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies
Serum samples were collected and tested for the presence of anti-AUX-I and anti-AUX-II antibodies.
Measured: Day 95
Number of Participants Positive for Neutralizing Antibodies
Serum samples were collected and tested for the presence of anti-AUX-I and anti-AUX-II antibodies. Only samples positive for anti-AUX-I and anti-AUX-II antibodies were analyzed for neutralizing antibodies.
Measured: Day 95
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2020
- Study start29 Jul 2020
- Primary completion14 Apr 2022
- Study completion14 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adhesive CapsulitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Luis Ortega, MD, Study director, Endo USA Inc., a Keenova Therapeutics Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04496167
- Sponsor's protocol ID
- EN3835-210
- Status last verified
- Aug 2023
- First submitted
- 29 Jul 2020
- Last updated
- 13 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04496167
- Acronym / sponsor ID
- EN3835-210
- Conditions
- Adhesive Capsulitis, Frozen Shoulder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- 14 Apr 2022 (actual)
- Study completion
- 14 Apr 2022 (actual)
- First posted
- 3 Aug 2020 (actual)
- Results
- Posted 13 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of EN3835 for the treatment of adhesive capsulitis of the shoulder (frozen shoulder).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EN3835 | Experimental | Drug: EN3835EN3835 up to 1.74 mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Have idiopathic unilateral adhesive capsulitis (also known as frozen shoulder).
- Have unaffected range of motion in the contralateral shoulder as determined by the investigator.
- Be willing to undergo x-ray and magnetic resonance imaging (MRI) of both affected and unaffected shoulder.
- Agree to participate in supervised, in-office physical therapy sessions and to complete home exercises at designated time points during the study.
- Agree to avoid general lifting and carrying during the study as instructed.
Key exclusion criteria (22 listed)
- Has a known allergy to collagenase or any other excipient of EN3835 or any other procedural medication (including local anesthetics).
- 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:
- Has any abnormalities/conditions in the affected shoulder that would be potentially confounding as determined by the central MRI review committee grading criteria.
- Has a prosthesis or replacement of right or left shoulder, elbow, wrist, and/or hand.
- Has systemic conditions (malignancy, hypertension, diabetes, thyroid disease, thrombosis, physical impairment, infection, significant medical condition) that restricts study participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EN3835Collagenase clostridium histolyticum | Drug | EN3835 |
| PlaceboPlacebo comparator | Drug | Placebo |
Primary outcome
Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95
Time frame: Baseline, Day 95
Adapted ASES is a self-administered participant reported outcome measure, divided into 2 sections: pain and function. Pain subscale is a single item, 11-point numeric rating scale, ranging from 0 (no pain at all) to 10 (worst pain), calculated as 10 - pain raw score and multiplying by 5, score ranging from 0 (worst pain) to 50 (no pain). Function subscale consists of 10 activities, 4-point ordinal scale about their ability to do the activity with the affected arm, ranging from 0 (unable to do) to 3 (not difficult), calculated by multiplying total score for 10 items by 5 and then dividing it by 3, score range of 0 (no function) to 50 (full function). Adapted ASES composite score is the sum of the pain subscale score (50% of the composite score) and function subscale score (50% of the composite score), score range of 0 (worst pain) to 100 (least pain). Positive change from Baseline score means an improvement in pain and/or shoulder function.
30 secondary outcomes
Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Internal Rotation in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for External Rotation in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Abduction in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Internal Rotation in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for External Rotation in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Abduction in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline
Time frame: Baseline, Days 22, 43, 64, and 95
Change From Baseline in the Adapted ASES Composite Score
Time frame: Baseline, Day 22, 43, and 64
Change From Baseline in the Adapted ASES Function Subscale Score
Time frame: Baseline, Day 22, 43, 64, and 95
Change From Baseline in the Adapted ASES Pain Subscale Score
Time frame: Baseline, Day 22, 43, 64, and 95
Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder
Time frame: Baseline, Days 64 and 95
Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale
Time frame: Baseline, Day 22, 43, 64, and 95
Patient-reported Change in Severity of Adhesive Capsulitis Scale
Time frame: Days 22, 43, 64 and 95
Number of Responders Assessed With Investigator Assessment of Improvement
Time frame: Days 64 and 95
Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment
Time frame: Days 64 and 95
Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies
Time frame: Day 95
Number of Participants Positive for Neutralizing Antibodies
Time frame: Day 95
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis Ortega, MD study director
Endo USA Inc., a Keenova Therapeutics Company
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EN3835 in people with Adhesive Capsulitis and Frozen Shoulder, run by Endo USA Inc., a Keenova Therapeutics Company at 38 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Baseline, Day 95). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.