Study Description
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.
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).
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.
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.
Rational for placebo arm
The placebo effect in interventional trials in the treatment of RCT is considerable; hence, a placebo control is warranted.
Interventions
Placebo
Secukinumab
Eligibility Criteria
Inclusion Criteria:
Unilateral rotator cuff tendinopathy with ≥ 6 weeks to ≤ 6 months symptom duration at BSL.
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.
Total WORC percentage score ≤ 40 at the Screening and Baseline visits.
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.
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.
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).
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:
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.
Rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies positive at Screening.
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.
Lack of compliance with adhering to NSAID (unless intolerant or contraindicated) and physiotherapy regimen during run-in period.
Positive painful arc test result in contralateral shoulder
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 Location
Novartis Investigative Site
Recruiting
Buenos Aires,C1114AAP,Argentina
Novartis Investigative Site
Recruiting
Tucuman,4000,Argentina
Novartis Investigative Site
Recruiting
Ciudad Autonoma de Bs As,Buenos Aires,C1055AAF,Argentina
Novartis Investigative Site
Recruiting
Sofia,1336,Bulgaria
Novartis Investigative Site
Recruiting
Sofia,1632,Bulgaria
Novartis Investigative Site
Recruiting
Sherbrooke,Quebec,J1L 0H8,Canada
Novartis Investigative Site
Recruiting
Quebec,G1V 3M7,Canada
Novartis Investigative Site
Recruiting
Santiago,7500571,Chile
Novartis Investigative Site
Recruiting
Santiago,RM,7500588,Chile
Novartis Investigative Site
Recruiting
Vitacura,Santiago,7640881,Chile
Novartis Investigative Site
Recruiting
Praha,Czech Republic,19000,Czech Republic
Novartis Investigative Site
Recruiting
Kolin,280 02,Czech Republic
Novartis Investigative Site
Recruiting
Pardubice,53002,Czech Republic
Novartis Investigative Site
Recruiting
Brno,Czech Republic,66250,Czech Republic
Novartis Investigative Site
Recruiting
Vejle,7100,Denmark
Novartis Investigative Site
Recruiting
Nantes Cedex 1,44093,France
Novartis Investigative Site
Recruiting
Orleans,Cedex 2,45067,France
Novartis Investigative Site
Recruiting
St-Priest-en-Jarez,42270,France
Novartis Investigative Site
Recruiting
Dijon,21034,France
Novartis Investigative Site
Recruiting
Le Mans,72037,France
Novartis Investigative Site
Recruiting
Limoges,Haute Vienne,87000,France
Novartis Investigative Site
Recruiting
Kota Kinabalu,Sabah,88300,Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur,59100,Malaysia
Novartis Investigative Site
Recruiting
Selangor Darul Ehsan,68100,Malaysia
Novartis Investigative Site
Recruiting
Ponte de Lima,4990 041,Portugal
Novartis Investigative Site
Recruiting
Lisboa,1050-034,Portugal
Novartis Investigative Site
Recruiting
Bratislava,831 03,Slovakia
Novartis Investigative Site
Recruiting
Dolny Kubin,026 01,Slovakia
Novartis Investigative Site
Recruiting
Piestany,92101,Slovakia
Novartis Investigative Site
Recruiting
Bratislava,SK-82606,Slovakia
Novartis Investigative Site
Recruiting
Izmir,35040,Turkey
Novartis Investigative Site
Recruiting
Bursa,Gorukle,16059,Turkey
Novartis Investigative Site
Recruiting
Ankara,06100,Turkey
Novartis Investigative Site
Recruiting
Ankara,06620,Turkey
Novartis Investigative Site
Recruiting
Istanbul,TUR,34098,Turkey
Novartis Investigative Site
Recruiting
London,SW17 0QT,United Kingdom
Medical Univ of South Carolina .
Recruiting
Charleston,Bobby Reis (843-792-1414) email: [email protected] -- Josef Eichinger,29425 - South Carolina,United States
CoastalOrthoandSportsMedofSWFlorida .
Recruiting
Bradenton,Caitlin Towsley (941-792-1404) email: [email protected] -- Avinash Kumar,34209 - Florida,United States
Precision Clinical Research LLC
Recruiting
Sunrise,Nara Neiva email: [email protected] -- Richard Linn,33351 - Florida,United States
Affinity Health Corp
Recruiting
Oak Brook,Bilhana Toshanova (630-491-1901) email: [email protected] -- Manohar Jethani,60523 - Illinois,United States
Millennium Clinical Trials
Recruiting
Simi Valley,Jasmine Medina email: [email protected] -- Elvira Lindwall,93065 - California,United States
Virginia Ispine Physicians PC
Recruiting
Richmond,Devon Withers email: [email protected] -- Michael Depalma,23238 - Virginia,United States
Elite Clinical Studies .
Recruiting
Phoenix,Cynthia Pena (602-788-3437) email: [email protected] -- Joseph L Lillo,85018 - Arizona,United States
Purushotham Akther and Roshan Kotha MD Inc
Recruiting
La Mesa,Eva Duran (619-229-1995) email: [email protected] -- Roshan Kotha,91942 - California,United States
Altoona Center for Clin Res .
Recruiting
Duncansville,Mary Beyer email: [email protected] -- Alan J Kivitz,16635 - Pennsylvania,United States
West Clinical Research
Recruiting
Morehead City,Fuchsia Carraway (252-808-3100) email: [email protected] -- Jeffrey K Moore,28557 - North Carolina,United States
Fiel Family Sports Medicine
Recruiting
Tempe,Kathleen May (480-831-6328) email: [email protected] -- Thomas Fiel,85283 - Arizona,United States
Sundance Clinical Research LLC
Recruiting
Saint Louis,Agatha Kinuthia email: [email protected] -- Larkin T Wadsworth,63141 - Missouri,United States
Antria Inc .
Recruiting
Indiana,(724-349-0520) -- David Bizousky,15701 - Pennsylvania,United States
West Tennessee Research Institute
Recruiting
Jackson,Sherry Wiggins (731-664-7824) email: [email protected] -- Jacob A. Aelion,38305 - Tennessee,United States
Healthy Life Research .
Recruiting
Miami,(305-222-0155) -- Eduardo Gonzalez-Hernandez,33184 - Florida,United States
TriWest Reserach Associates .
Recruiting
El Cajon,John Names (619-334-4735) email: [email protected] -- Arthur Mabaquiao,92020 - California,United States
Arizona Research .
Recruiting
Phoenix,Cesar Rodarte email: [email protected] -- Louise Anne Taber,85053 - Arizona,United States
Inspire Santa Fe Medical Group Rheumatology
Recruiting
Santa Fe,Lisa Kaufman email: [email protected] -- Hillary Norton,87505 - New Mexico,United States
Tucson Orthopedic Institute PC
Recruiting
Tucson,Melissa Campos (520-784-6200) email: [email protected] -- Nebojsa Skrepnik,85712 - Arizona,United States
Chicago Clinical Research Inst
Recruiting
Chicago,Saad Hussaini Syed (+1 312 791 3241) email: [email protected] -- Dennis Levinson,60607 - Illinois,United States
Integral Rheumatology and Immunology Specialists IRIS
Recruiting
Plantation,Ana Santana (954-476-2338) email: [email protected] -- Guillermo Valenzuela,33324 - Florida,United States
Universal Axon Clinical Research
Recruiting
Doral,(305-898-7888) -- Luis Martinez,33166 - Florida,United States
Coastal Carolina Research Center .
Recruiting
Mount Pleasant,Lechey Dawson email: [email protected] -- Shailesh Patel,29464 - South Carolina,United States
Worldwide Contacts
If the location of your choosing does not feature any contact detail, please reach out using the information below.