Study of the Human Anti-Tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis (JIA) - Full Text View

Sponsor:	Abbott
Information provided by:	Abbott
ClinicalTrials.gov Identifier:	NCT00048542

Purpose

This is a multicenter, Phase 3 randomized, placebo-controlled study designed to evaluate adalimumab in subjects with polyarticular juvenile idiopathic arthritis (JIA) who are either methotrexate (MTX) treated or non-MTX treated.

Condition	Intervention	Phase
Arthritis, Juvenile Idiopathic	Biological: Adalimumab Biological: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-Tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis

Resource links provided by NLM:

MedlinePlus related topics: Cancer Juvenile Rheumatoid Arthritis

Drug Information available for: Immunoglobulins Tumor Necrosis Factors Adalimumab Globulin, Immune

U.S. FDA Resources

Further study details as provided by Abbott:

Primary Outcome Measures:

Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-blind Phase. [ Time Frame: Week 16 to Week 48 (32 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-label lead-in Phase [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Number of Subjects in the MTX Stratum With Disease Flare During the Double-blind Phase [ Time Frame: Week 16 to Week 48 (32 Weeks) ] [ Designated as safety issue: No ]
Time to Onset of Disease Flare During the Double-blind Phase in Subjects in the Non-MTX Stratum [ Time Frame: Week 16 to Week 48 (32 weeks) ] [ Designated as safety issue: No ]
Time to Onset of Disease Flare During the Double-blind Phase in Subjects in the MTX Stratum [ Time Frame: Week 16 to Week 48 (32 weeks) ] [ Designated as safety issue: No ]
Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-blind Phase [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-blind Phase [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-blind Phase [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Physician's Global Assessment of Disease Activity [ Time Frame: Screening through Week 48 ] [ Designated as safety issue: No ]
Parent/Patient's Global Assessment of Disease Activity [ Time Frame: Screening through Week 48 ] [ Designated as safety issue: No ]
C-reactive Protein Levels [ Time Frame: Screening through Week 48 ] [ Designated as safety issue: No ]

Enrollment:	171
Study Start Date:	September 2002
Primary Completion Date:	January 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Adalimumab + MTX: Experimental Subjects received adalimumab plus concomitant methotrexate (MTX) during the double-blind phase.	Biological: Adalimumab Subcutaneous injection of 24 mg adalimumab per square meter of body surface area (BSA) every other week (eow) for 32 weeks during the double-blind phase. Total body dose of adalimumab was not to exceed 40 mg.
Placebo + MTX: Placebo Comparator Subjects received placebo plus concomitant methotrexate (MTX) during the double-blind phase.	Biological: Placebo Subcutaneous injection of placebo every other week (eow) for 32 weeks during the double-blind phase.
Adalimumab: Experimental Subjects received adalimumab during the double-blind phase.	Biological: Adalimumab Subcutaneous injection of 24 mg adalimumab per square meter of body surface area (BSA) every other week (eow) for 32 weeks during the double-blind phase. Total body dose of adalimumab was not to exceed 40 mg.
Placebo: Placebo Comparator Subjects received placebo during the double-blind phase.	Biological: Placebo Subcutaneous injection of placebo every other week (eow) for 32 weeks during the double-blind phase.

Detailed Description:

The study design for this clinical trial was chosen to evaluate adalimumab in subjects who are either MTX-naïve (non-MTX stratum) or are inadequate responders or are intolerant to MTX (MTX stratum). All subjects who met entry criteria were enrolled into one of the appropriate strata and received adalimumab (plus concomitant MTX in the MTX stratum) in the 16 week open-label lead-in phase of the study. All subjects who responded to adalimumab during the open-label lead-in phase were to be enrolled in the double-blind phase of the study and randomized to receive adalimumab (plus concomitant MTX in the MTX stratum) or placebo (plus concomitant MTX in the MTX stratum). Adalimumab or placebo was administered for an additional 32 weeks or until flare of disease, whichever was earlier. For subjects who did not have a disease flare, the double-blind phase was completed at Week 48. Subjects who experienced disease flare during the double-blind phase or subjects who completed 48 weeks of the study were given the option to receive adalimumab for up to an additional 240 weeks in an open-label extension phase.

Eligibility

Ages Eligible for Study:	4 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects must have a diagnosis of polyarticular juvenile idiopathic arthritis (JIA) age 4 to 17 by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular. If the disease was systemic onset, then the subjects must be free of any systemic JIA manifestations for at least 3 months before the time of qualification.
At the time of study screening, the subject must have continuing active disease defined as >= 5 swollen joints and >= 3 joints with limitation of motion (LOM). These joints are not mutually exclusive.
Subjects may be either naïve to MTX, inadequate responders to MTX, or intolerant to MTX. Intolerance to MTX will be defined by the subject's physician. The MTX must be maintained at a dose of at least 10 mg/m2 body surface area/week for a minimum of 3 months, prior to screening.
Duration of disease is not limited, but must have been long enough for a subject to have been given an adequate trial of nonsteroidal anti-inflammatory drugs (NSAIDs).
Have not received other disease-modifying anti-rheumatic drugs (DMARDs) including penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold, cyclosporin; or intravenous immunoglobulin (IV Ig); or cytotoxic agents, for at least 4 weeks prior to receiving 1st dose of study drug. Subjects currently on one or more of these DMARDs must demonstrate active disease (defined above) prior to a minimum 4 weeks (28 days) washout of all DMARDs.
Subjects who are refractory to MTX after 3 months of treatment must demonstrate active disease (defined above) prior to enrollment in the open-label part of the trial.
Have not received an intra-articular glucocorticoid injection within 4 weeks (28 days) prior to enrollment into the study.
Have good venous access and stable hematocrit >= 24%.
All sexually active male and female study participants must be practicing adequate contraception. Post-pubertal females must have a negative serum pregnancy test no greater than 10 days prior to the first dose of study drug.
Parent or guardian has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject's parent or legal guardian has had the opportunity to ask questions.

Exclusion Criteria:

Pregnant or nursing female.
Functional class IV by ACR criteria.
Laboratory parameters outside limits established in the protocol.
Medical history, medical condition, or previous treatment not allowed by the protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00048542

Show 35 Study Locations

Sponsors and Collaborators

Abbott

Investigators

Study Director:

Laura Redden, M.D., Ph.D.

Abbott

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Abbott

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, Nemcova D, Mouy R, Sandborg C, Bohnsack J, Elewaut D, Foeldvari I, Gerloni V, Rovensky J, Minden K, Vehe RK, Weiner LW, Horneff G, Huppertz HI, Olson NY, Medich JR, Carcereri-De-Prati R, McIlraith MJ, Giannini EH, Martini A; Pediatric Rheumatology Collaborative Study Group; Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008 Aug 21;359(8):810-20.

Responsible Party:	Abbott ( Laura Redden, M.D., Ph.D., Project Director )
Study ID Numbers:	DE038
Study First Received:	November 1, 2002
Results First Received:	December 7, 2009
Last Updated:	February 3, 2010
ClinicalTrials.gov Identifier:	NCT00048542 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Abbott:

Polyarticular Juvenile Idiopathic Arthritis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Arthritis, Juvenile Rheumatoid
Autoimmune Diseases
Immune System Diseases
Immunologic Factors
Joint Diseases
Physiological Effects of Drugs
Arthritis, Rheumatoid
Rheumatic Diseases

Adalimumab
Pharmacologic Actions
Antibodies, Monoclonal
Musculoskeletal Diseases
Therapeutic Uses
Arthritis
Connective Tissue Diseases
Antirheumatic Agents

ClinicalTrials.gov processed this record on March 18, 2010