Blocking Tumor Necrosis Factor in Ankylosing Spondylitis - Full Text View

Sponsored by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00000433

Purpose

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.

Condition	Intervention	Phase
Spondylitis, Ankylosing	Drug: Anti-Tumor Necrosis Factor	Phase II

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis Cancer

Drug Information available for: Etanercept Tumor Necrosis Factors

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study
Official Title:	Anti-Tumor Necrosis Factor (TNFR:Fc) in Ankylosing Spondylitis

Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Estimated Enrollment:	42
Study Start Date:	October 1999
Estimated Study Completion Date:	March 2002

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000433

Locations

United States, California
UCSF-Clinical Trials Center
San Francisco, California, United States, 94143-0792

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

Principal Investigator:

John C. Davis, MD, MPH

Division of Rheumatology, University of California - San Francisco Department of Medicine

More Information

Publications:

Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. 2002 May 2;346(18):1349-56.

Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W; Enbrel Ankylosing Spondylitis Study Group. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 2003 Nov;48(11):3230-6.

Davis JC Jr, Huang F, Maksymowych W. New therapies for ankylosing spondylitis: etanercept, thalidomide, and pamidronate. Rheum Dis Clin North Am. 2003 Aug;29(3):481-94, viii. Review.

Study ID Numbers:	N01 AR92244, NIAMS-043
Study First Received:	January 18, 2000
Last Updated:	January 2, 2007
ClinicalTrials.gov Identifier:	NCT00000433
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Spondylitis
Etanercept
ENBREL
Tumor necrosis factor-alpha

Study placed in the following topic categories:

Spinal Diseases
Necrosis
Musculoskeletal Diseases
Spondylarthropathy
Arthritis
Joint Diseases

Spondylitis, Ankylosing
Spondylarthritis
Bone Diseases
Spondylitis
Ankylosis
Spondylarthropathies

Additional relevant MeSH terms:

Pathologic Processes
Infection
Bone Diseases, Infectious

ClinicalTrials.gov processed this record on January 16, 2009