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

April 15, 2024 updated by: Novartis Pharmaceuticals

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 is 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

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The trial is designed as a randomized, double-blind, placebo-controlled Phase III study over 24 weeks in approximately 234 participants with moderate to severe rotator cuff tendinopathy (RCT), refractory to Standard of Care (Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) course as per local standard practice, if not intolerant or contraindicated, and a course of physiotherapy over a period of 8 weeks).

  1. The trial comprises the following periods:

    - Screening / run-in period

    A screening period of up to maximum of 56 days will be used to assess participant eligibility. During this time, the participant can demonstrate that they are refractory to Standard of Care. During the 2-week run-in period prior to the Baseline visit, the participant will need to have 2 weeks of stable NSAID intake and standardized physiotherapy. This is important in order to ensure the participants are refractory to SoC and to establish compliancy with the stabilized dosing of NSAID treatment and physiotherapy regimen to be maintained throughout the study.

    MRI will be performed during Screening period to exclude other shoulder pathologies and tears (if present) >50%. Evidence of tendinopathy should be established by a centrally read Magnetic Resonance Imaging (MRI). MRI performed within 3 months from baseline may be accepted if deemed suitable by the central reader.

    Shoulder x-rays will also be performed in order to rule out other shoulder pathologies. Historic x-rays will be accepted if performed ≤ 3 months prior to Baseline.

    - Study period 1 (Baseline to Week 16)

    During Study period 1, double-blinded treatment is administered over 12 weeks, reflecting 16 weeks of total drug exposure. Approximately 234 eligible participants will be randomized at Baseline (BSL) in a 1:1 ratio to one of the following arms:

    • Arm 1 (N=117): secukinumab 300 mg s.c. at Day 1 and Weeks 1, 2, 3, 4, 8, and 12
    • Arm 2 (N=117): placebo at Day 1 and Weeks 1, 2, 3, 4, 8, and 12 The last dose of study treatment will be administered at Week 12; the primary outcome assessments will be performed at Week 16.

    Randomization will be stratified by tear status (no tear/partial tear). Participants should continue on stable NSAID pain medication and a standardized physiotherapy regimen. Reduction in NSAID dose is permitted after BSL, but participants must not increase above dose established during run-in. Use of corticosteroid injections is not permitted during this time.

    - Study period 2 (Follow-up period)

    A follow-up period of 8 weeks after the end of the treatment period is planned to assess the maintenance of effect and collect follow-up safety data up to Week 24. Investigator, site personnel, persons performing the assessments and participants will remain blinded, but Novartis clinical trial and submission teams will be unblinded after Week 16 readout. Participants should continue on stable NSAID therapy and physiotherapy during this period. Reduction in NSAID dose is permitted after BSL, but participants must not increase above dose established during run-in. Corticosteroid injections are also not permitted after Week 16.

    - Off-site procedures

    At the Investigator's discretion, participants may avail of home administration of study drug (self-administered or by a care-giver) at Week 1 and Week 3. Participant and/or caregiver would need to be trained and approved by Investigator for these administrations. Site should have confirmed contact with participant for these home administrations. Tele-visits, i.e., secure videoconferencing, between the Participant and Investigator or designated site staff may also be utilized to support administration of study drug at home.

  2. Rescue Medicine

    Any changes to type of NSAID taken by the participant or any increase in NSAID dosages from stable dose established during run-in period are considered prohibited throughout the duration of the study.

    If pain or discomfort is intolerable, participants may use non-NSAID medication including, for example, acetaminophen/paracetamol, low-dose opioids and tramadol, as needed. If the participant continues to experience intolerable pain or discomfort, then any increase to the dose of NSAID taken should be kept to an absolute minimum in terms of dosage and duration. Any changes to NSAID type and/or increase in dose will be recorded as a deviation to the protocol but would not result in withdrawal of the participant.

  3. Rational for placebo arm

The placebo effect in interventional trials in the treatment of RCT is considerable; hence, a placebo control is warranted.

Study Type

Interventional

Enrollment (Estimated)

234

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1114AAP
        • Recruiting
        • Novartis Investigative Site
      • Tucuman, Argentina, 4000
        • Recruiting
        • Novartis Investigative Site
    • Buenos Aires
      • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1055AAF
        • Recruiting
        • Novartis Investigative Site
    • Tucuman
      • San Miguel De Tucuman, Tucuman, Argentina, 4000
        • Recruiting
        • Novartis Investigative Site
  • Bulgaria
      • Sofia, Bulgaria, 1336
        • Recruiting
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1632
        • Recruiting
        • Novartis Investigative Site
  • Canada
      • Quebec, Canada, G1V 3M7
        • Recruiting
        • Novartis Investigative Site
    • Quebec
      • Sherbrooke, Quebec, Canada, J1L 0H8
        • Recruiting
        • Novartis Investigative Site
  • Chile
      • Santiago, Chile, 7500571
        • Recruiting
        • Novartis Investigative Site
    • RM
      • Santiago, RM, Chile, 7500588
        • Recruiting
        • Novartis Investigative Site
    • Santiago
      • Vitacura, Santiago, Chile, 7640881
        • Recruiting
        • Novartis Investigative Site
  • Czechia
      • Kolin, Czechia, 280 02
        • Recruiting
        • Novartis Investigative Site
      • Pardubice, Czechia, 53002
        • Recruiting
        • Novartis Investigative Site
    • Czech Republic
      • Brno, Czech Republic, Czechia, 66250
        • Recruiting
        • Novartis Investigative Site
      • Praha, Czech Republic, Czechia, 19000
        • Recruiting
        • Novartis Investigative Site
  • Denmark
      • Vejle, Denmark, 7100
        • Recruiting
        • Novartis Investigative Site
  • France
      • Dijon, France, 21034
        • Recruiting
        • Novartis Investigative Site
      • Le Mans, France, 72037
        • Recruiting
        • Novartis Investigative Site
      • Nantes Cedex 1, France, 44093
        • Recruiting
        • Novartis Investigative Site
      • St-Priest-en-Jarez, France, 42270
        • Recruiting
        • Novartis Investigative Site
    • Cedex 2
      • Orleans, Cedex 2, France, 45067
        • Recruiting
        • Novartis Investigative Site
    • Haute Vienne
      • Limoges, Haute Vienne, France, 87000
        • Recruiting
        • Novartis Investigative Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • Recruiting
        • Novartis Investigative Site
      • Selangor Darul Ehsan, Malaysia, 68100
        • Recruiting
        • Novartis Investigative Site
    • Sabah
      • Kota Kinabalu, Sabah, Malaysia, 88300
        • Recruiting
        • Novartis Investigative Site
  • Portugal
      • Lisboa, Portugal, 1050-034
        • Recruiting
        • Novartis Investigative Site
      • Ponte de Lima, Portugal, 4990 041
        • Recruiting
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 831 03
        • Recruiting
        • Novartis Investigative Site
      • Bratislava, Slovakia, SK-82606
        • Recruiting
        • Novartis Investigative Site
      • Dolny Kubin, Slovakia, 026 01
        • Recruiting
        • Novartis Investigative Site
      • Piestany, Slovakia, 92101
        • Recruiting
        • Novartis Investigative Site
  • Turkey
      • Ankara, Turkey, 06100
        • Recruiting
        • Novartis Investigative Site
      • Ankara, Turkey, 06620
        • Recruiting
        • Novartis Investigative Site
      • Izmir, Turkey, 35040
        • Recruiting
        • Novartis Investigative Site
    • Gorukle
      • Bursa, Gorukle, Turkey, 16059
        • Recruiting
        • Novartis Investigative Site
    • TUR
      • Istanbul, TUR, Turkey, 34098
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom, SW17 0QT
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85018
        • Recruiting
        • Elite Clinical Studies .
        • Principal Investigator:
          • Joseph L Lillo
        • Contact:
      • Phoenix, Arizona, United States, 85053
      • Tempe, Arizona, United States, 85283
        • Recruiting
        • Fiel Family Sports Medicine
        • Principal Investigator:
          • Thomas Fiel
        • Contact:
      • Tucson, Arizona, United States, 85712
        • Recruiting
        • Tucson Orthopedic Institute PC
        • Principal Investigator:
          • Nebojsa Skrepnik
        • Contact:
    • California
      • El Cajon, California, United States, 92020
        • Recruiting
        • TriWest Reserach Associates .
        • Principal Investigator:
          • Arthur Mabaquiao
        • Contact:
      • La Mesa, California, United States, 91942
        • Recruiting
        • Purushotham Akther and Roshan Kotha MD Inc
        • Principal Investigator:
          • Roshan Kotha
        • Contact:
      • Simi Valley, California, United States, 93065
        • Recruiting
        • Millennium Clinical Trials
        • Principal Investigator:
          • Elvira Lindwall
        • Contact:
    • Florida
      • Bradenton, Florida, United States, 34209
        • Recruiting
        • CoastalOrthoandSportsMedofSWFlorida .
        • Contact:
        • Principal Investigator:
          • Avinash Kumar
      • Doral, Florida, United States, 33166
        • Recruiting
        • Universal Axon Clinical Research
        • Contact:
          • Phone Number: 305-898-7888
        • Principal Investigator:
          • Luis Martinez
      • Miami, Florida, United States, 33184
        • Recruiting
        • Healthy Life Research .
        • Contact:
          • Phone Number: 305-222-0155
        • Principal Investigator:
          • Eduardo Gonzalez-Hernandez
      • Plantation, Florida, United States, 33324
        • Recruiting
        • Integral Rheumatology and Immunology Specialists IRIS
        • Principal Investigator:
          • Guillermo Valenzuela
        • Contact:
      • Sunrise, Florida, United States, 33351
        • Recruiting
        • Precision Clinical Research LLC
        • Contact:
        • Principal Investigator:
          • Richard Linn
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Recruiting
        • Chicago Clinical Research Inst
        • Contact:
          • Saad Hussaini Syed
          • Phone Number: +1 312 791 3241
          • Email: ssyed@ccrii.us
        • Principal Investigator:
          • Dennis Levinson
      • Oak Brook, Illinois, United States, 60523
        • Recruiting
        • Affinity Health Corp
        • Contact:
        • Principal Investigator:
          • Manohar Jethani
    • Missouri
      • Saint Louis, Missouri, United States, 63141
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • Recruiting
        • Inspire Santa Fe Medical Group Rheumatology
        • Principal Investigator:
          • Hillary Norton
        • Contact:
    • North Carolina
      • Morehead City, North Carolina, United States, 28557
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
      • Indiana, Pennsylvania, United States, 15701
        • Recruiting
        • Antria Inc .
        • Contact:
          • Phone Number: 724-349-0520
        • Principal Investigator:
          • David Bizousky
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical Univ of South Carolina .
        • Contact:
        • Principal Investigator:
          • Josef Eichinger
      • Mount Pleasant, South Carolina, United States, 29464
    • Tennessee
      • Jackson, Tennessee, United States, 38305
        • Recruiting
        • West Tennessee Research Institute
        • Principal Investigator:
          • Jacob A. Aelion
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23238
        • Recruiting
        • Virginia Ispine Physicians PC
        • Contact:
        • Principal Investigator:
          • Michael Depalma

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 BSL.
  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: 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 must agree to remain on stable NSAID dosage regimen (if not intolerant or having contraindications; NSAID dose is 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; 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 are not compatible with performing an MRI) to fulfill eligibility criteria (unless centrally read MRI images acquired within 3 months of Baseline can be provided and the quality of images is deemed sufficient).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Secukinumab
  • Name and Strength: 2 X Secukinumab 150 mg / 1 mL
  • Pharmaceutical Dosage Form: Solution for subcutaneous (s.c.) injection
  • Randomized in a 1:1 ratio
Drug: Secukinumab
The participants will receive Secukinumab 300 mg s.c. at randomization (Baseline visit), Week 1, 2, 3, 4, 8, and 12
Other Names:
  • AIN457
Placebo Comparator: Placebo
  • Name and Strength: 2 X Placebo / 1 mL
  • Pharmaceutical Dosage Form: Solution for subcutaneous (s.c.) injection
  • Randomized in a 1:1 ratio
Drug: Placebo
The participants will receive placebo s.c. at randomization (Baseline visit), Week 1, 2, 3, 4, 8, and 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from BSL in in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) score
Time Frame: At Week 16

Improving physical shoulder symptoms in participants with moderate to severe RCT 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 RCT relating to pain, weakness, stiffness, and mechanical symptoms. A score of 0 is the best outcome in terms of physical symptoms and a score of 60 is the worst possible score
At Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants who achieve an improvement (increase) of at least 40 points from BSL in the WORC PSD
Time Frame: At Week 16
Achieving a clinically meaningful response in improving physical shoulder symptoms in participants with moderate to severe RCT at Week 16
At Week 16
Proportion of participants who achieve an improvement (increase) of at least 50 points from BSL in the WORC total score
Time Frame: At Week 16
Improving symptoms caused by RCT and the associated impact on day-to-day functioning in participants with moderate to severe RCT at Week 16
At Week 16
Change from BSL in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity score
Time Frame: At Week 16

Improving physical function in participants with moderate to severe RCT at Week 16.

PROMIS-SF Upper Extremity measures self-reported capability of Physical Function. Participants will be 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 is scored from 5 (Without any difficulty) to 1 (Unable to do)
At Week 16
Proportion of participants who achieve an improvement (increase) of at least 40 points from BSL in the WORC PSD. Change from BSL in the WORC PSD score
Time Frame: At Week 24
Improvement of physical symptoms at Week 24
At Week 24
Secukinumab serum concentrations
Time Frame: Day 1 and Weeks 4 and 16
Pharmacokinetic parameters (measures of treatment exposure) will be evaluated in all participants, with moderate to severe RCT, treated with secukinumab 300 mg s.c.
Day 1 and Weeks 4 and 16
Safety and tolerability of secukinumab
Time Frame: Up to Week 24
Evaluate safety and tolerability of 300 mg s.c. secukinumab, in participants with moderate to severe RCT: Adverse Events and Serious Adverse Events (incidence, severity, and relationship with study drug), incidence of clinically significant changes in laboratory parameters and vital signs
Up to Week 24
Incidence of binding and neutralizing Anti-drug antibodies
Time Frame: At Day 1 and Week 16
Evaluate immunogenicity of 300 mg s.c. secukinumab, in participants with moderate to severe RCT
At Day 1 and Week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 10, 2023

Primary Completion (Estimated)

November 28, 2024

Study Completion (Estimated)

January 23, 2025

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)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAIN457O12301
  • 2021-002038-18 (EudraCT 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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