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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 5
- 主要终点
- Change From Baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) Score at Week 16
研究概览
简要总结
The purpose of the present study was 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.
详细描述
This was a randomized, double-blind, placebo-controlled Phase III study, stratified by tear status (no tear/ partial tear) in participants with moderate to severe rotator cuff tendinopathy (RCT), experiencing active disease from at least 6 weeks to 6 months at baseline, and were refractory to standard of care (non-steroidal anti-inflammatory drug [NSAIDs] and course of physiotherapy) over a period of 8 weeks.
The study was terminated due to the project being discontinued in order to prioritize other key programs in the portfolio. Due to the early termination and small sample size, the analysis by tear status stratification was not performed.
The study duration was up to 32 weeks, consisting of a screening period lasting up to 8 weeks (inclusive of a mandatory 2-week run-in period), a 16-week treatment period with last dose administered at Week 12, and an 8-week safety follow-up period. The primary endpoint assessment was at Week 16, and the safety follow-up data collection was through to Week 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Investigator, site personnel, persons performing the assessments and participants remained blinded through the Week 24 final database lock. The Novartis clinical trial and submission teams remained blinded to the identity of the treatment from the time of randomization until the Week 16 database lock (for the primary endpoint analysis). The following methods were utilized for blinding: (1) Randomization data were kept strictly confidential until the time of unblinding and were not accessible by anyone else involved in the study with the following exceptions: bioanalyst; (2) the identity of the treatments was concealed by the use of study treatments that were all identical in packaging, labeling, schedule of administration, and appearance.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unilateral rotator cuff tendinopathy with ≥ 6 weeks to ≤ 6 months symptom duration at baseline.
- •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: non-steroidal anti-inflammatory drug (NSAIDs) course as per local standard practice (if not intolerant or contraindicated) and a course of physiotherapy over a period of 8 weeks.
- •Participant agreed to remain on stable NSAID dosage regimen (if not intolerant or having contraindications; NSAID dose was 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; anteroposterior (AP) length maximum 10 mm)
排除标准
- •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 were not compatible with performing an MRI) to fulfill eligibility criteria (unless centrally read MRI images acquired within 3 months of baseline could be provided and the quality of images was deemed sufficient).
研究组 & 干预措施
Secukinumab
Participants received secukinumab 300 mg at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.
干预措施: Secukinumab (Drug)
Placebo
Participants received placebo at randomization (baseline visit) and Weeks 1, 2, 3, 4, 8, and 12.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) Score at Week 16
时间窗: 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 rotator cuff tendinopathy (RCT) relating to pain, weakness, stiffness, and mechanical symptoms. The raw score was converted to a scale of 0 to 100, where 0 represents the most symptomatic score, and 100 represents no symptoms.
次要结局
- Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity Score(At Week 16)
- Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 16(At Week 16)
- Percentage of Participants Who Achieved an Improvement (Increase) of at Least 50 Points From Baseline in the WORC Total Score(At Week 16)
- Percentage of Participants Who Achieved an Improvement (Increase) of at Least 40 Points From Baseline in the WORC PSD Score at Week 24(At Week 24)
- Change From Baseline in WORC PSD Score at Week 24(At Week 24)
- Secukinumab Serum Concentrations(Day 1 and Weeks 4 and 16)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), by Maximum Severity(Up to Week 24)
- Percentage of Participants With Clinically Significant Changes in Laboratory Parameters(Up to Week 24)
- Percentage of Participants With Clinically Significant Changes in Vital Signs(Up to Week 24)
- Percentage of Participants With Binding and Neutralizing Anti-drug Antibodies(At Day 1 and Week 16)