Clinical trial NCT02638896: Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
Official title: Efficacy and Safety of Etanercept Dose Reduction in Patients With Ankylosing Spondylitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Keywords: Ankylosing Spondylitis
Etanercept
Sulfasalazine
Efficacy
Safety
dose
reduction
Lead sponsor: Health and Family Planning Commission of Guangdong
Sponsor class: OTHER_GOV
First posted: 2015-12-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients 18 to 45 years of age.
2. Proven AS according to the modified New York criteria
3. 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.
4. Sexually active women of childbearing potential must agree and commit to use a medically accepted form of contraception.
5. ASDAS score ≥2.1
6. Ability to reconstitute the drug and self-inject it or have a person who can do so.
7. Capability to understand and voluntarily give written informed consent that is signed and dated, before any specific procedure of the protocol is performed.
8. Ability to store injectable test article at 2º to 8º C.

Exclusion Criteria:

1. Pregnancy/lactation.
2. Previously exposure to murine or chimeric monoclonal antibodies.
3. Receipt of any live (attenuated) vaccines within 4 weeks before screening visit.
4. History of chronic or a recent serious infection.
5. History of tuberculosis within the last 3 years.
6. History of malignancy.
7. 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.
8. Presence or history of confirmed blood dyscrasias.
9. History of any viral hepatitis within 1 year prior screening or history of any drug-induced liver injury at any time prior to screening.
10. 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.
11. Participation in trials of other investigational medications within 30 days of entering the study.
12. Clinical examination showing significant abnormalities of clinical relevance.
13. Concomitant medication with disease-modifying anti-rheumatic drugs (DMARDs) or corticosteroids.
14. Hypersensitivity to any regent of study.

Primary outcomes:
measure: Change in ASDAS from baseline to week48.
timeFrame: Baseline, Week12, Week24, Week48
Secondary outcomes:
measure: Change in ESR from baseline to week48.
timeFrame: Baseline, Week12, Week24, Week48
measure: Change in CRP from baseline to week48.
timeFrame: Baseline, Week12, Week24, Week48
measure: Change in BASFI from baseline to Week48.
timeFrame: Baseline, Week12, Week24, Week48
measure: Change in BASMI from baseline to Week48.
timeFrame: Baseline, Week12, Week24, Week48
measure: Change in SPARCC score for the sacroiliac joint from baseline to Week48.
timeFrame: Baseline, Week12, Week24, Week48
measure: Percentage of participants with serious adverse events (SAEs) or adverse events (AEs) by co-morbidity from baseline to Week48.
timeFrame: Baseline, Week12, Week24, Week48
Other outcomes:
Locations:
Study officials:
affiliation: Guangdong No.2 Provincial People's Hospital
name: Tianwang Li, MD
role: PRINCIPAL_INVESTIGATOR
References: