Efficacy and Safety of Etanercept Dose Reduction in Patients With Ankylosing Spondylitis
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 100
- 主要终点
- Change in ASDAS from baseline to week48.
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of safety of etanercept dose reduction combined with sulfasalazine in ankylosing spondylitis (AS) patients who have achieved a significant clinical response.
详细描述
This single-centre, open-labeled randomized study will evaluate the efficacy of safety of etanercept dose reduction combined with sulfasalazine in patients who achieved a significant clinical response. AS patients who meet the inclusion criteria will take celecoxib (0.4g/d) during the whole period of study. In the first period, all patients will be given etanercept 50 mg subcutaneous injections weekly from baseline to week12. In the second period, patients who satisfied the criteria for disease remission will be randomized to one of the following three treatment arms: (1) Dose reduction arm: Patients will receive etanercept 50 mg subcutaneous injections every other weeks plus sulfasalazine (2g/d) oral administration till week24. (2) Dose maintenance arm: Etanercept remains unchange from week12 to week24. (3) Etanercept discontinuation arm: Patients will be treated with sulfasalazine (2g/d) oral administration till week24. In the third period, all patients will take sulfasalazine (2g/d) till week 48. Ankylosing spondylitis disease activity score (ASDAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI),Spondyloarthritis research consortium of Canada(SPARCC) score for the sacroiliac joint and adverse effect will be assessed in the study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18 to 45 years of age.
- •Proven AS according to the modified New York criteria
- •Negative result of a pregnancy test in serum in screening visit and in urine in baseline visit, done in all women, except those surgically sterilized and those who have at least one year of menopause.
- •Sexually active women of childbearing potential must agree and commit to use a medically accepted form of contraception.
- •ASDAS score ≥2.1
- •Ability to reconstitute the drug and self-inject it or have a person who can do so.
- •Capability to understand and voluntarily give written informed consent that is signed and dated, before any specific procedure of the protocol is performed.
- •Ability to store injectable test article at 2º to 8º C.
排除标准
- •Pregnancy/lactation.
- •Previously exposure to murine or chimeric monoclonal antibodies.
- •Receipt of any live (attenuated) vaccines within 4 weeks before screening visit.
- •History of chronic or a recent serious infection.
- •History of tuberculosis within the last 3 years.
- •History of malignancy.
- •Significant concurrent medical diseases including uncompensated congestive heart failure, myocardial infarction within 12 months, stable or unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, history of human immunodeficiency virus (HIV) infection, central nervous system demyelinating events suggestive of multiple sclerosis.
- •Presence or history of confirmed blood dyscrasias.
- •History of any viral hepatitis within 1 year prior screening or history of any drug-induced liver injury at any time prior to screening.
- •Laboratory exclusions are: hemoglobin level < 8.5 mg/dl white blood cell count < 3.5×10e9/l, platelet count < 125 ×10e9/l, creatinine level > 175 mcmol/l, liver enzymes > 1.5 times the upper limit of normal or alkaline phosphatase > 2 times the upper limit of normal.
- •Participation in trials of other investigational medications within 30 days of entering the study.
- •Clinical examination showing significant abnormalities of clinical relevance.
- •Concomitant medication with disease-modifying anti-rheumatic drugs (DMARDs) or corticosteroids.
- •Hypersensitivity to any regent of study.
研究组 & 干预措施
Dose reduction arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every other weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: etanercept (Half-Dose) (Drug)
Dose reduction arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every other weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: Sulfasalazine (Drug)
Dose reduction arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every other weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: Celecoxib (Drug)
Dose maintenance arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: etanercept (Full-Dose) (Drug)
Dose maintenance arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: Sulfasalazine (Drug)
Dose maintenance arm
AS patients who achieved remission will receive etanercept 50 mg subcutaneous injections every weeks plus sulfasalazine (2g/d) oral administration till week24. Celecoxib will be the background therapy.
干预措施: Celecoxib (Drug)
Etanercept discontinuation arm
AS patients who achieved remission will take sulfasalazine (2g/d) till week24. Celecoxib will be the background therapy.
干预措施: Sulfasalazine (Drug)
Etanercept discontinuation arm
AS patients who achieved remission will take sulfasalazine (2g/d) till week24. Celecoxib will be the background therapy.
干预措施: Celecoxib (Drug)
结局指标
主要结局
Change in ASDAS from baseline to week48.
时间窗: Baseline, Week12, Week24, Week48
ASDAS includes CRP (mg/L); Apart from the value of CRP, the four additional self-reported items (rated on 0-10 numerical rating scale \[NRS\]) included in this index are back pain, duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity. The ASDAS scores are calculated as follows: ASDAS= (0.121×total back pain) + (0.110×subject global) + (0.073×peripheral pain/swelling) + (0.058×duration of morning stiffness) + (0.579×Ln(CRP+1)).
次要结局
- Change in ESR from baseline to week48.(Baseline, Week12, Week24, Week48)
- Change in CRP from baseline to week48.(Baseline, Week12, Week24, Week48)
- Change in BASFI from baseline to Week48.(Baseline, Week12, Week24, Week48)
- Change in BASMI from baseline to Week48.(Baseline, Week12, Week24, Week48)
- Change in SPARCC score for the sacroiliac joint from baseline to Week48.(Baseline, Week12, Week24, Week48)
- Percentage of participants with serious adverse events (SAEs) or adverse events (AEs) by co-morbidity from baseline to Week48.(Baseline, Week12, Week24, Week48)
研究者
Zhixiang Huang
MD
Health and Family Planning Commission of Guangdong