Tendinopathy
Conditions
Keywords
Overuse tendinopathy, shoulder, rotator cuff, IL-17A-Ab, AIN457X
Brief summary
This was a randomized, double-blind, placebo-controlled, multi-center, Phase II study of s.c. secukinumab 300 mg in 98 randomized patients with overuse rotator-cuff tendinopathy without systemic inflammatory disease.
Detailed description
This was a randomized, double-blind, placebo-controlled, multi-center, Phase II study of s.c. secukinumab 300 mg in 98 randomized patients with overuse rotator-cuff tendinopathy without systemic inflammatory disease and refractory to NSAIDs/acetaminophen, physiotherapy or corticosteroids. The study consisted of a 4-week screening period, a 2-week run-in period, a 12-week treatment period and a 12-week follow-up period after last treatment. The population consisted of patients with unilateral overuse (non-systemic inflammatory) shoulder tendinopathy, 18 - 65 years of age. Safety assessments included physical examinations, ECGs, vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), adverse event and serious adverse event monitoring.
Interventions
DRUGsecukinumab
AIN457 300 mg subcutaneously for 12 weeks
OTHERPlacebo
Placebo to match AIN457 subcutaneously for 12 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients and investigators were blinded until EOS. Sponsor was blinded until after the analysis of the primary endpoint at week 14.
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant, non-lactating female patients 18 to 65 years of age at randomization 2. Presence of unilateral rotator cuff tendinopathy with: 1. Symptoms present ≥6 weeks, but \<12 months prior to randomization 2. Tendinopathy with no more than a 50% tear as established by ultrasound at screening (historic data acceptable if not older than 3 months) and MRI at baseline: Sein MRI tendinopathy scoring system grade I-III; with no tear or partial tear \[maximum 50% tendon thickness (Bauer tendon thickness score maximum 2); AP length maximum 10 mm (Bauer tendon length score max 2)\]. Maximum 50% of patients with partial tear 3. Pain in the affected shoulder (at rest or on movement) on at least 3 days out of 7 days in the past week prior to baseline and a score of ≥4 out of 10 on a VAS pain scale 4. Positive Painful Arc Test on examination and/or nightly pain in the affected shoulder on at least 4 out of 7 days in the past week prior to baseline 3. The rotator-cuff tendinopathy must have been refractory to standard treatment, including NSAIDs and physiotherapy
Exclusion criteria
1\. Rheumatologic, inflammatory diseases, including but not limited to: PsA, AS and RA 2. Previous shoulder surgery in affected shoulder 3. History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or contralateral shoulder) confirmed by X-Ray, historic X-Rays can be used if performed within 3 months of baseline 4. Symptomatic osteoarthritis of the shoulder (gleno-humeral, acromioclavicular) (in affected or contralateral shoulder confirmed by X-Ray, historic X-Rays can be used if performed within 3 months of baseline 5. Neck conditions, including but not limited to cervical spine syndrome, which in the opinion of the investigator, may explain the patient's symptoms 6. Previous platelet rich plasma injections within the last 12 months prior to randomization 7. Previous treatment with any cell-depleting therapies including but not limited to anti- CD20, investigational agents (e.g. Campath, anti-CD4, anti-CD5, anti-CD3, anti-CD19) 8. Previous exposure to any biologic immunomodulating agents, including but not limited to TNFalpha inhibitors (including, but not limited to adalimumab, infliximab), or biologics targeting IL-17 (including, but not limited to secukinumab, ixekizumab or brodalumab) or the IL-17 receptor within the last 12 months prior to baseline 9. Any intraarticular/subacromial corticosteroid treatment within 8 weeks prior to randomization and more than 3 injections for the current tendinopathy. Oral, intramuscular or i.v. corticosteroid treatment within the last 12 months prior to randomization \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14 | Week 14 (Day 99) | WORC PRO score at week 14. The WORC Index consists of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). The total scores and sub scores used were the percentages of the normal scores with 0 being worst and 100 being best. All Patients - Statistical analysis results of WORC scores at Week 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Days 15, 29, 57, 85, 127, and End of Study | WORC score at Days 15, 29, 57, 85, 127, and End of Study (day 169). The scale range for WORC total score is 0-100, 0 being the worst possible outcome (highly symptomatic patient) and 100 being the best possible outcome (asymptomatic patient) |
| Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Days 15, 29, 57, 85, 99, 127, and End of Study | Patient Reported Outcome: Disability of Arm, Shoulder and Hand (QuickDASH) This questionnaire asks about symptoms as well participant's ability to do certain activities - ranging from 1 (No difficulty) to 5 (Unable). The scale range for QuickDASH total score is 0-100, 0 being the best possible outcome and 100 being the worst possible outcome |
| American Shoulder and Elbow Surgeons (ASES) Score Over Time | Days 15, 29, 57, 85, 99, 127, and End of Study | Patient Reported Outcome: American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES) score is self-administered and has 17 questions in the areas of shoulder symptoms and functions. The ASES total score ranges from 0 to 100 (best). |
| EQ-5D-5L Index Score Over Time | Days 15, 29, 57, 85, 99, 127 and End of Study | Patient Reported Outcome: Statistical analysis results of EQ-5D-5L Index score, which contains 5 items to assess Health Status (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Overall scores range from 0 to 1 with lower scores representing a higher level of dysfunction. |
| Pain Score Over Time Using a VAS Scale | Days 15, 29, 57, 85, 99, 127 and End of Study | Pain intensity is assessed by a Visual Analog Scale (VAS) which is measured on a 100mm line that represents a continuum between no pain and worst pain. The scale range for pain score is 0-100, 0 being the best possible outcome (no pain) and 100 being the worst possible outcome (worst pain). |
| Your Health Today Score Over Time | Days 15, 29, 57, 85, 99, 127, and End of Study | Patient Reported Outcome: Statistical analysis results of EQ-5D-5L for Your health Today questionnaire, which reflects how good or bad the subjets Health is on a scale from 0 (worst health) to 100 (best health). |
| Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Days 15, 29, 57, 85, 99, 127 and End of Study | Physician global assessment (PhGA) score using a VAS scale (considering the last 24 hours). The scale range for PhGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity). |
| Pharmacokinetics - Cmin | Days 1, 29, 85 and EoS (End of Study) | Mean trough concentrations Cmin is a pharmacokinetics term for the minimum blood plasma concentration reached by a drug prior to administration of a second dose (mass/volume) Serum trough concentrations of secukinumab 300 mg group was measured at Days 1, 29, 85 and EoS |
| Immunogenicity Assessment - Treatment Emergent ADAs | Day 1 and EoS | Number of Participants with Treatment emergent Anti-secukinumab antibodies |
| Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline and Day 99 | Assessment of structural changes in the rotator cuff tendinopathy over time The MRI Sein score was used to grade supraspinatus tendinosis using a modified 4-point scale from 0 to 3 and changes in grading over time were captured in the shift table. Grade 0 is normal, grade 1 is mild, Grade 2 is moderate and grade 3 is marked tendinosis. In this Sein score assessment, only data from Day 99 and baseline could be compared, as only those two time points were double read and adjudicated in case the 2 readers had different results. At any other time-points (Day 57 and EOS), images were assessed only by one reader and thus could not be compared to baseline. |
| Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Days 15, 29, 57, 85, 99, 127 and End of Study | The patient's global assessment of disease activity is performed using a 100 mm Visual Analog Scale (VAS) ranging from no activity to most active in the last 24 hours. The scale range for PGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity). |
Countries
Czechia, Germany, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
Of all patients randomized (N= 98; 100%) in the study, a total of 96 patients (98%) were dosed (49 patients in the secukinumab 300 mg group and 47 patients in the placebo group)
Pre-assignment details
2 patients were not dosed, one patient decided to discontinue on Day 1 due to a common cold and one patient was a run-in failure
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab AIN457 300 mg subcutaneously (s.c.) | 49 |
| Placebo Placebo s.c. | 47 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Epoch | Withdrawal by Subject | 0 | 2 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Secukinumab |
|---|---|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 10.56 | 46.9 years STANDARD_DEVIATION 11.2 | 44.8 years STANDARD_DEVIATION 11.51 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 45 Participants | 88 Participants | 43 Participants |
| Sex: Female, Male Female | 23 Participants | 40 Participants | 17 Participants |
| Sex: Female, Male Male | 24 Participants | 56 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 47 |
| other Total, other adverse events | 36 / 49 | 34 / 47 |
| serious Total, serious adverse events | 0 / 49 | 0 / 47 |
Outcome results
Primary
The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14
WORC PRO score at week 14. The WORC Index consists of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). The total scores and sub scores used were the percentages of the normal scores with 0 being worst and 100 being best. All Patients - Statistical analysis results of WORC scores at Week 14
Time frame: Week 14 (Day 99)
Population: Pharmacodynamic (PD) Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14 | 37.00 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14 | 37.77 Scores on a scale |
Comparison: All Patients at day 99p-value: 0.87590% CI: [-8.84, 7.3]LS mean
Secondary
American Shoulder and Elbow Surgeons (ASES) Score Over Time
Patient Reported Outcome: American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES) score is self-administered and has 17 questions in the areas of shoulder symptoms and functions. The ASES total score ranges from 0 to 100 (best).
Time frame: Days 15, 29, 57, 85, 99, 127, and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 57 | 24.15 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 99 | 31.29 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 29 | 17.53 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 127 | 34.92 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 85 | 30.50 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | End of Study | 37.29 Scores on a scale |
| Secukinumab | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 15 | 8.66 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | End of Study | 36.15 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 15 | 5.26 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 29 | 14.37 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 57 | 22.56 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 85 | 26.97 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 99 | 27.79 Scores on a scale |
| Placebo | American Shoulder and Elbow Surgeons (ASES) Score Over Time | Day 127 | 32.94 Scores on a scale |
Comparison: Statistical analysis results of ASES total score (PD analysis) at day 99p-value: 0.41190% CI: [-3.54, 10.54]LS Mean
Comparison: Statistical analysis results of ASES total score (PD analysis) at End of Study set)p-value: 0.80490% CI: [-6.5, 8.78]LS Mean
Secondary
Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time
Patient Reported Outcome: Disability of Arm, Shoulder and Hand (QuickDASH) This questionnaire asks about symptoms as well participant's ability to do certain activities - ranging from 1 (No difficulty) to 5 (Unable). The scale range for QuickDASH total score is 0-100, 0 being the best possible outcome and 100 being the worst possible outcome
Time frame: Days 15, 29, 57, 85, 99, 127, and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 57 | -22.43 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 99 | -29.45 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 29 | -18.31 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 127 | -32.86 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 85 | -28.14 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | End of Study | -33.89 Scores on a scale |
| Secukinumab | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 15 | -11.64 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | End of Study | -35.40 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 15 | -8.23 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 29 | -16.95 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 57 | -24.01 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 85 | -27.22 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 99 | -30.69 Scores on a scale |
| Placebo | Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Day 127 | -31.99 Scores on a scale |
Comparison: Statistical analysis results of QuickDASH total score (PD Analysis Set) at day 99p-value: 0.73590% CI: [-4.81, 7.28]LS Mean
Comparison: Statistical analysis results of QuickDASH total score (PD analysis set) at End of Studyp-value: 0.68990% CI: [-4.76, 7.79]LS Mean
Secondary
EQ-5D-5L Index Score Over Time
Patient Reported Outcome: Statistical analysis results of EQ-5D-5L Index score, which contains 5 items to assess Health Status (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Overall scores range from 0 to 1 with lower scores representing a higher level of dysfunction.
Time frame: Days 15, 29, 57, 85, 99, 127 and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 57 | 0.12 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 99 | 0.16 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 29 | 0.10 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 127 | 0.19 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 85 | 0.16 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | End of Study | 0.19 Scores on a scale |
| Secukinumab | EQ-5D-5L Index Score Over Time | Day 15 | 0.07 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | End of Study | 0.18 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 15 | 0.04 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 29 | 0.09 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 57 | 0.11 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 85 | 0.14 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 99 | 0.15 Scores on a scale |
| Placebo | EQ-5D-5L Index Score Over Time | Day 127 | 0.17 Scores on a scale |
Comparison: Statistical analysis results of of EQ-5D-5L Index score at day 99 (PD Analysis Set)p-value: 0.61390% CI: [-0.03, 0.06]LS Mean
Comparison: Statistical analysis results of of EQ-5D-5L Index score at End of Study (PD Analysis Set)p-value: 0.7490% CI: [-0.04, 0.06]LS Mean
Secondary
Immunogenicity Assessment - Treatment Emergent ADAs
Number of Participants with Treatment emergent Anti-secukinumab antibodies
Time frame: Day 1 and EoS
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Immunogenicity Assessment - Treatment Emergent ADAs | Day 1 | 0 Participants |
| Secukinumab | Immunogenicity Assessment - Treatment Emergent ADAs | End of Study | 0 Participants |
| Placebo | Immunogenicity Assessment - Treatment Emergent ADAs | Day 1 | 1 Participants |
| Placebo | Immunogenicity Assessment - Treatment Emergent ADAs | End of Study | 0 Participants |
Secondary
Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores
Assessment of structural changes in the rotator cuff tendinopathy over time The MRI Sein score was used to grade supraspinatus tendinosis using a modified 4-point scale from 0 to 3 and changes in grading over time were captured in the shift table. Grade 0 is normal, grade 1 is mild, Grade 2 is moderate and grade 3 is marked tendinosis. In this Sein score assessment, only data from Day 99 and baseline could be compared, as only those two time points were double read and adjudicated in case the 2 readers had different results. At any other time-points (Day 57 and EOS), images were assessed only by one reader and thus could not be compared to baseline.
Time frame: Baseline and Day 99
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 1 | 31 participants |
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 2 | 11 participants |
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 3 | 3 participants |
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 1 | 31 participants |
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 2 | 11 participants |
| Secukinumab | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 3 | 3 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 2 | 9 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 1 | 25 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 1 | 26 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 2 | 10 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Day 99 grade 3 | 3 participants |
| Placebo | Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores | Baseline grade 3 | 3 participants |
Secondary
Pain Score Over Time Using a VAS Scale
Pain intensity is assessed by a Visual Analog Scale (VAS) which is measured on a 100mm line that represents a continuum between no pain and worst pain. The scale range for pain score is 0-100, 0 being the best possible outcome (no pain) and 100 being the worst possible outcome (worst pain).
Time frame: Days 15, 29, 57, 85, 99, 127 and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 99 | -46.11 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 15 | -12.11 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 29 | -26.04 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 57 | -35.52 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 85 | -42.63 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | Day 127 | -49.44 Scores on a scale |
| Secukinumab | Pain Score Over Time Using a VAS Scale | End of Study | -52.23 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 127 | -45.27 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 85 | -37.97 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 15 | -9.50 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 99 | -40.56 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 29 | -23.13 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | End of Study | -50.74 Scores on a scale |
| Placebo | Pain Score Over Time Using a VAS Scale | Day 57 | -32.83 Scores on a scale |
Comparison: Statistical analysis results of pain score using VAS scale (PD Analysis Set) at day 99p-value: 0.28190% CI: [-14.07, 2.97]LS Mean
Comparison: Statistical analysis results of pain score using VAS scale (PD Analysis Set) at End of Studyp-value: 0.7890% CI: [-10.33, 7.35]LS Mean
Secondary
Patient Global Assessment (PGA) Score Over Time Using a VAS Scale
The patient's global assessment of disease activity is performed using a 100 mm Visual Analog Scale (VAS) ranging from no activity to most active in the last 24 hours. The scale range for PGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity).
Time frame: Days 15, 29, 57, 85, 99, 127 and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 57 | -29.40 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 99 | -38.43 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 29 | -22.25 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 127 | -43.78 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 85 | -37.57 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | End of Study | -47.72 Scores on a scale |
| Secukinumab | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 15 | -6.33 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | End of Study | -39.43 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 15 | -8.09 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 29 | -16.38 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 57 | -25.69 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 85 | -31.75 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 99 | -35.10 Scores on a scale |
| Placebo | Patient Global Assessment (PGA) Score Over Time Using a VAS Scale | Day 127 | -38.32 Scores on a scale |
Comparison: Statistical analysis results of pain score using VAS scale (PD Analysis Set) at day 99p-value: 0.48990% CI: [-11.28, 4.64]LS Mean
Comparison: Statistical analysis results of pain score using VAS scale at End of Studyp-value: 0.08790% CI: [-16.26, -0.32]LS Mean
Secondary
Pharmacokinetics - Cmin
Mean trough concentrations Cmin is a pharmacokinetics term for the minimum blood plasma concentration reached by a drug prior to administration of a second dose (mass/volume) Serum trough concentrations of secukinumab 300 mg group was measured at Days 1, 29, 85 and EoS
Time frame: Days 1, 29, 85 and EoS (End of Study)
Population: PD Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab | Pharmacokinetics - Cmin | Mean trough concentration after first 4 wkly doses | 90.4 ug/mL | Standard Deviation 30.7 |
| Secukinumab | Pharmacokinetics - Cmin | Week 12 | 13.2 ug/mL | Standard Deviation 6.67 |
Secondary
Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time
Physician global assessment (PhGA) score using a VAS scale (considering the last 24 hours). The scale range for PhGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity).
Time frame: Days 15, 29, 57, 85, 99, 127 and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 57 | -30.78 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 99 | -35.72 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 29 | -25.01 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 127 | -41.72 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 85 | -33.42 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | End of Study | -44.64 Score on a scale |
| Secukinumab | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 15 | -13.99 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | End of Study | -44.26 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 15 | -9.11 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 29 | -19.42 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 57 | -27.83 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 85 | -37.88 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 99 | -41.73 Score on a scale |
| Placebo | Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time | Day 127 | -44.18 Score on a scale |
Comparison: Statistical analysis results of PhGA score using VAS scale at day 99p-value: 0.2190% CI: [-1.9, 13.91]LS Mean
Comparison: Statistical analysis results of PhGA score using VAS scale at End of Studyp-value: 0.94290% CI: [-8.86, 8.11]LS Mean
Secondary
The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients
WORC score at Days 15, 29, 57, 85, 127, and End of Study (day 169). The scale range for WORC total score is 0-100, 0 being the worst possible outcome (highly symptomatic patient) and 100 being the best possible outcome (asymptomatic patient)
Time frame: Days 15, 29, 57, 85, 127, and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 15 | 12.39 Scores on a scale |
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 29 | 22.35 Scores on a scale |
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 57 | 28.74 Scores on a scale |
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 85 | 34.86 Scores on a scale |
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 127 | 41.86 Scores on a scale |
| Secukinumab | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | End of Study | 43.41 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 127 | 38.50 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 15 | 8.42 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 85 | 33.48 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 29 | 19.49 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | End of Study | 40.97 Scores on a scale |
| Placebo | The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients | Day 57 | 30.11 Scores on a scale |
Comparison: All patients at day 2990% CI: [-3.39, 9.11]LS Mean
Comparison: All patientts at day 15p-value: 0.1990% CI: [-1.03, 8.97]LS mean
Comparison: All patients at day 57p-value: 0.76190% CI: [-8.81, 6.08]LS Mean
Comparison: All patients at day 85p-value: 0.76590% CI: [-6.27, 9.03]LS Mean
Comparison: All patients at day 127p-value: 0.49190% CI: [-4.73, 11.45]LS Mean
Comparison: All patients at end of studyp-value: 0.63990% CI: [-6.19, 11.07]LS Mean
Secondary
Your Health Today Score Over Time
Patient Reported Outcome: Statistical analysis results of EQ-5D-5L for Your health Today questionnaire, which reflects how good or bad the subjets Health is on a scale from 0 (worst health) to 100 (best health).
Time frame: Days 15, 29, 57, 85, 99, 127, and End of Study
Population: PD Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab | Your Health Today Score Over Time | Day 57 | 3.19 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | Day 99 | 8.75 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | Day 29 | 3.27 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | Day 127 | 9.55 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | Day 85 | 7.36 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | End of Study | 10.22 Scores on a scale |
| Secukinumab | Your Health Today Score Over Time | Day 15 | -0.22 Scores on a scale |
| Placebo | Your Health Today Score Over Time | End of Study | 12.13 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 15 | 0.02 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 29 | 3.56 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 57 | 9.02 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 85 | 7.79 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 99 | 10.01 Scores on a scale |
| Placebo | Your Health Today Score Over Time | Day 127 | 13.59 Scores on a scale |
Comparison: Statistical analysis results of Your Health Today EQ-5D-5L Index score at day 99 (PD Analysis Set)p-value: 0.70690% CI: [-6.81, 4.29]LS Mean
Comparison: Statistical analysis results of Your Health Today EQ-5D-5L Index score at End of Studyp-value: 0.64790% CI: [-8.79, 4.99]LS Mean