Arthritis, Juvenile IdiopathicPhase 3NCT00048542
Study of Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis (JIA)
A Phase 3 study testing OLE BSA Adalimumab +/- MTX and OLE FD Adalimumab +/- MTX in people with Arthritis, Juvenile Idiopathic, run by Abbott at 31 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Arthritis, Juvenile Idiopathic
- What is being tested?
- OLE BSA Adalimumab +/- MTX and OLE FD Adalimumab +/- MTX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 171 participants
- Where
- 31 sitesin 8 countries
- Study dates
- Sep 2002to Jun 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
31 sites in 8 countries.
31 sites in 8 countries
United States15 sites
Site Ref # / Investigator 45524
Birmingham, Alabama, 35294-3300
Site Ref # / Investigator 45544
Chapel Hill, North Carolina, 27599-7220
Site Reference ID/Investigator# 640
Chicago, Illinois, 60649
Site Reference ID/Investigator# 386
Columbus, Ohio, 43205
Site Reference ID/Investigator# 638
Delray Beach, Florida, 33406
Site Reference ID/Investigator# 644
Kansas City, Kansas, 66160
Site Reference ID/Investigator# 2501
Livingston, New Jersey, 07039
Site Reference ID/Investigator# 2235
Los Angeles, California, 90027
Site Reference ID/Investigator# 641
Minneapolis, Minnesota, 55455
Site Ref # / Investigator 45542
New Hyde Park, New York, 11040
Site Reference ID/Investigator# 406
Norfolk, Virginia, 23507
Site Reference ID/Investigator# 645
Omaha, Nebraska, 68131
Site Ref # / Investigator 45525
Salt Lake City, Utah, 84312-2206
Site Ref # / Investigator 45543
St. Petersburg, Florida, 33701
Site Reference ID/Investigator# 642
Stanford, California, 94305
Germany5 sites
Site Reference ID/Investigator# 627
Berlin, 13353
Site Reference ID/Investigator# 625
Bremen, D-28205
Site Ref # / Investigator 45522
Garmisch-Partenkirchen, 82467
Site Reference ID/Investigator# 628
Halle, D-06120
Site Reference ID/Investigator# 622
Hamburg, 22081
Belgium2 sites
Site Reference ID/Investigator# 621
Ghent, 9000
Site Reference ID/Investigator# 2538
Leuven, 3000
Czechia2 sites
Site Reference ID/Investigator# 519
Prague, 120 00
Site Reference ID/Investigator# 518
Prague, 128 50
France2 sites
Site Reference ID/Investigator# 45545
Marseille, 13915
Site Reference ID/Investigator# 516
Paris, 75015
Italy2 sites
Site Reference ID/Investigator# 631
Genoa, 16147
Site Reference ID/Investigator# 636
Milan, 20122
Slovakia2 sites
Site Ref # / Investigator 45523
Košice, 004001
Site Reference ID/Investigator# 3425
Piešťany, 921 01
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis
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.
Read the 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
- Being tested
- Double-Blind Adalimumab/Placebo + MTX, Double-Blind Adalimumab/Placebo, OLE BSA Adalimumab +/- MTX, OLE FD Adalimumab +/- MTX
- Keywords
- Polyarticular Juvenile Idiopathic Arthritis
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double-Blind Adalimumab/Placebo + MTXBiological
Also called ABT-D2E7, Humira
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/PlaceboBiological
Also called ABT-D2E7, Humira
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 +/- MTXDrug
Also called ABT-D2E7, Humira
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 +/- MTXDrug
Also called ABT-D2E7, Humira
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: OLE FD Adalimumab +/- MTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Responders met the following criteria: >= 30% improvement in >= 3 of 6 JRA core set criteria, and >= 30% worsening in not more than 1 JRA criterion, compared with the open-label baseline. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with limitation of motion [LOM] and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Measured: Week 16
Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase
Subjects met criteria for disease flare if they had >= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and >= 30% improvement in not more than 1 JRA criterion. JRA core set criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein.
Measured: 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
A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a >= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and >= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented.
Measured: Week 16 to Week 48 (32 weeks)
Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum
A log rank test was performed and the Kaplan-Meier curve for time to disease flare from double-blind baseline (Week 16) to Week 48 was generated. Disease flare was defined as a >= 30% worsening in at least 3 of 6 JRA core set criteria and a minimum of 2 active joints, and >= 30% improvement in not more than 1 JRA criterion. The percentage of subjects without disease flare at each time point is presented.
Measured: Week 16 to Week 48 (32 weeks)
Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: >= 30% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core criteria are included in PedACR criteria.
Measured: Week 48
Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: >= 50% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria.
Measured: Week 48
Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase
Responders met the following criteria: >= 70% improvement in >= 3 of 6 JIA core set criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with the OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; number of active joints (joints with swelling or with LOM and with pain, tenderness or both); number of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core variables are included in PedACR criteria.
Measured: Week 48
Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
A 100 mm horizontal visual analog scale (VAS) was used to assess the Physician Global Assessment of Disease Activity. The left end of the VAS scale (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement.
Measured: Baseline and Week 48
Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
A 100 mm horizontal visual analog scale (VAS) was used to assess the Parent's/Patient's Global Assessment of Disease Activity. The left end of the VAS (0 mm) signified the absence of symptoms and the right end (100 mm) maximum disease activity. The mean change from open-label baseline to Week 48 was determined. Negative mean changes indicated improvement.
Measured: Baseline and Week 48
Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase
Serum levels of C-reactive protein (CRP) were measured at screening (open-label baseline) and at Week 48. Negative mean changes in CRP from open-label baseline to Week 48 indicated improvement.
Measured: Baseline and Week 48
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Open-Label Lead-In Phase Baseline
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Week 56
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Week 104
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Baseline
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL-LI baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Week 48
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. All core assessments are included in PedACR criteria.
Measured: Week 112
Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase
Responders met the following criteria: >= 30%/50%/70% improvement in >= 3 of 6 JIA core criteria, and >= 30% worsening in not more than 1 JIA criterion, compared with OL baseline. JIA core criteria included: physician's global assessment of disease severity; parent's/patient's global assessment of overall well-being; # of active joints (joints with swelling or with LOM and with pain, tenderness or both); # of joints with LOM; physical function of the Disability Index of Childhood Health Assessment Questionnaire; C-reactive protein. Final Visit = last visit per subject (up to 224 weeks).
Measured: Final Visit (up to 224 weeks of OLE FD phase)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2002 (estimated)
- Study startSep 2002
- Primary completionJan 2005
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Arthritis, Juvenile IdiopathicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abbott
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Laura Redden, M.D., Ph.D., Study director, Abbott
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00048542
- Sponsor's protocol ID
- DE038
- Status last verified
- Aug 2011
- First submitted
- 1 Nov 2002
- Last updated
- 22 Aug 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30054164Lovell 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.
PubMed 18716298
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Idiopathic Arthritis
- ClinicalTrials.gov ID
- NCT00048542
- Acronym / sponsor ID
- DE038
- Conditions
- Arthritis, Juvenile Idiopathic
- Keywords
- Polyarticular Juvenile Idiopathic Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- AbbottIndustry (pharma, biotech, devices)
- Study start
- Sep 2002
- Primary completion
- Jan 2005 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 5 Nov 2002 (estimated)
- Results
- Posted 11 Jan 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Adalimumab + MTX | Experimental | Biological: Double-Blind Adalimumab/Placebo + MTXSubjects 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. |
| Double-Blind Placebo + MTX | Placebo comparator | Biological: Double-Blind Adalimumab/Placebo + MTXSubjects 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. |
| Double-Blind Adalimumab | Experimental | Biological: Double-Blind Adalimumab/PlaceboSubjects 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. |
| Double-Blind Placebo | Placebo comparator | Biological: Double-Blind Adalimumab/PlaceboSubjects 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. |
| OLE BSA Adalimumab + MTX | Experimental | Drug: OLE BSA Adalimumab +/- MTXAll 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. |
| OLE BSA Adalimumab | Experimental | Drug: OLE BSA Adalimumab +/- MTXAll 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. |
| OLE FD Adalimumab + MTX | Experimental | Drug: OLE FD Adalimumab +/- MTXSubjects 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. |
| OLE FD Adalimumab | Experimental | Drug: OLE FD Adalimumab +/- MTXSubjects 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. |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Double-Blind Adalimumab/Placebo + MTXAlso: ABT-D2E7, HumiraSubcutaneous 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. | Biological | Double-Blind Adalimumab + MTX, Double-Blind Placebo + MTX |
| Double-Blind Adalimumab/PlaceboAlso: ABT-D2E7, HumiraSubcutaneous 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. | Biological | Double-Blind Adalimumab, Double-Blind Placebo |
| OLE BSA Adalimumab +/- MTXAlso: ABT-D2E7, HumiraComparison 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. | Drug | OLE BSA Adalimumab, OLE BSA Adalimumab + MTX |
| OLE FD Adalimumab +/- MTXAlso: ABT-D2E7, HumiraComparison 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. | Drug | OLE FD Adalimumab, OLE FD Adalimumab + MTX |
Primary outcome
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)
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.
17 secondary outcomes
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
Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase
Time frame: 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
Time frame: Week 16 to Week 48 (32 weeks)
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)
Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase
Time frame: Week 48
Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase
Time frame: Week 48
Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase
Time frame: Week 48
Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
Time frame: Baseline and Week 48
Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
Time frame: Baseline and Week 48
Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase
Time frame: Baseline and Week 48
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase
Time frame: Open-Label Lead-In Phase Baseline
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase
Time frame: Week 56
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase
Time frame: Week 104
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase
Time frame: Baseline
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase
Time frame: Week 48
Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase
Time frame: Week 112
Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase
Time frame: Final Visit (up to 224 weeks of OLE FD phase)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30054164Horneff 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.
- Derived from this study: PubMed 18716298Lovell 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Redden, M.D., Ph.D. study director
Abbott
31 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OLE BSA Adalimumab +/- MTX and OLE FD Adalimumab +/- MTX in people with Arthritis, Juvenile Idiopathic, run by Abbott at 31 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Germany, Belgium, Czechia, France and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00048542, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2011.