A Phase III, Randomized, Double-blind, Placebo Controlled Multi-center Study of Subcutaneous Secukinumab (150 mg and 300 mg) in Prefilled Syringe to Demonstrate Efficacy (Including Inhibition of Structural Damage), Safety, and Tolerability up to 2 Years in Subjects With Active Psoriatic Arthritis (FUTURE 5)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 997
- 试验地点
- 172
- 主要终点
- Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16
研究概览
简要总结
The purpose of this study was to demonstrate efficacy including effect on inhibition of progression of structural damage, safety and tolerability up to 2 years with primary focus at Week 16 (week 24 for structural damage), to support the use of secukinumab pre-filled syringe (PFS) by subcutaneous (s.c.) self-administration with or without loading regimen in subjects with active Psoriatic Arthritis (PsA) despite current or previous NSAID, DMARD therapy and/or previous anti-TNFα therapy. Long term efficacy up to 2 years was based on signs and symptoms of joint/bone structure preservation (X-ray) and improvement in physical function measured by Health Assessment Questionnaire - Disability Index (HAQ-DI©), as well as skin and nail improvement for psoriasis signs.
详细描述
This multicenter study uses a randomized, double-blind, placebo-controlled, parallel-group design. A screening period (SCR) running up to 10 weeks before randomization will be used to assess subject eligibility followed by 104 weeks of treatment.
At BSL approximately 990 subjects whose eligibility is confirmed will be randomized to one of four treatment groups in 2:2:2:3 ratio:
- Group 1 - secukinumab 150 mg s.c. without loading regimen
- Group 2 - secukinumab 150 mg s.c. with loading dose regimen
- Group 3 - secukinumab 300 mg s.c. with loading dose regimen
- Group 4 - Placebo s.c. NOTE: Group 4 is split into 2 treatment arms, detailed description below. At randomization, subjects will be stratified on the basis of previous anti-TNF therapy as TNFα inhibitor naïve (TNF-naïve) or TNFα inhibitor inadequate responders (TNF-IR).
At each study treatment visit, one (for secukinumab 150 mg) or two (for secukinumab 300 mg) s.c. injections in the form of PFS will be administered, since secukinumab is available in 1.0 mL (150 mg) PFSs. Placebo to secukinumab is also available in 1.0 mL to match the active drug.
At Week 16, subjects who have been randomized to secukinumab groups at BSL (Groups 1-3) will be classified as either responders (≥20% improvement from BSL in both tender joint count (TJC) and swollen joint counts (SJC)) or non-responders (<20% improvement from BSL TJC or SJC), however they will continue on the same treatment irrespective of their response status.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at BSL ≥3 tender joints out of 78 and ≥3 swollen joints out of 76 (dactylitis of a digit counts as one joint each).
- •Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening.
- •Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a documented history of plaque psoriasis.
- •Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs.-Subjects who are regularly taking NSAIDs as part of their PsA therapy are required to be on a stable dose for at least 2 weeks before study randomization and should remain on a stable dose up to Week
- •Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week
- •Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week
- •Subjects on MTX must be on folic acid supplementation at randomization.
- •Subjects who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed.
- •Subjects who have been on a TNFα inhibitor must have experienced an inadequate response to previous or current treatment with a TNFα inhibitor given at an approved dose for at least 3 months or have stopped treatment due to safety/tolerability problems after at least one administration of a TNFα inhibitor.
- •Subjects who have previously been treated with TNFα inhibitors (investigational or approved) will be allowed entry into study after appropriate wash-out period prior to randomization
排除标准
- •Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process. - Subjects taking high potency opioid analgesics.
- •Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. - Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization.
- •Any intramuscular or intravenous or intra-articular corticosteroid treatment within 4 weeks before randomization.
- •Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα (investigational or approved).
- •Previous treatment with any cell-depleting therapies including but not limited to anti- CD20, investigational agents
- •Other protocol-defined exclusion criteria do apply
结局指标
主要结局
Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16
时间窗: Week 16
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement based on tender 78-joint count, swollen 76-joint count and at least 20% improvement in 3 of the following 5 measures: participant's assessment of PsA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, participant's self-assessed disability (Health Assessment Questionnaire Disability Index (HAQ-DI) score), and acute phase reactant evaluated as (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR)).
次要结局
- Count and Percentage of Patients Achieving an ACR50 Response(16 weeks)
- Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP))(16 weeks)
- Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS))(Baseline, Week 24)
- Change From Baseline in HAQ-DI© Score(16 weeks)
- Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response(16 weeks)
- Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response(Week 16)
- Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline(16 weeks)
- Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline(16 weeks)