A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II, 24-week Study Investigating the Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy Refractory to Oral NSAIDs/Acetaminophen, Physiotherapy or Corticosteroid Injections
Overview
- Phase
- Phase 2
- Intervention
- secukinumab
- Conditions
- Tendinopathy
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or non-pregnant, non-lactating female patients 18 to 65 years of age at randomization
- •Presence of unilateral rotator cuff tendinopathy with:
- •Symptoms present ≥6 weeks, but \<12 months prior to randomization
- •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
- •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
- •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
- •The rotator-cuff tendinopathy must have been refractory to standard treatment, including NSAIDs and physiotherapy
Exclusion Criteria
- •Rheumatologic, inflammatory diseases, including but not limited to: PsA, AS and RA
- •Previous shoulder surgery in affected shoulder
- •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
- •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
- •Neck conditions, including but not limited to cervical spine syndrome, which in the opinion of the investigator, may explain the patient's symptoms
- •Previous platelet rich plasma injections within the last 12 months prior to randomization
- •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)
- •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
- •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
Arms & Interventions
secukinumab
AIN457 300 mg subcutaneously (s.c.) for 12 weeks
Intervention: secukinumab
Placebo
Placebo subcutaneously for 12 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- 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)
- Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time(Days 15, 29, 57, 85, 99, 127, and End of Study)
- American Shoulder and Elbow Surgeons (ASES) Score Over Time(Days 15, 29, 57, 85, 99, 127, and End of Study)
- Your Health Today Score Over Time(Days 15, 29, 57, 85, 99, 127, and End of Study)
- EQ-5D-5L Index Score Over Time(Days 15, 29, 57, 85, 99, 127 and End of Study)
- Patient Global Assessment (PGA) Score Over Time Using a VAS Scale(Days 15, 29, 57, 85, 99, 127 and End of Study)
- Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores(Baseline and Day 99)
- Pain Score Over Time Using a VAS Scale(Days 15, 29, 57, 85, 99, 127 and End of Study)
- Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time(Days 15, 29, 57, 85, 99, 127 and End of Study)
- Pharmacokinetics - Cmin(Days 1, 29, 85 and EoS (End of Study))
- Immunogenicity Assessment - Treatment Emergent ADAs(Day 1 and EoS)