Study of Adalimumab in Subjects With Axial Spondyloarthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00939003
First received: July 10, 2009
Last updated: July 22, 2013
Last verified: July 2013
  Purpose

This study will study how well adalimumab works in the short and long term in subjects with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.


Condition Intervention Phase
Axial Spondyloarthritis
Biological: Adalimumab
Biological: Placebo
Biological: Open-label Adalimumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Axial Spondyloarthritis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Number of Participants Achieving ASAS40 Response (ASAS: Assessment of Spondyloarthritis International Society) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS40 response is improvement of >/=40% and absolute improvement of >/=20 units (scale of 0-100) in >/= 3 of 4 domains, plus absence of any deterioration (net worsening of > 0 units) in remaining domain: patient's global assessment of disease activity, pain (as total back pain), and physical function (Bath Ankylosing Spondylitis Function Index [BASFI]) (each domain with Visual Analog Scale [mm] scores of 0=best response to 100=worst response); and inflammation (morning stiffness level/duration [items 5 and 6] mean score [cm: 0=best to 10=worst] on Bath AS Disease Activity Index [BASDAI]).


Secondary Outcome Measures:
  • Number of Participants Achieving ASAS20 Response (ASAS: Assessment of Spondyloarthritis International Society) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS20 response is improvement of >/=20% and absolute improvement of >/=10 units (scale of 0-100) in >/= 3 of 4 domains, plus no deterioration (worsening of >/=20% and >/=10 units) in remaining domain: patient's global assessment of disease activity, pain (as total back pain), and physical function (Bath Ankylosing Spondylitis Function Index [BASFI]) (each domain with Visual Analog Scale [mm] scores of 0=best response to 100=worst response); and inflammation (morning stiffness level/duration [items 5 and 6] mean score [cm: 0=best to 10=worst] on Bath AS Disease Activity Index [BASDAI]).

  • Number of Participants Achieving a BASDAI50 Response (BASDAI: Bath Ankylosing Spondylitis Disease Activity Index) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (scale 0 to 10 cm) pertaining to symptoms experienced for the past week. For 5 questions (including #5 [level of morning stiffness]), the response is 0 (none) to 10 (very severe); for #6 (duration of morning stiffness), the response is 0 (0 hours) to 10 (>/= 2 hours). The overall BASDAI score has a maximum value of 10 cm. Lower scores indicate less disease activity. BASDAI50 is 50% improvement from Baseline in BASDAI score.

  • Number of Participants Achieving ASAS Partial Remission (ASAS: Assessment of Spondyloarthritis International Society) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS partial remission is an absolute score of <20 units on a 0 to 100 scale for each of 4 domains: patient's global assessment of disease activity, pain (as total back pain), and physical function (Bath AS Functional Index score [BASFI]) (each domain with Visual Analog Scale [mm] scores of 0=best response to 100=worst response); and inflammation (morning stiffness level/duration [items 5 and 6] mean score [cm: 0=best to 10=worst] on Bath AS Disability Activity Index [BASDAI]).

  • Number of Participants Achieving ASAS5/6 Response (ASAS: Assessment of Spondyloarthritis International Society) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS5/6 response is a 20% improvement in 5 of 6 domains: patient's global assessment of disease activity, pain (as total back pain), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]) (each domain with Visual Analog Scale [mm] scores of 0=best to 100=worst); inflammation (morning stiffness level/duration [items 5 and 6] mean score [cm: 0=best to 10=worst] on Bath AS Disease Activity Index [BASDAI]); spinal mobility (lateral lumbar flexion score (cm: range 0 to 10) from Bath AS Metrology Index [BASMI]); and C-reactive protein level (lower indicates less inflammation).


Other Outcome Measures:
  • Number of Participants Reporting Adverse Events [ Time Frame: Through Week 12 ] [ Designated as safety issue: Yes ]
    Adverse events were collected at designated study visits for all participants who received at least 1 dose of study drug. The number of participants experiencing any adverse event (serious and non-serious) are summarized. See the Reported Adverse Event section for details.

  • Number of Participants With Blood Hematology and Chemistry Values Common Toxicity Criteria Grade >/=3, Assessed by Central Laboratory [ Time Frame: Through Week 12 ] [ Designated as safety issue: Yes ]
    Blood was collected for analysis at designated study visits; hematology and chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher then upper normal limit or lower than lower normal limit) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized.


Enrollment: 192
Study Start Date: July 2009
Study Completion Date: July 2013
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab Biological: Adalimumab
40 mg Every Other week up to Week 12
Other Name: ABT-D2E7 Humira
Placebo Comparator: Placebo Biological: Placebo
Placebo Every Other Week up to Week 12
Experimental: Open-label Adalimumab Biological: Open-label Adalimumab
40 mg Every Other Week, Week 12 through Week 156
Other Name: ABT-D2E7 Humira

Detailed Description:

This is a Phase 3, placebo-controlled, double-blind randomized study with an open-label phase designed to evaluate the efficacy and safety of adalimumab 40 mg administered every other week in adult patients with active axial spondyloarthritis (SpA) who are not diagnosed with ankylosing spondylitis, psoriasis, or psoriatic arthritis and who have had an inadequate response or intolerance to 1 or more nonsteroidal anti-inflammatory drugs (NSAIDs) or had a contraindication to NSAIDs. Participants receive adalimumab or placebo for 12 weeks during the double-blind phase of the study. Following the double-blind phase, all participants enter the open-label phase of the study in which they receive adalimumab for up to an additional 144 weeks. Efficacy endpoints include the Assessment of Spondyloarthritis International Society (ASAS) Working Group response criteria for patients with SpA. These response criteria were used to determine participants who were responders. ASAS response involves evaluations in the following 4 domains: participant's global assessment of disease activity, pain, function, and inflammation. The patient's global assessment of disease activity score is assessed using a 100 millimeter (mm) visual analog scale (VAS; 0 for no disease activity to 100 for severe disease activity). Pain is represented as a total back pain score and is assessed using a 100 mm VAS (0 for no pain to 100 for most severe pain). Function score is represented as the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI) 100 mm VAS score (average of the ability to perform 10 activities, each scored as 0 for easy to 100 for impossible). Inflammation is determined using the morning stiffness overall level score (0 for none to 10 for very severe) and duration score (0 for 0 hours to 10 for >=2 hours) of the Bath AS Disease Activity Index (BASDAI) (mean of these items #5 and #6 scores). In addition, the BASDAI is used as an efficacy endpoint. The BASDAI is used by the participant to assess his/her disease activity. Using VAS scales, the participant answers 6 questions pertaining to symptoms experienced over the past week. For 5 questions (levels of: fatigue/tiredness; AS neck, back, or hip pain; pain/swelling; discomfort at areas tender to touch or pressure; and morning stiffness), the response scale is 0 (none) to 10 (very severe). For 1 question (duration of morning stiffness), the response scale is 0 hours to 2 or more hours. The BASDAI score has a maximum value of 10 cm. The double-blind phase of the study is complete, and results are reported for endpoints at Week 12.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects with inadequate response to >/= 1 non-steroidal anti-inflammatories (NSAIDs)
  • Chronic back pain with onset < 45 years of age
  • MRI indicating active sacroiliitis or positive HLA-B27 blood test in addition to meeting spondyloarthritis clinical criteria
  • Negative purified protein derivative (PPD) test and Chest X-Ray performed at Baseline Visit must be Negative
  • Ability to administer subcutaneous injections
  • General good health otherwise

Exclusion Criteria:

  • Prior anti-TNF therapy
  • Psoriasis or Psoriatic Arthritis
  • Fulfillment of modified New York criteria for Ankylosing Spondylitis
  • Recent infection requiring treatment
  • Significant medical events or conditions that may put patients at risk for participation
  • Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study
  • History of cancer, except successfully treated skin cancer
  • Recent history of drug or alcohol abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939003

  Show 38 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Aileen L Pangan, MD AbbVie
  More Information

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00939003     History of Changes
Other Study ID Numbers: M10-791, 2009-010643-14
Study First Received: July 10, 2009
Results First Received: February 2, 2012
Last Updated: July 22, 2013
Health Authority: Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Bone Diseases, Infectious
Infection
Antibodies, Monoclonal
Adalimumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 21, 2014