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

Tendinopathy Clinical Trial

— UnchAIN  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05569174
• Other study ID #: CAIN457FDE05
• Secondary ID: 2022-001516-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Tendinopathy

Intervention

Drug:
• secukinumab
AIN457 300 mg subcutaneously for 12 weeks

Other:
• Placebo
Placebo to match AIN457 subcutaneously for 12 weeks

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bad Doberan	Mecklenburg Vorpommern
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Cottbus
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Gladbeck
Germany	Novartis Investigative Site	Halle Saale
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heinsberg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenchen	Bavaria
Germany	Novartis Investigative Site	Reinfeld
Germany	Novartis Investigative Site	Schoenebeck

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients	WORC PRO score at week 24. 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.	Week 24
Secondary	The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score in each subdomain	WORC PRO score at week 24. 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.	Week 24
Secondary	Patient Global Assessment (PaGA) Score	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).	Week 24
Secondary	Disease activity and quality of life for the Short Form 36 (SF-36v2) score	To assess the effect of secukinumab compared to placebo measured by disease activity and quality of life measures at Week 52 for Short form 36v2; Score range is from 0 to 100. Higher scores indicate better health status.	Week 24
Secondary	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	Week 24
Secondary	Pain Score Using a Numeric Rating Scale (NRS)	Pain intensity is assessed by a Numeric Rating Scale (NRS) which is measured in a scale of 11 points.; The scale range for pain score is 0-10, 0 being the best possible outcome (no pain) and 10 being the worst possible outcome (worst pain).	Week 24
Secondary	EQ-5D-5L Index Score	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.	Week 24
Secondary	Number of participants with Adverse Events	Safety and tolerability assessments over time: incidence and severity of AEs and SAEs; routine safety laboratory parameters; To evaluate safety and tolerability of secukinumab 300 mg s.c. in participants with moderate to severe rotator cuff tendinopathy.	Baseline up to Week 24