Adhesive Capsulitis, Frozen Shoulder
Conditions
Brief summary
This study will evaluate the safety and efficacy of EN3835 for the treatment of adhesive capsulitis of the shoulder (frozen shoulder).
Interventions
DRUGEN3835
Collagenase clostridium histolyticum
DRUGPlacebo
Placebo comparator
Sponsors
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | PROM for internal rotation was measured using a goniometer and a spinal level. Positive change from Baseline means an improvement. |
| Change From Baseline in PROM for External Rotation in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | PROM for external rotation was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in PROM for Abduction in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | PROM for abduction was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | PROM for shoulder extension was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | AROM for forward flexion was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | AROM for internal rotation was measured using a goniometer and a spinal level. Positive change from Baseline means an improvement. |
| Change From Baseline in AROM for External Rotation in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | AROM for external rotation was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in AROM for Abduction in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | AROM for abduction was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | AROM for shoulder extension was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Baseline, Days 22, 43, 64, and 95 | PROM for forward flexion was measured using a goniometer. Positive change from Baseline means an improvement. |
| Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
| Change From Baseline in the Adapted ASES Composite Score | Baseline, Day 22, 43, and 64 | 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. |
| Change From Baseline in the Adapted ASES Function Subscale Score | Baseline, Day 22, 43, 64, and 95 | 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. |
| Change From Baseline in the Adapted ASES Pain Subscale Score | Baseline, Day 22, 43, 64, and 95 | 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. |
| Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder | Baseline, Days 64 and 95 | 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. |
| Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Baseline, Day 22, 43, 64, and 95 | 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. |
| Patient-reported Change in Severity of Adhesive Capsulitis Scale | Days 22, 43, 64 and 95 | 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. |
| Number of Responders Assessed With Investigator Assessment of Improvement | Days 64 and 95 | 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. |
| Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Days 64 and 95 | 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. |
| Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Day 95 | Serum samples were collected and tested for the presence of anti-AUX-I and anti-AUX-II antibodies. |
| Number of Participants Positive for Neutralizing Antibodies | Day 95 | 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. |
| Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Baseline, Days 22, 43, 64, and 95 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EN3835 Participants received EN3835 (up to 1.74 mg total) by pericapsular (periarticular) injection in up to 3 treatment sessions at least 21 days apart. | 101 |
| Placebo Participants received placebo by pericapsular (periarticular) injection in up to 3 treatment sessions at least 21 days apart. | 94 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 2 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Not Treated | 1 | 2 |
| Overall Study | Other Than Specified | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | EN3835 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 53.76 years STANDARD_DEVIATION 7.565 | 55.50 years STANDARD_DEVIATION 7.806 | 54.59 years STANDARD_DEVIATION 7.712 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 12 Participants | 11 Participants | 23 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 14 Participants | 16 Participants | 30 Participants |
| Race/Ethnicity, Customized Multiple Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 87 Participants | 78 Participants | 165 Participants |
| Race/Ethnicity, Customized Other Race | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 82 Participants | 72 Participants | 154 Participants |
| Sex: Female, Male Female | 65 Participants | 66 Participants | 131 Participants |
| Sex: Female, Male Male | 36 Participants | 28 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 94 |
| other Total, other adverse events | 69 / 101 | 22 / 94 |
| serious Total, serious adverse events | 1 / 101 | 1 / 94 |
Outcome results
Primary
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.
Time frame: Baseline, Day 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment and had both Baseline and Day 95 measurements. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EN3835 | Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95 | 41.35 score on a scale | Standard Deviation 22.432 |
| Placebo | Change From Baseline in the Adapted American Shoulder and Elbow Surgeons Shoulder Assessment Form (ASES) Composite Score for the Affected Shoulder at Day 95 | 41.16 score on a scale | Standard Deviation 21.942 |
Comparison: Mixed Model Repeated Measures (MMRM) was performed to estimate the change from Baseline treatment effect of the adapted ASES composite score in the affected shoulder comparing EN3835 to placebo treatment.p-value: 0.65995% CI: [-4.804, 7.577]MMRM
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 22 | 13.6 degrees | Standard Deviation 26.28 |
| EN3835 | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 43 | 21.9 degrees | Standard Deviation 30 |
| EN3835 | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 64 | 27.7 degrees | Standard Deviation 25.47 |
| EN3835 | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 95 | 31.7 degrees | Standard Deviation 25.31 |
| Placebo | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 95 | 30.1 degrees | Standard Deviation 31.2 |
| Placebo | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 22 | 13.0 degrees | Standard Deviation 26.55 |
| Placebo | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 64 | 29.6 degrees | Standard Deviation 28.85 |
| Placebo | Change From Baseline in Active Range of Motion (AROM) for Forward Flexion in the Affected Shoulder | Day 43 | 22.3 degrees | Standard Deviation 26.17 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 22 | 14.2 degrees | Standard Deviation 30.75 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 43 | 26.6 degrees | Standard Deviation 37.79 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 64 | 37.2 degrees | Standard Deviation 35.6 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 95 | 42.0 degrees | Standard Deviation 37.71 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 95 | 39.8 degrees | Standard Deviation 31.79 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 22 | 13.7 degrees | Standard Deviation 23.17 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 64 | 33.3 degrees | Standard Deviation 30.53 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder | Day 43 | 22.2 degrees | Standard Deviation 27.93 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -58.41 degrees | Standard Deviation 38.888 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -46.14 degrees | Standard Deviation 41.198 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -35.08 degrees | Standard Deviation 36.868 |
| EN3835 | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -30.74 degrees | Standard Deviation 38.227 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -33.01 degrees | Standard Deviation 39.718 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -57.28 degrees | Standard Deviation 36.353 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -39.82 degrees | Standard Deviation 38.397 |
| Placebo | Change From Baseline in AROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -49.32 degrees | Standard Deviation 34.988 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: All randomized participants who received at least 1 injection of study treatment who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment and had both Baseline and measurements at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 22 | 5.3 degrees | Standard Deviation 16.85 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 43 | 8.7 degrees | Standard Deviation 19.59 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 64 | 13.9 degrees | Standard Deviation 22.18 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 95 | 16.8 degrees | Standard Deviation 21.67 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 95 | 16.1 degrees | Standard Deviation 21 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 22 | 5.6 degrees | Standard Deviation 14.79 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 64 | 15.4 degrees | Standard Deviation 21.65 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder | Day 43 | 10.0 degrees | Standard Deviation 19.12 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -34.78 degrees | Standard Deviation 25.743 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -31.07 degrees | Standard Deviation 29.543 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -25.31 degrees | Standard Deviation 28.454 |
| EN3835 | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -22.52 degrees | Standard Deviation 26.313 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -25.42 degrees | Standard Deviation 26.075 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -35.82 degrees | Standard Deviation 22.666 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -25.84 degrees | Standard Deviation 26.291 |
| Placebo | Change From Baseline in AROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -31.23 degrees | Standard Deviation 23.379 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -38.34 degrees | Standard Deviation 30.007 |
| EN3835 | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -31.00 degrees | Standard Deviation 29.397 |
| EN3835 | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -23.62 degrees | Standard Deviation 29.115 |
| EN3835 | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -19.83 degrees | Standard Deviation 26.729 |
| Placebo | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -23.39 degrees | Standard Deviation 24.774 |
| Placebo | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -40.72 degrees | Standard Deviation 24.602 |
| Placebo | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -23.82 degrees | Standard Deviation 23.083 |
| Placebo | Change From Baseline in AROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -32.17 degrees | Standard Deviation 24.879 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 22 | 7.5 degrees | Standard Deviation 20.45 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 43 | 9.1 degrees | Standard Deviation 22.13 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 64 | 18.4 degrees | Standard Deviation 22.44 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 95 | 19.6 degrees | Standard Deviation 21.99 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 95 | 21.6 degrees | Standard Deviation 23.87 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 22 | 5.8 degrees | Standard Deviation 19.12 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 64 | 17.5 degrees | Standard Deviation 21.55 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder | Day 43 | 10.2 degrees | Standard Deviation 20.4 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -30.53 degrees | Standard Deviation 24.699 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -29.78 degrees | Standard Deviation 24.728 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -20.57 degrees | Standard Deviation 23.335 |
| EN3835 | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -19.27 degrees | Standard Deviation 23.646 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -12.66 degrees | Standard Deviation 27.685 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -27.94 degrees | Standard Deviation 24.757 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -16.99 degrees | Standard Deviation 24.708 |
| Placebo | Change From Baseline in AROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -23.45 degrees | Standard Deviation 24.923 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 22 | 7.0 degrees | Standard Deviation 17.37 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 64 | 16.2 degrees | Standard Deviation 19.29 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 43 | 13.7 degrees | Standard Deviation 21.63 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 95 | 19.7 degrees | Standard Deviation 19.91 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 43 | 12.0 degrees | Standard Deviation 16.72 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 22 | 8.5 degrees | Standard Deviation 15.84 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 95 | 17.3 degrees | Standard Deviation 17.17 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder | Day 64 | 15.3 degrees | Standard Deviation 16.7 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -13.65 degrees | Standard Deviation 19.893 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -7.55 degrees | Standard Deviation 20.771 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -4.29 degrees | Standard Deviation 20.214 |
| EN3835 | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -1.00 degrees | Standard Deviation 18.904 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -5.34 degrees | Standard Deviation 20.922 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -15.25 degrees | Standard Deviation 21.385 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -6.94 degrees | Standard Deviation 20.775 |
| Placebo | Change From Baseline in AROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -11.65 degrees | Standard Deviation 20.674 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 22 | 19.1 degrees | Standard Deviation 24.88 |
| EN3835 | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 43 | 25.6 degrees | Standard Deviation 26.89 |
| EN3835 | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 64 | 31.4 degrees | Standard Deviation 26.31 |
| EN3835 | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 95 | 32.8 degrees | Standard Deviation 25.59 |
| Placebo | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 95 | 29.7 degrees | Standard Deviation 27.08 |
| Placebo | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 22 | 13.9 degrees | Standard Deviation 22.4 |
| Placebo | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 64 | 27.3 degrees | Standard Deviation 23.68 |
| Placebo | Change From Baseline in Passive Range of Motion (PROM) for Forward Flexion in the Affected Shoulder | Day 43 | 21.4 degrees | Standard Deviation 20.14 |
Secondary
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.
Time frame: Baseline, Day 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 22 | -1.8 score on a scale | Standard Deviation 1.84 |
| EN3835 | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 43 | -3.0 score on a scale | Standard Deviation 2.21 |
| EN3835 | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 95 | -4.4 score on a scale | Standard Deviation 2.48 |
| EN3835 | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 64 | -4.0 score on a scale | Standard Deviation 2.41 |
| Placebo | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 95 | -4.0 score on a scale | Standard Deviation 2.87 |
| Placebo | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 64 | -3.6 score on a scale | Standard Deviation 2.61 |
| Placebo | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 43 | -2.3 score on a scale | Standard Deviation 2.16 |
| Placebo | Change From Baseline in Patient-reported Global Severity of Adhesive Capsulitis Scale | Day 22 | -1.5 score on a scale | Standard Deviation 1.87 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 22 | 15.6 degrees | Standard Deviation 28.47 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 43 | 29.6 degrees | Standard Deviation 30.19 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 64 | 35.6 degrees | Standard Deviation 36.76 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 95 | 42.1 degrees | Standard Deviation 38.17 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 95 | 36.0 degrees | Standard Deviation 33.35 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 22 | 13.1 degrees | Standard Deviation 23.89 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 64 | 31.1 degrees | Standard Deviation 29.27 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder | Day 43 | 18.9 degrees | Standard Deviation 27.13 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -54.90 degrees | Standard Deviation 40.162 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -41.37 degrees | Standard Deviation 39.918 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -34.87 degrees | Standard Deviation 39.86 |
| EN3835 | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -28.91 degrees | Standard Deviation 41.483 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -36.54 degrees | Standard Deviation 41.288 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -57.56 degrees | Standard Deviation 35.565 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -41.48 degrees | Standard Deviation 37.136 |
| Placebo | Change From Baseline in PROM for Abduction in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -53.17 degrees | Standard Deviation 36.106 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 22 | 7.3 degrees | Standard Deviation 19.39 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 43 | 11.2 degrees | Standard Deviation 20.98 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 64 | 17.4 degrees | Standard Deviation 24.87 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 95 | 19.1 degrees | Standard Deviation 21.24 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 95 | 19.2 degrees | Standard Deviation 18.2 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 22 | 8.8 degrees | Standard Deviation 15.61 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 64 | 17.8 degrees | Standard Deviation 17.87 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder | Day 43 | 14.5 degrees | Standard Deviation 18.87 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -35.12 degrees | Standard Deviation 22.928 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -31.30 degrees | Standard Deviation 25.102 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -22.94 degrees | Standard Deviation 22.153 |
| EN3835 | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -24.46 degrees | Standard Deviation 26.063 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -25.06 degrees | Standard Deviation 23.844 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -35.49 degrees | Standard Deviation 23.027 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -29.40 degrees | Standard Deviation 25.727 |
| Placebo | Change From Baseline in PROM for External Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -26.08 degrees | Standard Deviation 24.494 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -34.48 degrees | Standard Deviation 29.067 |
| EN3835 | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -22.14 degrees | Standard Deviation 27.983 |
| EN3835 | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -28.34 degrees | Standard Deviation 27.939 |
| EN3835 | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -20.82 degrees | Standard Deviation 26.245 |
| Placebo | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -30.24 degrees | Standard Deviation 26.369 |
| Placebo | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -37.33 degrees | Standard Deviation 27.179 |
| Placebo | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -21.06 degrees | Standard Deviation 25.198 |
| Placebo | Change From Baseline in PROM for Forward Flexion in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -23.01 degrees | Standard Deviation 24.2 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 22 | 6.9 degrees | Standard Deviation 23.95 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 43 | 11.0 degrees | Standard Deviation 25.97 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 64 | 18.0 degrees | Standard Deviation 24.65 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 95 | 19.9 degrees | Standard Deviation 22.59 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 95 | 21.6 degrees | Standard Deviation 23.11 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 22 | 7.0 degrees | Standard Deviation 17.94 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 64 | 18.3 degrees | Standard Deviation 21.95 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder | Day 43 | 12.4 degrees | Standard Deviation 19.92 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -30.76 degrees | Standard Deviation 24.692 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -26.81 degrees | Standard Deviation 24.95 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -20.50 degrees | Standard Deviation 21.561 |
| EN3835 | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -18.22 degrees | Standard Deviation 21.444 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -13.49 degrees | Standard Deviation 26.037 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -28.51 degrees | Standard Deviation 24.93 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -16.88 degrees | Standard Deviation 24.096 |
| Placebo | Change From Baseline in PROM for Internal Rotation in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -22.03 degrees | Standard Deviation 24.311 |
Secondary
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.
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 64 | 15.2 degrees | Standard Deviation 18.44 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 22 | 3.9 degrees | Standard Deviation 16.51 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 95 | 20.3 degrees | Standard Deviation 18.3 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 43 | 8.0 degrees | Standard Deviation 18.34 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 95 | 14.7 degrees | Standard Deviation 17.15 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 22 | 5.7 degrees | Standard Deviation 13.54 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 64 | 12.0 degrees | Standard Deviation 17.23 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder | Day 43 | 9.2 degrees | Standard Deviation 16.93 |
Secondary
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
Time frame: Baseline, Days 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -18.82 degrees | Standard Deviation 21.558 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -14.99 degrees | Standard Deviation 22.313 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -7.97 degrees | Standard Deviation 22.633 |
| EN3835 | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -2.87 degrees | Standard Deviation 20.756 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 95 | -7.33 degrees | Standard Deviation 17.676 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 22 | -17.11 degrees | Standard Deviation 19.106 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 64 | -9.91 degrees | Standard Deviation 18.869 |
| Placebo | Change From Baseline in PROM for Shoulder Extension in the Affected Shoulder Compared to the Contralateral (Unaffected) Shoulder at Baseline | Day 43 | -14.01 degrees | Standard Deviation 20.363 |
Secondary
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.
Time frame: Baseline, Day 22, 43, and 64
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in the Adapted ASES Composite Score | Day 22 | 14.87 score on a scale | Standard Deviation 15.684 |
| EN3835 | Change From Baseline in the Adapted ASES Composite Score | Day 43 | 25.15 score on a scale | Standard Deviation 21.532 |
| EN3835 | Change From Baseline in the Adapted ASES Composite Score | Day 64 | 38.21 score on a scale | Standard Deviation 22.837 |
| Placebo | Change From Baseline in the Adapted ASES Composite Score | Day 22 | 15.96 score on a scale | Standard Deviation 14.269 |
| Placebo | Change From Baseline in the Adapted ASES Composite Score | Day 43 | 21.77 score on a scale | Standard Deviation 18.199 |
| Placebo | Change From Baseline in the Adapted ASES Composite Score | Day 64 | 34.98 score on a scale | Standard Deviation 21.222 |
Secondary
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.
Time frame: Baseline, Day 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in the Adapted ASES Function Subscale Score | Day 22 | 7.56 score on a scale | Standard Deviation 8.245 |
| EN3835 | Change From Baseline in the Adapted ASES Function Subscale Score | Day 43 | 12.82 score on a scale | Standard Deviation 10.365 |
| EN3835 | Change From Baseline in the Adapted ASES Function Subscale Score | Day 95 | 21.05 score on a scale | Standard Deviation 11.538 |
| EN3835 | Change From Baseline in the Adapted ASES Function Subscale Score | Day 64 | 19.60 score on a scale | Standard Deviation 12.127 |
| Placebo | Change From Baseline in the Adapted ASES Function Subscale Score | Day 95 | 20.73 score on a scale | Standard Deviation 11.823 |
| Placebo | Change From Baseline in the Adapted ASES Function Subscale Score | Day 22 | 7.96 score on a scale | Standard Deviation 7.388 |
| Placebo | Change From Baseline in the Adapted ASES Function Subscale Score | Day 43 | 11.77 score on a scale | Standard Deviation 9.964 |
| Placebo | Change From Baseline in the Adapted ASES Function Subscale Score | Day 64 | 17.98 score on a scale | Standard Deviation 11.337 |
Secondary
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.
Time frame: Baseline, Day 22, 43, 64, and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 22 | 7.3 score on a scale | Standard Deviation 9.61 |
| EN3835 | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 64 | 18.6 score on a scale | Standard Deviation 12.67 |
| EN3835 | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 95 | 20.3 score on a scale | Standard Deviation 13.11 |
| EN3835 | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 43 | 12.3 score on a scale | Standard Deviation 12.73 |
| Placebo | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 95 | 20.4 score on a scale | Standard Deviation 12.28 |
| Placebo | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 22 | 8.0 score on a scale | Standard Deviation 9.49 |
| Placebo | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 43 | 10.0 score on a scale | Standard Deviation 11.87 |
| Placebo | Change From Baseline in the Adapted ASES Pain Subscale Score | Day 64 | 17.0 score on a scale | Standard Deviation 12.29 |
Secondary
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.
Time frame: Baseline, Days 64 and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had both Baseline and measurements at specified timepoints).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder | Day 64 | -3.6 score on a scale | Standard Deviation 2.6 |
| EN3835 | Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder | Day 95 | -4.1 score on a scale | Standard Deviation 2.59 |
| Placebo | Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder | Day 64 | -3.0 score on a scale | Standard Deviation 2.72 |
| Placebo | Change From Baseline in the Pain Upon Movement (PUM) Scale Score for the Affected Shoulder | Day 95 | -3.8 score on a scale | Standard Deviation 2.96 |
Secondary
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.
Time frame: Day 95
Population: Safety population included all participants who received at least 1 dose of study drug and had an assessment at the specified timepoint. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EN3835 | Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Anti-AUX-I Antibodies | 83 Participants |
| EN3835 | Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Anti-AUX-II Antibodies | 81 Participants |
| Placebo | Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Anti-AUX-I Antibodies | 3 Participants |
| Placebo | Number of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Anti-AUX-II Antibodies | 3 Participants |
Secondary
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.
Time frame: Day 95
Population: All participants who received at least 1 dose of study drug, were positive for anti-AUX-I and anti-AUX-II antibodies and had an assessment at the specified timepoint. Here, overall number of participants analyzed = participants evaluable for this outcome measure. Only samples positive for anti-AUX-I and anti-AUX-II antibodies were analyzed for neutralizing antibodies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EN3835 | Number of Participants Positive for Neutralizing Antibodies | Neutralizing AUX-I Antibodies | 31 Participants |
| EN3835 | Number of Participants Positive for Neutralizing Antibodies | Neutralizing AUX-II Antibodies | 4 Participants |
| Placebo | Number of Participants Positive for Neutralizing Antibodies | Neutralizing AUX-I Antibodies | 0 Participants |
| Placebo | Number of Participants Positive for Neutralizing Antibodies | Neutralizing AUX-II Antibodies | 0 Participants |
Secondary
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.
Time frame: Days 64 and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had measurement at specified timepoint).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Pain relief in treated shoulder | 80 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Pain relief in treated shoulder | 73 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Pain relief in treated shoulder compared to better shoulder | 74 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Stiffness relief in treated shoulder | 71 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Stiffness relief in treated shoulder | 74 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Stiffness relief in treated shoulder compared to better shoulder | 73 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Stiffness relief in treated shoulder compared to better shoulder | 68 Participants |
| EN3835 | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Pain relief in treated shoulder compared to better shoulder | 71 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Stiffness relief in treated shoulder compared to better shoulder | 65 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Pain relief in treated shoulder | 60 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Stiffness relief in treated shoulder | 59 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Pain relief in treated shoulder compared to better shoulder | 57 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 64: Stiffness relief in treated shoulder compared to better shoulder | 54 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Pain relief in treated shoulder | 69 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Stiffness relief in treated shoulder | 69 Participants |
| Placebo | Number of Responders Assessed by the Subject Satisfaction With Treatment Assessment | Day 95: Pain relief in treated shoulder compared to better shoulder | 68 Participants |
Secondary
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.
Time frame: Days 64 and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had measurement at specified timepoint).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EN3835 | Number of Responders Assessed With Investigator Assessment of Improvement | Day 64 | 71 Participants |
| EN3835 | Number of Responders Assessed With Investigator Assessment of Improvement | Day 95 | 80 Participants |
| Placebo | Number of Responders Assessed With Investigator Assessment of Improvement | Day 64 | 59 Participants |
| Placebo | Number of Responders Assessed With Investigator Assessment of Improvement | Day 95 | 65 Participants |
Secondary
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.
Time frame: Days 22, 43, 64 and 95
Population: Modified intent-to-treat population included all randomized participants who received at least 1 injection of study treatment and who had a valid baseline adapted ASES composite score in the affected shoulder and at least 1 valid adapted ASES composite score after the injection of the study treatment. Here, number analyzed = participants evaluable at specified time-point (had measurement at specified timepoint).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 22: Better Severity | 2.4 score on a scale | Standard Deviation 1.4 |
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 64: Better Severity | 4.5 score on a scale | Standard Deviation 1.29 |
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 43: Better Severity | 3.4 score on a scale | Standard Deviation 1.46 |
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 22: Worse Severity | -3.4 score on a scale | Standard Deviation 1.52 |
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 95: Better Severity | 4.7 score on a scale | Standard Deviation 1.27 |
| EN3835 | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 43: Worse Severity | -3.3 score on a scale | Standard Deviation 1.53 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 64: Better Severity | 4.2 score on a scale | Standard Deviation 1.4 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 95: Worse Severity | -3.5 score on a scale | Standard Deviation 1.91 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 95: Better Severity | 4.7 score on a scale | Standard Deviation 1.09 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 22: Worse Severity | -3.2 score on a scale | Standard Deviation 2.23 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 22: Better Severity | 2.5 score on a scale | Standard Deviation 1.29 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 43: Worse Severity | -4.0 score on a scale | Standard Deviation 2.16 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 43: Better Severity | 3.6 score on a scale | Standard Deviation 1.44 |
| Placebo | Patient-reported Change in Severity of Adhesive Capsulitis Scale | Day 64: Worse Severity | -4.8 score on a scale | Standard Deviation 0.5 |