Phase II Clinical Study of Thalidomide in the Treatment of Ankylosing Spondylitis

Study Overview
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Brief Summary
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Evaluate the efficacy and safety of taking thalidomide tablets once daily in the treatment of active ankylosing spondylitis. To explore dose-effect relationships of taking thalidomide tablets once daily in the treatment of active ankylosing spondylitis, as well as selecting the appropriate dose for the further larger scale clinical trials.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase II Clinical Study of Thalidomide in the Treatment of Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Thalidomide 150mg
* Drug: Thalidomide 100mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Active Ankylosing Spondylitis, Age 18-65, both outpatient or inpatient, both gender; (2) AS patients after traditional therapy (Using NSAIDs in a stable dose for 1 month, using oral corticosteroids, using NSAIDs for 3 months) still in active stage; (3) Pregnancy test must be negative in the female subjects of childbearing age or wife of the male subjects; (4)Female subjects with fertility during the trial (of 32 weeks) agreed to take a double medically accepted and reliable contraceptive measures, which includes a drug and a non-drug contraceptive measures; if the spouses of male subjects have fertility, agreed to use latex condoms for contraception; (5)Willing to have the treatment according to the plan as well as do the follow-up exam on time; (6)Understand and voluntarily signed informed consent. Exclusion Criteria: (1) Suffering from or have suffered from rheumatoid arthritis, disc prolapse, septic arthritis, diffuse idiopathic skeletal hyperostosis syndrome, iliac dense osteitis, psoriatic arthritis, bowel disease arthritis, Reiter syndrome; (2) Severe AS, spine completely stiff (X-ray class IV) or the disease has been shown to have a shorter survival period; (3) Previously had total hip arthroplasty surgical treatment or appropriate to have the surgery; (4) Previously received anti-TNF therapy; (5) Used leflunomide within 3 months before screening; (6) Severe or persistent infection requires antimicrobial therapy; (7) Hepatitis B surface antigen or hepatitis C antibody test positive; (8) HIV positive or have acquired immunodeficiency syndrome (AIDS) history; (9) Malignancy, lymphoproliferative disease history; (10) Severe diabetes; (11) Resting hypotension (BP<90/50 mmHg) or hypertension (BP>170/100 mmHg), and orthostatic hypotension and clinically significant ECG abnormalities; (12) Over the past six months had a stroke, heart attack or other serious cardiovascular disease (including heart failure, unstable angina or life-threatening arrhythmias and coronary artery bypass graft surgery); (13) WBC or neutrophils below the lower limit of normal; (14) Liver dysfunction, AST or ALT l> 2 times the upper limit of normal; (15) Renal dysfunction, Cr>2 times the upper limit of normal; (16) Female subjects or spouses of male subjects have positive pregnancy test or be in the sickling period or intend to fertility or unwilling to take effective contraception; (17) With clinical symptoms of serious drug abuse or alcohol abuse or mental illness history; (18) Participated in any clinical trials of drugs within 3 months before screening; (19) Workers engaged in dangerous (eg drivers, machine operator, high-altitude operations, etc.); (20) A history of deep venous thrombosis or pulmonary embolism; (21) Be allergic to Test drug ingredients (including excipients); (22) Other reasons for not be enrolled.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thalidomide 150mg<br>Thalidomide 25mg/qd.po.2weeks; 50mg/qd.po.2weeks;100mg/qd.po.2weeks; 150mg/qd.po.to the end | Drug: Thalidomide 150mg<br> <br> * Other names: Fan Ying Ting;|
| Active Comparator: Thalidomide 100mg<br>Thalidomide 25mg/qd.po.2weeks; 50mg/qd.po.2weeks; 100mg/qd.po.to the end | Drug: Thalidomide 100mg<br> <br> * Other names: Fan Ying Ting;|
| Placebo Comparator: Placebo<br>Placebo po. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) |  | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ASDAS score |  | week 12 | 
| Change of ASDAS score |  | week 24 | 
| Mean change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) |  | week 24 | 
| Mean change from baseline in Bath Ankylosing Spondylitis Function Index(BASFI) |  | week 24 | 
| Mean change from baseline in Nocturnal Pain using a Visual Analog Scale(VAS) |  | week 24 | 
| Mean change from baseline in back pain using a Visual Anolog Scale(VAS) |  | week 24 | 
| Morning stiffness |  | week 24 | 
| Number of Peripheral swollen joints |  | week 24 | 
| Number of Peripheral joint tenderness |  | week 24 | 
| Chest expansion |  | week 24 | 
| ESR |  | week 24 | 
| CRP |  | week 24 | 
| Schober test |  | week 24 | 
| Scoliosis |  | week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ankylosing spondylitis, thalidomide