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

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

1. Evaluate the efficacy and safety of taking thalidomide tablets once daily in the treatment of active ankylosing spondylitis.
2. 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.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: Placebo; Drug: Thalidomide 150mg; Drug: Thalidomide 100mg

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First affiliated hospital of bengbu medical college
  • Beijing
    • BeiJing, Beijing, China, 100853
      • The General Hospital of People's Liberation Army
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200052
      • Shanghai Guanghua Hospital
  • Shanxi
    • XiAn, Shanxi, China, 710032
      • Xijing Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Xinjiang
    • Wulumuqi, Xinjiang, China, 830001
      • The Xinjiang Uygur Autonomous Region people's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thalidomide 150mg; Thalidomide 25mg/qd.po.2weeks; 50mg/qd.po.2weeks;100mg/qd.po.2weeks; 150mg/qd.po.to the end	Drug: Thalidomide 150mg; Other Names: Thalomid; Fan Ying Ting
Active Comparator: Thalidomide 100mg; Thalidomide 25mg/qd.po.2weeks; 50mg/qd.po.2weeks; 100mg/qd.po.to the end	Drug: Thalidomide 100mg; Other Names: Thalomid; Fan Ying Ting
Placebo Comparator: Placebo; Placebo po.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: July 23, 2014
• First Submitted That Met QC Criteria: July 23, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: ankylosing spondylitis; thalidomide
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antifungal Agents; Thalidomide; Tolnaftate
• Other Study ID Numbers: SLDA-201