Study of Efficacy and Safety of Secukinumab in Participants With Moderate-severe Rotator Cuff Tendinopathy

A Randomized, Parallel-group, 24 Week, Double-blind, Placebo-controlled, Multicenter Phase 3 Study to Assess the Efficacy and Safety of Secukinumab Compared to Placebo in Adult Patients With Active Rotator Cuff Tendinopathy

The purpose of the present study was to assess the efficacy of secukinumab 300 mg s.c. (subcutaneous) compared to placebo, each in combination with standard of care, in improving signs, symptoms and physical function in participants with moderate to severe rotator cuff tendinopathy (RCT), using a randomized, double-blind, placebo controlled, parallel group design to minimize bias.

Study Overview

• Status: Terminated
• Conditions: Rotator Cuff Tendinopathy
• Intervention / Treatment: Drug: Secukinumab; Drug: Placebo

Detailed Description

This was a randomized, double-blind, placebo-controlled Phase III study, stratified by tear status (no tear/ partial tear) in participants with moderate to severe rotator cuff tendinopathy (RCT), experiencing active disease from at least 6 weeks to 6 months at baseline, and were refractory to standard of care (non-steroidal anti-inflammatory drug [NSAIDs] and course of physiotherapy) over a period of 8 weeks.

The study was terminated due to the project being discontinued in order to prioritize other key programs in the portfolio. Due to the early termination and small sample size, the analysis by tear status stratification was not performed.

The study duration was up to 32 weeks, consisting of a screening period lasting up to 8 weeks (inclusive of a mandatory 2-week run-in period), a 16-week treatment period with last dose administered at Week 12, and an 8-week safety follow-up period. The primary endpoint assessment was at Week 16, and the safety follow-up data collection was through to Week 24.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1114AAP
    • Novartis Investigative Site
  • San Miguel de Tucumán, Argentina, 4000
    • Novartis Investigative Site
  • Tucumán Province
    • San Miguel Tucuman, Tucumán Province, Argentina, 4000
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1336
    • Novartis Investigative Site
• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 3M7
      • Novartis Investigative Site
• Czechia
  • Kolín, Czechia, 280 02
    • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 66250
      • Novartis Investigative Site
• Malaysia
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88300
      • Novartis Investigative Site
• Portugal
  • Ponte de Lima, Portugal, 4990-041
    • Novartis Investigative Site
• United States
  • California
    • Westlake Village, California, United States, 91361
      • Millennium Clinical Trials
  • Florida
    • Miami, Florida, United States, 33184
      • Healthy Life Research
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research LLC
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • West Clinical Research
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Unilateral rotator cuff tendinopathy with ≥ 6 weeks to ≤ 6 months symptom duration at baseline.
2. Nocturnal pain in shoulder on at least 3 out of 7 nights in the week prior to baseline or "positive painful arc test" on examination.
3. Total WORC percentage score ≤ 40 at the screening and baseline visits.
4. Average weekly (i.e., the average of the 7 scores taken once a day) numerical rating scale (NRS) pain score of ≥5 during the past 7 days prior to the baseline visit.
5. Refractory to standard of care: non-steroidal anti-inflammatory drug (NSAIDs) course as per local standard practice (if not intolerant or contraindicated) and a course of physiotherapy over a period of 8 weeks.
6. Participant agreed to remain on stable NSAID dosage regimen (if not intolerant or having contraindications; NSAID dose was permitted to be reduced, but not increased above dose established at run-in) and physiotherapy regimen from run-in period until End of Study (EOS).
7. Presence of tendinopathy in the affected shoulder on a centrally read MRI (Magnetic Resonance Imaging), with the following conditions: with no tear or partial tear (maximum 50% tendon thickness; anteroposterior (AP) length maximum 10 mm)

Exclusion Criteria:

1. Rheumatological and non-rheumatological inflammatory diseases, including but not limited to polymyalgia rheumatica (PMR), psoriatic arthritis (PsA), axial spondyloarthritis (AS: ankylosing spondylitis, nr-axSpA: non-radiographic axial spondyloarthritis), psoriasis (PsO), and rheumatoid arthritis (RA); fibromyalgia or severe pain disorder unrelated to the target shoulder; gout; and systemic lupus erythematosus.
2. Rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies positive at screening.
3. Oral, intramuscular or intravenous (i.v.) corticosteroid treatment within the last 12 weeks prior to randomization, or presence of any condition that might require intermittent corticosteroid use.
4. Lack of compliance with adhering to NSAID (unless intolerant or contraindicated) and physiotherapy regimen during run-in period.
5. Positive painful arc test result in contralateral shoulder
6. Inability or unwillingness to undergo MRI of the shoulder (e.g., participants with pacemakers, or metal fragments/foreign objects in the body that were not compatible with performing an MRI) to fulfill eligibility criteria (unless centrally read MRI images acquired within 3 months of baseline could be provided and the quality of images was deemed sufficient).

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; Participants received secukinumab 300 mg at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.	Drug: Secukinumab; 2 X secukinumab 150 mg / 1 mL as solution for subcutaneous (s.c.) injection; Other Names: AIN457
Placebo Comparator: Placebo; Participants received placebo at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.	Drug: Placebo; 2 X placebo / 1 mL as solution for s.c. injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) Score at Week 16	The WORC PSD is a sub-domain of the WORC Patient-Reported Outcome (PRO) and comprises 6 questions that capture the key symptoms experienced by participants with rotator cuff tendinopathy (RCT) relating to pain, weakness, stiffness, and mechanical symptoms. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.	At Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 16	The WORC PSD is a sub-domain of the WORC Patient-Reported Outcome (PRO) and comprises 6 questions that capture the key symptoms experienced by participants with rotator cuff tendinopathy (RCT) relating to pain, weakness, stiffness, and mechanical symptoms. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.	At Week 16
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 50 Points From Baseline in the WORC Total Score	The WORC is a patient-reported outcome tool, uniquely developed for rotator cuff conditions. The WORC is self-administered and consists of 21 items divided into five domains: physical symptoms, sport/recreation, work function, lifestyle function, and emotional function. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.	At Week 16
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 24	The WORC PSD is a sub-domain of the WORC Patient-Reported Outcome (PRO) and comprises 6 questions that capture the key symptoms experienced by participants with rotator cuff tendinopathy (RCT) relating to pain, weakness, stiffness, and mechanical symptoms. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.	At Week 24
Change From Baseline in WORC PSD Score at Week 24	The WORC PSD is a sub-domain of the WORC Patient-Reported Outcome (PRO) and comprises 6 questions that capture the key symptoms experienced by participants with rotator cuff tendinopathy (RCT) relating to pain, weakness, stiffness, and mechanical symptoms. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.	At Week 24
Secukinumab Serum Concentrations	Pharmacokinetic parameters (measures of treatment exposure) were evaluated in all participants, with moderate to severe RCT, treated with secukinumab 300 mg s.c.	Day 1 and Weeks 4 and 16
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), by Maximum Severity	Severity: Mild - usually transient in nature and generally not interfering with normal activities; Moderate - sufficiently discomforting to interfere with normal activities; Severe - prevents normal activities.	Up to Week 24
Percentage of Participants With Clinically Significant Changes in Laboratory Parameters	Laboratory parameters included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, amylase, calcium, creatinine, bilirubin, glucose, lactate dehydrogenase, lipase, magnesium, phosphate, potassium, sodium, urate, and urea nitrogen.	Up to Week 24
Percentage of Participants With Clinically Significant Changes in Vital Signs	Vital signs included sitting systolic blood pressure, sitting diastolic blood pressure, and sitting pulse rate.	Up to Week 24
Percentage of Participants With Binding and Neutralizing Anti-drug Antibodies		At Day 1 and Week 16
Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity Score	PROMIS-SF Upper Extremity measures self-reported capability of physical function. Participants were asked a series of 7 questions rating their ability to perform a range of physical activities related to daily life that would be impacted by shoulder function. Each response was scored from 1 (unable to do) to 5 (without any difficulty). The responses for the 7 questions were added to the total raw score ranging from 7 (worst) to 35 (best) and converted to a T-score with a range from 16.3 (worst outcome) to 58.2 (best outcome), which was used for the analysis. Therefore, the theoretical range for the value for change from baseline for converted T-scores was between -41.9 to 41.9. A positive change from baseline indicated a better outcome.	At Week 16

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): October 17, 2024
• Study Completion (Actual): December 13, 2024

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 1, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Adult; Unilateral; Moderate to Severe Rotator Cuff Tendinopathy; Refractory to standard of care
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Wounds and Injuries; Tendon Injuries; Tendinopathy; secukinumab
• Other Study ID Numbers: CAIN457O12301; 2022-502068-19-00 (Registry Identifier: EU CT NUMBER)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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