Blocking Tumor Necrosis Factor in Ankylosing Spondylitis

Phase 2

Completed

• Conditions: Spondylitis, Ankylosing

• Registration Number: NCT00000433
• Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brief Summary

The Division of Rheumatology at University of California San Francisco is conducting a research study on the treatment of ankylosing spondylitis (AS) with a new therapy currently used for people with other forms of arthritis. The drug, called Enbrel (or etanercept), is a protein that is given twice weekly by injection underneath the skin. It blocks the action of tumor necrosis factor-alpha (TNF-alpha), a substance that may be involved in AS, rheumatoid arthritis, and other inflammatory conditions. We will randomly assign patients to receive either the drug or a placebo (inactive treatment) for 4 months. The results we will monitor include morning stiffness, spinal mobility, activities of daily life, and safety of the drug.

Detailed Description

In this Phase II clinical trial we will use tumor necrosis factor receptor p75 fusion protein (TNFR:Fc, or etanercept) to treat patients with ankylosing spondylitis (AS). TNFR:Fc is an antagonist of tumor necrosis factor (TNF), a cytokine that researchers have shown to play a possible role in disease pathogenesis of ankylosing spondylitis, rheumatoid arthritis, and vasculitis, as well as other inflammatory conditions.

TNFR:Fc consists of two molecules of the extracellular portion of the p75 receptor, each consisting of 235 amino acids. The two receptors are fused to the Fc portion of human IgG1, which consists of 232 amino acids. The gene fragments encoding the truncated TNFR and the Fc portion of human IgG1 are expressed in a Chinese hamster ovary cell line.

Recent observations from animal and human studies suggest that tumor necrosis factor-alpha (TNF-alpha) may play a role in disease activity in AS and other seronegative spondyloarthropathies. This study aims to test the efficacy of TNFR:Fc used in conjunction with standard medications in the treatment of AS. We will give patients either 25mg of TNFR:Fc or placebo subcutaneously twice a week for 4 months. Outcome measures will include measures of function, pain, morning stiffness, patient global assessment, and swollen joint count, as well as safety measures.

Study Timeline

• Study Start: 1999-10
• Study First Submitted: 2000-01-18
• Study First Submitted QC: 2000-01-18
• Study First Posted: 2000-01-19
• Study Completion: 2002-03
• Status Verified: 2003-02
• Last Update Submitted: 2007-01-02
• Last Update Posted: 2007-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Diagnosis of Ankylosing spondylitis
• Acceptable stable treatments during study: oral glucocorticoids (less than or equal to 10 mg/d) and/or NSAIDs at recommended doses and/or one of the following options: methotrexate (less than or equal to 20.0 mg/week); sulfasalazine (less than or equal to 3 grams/d); azathioprine (less than or equal to 2 mg/kg/d); methotrexate and sulfasalazine combination at doses listed above; 6-mercaptopurine (less than or equal to 1.5 mg/kg/d)

Exclusion Criteria

• Diagnosis of psoriatic arthritis, inflammatory bowel disease, reactive arthritis, or Behýet disease
• Significant medical problems, such as diabetes mellitus
• History of active or recurrent infections
• Complete ankylosis of the entire spine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Trial Locations

Locations (1)

UCSF-Clinical Trials Center; 🇺🇸 San Francisco, California, United States