Study of efficacy and safety of secukinumab in participants with moderate-severe rotator cuff tendinopathy

Overview

Sponsor-declared trial summary

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 Oct 2023 → 11 Dec 2024

Decision date (initial)

2023-09-04

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: Pharmacodynamic, Pharmacogenetic, Therapy, Pharmacokinetic, Safety, Pharmacogenomic, Efficacy

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

1. 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
2. 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
3. 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
4. Evaluate the ability of secukinumab 300 mg s.c. compared to placebo, to improve physical symptoms at Week 24
5. Evaluate the pharmacokinetics (PK) of secukinumab 300 mg s.c., in the population of participants with moderate to severe RCT
6. 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

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

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 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 6

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 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline (BSL) in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) score at Week 16

Secondary endpoints 6

1. Proportion of participants who achieve an improvement (increase) of at least 40 points from BSL in WORC PSD at Week 16
2. Proportion of participants receiving AIN457 compared to placebo who achieve an increase of 50 points in WORC Total score at Week 16
3. Change from BSL in Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity score at Week 16
4. 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
5. Secukinumab serum concentrations on Day 1 and Weeks 4 and 16
6. 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

Placebo 1

Auxiliary 3

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 25

Locations

6 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

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

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications