Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy

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

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.

Study Overview

• Status: Completed
• Conditions: Tendinopathy
• Intervention / Treatment: Drug: secukinumab; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia
    • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 66250
      • Novartis Investigative Site
    • Kolin, Czech Republic, Czechia, 280 02
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Novartis Investigative Site
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Novartis Investigative Site
  • California
    • La Mesa, California, United States, 91942
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Novartis Investigative Site
    • Miami Lakes, Florida, United States, 33014
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33603
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: secukinumab; AIN457 300 mg subcutaneously (s.c.) for 12 weeks	Drug: secukinumab; AIN457 300 mg subcutaneously for 12 weeks; Other Names: AIN457
Placebo Comparator: Placebo; Placebo subcutaneously for 12 weeks	Other: Placebo; Placebo to match AIN457 subcutaneously for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 14 (Day 99)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Days 15, 29, 57, 85, 127, and End of Study
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	Days 15, 29, 57, 85, 99, 127, and End of Study
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).	Days 15, 29, 57, 85, 99, 127, and End of Study
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).	Days 15, 29, 57, 85, 99, 127, and End of Study
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.	Days 15, 29, 57, 85, 99, 127 and End of Study
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).	Days 15, 29, 57, 85, 99, 127 and End of Study
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).	Days 15, 29, 57, 85, 99, 127 and End of Study
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).	Days 15, 29, 57, 85, 99, 127 and End of Study
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	Days 1, 29, 85 and EoS (End of Study)
Immunogenicity Assessment - Treatment Emergent ADAs	Number of Participants with Treatment emergent Anti-secukinumab antibodies	Day 1 and EoS
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.	Baseline and Day 99

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): August 2, 2019
• Study Completion (Actual): October 17, 2019

Study Registration Dates

• First Submitted: November 14, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: shoulder; rotator cuff; IL-17A-Ab; AIN457X; Overuse tendinopathy
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy
• Other Study ID Numbers: CAIN457X2201; 2017-003099-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No