Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis

NCT00085644 | Completed Phase 3 Results

• 1 other identifier: M03-607
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 22

Brief Summary

The objective of this study was to evaluate the safety and efficacy of adalimumab 40 mg given every other week (eow) in subjects with active ankylosing spondylitis (AS) who have had an inadequate response to, or who are intolerant to, treatment with at least 1 nonsteroidal anti-inflammatory drug (NSAID) and who may have also failed treatment with at least 1 disease-modifying antirheumatic drug (DMARD).

Conditions

Ankylosing Spondylitis

Outcome Measures

Primary Outcomes (2)

• Number of Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20).

  ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 \[none\]-100 \[severe\]), Total Back Pain VAS (0 \[no pain\]-100 \[severe\]), BASFI VAS (0 \[easy\]-100\[impossible\]); and Inflammation VAS (0 \[none\]-10 \[very severe\]) and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

  Week 12

• Mean Change in the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Compared Against a Historical Control Group (Outcomes in Ankylosing Spondylitis International Study [OASIS]) Using the ANCOVA Model Adjusting for Baseline mSASSS Score

  Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 \[no change\] to 72 \[progression\]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.

  Week 104

Secondary Outcomes (35)

• Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) 20 - Through Week 260 of Adalimumab Exposure

  Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260

• Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) 50 - Through Week 260 of Adalimumab Exposure

  Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260

• Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) 70 - Through Week 260 of Adalimumab Exposure

  Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260

• Mean Change in Patient's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260

  Baseline, Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260

• Number of Subjects With a Reduction of Signs and Symptoms as Measured in Patient's Global Assessment of Disease Activity (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure

  Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260

Study Arms (2)

Adalimumab

EXPERIMENTAL

Biological: adalimumab (D2E7)

Placebo

PLACEBO COMPARATOR

Biological: placebo

Interventions

adalimumab (D2E7) BIOLOGICAL

Adalimumab 40 mg every other week, subcutaneous

Also known as: ABT-D2E7, adalimumab, Humira

Adalimumab

placebo BIOLOGICAL

Placebo every other week, subcutaneous

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be \>= 18 years of age
• meet Modified NY Criteria definition of ankylosing spondylitis (AS)
• have diagnosis of active AS based on protocol specified criteria
• inadequate response or intolerance to \>= 1 nonsteroidal antiinflammatory drug (NSAID)
• be able and willing to learn to self-administer subcutaneous (SC) injections

You may not qualify if:

• Active tuberculosis, listeriosis,or hepatitis B, or any history of hepatitis C
• History of demyelinating disease, multiple sclerosis, cancer, or lymphoproliferative disease
• Previous anti-tumor necrosis factor therapy
• Treatment with disease-modifying antirheumatic drugs (DMARDs - other than methotrexate, hydroxychloroquine, and sulfasalazine)
• Treatment with intra-articular corticosteroid joint injections within 4 weeks of study dosing
• Biologic or investigational therapy within 6 weeks of study dosing
• Treatment with intravenous (IV) antibiotics within 30 days of study dosing
• Treatment with oral antibiotics within 14 days of study dosing

Sponsors & Collaborators

• Abbott: lead

Study Sites (22)

Unknown Facility

Birmingham, Alabama, 35924, United States

Location

Unknown Facility

Mobile, Alabama, 36608, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Unknown Facility

Colorado Springs, Colorado, 80910, United States

Location

Unknown Facility

Denver, Colorado, 80230, United States

Location

Unknown Facility

Boise, Idaho, 83706, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Indianapolis, Indiana, 46260, United States

Location

Unknown Facility

Portland, Maine, 04102, United States

Location

Unknown Facility

Baltimore, Maryland, 21224, United States

Location

Unknown Facility

Wheaton, Maryland, 20902, United States

Location

Unknown Facility

Omaha, Nebraska, 68114, United States

Location

Unknown Facility

Lebanon, New Hampshire, 03756, United States

Location

Unknown Facility

Albany, New York, 12206, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73112, United States

Location

Unknown Facility

Duncansville, Pennsylvania, 16635, United States

Location

Unknown Facility

West Reading, Pennsylvania, 19611, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Houston, Texas, 77074, United States

Location

Unknown Facility

Salt Lake City, Utah, 84132, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Related Publications (9)

• van der Heijde D, Breban M, Halter D, DiVittorio G, Bratt J, Cantini F, Kary S, Pangan AL, Kupper H, Rathmann SS, Sieper J, Mease PJ. Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology (Oxford). 2015 Jul;54(7):1210-9. doi: 10.1093/rheumatology/keu438. Epub 2014 Dec 25.

  PMID: 25541333 DERIVED

• Kimel M, Revicki D, Rao S, Fryback D, Feeny D, Harnam N, Thompson C, Cifaldi M. Norms-based assessment of patient-reported outcomes associated with adalimumab monotherapy in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2011 Jul-Aug;29(4):624-32. Epub 2011 Aug 31.

  PMID: 21813060 DERIVED

• Revicki DA, Rentz AM, Luo MP, Wong RL. Psychometric characteristics of the short form 36 health survey and functional assessment of chronic illness Therapy-Fatigue subscale for patients with ankylosing spondylitis. Health Qual Life Outcomes. 2011 May 22;9:36. doi: 10.1186/1477-7525-9-36.

  PMID: 21600054 DERIVED

• Reilly MC, Gooch KL, Wong RL, Kupper H, van der Heijde D. Validity, reliability and responsiveness of the Work Productivity and Activity Impairment Questionnaire in ankylosing spondylitis. Rheumatology (Oxford). 2010 Apr;49(4):812-9. doi: 10.1093/rheumatology/kep457. Epub 2010 Jan 25.

  PMID: 20100797 DERIVED

• van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R; Canadian (M03-606) study group; ATLAS study group. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11(4):R127. doi: 10.1186/ar2794. Epub 2009 Aug 24.

  PMID: 19703304 DERIVED

• van der Heijde DM, Revicki DA, Gooch KL, Wong RL, Kupper H, Harnam N, Thompson C, Sieper J; ATLAS Study Group. Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis. Arthritis Res Ther. 2009;11(4):R124. doi: 10.1186/ar2790. Epub 2009 Aug 17.

  PMID: 19686597 DERIVED

• van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC Jr; ATLAS Study Group. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis. 2009 Jun;68(6):922-9. doi: 10.1136/ard.2007.087270. Epub 2008 Aug 13.

  PMID: 18701556 DERIVED

• Dougados M, Luo MP, Maksymowych WP, Chmiel JJ, Chen N, Wong RL, Davis JC Jr, van der Heijde D; ATLAS STUDY GROUP. Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial. Arthritis Rheum. 2008 Apr 15;59(4):553-60. doi: 10.1002/art.23527.

  PMID: 18383418 DERIVED

• van der Heijde D, Pangan AL, Schiff MH, Braun J, Borofsky M, Torre J, Davis JC Jr, Wong RL, Kupper H, Collantes E; ATLAS Study Group. Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis. Ann Rheum Dis. 2008 Sep;67(9):1218-21. doi: 10.1136/ard.2007.082529. Epub 2007 Dec 4.

  PMID: 18056755 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Interim results are shown for subjects after 12 weeks for efficacy parameters and 24 weeks for safety parameters. Subjects who discontinued the study before Week 12 and subjects with missing values were classified as nonresponders for efficacy.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Laura Redden, MD, PhD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 16, 2004
• Study Start: January 1, 2004
• Primary Completion: December 1, 2004
• Study Completion: July 1, 2009
• Last Updated: April 21, 2011
• Results First Posted: March 11, 2010

Record last verified: 2011-04

Locations

US (22)