Study of Efficacy and Safety of AIN457/Secukinumab in Patients With Rotator Cuff Tendinopathy (UnchAIN)

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter, 24-week Study Investigating the Efficacy and Safety of Secukinumab Compared to Placebo in Adult Patients With Moderate to Severe Rotator Cuff Tendinopathy and Failure to Conventional Therapy

The purpose of this study was to investigate the efficacy and safety of secukinumab subcutaneously (s.c.) compared to placebo in adult patients with moderate to severe rotator cuff tendinopathy and failure to conventional therapy.

Study Overview

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

Detailed Description

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase IIIb, 24-week study to investigate the superior efficacy of secukinumab and safety in participants with rotator cuff tendinopathy.

Secukinumab 300 mg s.c. was compared to placebo (both arms in combination with patient individualized conventional therapy) in relieving clinical symptoms at Week 24.

The study consisted of a screening period up to 6 weeks, a 2-week run-in period, a 12-week treatment period and a 12-week follow-up period. Treatment and follow-up periods were blinded. Participants who met the eligibility criteria at screening continued to the run-in period and were randomized. In the run-in period, participants performed 2 weeks of home-based standardized physiotherapy.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Berlin, Germany, 12627
    • Novartis Investigative Site
  • Berlin, Germany, 10787
    • Novartis Investigative Site
  • Cottbus, Germany, 03042
    • Novartis Investigative Site
  • Dresden, Germany, 01069
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt am Main, Germany, 60313
    • Novartis Investigative Site
  • Gladbeck, Germany, 45968
    • Novartis Investigative Site
  • Hamburg, Germany, 20095
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
  • Hamburg, Germany, 20149
    • Novartis Investigative Site
  • Heinsberg, Germany, 52525
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Schönebeck, Germany, 39218
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Karlsruhe, Baden-Wurttemberg, Germany, 76133
      • Novartis Investigative Site
  • Bavaria
    • Munich, Bavaria, Germany, 80809
      • Novartis Investigative Site
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30159
      • Novartis Investigative Site
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent had to be obtained prior to participation in the study.
• Males and non-pregnant, non-nursing females were between 18 and 65 years of age.
• Rotator cuff tendinopathy (unilateral) was present with a positive "Painful Arc Test" on examination.
• Symptoms had been present for at least 6 weeks but not more than 6 months at Baseline.

• Moderate to severe rotator cuff tendinopathy was demonstrated by all of the following criteria:

  1. WORC score was ≤ 40 at Baseline.
  2. NRS pain score was ≥ 5 at Baseline and for at least 3 days of the 7 days prior to Baseline.
  3. Nocturnal pain occurred at least 4 out of the 7 days in the week prior to Baseline.
• Patients had failed at least 8 weeks of conventional therapy prior to Baseline: inadequate response to NSAIDs and/or paracetamol and physiotherapy; or intolerance to NSAIDs and/or paracetamol.

Exclusion Criteria:

• Greater than 50% partial thickness tear had been established by MRI or ultrasound during assessment in the Run-in phase.
• Patients were expected to require glucocorticoid treatment throughout the trial duration at Baseline (e.g., systemic, intramuscular, local injections in shoulder).
• Previous surgery, or plans for surgery, during the study period, in the affected shoulder.
• Rheumatologic and chronic inflammatory diseases, including but not limited to inflammatory bowel disease, polymyalgia rheumatica (PMR), PsA, axSpA and rheumatoid arthritis (RA), fibromyalgia or - severe pain disorder unrelated to the target shoulder.
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were positive at Screening.
• History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or contralateral shoulder) had been confirmed clinically or by medical imaging.
• Symptomatic osteoarthritis of the shoulder (glenohumeral, acromioclavicular) in affected or contralateral shoulder had been confirmed by medical imaging.
• Patients had traumatic rupture that would have been considered eligible for surgery for repair of cuff tear.
• Neurological conditions including but not limited to cervical radiculopathy, which in the opinion of the investigator could have explained the patient's symptoms.
• Any intra-articular/subacromial glucocorticoid treatment had occurred within 12 weeks prior to Baseline or more than 2 injections for the current tendinopathy.
• Any oral, intramuscular or i.v. glucocorticoid treatment had occurred 12 weeks prior to Baseline or during the current tendinopathy, whichever was longer.
• Previous platelet rich plasma (PRP) injections or fluoroquinolone/quinolone antibiotics had occurred within 12 weeks prior to Baseline or during the current tendinopathy, whichever was longer.
• Neuromuscular or primary/secondary muscular deficiency had limited the ability to perform functional measurement (e.g., shoulder strength test).
• Previous hyaluronic injections had occurred within 12 weeks prior to Baseline or during the current tendinopathy, whichever was longer.

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 300 mg of secukinumab s.c. for 12 weeks	Drug: Secukinumab; Secukinumab 300 mg s.c for 12 weeks in a pre-filled syringe (PFS); Other Names: AIN457
Placebo Comparator: Placebo; Participants received placebo s.c. for 12 weeks	Other: Placebo; Placebo to match secukinumab s.c. for 12 weeks in a PFS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Percentage Score at Week 24	The WORC Index consisted 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). Each of the 21 items in the WORC was rated using a visual analogue scale (VAS) ranging from 0 (no impact on quality of life) to 100 (worst possible impact). Thus, the total score ranged from 0 to 2100 points. The score was reported as a percentage of normal by subtracting the total score from 2100, dividing by 2100, and multiplying by 100. Total final WORC percentage scores ranged from 0%, the lowest functional status level, to 100%, the highest functional status level. Change from baseline in the WORC percentage total score was assessed at Week 24. A positive change from baseline indicated an improvement.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the WORC Percentage Sub-scores at Week 24	The WORC Index consisted 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). Each of the 21 items in the WORC was rated using a VAS ranging from 0 (no impact on quality of life) to 100 (worst possible impact). Each subdomain score was calculated as a percentage of normal function, ranging from 0% (worst condition) to 100% (best condition). Change from baseline in the WORC Index percentage sub-domain score was assessed at Week 24. A positive change from baseline indicated an improvement	Baseline, Week 24
Change From Baseline in Participant's Global Assessment of Disease Activity Score at Week 24	The participant's global assessment of disease activity was performed using 100 mm VAS ranging from 0="no activity" to 100= "most active", after the question " Please indicate with a vertical mark ( | ) through the horizontal line the global activity of your disease in the last 24 hours". Change from baseline in the participant's global assessment of disease activity score was assessed at Week 24. A negative change from baseline indicated improvement	Baseline, Week 24
Change From Baseline in Short Form 36 (SF-36v2) Score at Week 24	The SF-36 Health Survey was a validated questionnaire assessing health-related quality of life. Participants completed the survey throughout the study, reflecting their health status over the previous 4 weeks. It consisted of eight subscales that were scored individually; and two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component summary scores (PCS and MCS) were derived from weighted combinations of the eight subscales. Each domain and component summary score ranged from 0 to 100, with higher scores indicating better quality of life. Change from baseline to Week 24 in all subscale and summary scores was assessed, where a positive change indicated improvement.	Baseline, Week 24
Change From Baseline in Quick Disability of the Arm, Shoulder and Hand (DASH) Questionnaire Score at Week 24	The QuickDASH was an abbreviated form of the DASH. The QuickDASH Index was self-administered and used 11 items to measure physical function and symptoms in participants with any or multiple musculoskeletal disorders of the upper limb. It had a recall period of 1 week. Each item of the QuickDASH had five response options. The raw score was calculated as the sum of responses, converted to an average, and rescaled to a total score ranging from 0 (no disability) to 100 (most severe disability) Change from baseline to Week 24 was assessed. A negative change from baseline indicated improvement.	Baseline, Week 24
Change From Baseline in the Numeric Rating Scale (NRS) Pain Score at Week 24	The score for pain was assessed by using an 11-point NRS ranging from 0 "no pain at all" to 10 "worst possible pain", after the question "On a numeric scale of 0-10 where would you rate your pain at this time". Change from baseline to Wek 24 was assessed. A negative change from baseline indicated improvement	Baseline, Week 24
Change From Baseline in EuroQol 5 Dimensions- 5 Levels (EQ-5D-5L) at Week 24- Total Score	The EQ-5D-5L was a standardized instrument used to evaluate patients' overall health-related quality of life (QoL). It consisted of two components: the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system assessed five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension was rated on five levels, from 1 (no problems) to 5 (extreme problems). These ratings were combined to generate a composite health index, which could be converted into a single summary health utility score using published value sets. Total scores ranged from 0 to 1, with lower scores indicating greater health impairment. Changes in total scores from baseline to Week 24 were analyzed, with positive changes indicating improvement in health-related quality of life.	Baseline, Week 24
Change From Baseline in EuroQol 5 Dimensions- 5 Levels (EQ-5D-5L) at Week 24- EQ VAS	The EQ-5D-5L was a standardized instrument used to evaluate patients' overall health-related quality of life (QoL). It consisted of two components: the descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS captured the respondent's self-rated health on a vertical scale ranging from 0 (worst imaginable health) to 100 (best imaginable health). Changes in EQ VAS scores from baseline to Week 24 were analyzed, with positive changes indicating improvement in health-related quality of life.	Baseline, Week 24

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: shoulder; rotator cuff; IL-17A-Ab; AIN457X; Impingement syndrome
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Wounds and Injuries; Tendon Injuries; Tendinopathy; secukinumab
• Other Study ID Numbers: CAIN457FDE05; 2022-001516-26 (EudraCT Number)

Plan for Individual participant data (IPD)

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

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes