Safety and Efficacy of Prefilled Liquid Etanercept(Yisaipu) for Active Ankylosing Spondylitis on the Basis of NSAID Therapy: A Multicenter Randomized, Double-blind, Parallel Group Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 640
- 试验地点
- 1
- 主要终点
- the proportion of patients who achieved ASAS20
研究概览
简要总结
This randomized, double-blind, phase III parallel-group non-inferiority study aimed to investigate the efficacy and safety of prefilled liquid etanercept (Yisaipu) versus lyophilized etanercept powder (Yisaipu) in active ankylosing spondylitis patients.
详细描述
The study carried out between March 6, 2014 and July 13, 2015 across multiple medical centers in China enrolled adult active ankylosing spondylitis patients aged between 18 and 65 years. Patients were randomized in a 3:1:1 ratio to receive twice weekly 25 mg prefilled liquid etanercept for totally 24 injections (group I) or once weekly 50 mg prefilled liquid etanercept for totally 48 injections (group II), or 25 mg twice weekly lyophilized etanercept powder for totally 48 injections (group III). The primary efficacy outcome was the proportion of patients who achieved ASAS20 at 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
- Triple (Participant, Care Provider, Investigator)
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
- •age 18-65，male or female
- •Sign the informed consent
- •Fulfill the 1966 AS New York criteria for axial spondyloarthritis(SpA)
- •Active disease phase of SpA, defined as BASDAI≥4 or night back pain≥4 at screening
- •Inadequate response to NSAID≥4 week
- •Application of NSAID with stable dose for no less than 2 weeks at screening
- •Stable dose of prenisone for at least four weeks at ≤10mg per day if used at screening, or stop oral use for at least 4 weeks or stop local injection at least 12 weeks
- •Stable dose of any DMARD for at least four weeks if used at screening, or stop use for at least 4 weeks
- •Stop and receiving washing out for at least 4 week if receiving Chinese traditional drug for AS, physical treatment, vaccication or IVIG
- •Stop and receiving washing out for at least 12 week if receiving other biologics or other drug trials
- •The lab exam should achieve the criteria as below
- •Hb≥85g/L, 3.5×109/L≤WBC count≤10×109/L, PLT≥ lower limit of normal range, ALT≤2 fold of upper limit of normal range, serum creatine ≤upper limit of normal range. Negative pregnacy test for female patients. And promise to carry out contraception during the trial and 6 weeks after the trial is ended
排除标准
- •Allergic condition or Allergic to IgG or any element of Yisaipu®
- •Clinical or radiographic evidence of Complete ankylosis of spine
- •Previous receiving TNF-a blockers therapy ≥3 months with poor response
- •Achieve any following tuberculosis criteria
- •History of active tubercolosis, or radiographic evidence of present or previous history of pulmonary tubercolosis
- •close contact with patients with tubercolosis, or with high risk of infection of tubercolosis such as immune suppression status
- •Strong positive of PPD skin test with diameter ≥10mm. at screen or within 3 weeks prior to screen
- •Presence of acute infection or acute onset of chronic infection at screen
- •Invasive fungal infection or conditional infection within 6 months prior to screen
- •HBS-Ag or HBC-Ab positive at screen or history of HBS/HBC infection
- •History of infection on artifitial joints
- •Organ transplantation surgery within 6 months prior to screen
- •Presence of other autoimmune diseases, including IBD, psoriasis, uveitis, SLE, multiple sclerosis, etc.
- •History of congestive heart failure
- •History of malignancies within 5 years prior to screen, excluding complete resection of squamous cell carcinoma, or basal cell carcinoma or cervical carcinoma in situ.
- •AIDS or HIV infection
- •History of lymphoma or lymphoproliferative disorders
- •Presence of serious disorder of important organs or system
- •Presence of factors which may influence the compliance
研究组 & 干预措施
group I
twice weekly 25 mg prefilled liquid etanercept
干预措施: prefilled liquid etanercept(Yisaipu) (Drug)
group II
once weekly 50 mg prefilled liquid etanercept
干预措施: prefilled liquid etanercept(Yisaipu) (Drug)
group III
25 mg twice weekly lyophilized etanercept powder
干预措施: lyophilized etanercept powder(Yisaipu) (Drug)
结局指标
主要结局
the proportion of patients who achieved ASAS20
时间窗: at week 24
Axial SpondyloArthritis international Society (ASAS) ASAS20 was defined as an improvement of at least 20% in at least three of the following four domains: 1) patient global assessment VAS, 2) nocturnal back pain and total back pain VAS, 3) Bath AS Function Index (BASFI) VAS, and 4) inflammation (mean of intensity and duration of morning stiffness components from the an improvement at least one unit relative to baseline VAS score; no worsening in the remaining fourth domain.
次要结局
- the proportion of patients who achieved ASAS40, ASAS partial remission(at weeks 12 and 24)
- the proportion of patients who achieved ASAS 5/6(at weeks 12 and 24)
- the proportion of patients who achieved the ASDAS clinically important and major improvement and inactive disease(at weeks 12 and 24)
- the proportion of patients who achieved improvement in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)(at weeks 12 and 24)
- the proportion of patients who achieved improvement in number of swollen joints and number of tender joints(at weeks 12 and 24)
- the proportion of patients who achieved improvement in BASDAI(at weeks 12 and 24)
- the proportion of patients who achieved improvement in BASFI(at weeks 12 and 24)
- the proportion of patients who achieved BASDAI50(at weeks 12 and 24)
- the proportion of patients who achieved improvement in ESR and CRP(at weeks 12 and 24)
- the proportion of patients who achieved improvement in BASMI scores(at weeks 12 and 24)
- the proportion of patients who achieved improvement in nocturnal back pain and total back pain VAS(at weeks 12 and 24)
- the proportion of patients who achieved improvement in patient global assessment and physician global assessment(at weeks 12 and 24)