Back to resultsDose Reduction of Etanercept in Patients With Ankylosing Spondylitis
Primary Purpose
Ankylosing Spondylitis
Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
etanercept (Half-Dose)
etanercept (Full-Dose)
Sulfasalazine
Celecoxib
Sponsored by
About this trial
This is an interventional treatment trial for Ankylosing Spondylitis focused on measuring Ankylosing Spondylitis, Etanercept, Sulfasalazine, Efficacy, Safety, dose, reduction
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Other
Arm Label
Dose reduction arm
Dose maintenance arm
Etanercept discontinuation arm
Arm Description
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.
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.
AS patients who achieved remission will take sulfasalazine (2g/d) till week24. Celecoxib will be the background therapy.
Outcomes
Primary Outcome Measures
Change in ASDAS from baseline to 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)).
Secondary Outcome Measures
Change in ESR from baseline to week48.
ESR is a laboratory test that provides a non-specific measure of inflammation. This test assesses the rate at which red blood cells fall in a test tube and is measured in mm/h. Normal range is 0 to 30 mm/h. A higher rate is consistent with inflammation.
Change in CRP from baseline to week48.
CRP is a marker of inflammation and measured in mg/L. A higher level is consistent with inflammation.
Change in BASFI from baseline to Week48.
BASFI is a validated self assessment tool that determines the degree of functional limitation in AS patients. Participants answered 10 questions, consisting of 8 specific questions regarding function in AS patients and 2 questions reflecting the participant's ability to cope with everyday life. Each question was answered on a 0-10 scale (0 being no problem and 10 being the worst problem), the sum of which (divided by 10) resulted in the BASFI score (0-10).
Change in BASMI from baseline to Week48.
BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10.
Change in SPARCC score for the sacroiliac joint from baseline to Week48.
SPARCC score for the sacroiliac joint was based on 6 consecutive coronal slices from posterior to anterior. Each joint was divided into 4 quadrants. Each quadrant was assigned a score of 0 = no lesion/1 = increased signal. For each slice, the score is increased by 1 for each joint that exhibits an intense signal in any quadrant. Also, for each slice, an additional score of 1 will be given for each joint that includes a lesion demonstrating continuous increased signal of a depth ≥1 cm from the articular surface. The maximum possible score is 72.
Percentage of participants with serious adverse events (SAEs) or adverse events (AEs) by co-morbidity from baseline to Week48.
Any untoward medical occurrence in a participant who received study regents was considered an AE, without regard to possibility of relationship. An AE resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be a SAE: death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02638896
Brief Title
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
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Unknown status
Study Start Date
January 2016 (undefined)
Primary Completion Date
February 2017 (Anticipated)
Study Completion Date
April 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zhixiang Huang
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis
Keywords
Ankylosing Spondylitis, Etanercept, Sulfasalazine, Efficacy, Safety, dose, reduction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose reduction arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose maintenance arm
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Etanercept discontinuation arm
Arm Type
Other
Arm Description
AS patients who achieved remission will take sulfasalazine (2g/d) till week24. Celecoxib will be the background therapy.
Intervention Type
Drug
Intervention Name(s)
etanercept (Half-Dose)
Other Intervention Name(s)
Enbrel
Intervention Description
AS patients who satisfied the criteria for disease remission (ASDAS<1.3) will be randomized to one of the three treatment arms. In the dose reduction arm, patients will receive etanercept 50 mg subcutaneous injections every other weeks .
Intervention Type
Drug
Intervention Name(s)
etanercept (Full-Dose)
Other Intervention Name(s)
Enbrel
Intervention Description
AS patients who satisfied the criteria for disease remission (ASDAS<1.3) will be randomized to one of the three treatment arms. In the dose maintenance arm, patients will receive etanercept 50 mg subcutaneous injections every weeks.
Intervention Type
Drug
Intervention Name(s)
Sulfasalazine
Other Intervention Name(s)
Sulazine
Intervention Description
AS patients who satisfied the criteria for disease remission (ASDAS<1.3) will take sulfasalazine (2g/d) from week12 to week48.
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Description
Celecoxib (0.4g/d) will be the background therapy.
Primary Outcome Measure Information:
Title
Change in ASDAS from baseline to week48.
Description
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)).
Time Frame
Baseline, Week12, Week24, Week48
Secondary Outcome Measure Information:
Title
Change in ESR from baseline to week48.
Description
ESR is a laboratory test that provides a non-specific measure of inflammation. This test assesses the rate at which red blood cells fall in a test tube and is measured in mm/h. Normal range is 0 to 30 mm/h. A higher rate is consistent with inflammation.
Time Frame
Baseline, Week12, Week24, Week48
Title
Change in CRP from baseline to week48.
Description
CRP is a marker of inflammation and measured in mg/L. A higher level is consistent with inflammation.
Time Frame
Baseline, Week12, Week24, Week48
Title
Change in BASFI from baseline to Week48.
Description
BASFI is a validated self assessment tool that determines the degree of functional limitation in AS patients. Participants answered 10 questions, consisting of 8 specific questions regarding function in AS patients and 2 questions reflecting the participant's ability to cope with everyday life. Each question was answered on a 0-10 scale (0 being no problem and 10 being the worst problem), the sum of which (divided by 10) resulted in the BASFI score (0-10).
Time Frame
Baseline, Week12, Week24, Week48
Title
Change in BASMI from baseline to Week48.
Description
BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10.
Time Frame
Baseline, Week12, Week24, Week48
Title
Change in SPARCC score for the sacroiliac joint from baseline to Week48.
Description
SPARCC score for the sacroiliac joint was based on 6 consecutive coronal slices from posterior to anterior. Each joint was divided into 4 quadrants. Each quadrant was assigned a score of 0 = no lesion/1 = increased signal. For each slice, the score is increased by 1 for each joint that exhibits an intense signal in any quadrant. Also, for each slice, an additional score of 1 will be given for each joint that includes a lesion demonstrating continuous increased signal of a depth ≥1 cm from the articular surface. The maximum possible score is 72.
Time Frame
Baseline, Week12, Week24, Week48
Title
Percentage of participants with serious adverse events (SAEs) or adverse events (AEs) by co-morbidity from baseline to Week48.
Description
Any untoward medical occurrence in a participant who received study regents was considered an AE, without regard to possibility of relationship. An AE resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be a SAE: death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame
Baseline, Week12, Week24, Week48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhixiang Huang, MD
Phone
86-20-89169091
Email
huang-zhix@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Weiming Deng, MD
Phone
86-20-89169090
Email
15088097855@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tianwang Li, MD
Organizational Affiliation
Guangdong No.2 Provincial People's Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
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