Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
234
Countries
6
Sites
23
Moderate to severe rotator cuff tendinopathy
Demonstrate that the efficacy of secukinumab 300 mg s.c., is superior to placebo, in improving physical shoulder symptoms in participants with moderate to severe RCT at Week 16
Key facts
- Sponsor
- Novartis Pharma AG
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 16 Nov 2023 → 13 Dec 2024
- Decision date (initial)
- 2023-08-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Novartis Pharma AG
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacodynamic, Therapy, Safety, Pharmacogenetic, Pharmacogenomic, Pharmacokinetic
Demonstrate that the efficacy of secukinumab 300 mg s.c., is superior to placebo, in improving physical shoulder symptoms in participants with moderate to severe RCT at Week 16
Secondary objectives 6
- Demonstrate that the efficacy of secukinumab 300 mg s.c. is superior to placebo, in achieving a clinically meaningful response in improving physical shoulder symptoms in participants with moderate to severe RCT at Week 16
- Demonstrate that the efficacy of secukinumab 300 mg s.c. is superior to placebo, in improving symptoms caused by RCT and the associated impact on day-to-day functioning in participants with moderate to severe RCT at Week 16
- Demonstrate that the efficacy of secukinumab 300 mg s.c. is superior to placebo, in improving physical function in participants with moderate to severe RCT at Week 16
- Evaluate the ability of secukinumab 300 mg s.c. compared to placebo, to improve physical symptoms at Week 24
- Evaluate the pharmacokinetics (PK) of secukinumab 300 mg s.c., in the population of participants with moderate to severe RCT
- Evaluate safety, immunogenicity and tolerability of 300 mg s.c. secukinumab, in participants with moderate to severe RCT
Conditions and MedDRA coding
Moderate to severe rotator cuff tendinopathy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10028395 | Musculoskeletal and connective tissue disorders | 17 |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency, Food And Drug Administration
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- 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 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 6
- 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 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)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change from Baseline (BSL) in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) score at Week 16
Secondary endpoints 6
- Proportion of participants who achieve an improvement (increase) of at least 40 points from BSL in WORC PSD at Week 16
- Proportion of participants receiving AIN457 compared to placebo who achieve an increase of 50 points in WORC Total score at Week 16
- Change from BSL in Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity score at Week 16
- Proportion of participants who achieve an improvement (increase) of at least 40 points from BSL in WORC PSD at Week 24 Change from BSL in WORC PSD at Week 24
- Secukinumab serum concentrations on Day 1 and Weeks 4 and 16
- Safety and tolerability demonstrated by assessing: AEs and SAEs (incidence, severity, and relationship with study drug) Incidence of clinically significant changes in laboratory parameters and vital signs Incidence of binding and neutralizing anti-drug antibodies (ADAs) at Day 1 and Week 16
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB33242 · Substance
- Active substance
- Secukinumab
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 2100 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Different secondary packaging site used in comparison to authorized product.
Placebo 1
Placebo to AIN457 150mg/1mL Solution for injection in pre-filled syringe
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 3
-
N02B · Product
- Pharmaceutical form
- -
- Route of administration
- ORAL USE
- Max daily dose
- 3900 mg milligram(s)
- Max total dose
- 655.2 g gram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- N02B — OTHER ANALGESICS AND ANTIPYRETICS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
N02A · Product
- Pharmaceutical form
- -
- Route of administration
- ORAL USE
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 67.2 g gram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- N02A — OPIOIDS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
M01A · Product
- Pharmaceutical form
- -
- Route of administration
- ORAL USE
- Max daily dose
- 3200 mg milligram(s)
- Max total dose
- 896 g gram(s)
- Max treatment duration
- 40 Week(s)
- Authorisation status
- Authorised
- ATC code
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Novartis Pharma AG
- Sponsor organisation
- Novartis Pharma AG
- Address
- Lichtstrasse 35
- City
- Basel Town
- Postcode
- 4056
- Country
- Switzerland
Scientific contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Third parties 18
| Organisation | City, country | Duties |
|---|---|---|
| Iqvia Rds Inc. ORG-100043858
|
Durham, United States | Code 14, Interactive response technologies (IRT) |
| Iqvia Limited ORG-100008655
|
Reading, United Kingdom | Other |
| Specific Pharma A/S ORG-100015041
|
Copenhagen Sv, Denmark | Code 14, Other |
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Laboratory analysis |
| S & D Pharma Logistics BG EOOD ORG-100017521
|
Sofia, Bulgaria | Code 14 |
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Laboratory analysis |
| Epl Pathology Archives LLC ORG-100042096
|
Sterling, United States | Other |
| Q Squared Solutions LLC ORG-100043195
|
Durham, United States | Laboratory analysis |
| Kayentis ORG-100037894
|
Meylan, France | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Epl Pathology Archives LLC ORG-100042096
|
Sterling, United States | Other |
| RWS Life Sciences Inc. ORG-100042348
|
East Hartford, United States | Other |
| SGS France ORG-100011566
|
St Benoit, France | Laboratory analysis |
| Biotel Research LLC ORG-100039864
|
Rochester, United States | Other |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Code 12 |
| DHL Supply Chain Operations GmbH ORG-100040715
|
Florstadt, Germany | Other |
| Q Squared Solutions LLC ORG-100043195
|
Durham, United States | Laboratory analysis |
| World Courier Bulgaria Ltd ORL-000001024
|
Sofia, Bulgaria | Other |
Locations
6 EU/EEA countries · 23 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Bulgaria | Ended | 12 | 2 |
| Czechia | Ended | 15 | 4 |
| Denmark | Ended | 9 | 1 |
| France | Ended | 23 | 8 |
| Portugal | Ended | 5 | 2 |
| Slovakia | Ended | 17 | 6 |
| Rest of world
Malaysia, Chile, Canada, Turkey, Argentina, United States, United Kingdom
|
— | 153 | — |
Investigational sites
Mbal Lyulin EAD
2001 Department of Orthopedics and Traumatology, Lyulin 6, Ulitsa D-R Petir Dertliev 81, Sofiya
MBAT-Doverie AD
2002 Department of Orthopedics and Traumatology, Friedrich Gruenanger 2, 1632, Sofia
Ortopedicko-traumatologicka privatni ambulance MUDr. Jan Balik s.r.o.
#2501, Jaselska 265 Kolin III, 280 02, Kolin
H Praxe s.r.o.
#2505, Masarykovo Namesti 2667, Zelene Predmesti, Pardubice I
Mabi s.r.o.
#2503, Lovosicka 440/40, 190 00, Prague 9
Research Institute For Special Surgery And Trauma
#2502: Orthopaedics, Ponávka 6, 60200, Brno
Groupe Hospitalier Diaconesses Croix Saint Simon
2107 Rheumatology, 125 Rue D Avron, 75020, Paris
Centre Hospitalier Le Mans
2108 Rheumatology, 194 Avenue Rubillard, 72037, Le Mans Cedex 9
Hospital Hotel Dieu
2101 Rheumatology, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Universitaire De Saint Etienne
2104 Rheumatology, Avenue Albert Raimond, 42270, Saint-Priest-En-Jarez
Centre Hospitalier Regional Universitaire De Tours
2102 Rheumatology, Avenue De La Republique, 37170, Chambray Les Tours
Centre Hospitalier Universitaire De Limoges
2106 Rheumatology, 2 Avenue Martin Luther King, 87000, Limoges
Centre Hospitalier Regional D'orleans
2103 Rheumatology (IPROS), 14 Avenue De L Hopital, Cs 86709, Orleans Cedex 2
Centre Hospitalier Universitaire De Dijon
2105 Rheumatology, 14 Rue Paul Gaffarel, 21000, Dijon
Instituto Portugues De Reumatologia
#2201, Rua Da Beneficencia Nr 7, 1050-034, Lisbon
Unidade Local De Saude Do Alto Minho E.P.E.
#2202: Serviço de Reumatologia, Largo Conde De Bertiandos, 4990-041, Ponte De Lima
Artromac N.O.
2301: Reumatologická ambulancia, Toryska 275/1, Zapad, Kosice
Narodny Ustav Reumatickych Chorob
2305: Ortopedická ambulancia, Nabrezie Ivana Krasku 4782/4, 921 01, Piestany
Orthos Paidion s.r.o.
2306: Ortopedická ambulancia, Vajnorska 40, 831 04, Bratislava
Algmed s.r.o.
2309: Algeziologická ambulancia, Rastislavova 45, Juh, Kosice - Juh
University Hospital Bratislava
2302:I. ortopedicko-traumatologická klinika LF UK, SZU a UNB, Ruzinovska 6, Ruzinov, Bratislava
Dolnooravska Nemocnica S Poliklinikou Mudr. L. N. Jegeho
2308:Ortopedická príjmová ambulancia, Nemocnicna 1944/10, 026 01, Dolny Kubin
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Bulgaria | 2023-12-21 | 2024-10-07 | 2023-12-21 | 2024-05-07 | |
| Czechia | 2023-11-22 | 2024-10-15 | 2023-11-22 | 2024-05-07 | |
| Denmark | 2023-11-16 | 2023-11-16 | 2024-02-15 | ||
| France | 2023-11-20 | 2023-11-20 | 2024-05-07 | ||
| Portugal | 2023-11-20 | 2024-07-01 | 2023-11-20 | 2024-05-07 | |
| Slovakia | 2024-01-22 | 2024-01-22 | 2024-05-07 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 6 · Art. 38 CTR
Temporary halt TH-24343
- Halt date
- 2024-05-07
- Member states concerned
- Bulgaria
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-24340
- Halt date
- 2024-05-07
- Member states concerned
- Denmark
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-24341
- Halt date
- 2024-05-07
- Member states concerned
- Czechia
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-24337
- Halt date
- 2024-05-07
- Member states concerned
- France
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-24335
- Halt date
- 2024-05-07
- Member states concerned
- Portugal
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-24333
- Halt date
- 2024-05-07
- Member states concerned
- Slovakia
- Publication date
- 2024-05-08
- Reason
- Feasibility (recruitment issues etc.)
- Explanation
- Significant challenges in trial recruitment due to a high screen failure rate in the CAIN457O12301 study, as well as in the second ongoing Phase-3 study CAIN457O12302, resulted in the decision to terminate the trials and the rotator cuff tendinopathy development program overall. There were no safety findings that contributed to this decision.
- Follow-up measures
- Study Investigators have been asked to permanently halt recruitment of the study and take the following actions:
• Inform participants about the plans to terminate the study and development of secukinumab for rotator cuff tendinopathy
• For patients who have already been randomized into the study: Inform participants of the possibility for them to continue the study as per protocol through Week 24.
• For patients currently in screening: Inform participants that they may continue in the study (on condition that all Visit 1 procedures are completed by 31-May-2024) and, if eligible, may proceed to randomization.
• No new patients should grant consent from (and including) 7th May 2024 - Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| CAIN457O12301 summary of results SUM-102666
|
2025-10-17T17:07:47 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| CAIN457O12301-Patient Summary-English-US | 2025-11-24T17:28:24 | Submitted | Laypersons Summary of Results |
| CAIN457O12301- Patient Summary - Bulgarian | 2026-04-10T15:34:31 | Submitted | Laypersons Summary of Results |
| CAIN457O12301 - Patient Summary - Czech | 2026-04-10T15:34:25 | Submitted | Laypersons Summary of Results |
| CAIN457O12301 - Patient Summary - French-Canada | 2026-04-10T15:34:20 | Submitted | Laypersons Summary of Results |
| CAIN457O12301 - Patient Summary - Portuguese | 2026-04-10T15:34:14 | Submitted | Laypersons Summary of Results |
| CAIN457O12301 - Patient Summary - Spanish-Argentina | 2026-04-10T15:34:09 | Submitted | Laypersons Summary of Results |
| CAIN457O12301 - Patient Summary - Spanish-US | 2026-04-10T15:34:02 | Submitted | Laypersons Summary of Results |
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_Bulgarian | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_Czech | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_English-US | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_French-Canada | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_Portuguese | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_Spanish-Argentina | 1 |
| Laypersons summary of results (for publication) | CAIN457O12301_PatientSummary_Spanish-US | 1 |
| Summary of results (for publication) | CAIN457O12301 EU | 2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-04-28 | Denmark | Acceptable with conditions 2023-08-21
|
2023-08-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-02-16 | Denmark | Acceptable 2024-04-15
|
2024-04-15 |