Clinical trial NCT05569174: Study of Efficacy and Safety of AIN457/Secukinumab in Patients With Rotator Cuff Tendinopathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tendinopathy
Keywords: shoulder
rotator cuff
IL-17A-Ab
AIN457X
Impingement syndrome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-10-06
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the efficacy and safety of AIN457 (secukinumab s.c.) compared to placebo in adult patients with moderate to severe rotator cuff tendinopathy and failure to conventional therapy.

* The study duration will be 24 weeks.
* The treatment duration will 12 weeks with 12 weeks follow-up.
* The visit frequency will be weekly until visit 7 and 4-weekly until end of treatment and 4 follow-up visits.

Detailed description: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase IIIb, 24-week study to investigate the superior efficacy of AIN457/secukinumab and safety in participants with rotator cuff tendinopathy.

Secukinumab 300 mg s.c. will be compared to placebo (both arms in combination with patient individualized conventional therapy) in relieving clinical symptoms at week 24. Approximately 430 participants (215 per treatment group) will be included with a diagnosis of moderate to severe rotator cuff tendinopathy with no tear or partial tear, who are experiencing active disease for at least 6 weeks and no more than 6 months at Baseline and who have failed to respond to conventional therapy.

The study consists 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 period will be blinded. The Screening period will assess eligibility. Participants who meet the eligibility criteria at Screening will continue to Run-in period and will be randomized. In the Run-in period participants should perform 2 weeks of home-based standardized physiotherapy. The Run-in period is initiated by a telephone visit 14 days prior to Randomization. The study comprises a total of 13 visits.

Eligible participants will be randomized 1:1 to either receive secukinumab 300 mg s.c. or placebo s.c. at Baseline, week 1, 2, 3, 4, 8 and 12 (7 injections in total).

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Males and non-pregnant, non-nursing females between 18 and 65 years of age
3. Rotator cuff tendinopathy (unilateral) with positive "Painful Arc Test" on examination
4. Symptoms present for at least 6 weeks but not more than 6 months at Baseline
5. Moderate to severe rotator cuff tendinopathy demonstrated by all of the following criteria:

   1. WORC score ≤ 40 at Baseline
   2. NRS pain score ≥ 5 at Baseline and at least 3 days of the past 7 days prior to Baseline
   3. Nocturnal pain at least 4 out of past 7 days in the week prior to Baseline
6. Failure to 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:

1. Greater than 50% partial thickness tear as established by MRI or ultrasound during assessment in Run-in phase
2. Patients who are expected to require glucocorticoid treatment throughout the trial duration at Baseline (e.g., systemic, intramuscular, local injections in shoulder)
3. Previous surgery, or plans for surgery, during the study period, in the affected shoulder
4. 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
5. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies positive at Screening
6. History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or contralateral shoulder) confirmed clinically or by medical imaging
7. Symptomatic osteoarthritis of the shoulder (glenohumeral, acromioclavicular) in affected or contralateral shoulder confirmed by medical imaging
8. Patients with traumatic rupture that would be considered eligible for surgery for repair of cuff tear.
9. Neurological conditions including but not limited to cervical radiculopathy, which in the opinion of the investigator may explain the patient's symptoms
10. Any intra-articular/subacromial glucocorticoid treatment within 12 weeks prior to Baseline or more than 2 injections for the current tendinopathy.
11. Any oral, intramuscular or i.v. glucocorticoid treatment 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer
12. Previous platelet rich plasma (PRP) injections or fluoroquinolone/quinolone antibiotics within 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer
13. Neuromuscular or primary/secondary muscular deficiency which limits the ability to perform functional measurement (e.g., shoulder strength test)
14. Previous hyaluronic injections within 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer

Primary outcomes:
measure: The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients
timeFrame: Week 24
Secondary outcomes:
measure: The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score in each subdomain
timeFrame: Week 24
measure: Patient Global Assessment (PaGA) Score
timeFrame: Week 24
measure: Disease activity and quality of life for the Short Form 36 (SF-36v2) score
timeFrame: Week 24
measure: Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time
timeFrame: Week 24
measure: Pain Score Using a Numeric Rating Scale (NRS)
timeFrame: Week 24
measure: EQ-5D-5L Index Score
timeFrame: Week 24
measure: Number of participants with Adverse Events
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Hannover
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Bad Doberan
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Cottbus
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Gladbeck
country: Germany
facility: Novartis Investigative Site
city: Halle S
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heinsberg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Karlsruhe
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Schoenebeck
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: