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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05758415

Enrollment

Registered

2023-03-07

Start date

2023-08-02

Completion date

2024-12-11

Last updated

2025-12-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rotator Cuff Tendinopathy

Keywords

Moderate to Severe Rotator Cuff Tendinopathy, Adult, Unilateral, Refractory to standard of care

Brief summary

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.

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.

Interventions

DRUGSecukinumab

2 X secukinumab 150 mg / 1 mL as solution for subcutaneous (s.c.) injection

DRUGPlacebo

2 X placebo / 1 mL as solution for s.c. injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Investigator, site personnel, persons performing the assessments and participants remained blinded through the Week 24 final database lock. The Novartis clinical trial and submission teams remained blinded to the identity of the treatment from the time of randomization until the Week 16 database lock (for the primary endpoint analysis). The following methods were utilized for blinding: (1) Randomization data were kept strictly confidential until the time of unblinding and were not accessible by anyone else involved in the study with the following exceptions: bioanalyst; (2) the identity of the treatments was concealed by the use of study treatments that were all identical in packaging, labeling, schedule of administration, and appearance.

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) Score at Week 16	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.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 16	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.
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 50 Points From Baseline in the WORC Total Score	At Week 16	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.
Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 24	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.
Change From Baseline in WORC PSD Score at Week 24	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.
Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity Score	At Week 16	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.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), by Maximum Severity	Up to Week 24	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.
Percentage of Participants With Clinically Significant Changes in Laboratory Parameters	Up to Week 24	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.
Percentage of Participants With Clinically Significant Changes in Vital Signs	Up to Week 24	Vital signs included sitting systolic blood pressure, sitting diastolic blood pressure, and sitting pulse rate.
Percentage of Participants With Binding and Neutralizing Anti-drug Antibodies	At Day 1 and Week 16	—
Secukinumab Serum Concentrations	Day 1 and Weeks 4 and 16	Pharmacokinetic parameters (measures of treatment exposure) were evaluated in all participants, with moderate to severe RCT, treated with secukinumab 300 mg s.c.

Countries

China, Italy, Poland, Spain, Thailand, United States

Participant flow

Pre-assignment details

272 participants were screened in this study, of which 212 discontinued prior to randomization.

Participants by arm

Arm	Count
Secukinumab Participants received secukinumab 300 mg at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.	30
Placebo Participants received placebo at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.	30
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	0	1
Overall Study	Subject Decision	2	5

Baseline characteristics

Characteristic	Secukinumab	Placebo	Total
Age, Continuous	47.5 years STANDARD_DEVIATION 9.74	49.5 years STANDARD_DEVIATION 9.62	48.5 years STANDARD_DEVIATION 9.65
Age, Customized 25 - < 45 years	13 participants	9 participants	22 participants
Age, Customized 45 - <= 65 years	17 participants	21 participants	38 participants
Race/Ethnicity, Customized Asian	10 participants	5 participants	15 participants
Race/Ethnicity, Customized Black or African American	1 participants	0 participants	1 participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants	1 participants	1 participants
Race/Ethnicity, Customized White	19 participants	24 participants	43 participants
Sex: Female, Male Female	17 Participants	18 Participants	35 Participants
Sex: Female, Male Male	13 Participants	12 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30
other Total, other adverse events	0 / 30	4 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Outcome results

Primary

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.

Time frame: At Week 16