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

NCT ID: NCT00048542

Last Updated: 2011-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 171 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2010-06-30

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.

Detailed Description

The study design for this clinical trial was chosen to evaluate adalimumab in subjects who were either methotrexate (MTX)-naive or had been withdrawn from MTX at least 2 weeks prior to study drug administration (non-MTX stratum) or were inadequate responders to MTX and continued MTX treatment (MTX stratum). The study consisted of 4 phases: a 16-week Open-label Lead-in (OL LI), a 32-week Double-blind (DB) phase, an up to 136-week Open-label Extension Body Surface Area (OLE BSA) phase, and an up to 224-week OLE Fixed Dose (FD) phase. 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 OL LI phase of the study. All subjects who responded to adalimumab during the OL LI phase were to be enrolled in the DB 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). Subjects in the DB phase received either adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose) or placebo subcutaneously (SC) administered every other week (eow). Adalimumab or placebo was administered for an additional 32 weeks or until flare of disease (based on PedACR30 response criteria = a worsening of 30% or more in 3 of the 6 response variables (Parent's global assessment of subject's overall well-being by visual analog scale [VAS], Physician's global assessment [PhGA] of subject's disease severity by VAS, number of active joints [joints with swelling not due to deformity or joints with limitation of passive motion (LOM)], pain, tenderness, or both, number of joints with LOM, Childhood Health Assessment Questionnaire [CHAQ], and CRP levels), a minimum of 2 active joints, and no more than 1 indicator improving by 30% or more), whichever occurred earlier. For subjects who did not have a disease flare, the DB phase was completed at Week 48. Subjects who experienced disease flare during the DB phase or subjects who completed 48 weeks of the study were given the option to receive adalimumab for up to a minimum of 44 weeks (up to a maximum of 136 weeks) in the OLE BSA phase before being eligible to switch to the OLE FD phase. In this phase, subjects received OL adalimumab (24 mg/m2 BSA up to a maximum of 40 mg total body dose SC eow). All subjects who completed at least 44 weeks of OLE BSA treatment were given the opportunity to continue into the OLE FD phase for up to 224 weeks of additional adalimumab exposure. In this phase, subjects weighing less than 30 kg were treated with a fixed dose of 20 mg of adalimumab SC eow. Subjects weighing 30 kg or more were treated with a fixed dose of 40 mg of adalimumab SC eow.

Conditions

Arthritis, Juvenile Idiopathic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Double-Blind Adalimumab + MTX

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.

Group Type: EXPERIMENTAL

Double-Blind Adalimumab/Placebo + MTX

Intervention Type: 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.

Double-Blind Placebo + MTX

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.

Group Type: PLACEBO_COMPARATOR

Double-Blind Adalimumab/Placebo + MTX

Intervention Type: 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.

Double-Blind Adalimumab

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.

Group Type: EXPERIMENTAL

Double-Blind Adalimumab/Placebo

Intervention Type: 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.

Double-Blind Placebo

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.

Group Type: PLACEBO_COMPARATOR

Double-Blind Adalimumab/Placebo

Intervention Type: 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.

OLE BSA Adalimumab + MTX

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.

Group Type: EXPERIMENTAL

OLE BSA Adalimumab +/- MTX

Intervention Type: 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.

OLE BSA Adalimumab

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.

Group Type: EXPERIMENTAL

OLE BSA Adalimumab +/- MTX

Intervention Type: 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.

OLE FD Adalimumab + MTX

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.

Group Type: EXPERIMENTAL

OLE FD Adalimumab +/- MTX

Intervention Type: 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.

OLE FD Adalimumab

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.

Group Type: EXPERIMENTAL

OLE FD Adalimumab +/- MTX

Intervention Type: 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.

Interventions

Double-Blind Adalimumab/Placebo + MTX

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.

Intervention Type: BIOLOGICAL

Double-Blind Adalimumab/Placebo

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.

Intervention Type: BIOLOGICAL

OLE BSA Adalimumab +/- MTX

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.

Intervention Type: DRUG

OLE FD Adalimumab +/- MTX

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.

Intervention Type: DRUG

Other Intervention Names

ABT-D2E7; Humira; ABT-D2E7; Humira; ABT-D2E7; Humira; ABT-D2E7; Humira

Eligibility 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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Role: STUDY_DIRECTOR

Abbott

Locations

Site Ref # / Investigator 45524

Birmingham, Alabama, United States

Site Reference ID/Investigator# 2235

Los Angeles, California, United States

Site Reference ID/Investigator# 642

Stanford, California, United States

Site Reference ID/Investigator# 638

Delray Beach, Florida, United States

Site Ref # / Investigator 45543

St. Petersburg, Florida, United States

Site Reference ID/Investigator# 640

Chicago, Illinois, United States

Site Reference ID/Investigator# 644

Kansas City, Kansas, United States

Site Reference ID/Investigator# 641

Minneapolis, Minnesota, United States

Site Reference ID/Investigator# 645

Omaha, Nebraska, United States

Site Reference ID/Investigator# 2501

Livingston, New Jersey, United States

Site Ref # / Investigator 45542

New Hyde Park, New York, United States

Site Ref # / Investigator 45544

Chapel Hill, North Carolina, United States

Site Reference ID/Investigator# 386

Columbus, Ohio, United States

Site Ref # / Investigator 45525

Salt Lake City, Utah, United States

Site Reference ID/Investigator# 406

Norfolk, Virginia, United States

Site Reference ID/Investigator# 621

Ghent, , Belgium

Site Reference ID/Investigator# 2538

Leuven, , Belgium

Site Reference ID/Investigator# 519

Prague, , Czechia

Site Reference ID/Investigator# 518

Prague, , Czechia

Site Reference ID/Investigator# 45545

Marseille, , France

Site Reference ID/Investigator# 516

Paris, , France

Site Reference ID/Investigator# 627

Berlin, , Germany

Site Reference ID/Investigator# 625

Bremen, , Germany

Site Ref # / Investigator 45522

Garmisch-Partenkirchen, , Germany

Site Reference ID/Investigator# 628

Halle, , Germany

Site Reference ID/Investigator# 622

Hamburg, , Germany

Site Reference ID/Investigator# 631

Genoa, , Italy

Site Reference ID/Investigator# 636

Milan, , Italy

Site Ref # / Investigator 45523

Košice, , Slovakia

Site Reference ID/Investigator# 3425

Piešťany, , Slovakia

Site Reference ID/Investigator# 3713

Madrid, , Spain

Countries

United States; Belgium; Czechia; France; Germany; Italy; Slovakia; Spain

References

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.

Reference Type: DERIVED

PMID: 30054164 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 18716298 (View on PubMed)

Other Identifiers

DE038

Identifier Type: -

Identifier Source: org_study_id