Study of Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis (JIA)

NCT00048542 | Completed Phase 3 Results DMC

• 1 other identifier: DE038
• Study Type: interventional
• Target: 171
• Locations: 8 countries
• Sites: 31

Brief Summary

This is a multicenter, Phase 3 randomized, placebo-controlled study designed to evaluate adalimumab in children 4 to 17 years old with polyarticular juvenile idiopathic arthritis (JIA) who are either methotrexate (MTX) treated or non-MTX treated.

Conditions

Arthritis, Juvenile Idiopathic

Keywords

Polyarticular Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Subjects in the Non-MTX Stratum With Disease Flare During the Double-Blind Phase

  The primary efficacy endpoint was the number of adalimumab-treated subjects in the non-MTX stratum with disease flare during the Double-Blind Phase compared with the number of placebo-treated subjects in the non-MTX stratum with disease flare during the double-blind phase. Subjects met the criteria for disease flare if they had 1) \>= 30% worsening in at least 3 of the 6 Juvenile Rheumatoid Arthritis (JRA) core set criteria and a minimum of 2 active joints, and 2) \>= 30% improvement in not more than 1 of the 6 JRA core set criteria.

  Week 16 to Week 48 (32 weeks)

Secondary Outcomes (17)

• Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase

  Week 16

• Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase

  Week 16 to Week 48 (32 Weeks)

• Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum

  Week 16 to Week 48 (32 weeks)

• Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum

  Week 16 to Week 48 (32 weeks)

• Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase

  Week 48

Other Outcomes (4)

• Baseline Measure: Gender, Female/Male - OLE BSA Phase

  Baseline OLE BSA Phase

• Baseline Measure: Age Continuous - OLE BSA Phase

  Baseline OLE BSA Phase

• Baseline Measure: Gender, Female/Male - OLE FD Phase

  Baseline OLE FD Phase

Study Arms (8)

Double-Blind Adalimumab + MTX

EXPERIMENTAL

Subjects who were inadequate responders to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase received adalimumab plus concomitant MTX during the Double-Blind Phase. MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening.

Biological: Double-Blind Adalimumab/Placebo + MTX

Double-Blind Placebo + MTX

PLACEBO COMPARATOR

Subjects who were inadequate responders to MTX and were adalimumab responders during the Open-Label Lead-In (OL-LI) phase received placebo plus concomitant MTX during the Double-Blind Phase. MTX-treated inadequate responders must have had active disease on MTX treatment for at least 3 months prior to screening.

Biological: Double-Blind Adalimumab/Placebo + MTX

Double-Blind Adalimumab

EXPERIMENTAL

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received adalimumab, but no concomitant MTX treatment, during the Double-Blind Phase.

Biological: Double-Blind Adalimumab/Placebo

Double-Blind Placebo

PLACEBO COMPARATOR

Subjects in the non-methotrexate (MTX) stratum who were either naïve to MTX or withdrawn from MTX at least 2 weeks prior to study drug administration, and were adalimumab responders during the OL-LI phase, received placebo, but no concomitant MTX treatment, during the Double-Blind Phase.

Biological: Double-Blind Adalimumab/Placebo

OLE BSA Adalimumab + MTX

EXPERIMENTAL

All subjects received subcutaneous injections of 24 mg adalimumab per square meter of body surface area (BSA) up to a maximum of 40 mg total body dose every other week (eow), concomitantly with MTX treatment, during the Open-Label Extension (OLE) BSA Phase of the study.

Drug: OLE BSA Adalimumab +/- MTX

OLE BSA Adalimumab

EXPERIMENTAL

All subjects received subcutaneous injections of 24 mg adalimumab per square meter of body surface area (BSA) up to a maximum of 40 mg total body dose every other week (eow), but not MTX treatment, during the Open-Label Extension (OLE) BSA Phase of the study.

Drug: OLE BSA Adalimumab +/- MTX

OLE FD Adalimumab + MTX

EXPERIMENTAL

Subjects received adalimumab concomitantly with MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study in which only body weight (not BSA) determined dosing; subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Drug: OLE FD Adalimumab +/- MTX

OLE FD Adalimumab

EXPERIMENTAL

Subjects received placebo without concomitant MTX treatment during the Open-Label Extension (OLE) Fixed Dose (FD) Phase of the study in which only body weight (not BSA) determined dosing; subjects weighing less than 30 kg were dosed with 20 mg of adalimumab SC eow, and subjects weighing 30 kg or more were dosed with 40 mg of adalimumab SC eow.

Drug: OLE FD Adalimumab +/- MTX

Interventions

Double-Blind Adalimumab/Placebo + MTX BIOLOGICAL

Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) concomitantly with MTX treatment for 32 weeks during the Double-Blind phase. Total body dose of adalimumab was not to exceed 40 mg.

Also known as: ABT-D2E7, Humira

Double-Blind Adalimumab + MTX; Double-Blind Placebo + MTX

Double-Blind Adalimumab/Placebo BIOLOGICAL

Subcutaneous injection of 24 mg adalimumab or placebo per square meter of body surface area (BSA) every other week (eow) without MTX treatment for 32 weeks during the Double-Blind Phase. Total body dose of adalimumab was not to exceed 40 mg.

Also known as: ABT-D2E7, Humira

Double-Blind Adalimumab; Double-Blind Placebo

OLE BSA Adalimumab +/- MTX DRUG

Comparison of subcutaneous injection of 24 mg adalimumab per square meter of body surface area (BSA) every other week (eow) either with or without concomitant MTX treatment for a minimum of 44 weeks (up to a maximum of 136 weeks) during the Open-Label Extension BSA Phase.

Also known as: ABT-D2E7, Humira

OLE BSA Adalimumab; OLE BSA Adalimumab + MTX

OLE FD Adalimumab +/- MTX DRUG

Comparison of adalimumab administered subcutaneously every other week (eow) either with or without concomitant MTX treatment for up to 224 weeks during the Open-Label Extension Fixed Dose (FD) Phase.

Also known as: ABT-D2E7, Humira

OLE FD Adalimumab; OLE FD Adalimumab + MTX

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (31)

Site Ref # / Investigator 45524

Birmingham, Alabama, 35294-3300, United States

Location

Site Reference ID/Investigator# 2235

Los Angeles, California, 90027, United States

Location

Site Reference ID/Investigator# 642

Stanford, California, 94305, United States

Location

Site Reference ID/Investigator# 638

Delray Beach, Florida, 33406, United States

Location

Site Ref # / Investigator 45543

St. Petersburg, Florida, 33701, United States

Location

Site Reference ID/Investigator# 640

Chicago, Illinois, 60649, United States

Location

Site Reference ID/Investigator# 644

Kansas City, Kansas, 66160, United States

Location

Site Reference ID/Investigator# 641

Minneapolis, Minnesota, 55455, United States

Location

Site Reference ID/Investigator# 645

Omaha, Nebraska, 68131, United States

Location

Site Reference ID/Investigator# 2501

Livingston, New Jersey, 07039, United States

Location

Site Ref # / Investigator 45542

New Hyde Park, New York, 11040, United States

Location

Site Ref # / Investigator 45544

Chapel Hill, North Carolina, 27599-7220, United States

Location

Site Reference ID/Investigator# 386

Columbus, Ohio, 43205, United States

Location

Site Ref # / Investigator 45525

Salt Lake City, Utah, 84312-2206, United States

Location

Site Reference ID/Investigator# 406

Norfolk, Virginia, 23507, United States

Location

Site Reference ID/Investigator# 621

Ghent, 9000, Belgium

Location

Site Reference ID/Investigator# 2538

Leuven, 3000, Belgium

Location

Site Reference ID/Investigator# 519

Prague, 120 00, Czechia

Location

Site Reference ID/Investigator# 518

Prague, 128 50, Czechia

Location

Site Reference ID/Investigator# 45545

Marseille, 13915, France

Location

Site Reference ID/Investigator# 516

Paris, 75015, France

Location

Site Reference ID/Investigator# 627

Berlin, 13353, Germany

Location

Site Reference ID/Investigator# 625

Bremen, D-28205, Germany

Location

Site Ref # / Investigator 45522

Garmisch-Partenkirchen, 82467, Germany

Location

Site Reference ID/Investigator# 628

Halle, D-06120, Germany

Location

Site Reference ID/Investigator# 622

Hamburg, 22081, Germany

Location

Site Reference ID/Investigator# 631

Genoa, 16147, Italy

Location

Site Reference ID/Investigator# 636

Milan, 20122, Italy

Location

Site Ref # / Investigator 45523

Košice, 004001, Slovakia

Location

Site Reference ID/Investigator# 3425

Piešťany, 921 01, Slovakia

Location

Site Reference ID/Investigator# 3713

Madrid, 28034, Spain

Location

Related Publications (2)

• Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.

  PMID: 30054164 DERIVED

• 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. doi: 10.1056/NEJMoa0706290.

  PMID: 18716298 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Laura Redden, M.D., Ph.D.

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2002
• First Posted: November 5, 2002
• Study Start: September 1, 2002
• Primary Completion: January 1, 2005
• Study Completion: June 1, 2010
• Last Updated: August 22, 2011
• Results First Posted: January 11, 2010

Record last verified: 2011-08

Locations

BE (2); ES (1); US (15); IT (2); DE (5); CZ (2); SL (2); FR (2)