Juvenile Idiopathic Arthritis
Conditions
Keywords
Juvenile Idiopathic Arthritis, golimumab, juvenile arthritis, GO KIDS, anti TNF alpha medications, juvenile psoriatic arthritis
Brief summary
The purpose of this study is to evaluate the efficacy and safety of golimumab (CNTO 148) in patients who have active juvenile idiopathic arthritis (JIA) and at least 5 joints with active arthritis that have poor response to methotrexate.
Detailed description
Approximately 170 juvenile patients will take part in the study worldwide. All patients will receive 30mg/m2 (milligrams per meter squared, up to 50 mg per dose) of golimumab subcutaneously (injection under the skin) every 4 weeks from Week 0 through Week 12. At Week 16, patients who have shown at least a 30 percent improvement in their signs and symptoms from when they started the study will be randomized to receive either placebo (sham medicine injection) or 30 mg/m2 of golimumab injections every 4 weeks from week 16 through week 48. If a patient gets markedly worse and is receiving placebo injections, they will be restarted on golimumab at the next scheduled visit and will continue on golimumab. Patients can leave the study at any time without question. Between the Week 48 analyses timepoint to Week 144, which is subsequently amended to Week 248, all patients will receive golimumab 30mg/meter squared, unless, by measurements, they have been nearly cured (clinical remission) by being on placebo, whereby they will be discontinued from the study. Patients may have a change in background treatment after Week 48 based on therapeutic effect. Patients will continue active treatment after Week 48 in a long-term extension until Week 144, which is subsequently amended to Week 248. All patients will receive their fixed dose of commercial methotrexate throughout the study duration. Safety will be monitored up to 152 week, which is subsequently amended to 256 weeks including drawing blood and looking at laboratory tests, vital signs (eg, blood pressure), and the frequency and type of adverse events (side effects).
Interventions
DRUGCNTO 148 (Golimumab)
Patients will receive subcutaneous (SC) (under the skin) injection of golimumab 30 mg per square meter every 4 weeks from Week 0 through Week 248.
DRUGPlacebo
Patients who have a clinical response to golimumab at Week 16 and are randomly allocated to placebo, will receive SC injection of placebo every 4 weeks from Week 16 through Week 48.
DRUGMethotrexate
All patients will receive their fixed dose of commercial methotrexate (10 to 30 mg per square meter) weekly throughout the study duration.
Sponsors
Schering-Plough
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis must have been before the patient's 16th birthday * Disease duration of at least 6 months before study entry * Must have 5 or more joints with active arthritis * Must be taking a stable dose of methotrexate 10-30 mg/meter squared (patients with body surface area \[BSA\] 1.67 square meter or more must be taking a minimum of 15 mg/week of methotrexate) * May take a stable dose of prednisone less than 10 mg/day 4 weeks prior to entry or may take a stable dose of NSAIDS (non-steroidal anti-inflammatory drugs) 2 weeks prior to entry * Must have qualifying laboratory values at the first visit.
Exclusion criteria
* Have known allergies, hypersensitivity, or intolerance to golimumab or similar therapeutics * Are pregnant or breast-feeding, or planning a pregnancy or fathering a child within 6 months after the last study agent administration * Have initiated DMARDS and/or immunosuppressive therapy within 4 weeks prior to study initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 16 Who Did Not Experienced a Flare of Disease Through Week 48 | Week 16 through Week 48 | Percentage of participants with American College of Rheumatology (ACR) Ped 30 responders at Week 16 who did not experience a flare of disease between Week 16 and Week 48 calculated as number of participants with response and who did not experience flare divided by number of participants randomized. Flare of disease was defined as the worsening from Week 16 by 30% or more in 3 of the 6 ACR Pediatric (Ped) Core Set Variables with no more than 1 of the 6 ACR Ped Core Set variables improving by more than 30% at the time of the flare. The 6 variables are: physicians global assessment of disease, participants/parent global assessment of overall well-being, number of active joints (defined as either swelling, or in absence of swelling, limited range of motion associated with pain on motion or tenderness), number of joints with limited range of motion, physical function by childhood health assessment questionnaire, and erythrocyte sedimentation rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 48 | Week 16 through Week 48 | Percentage of participants with ACR 30 response at Week 48 was calculated as number of participants with ACR 30 response at Week 48 divided by number of participants randomized. ACR Ped 30 response was defined as the worsening from Week 16 by 30% or more in 3 of the 6 ACR Pediatric (Ped) Core Set Variables with no more than 1 of the 6 ACR Ped Core Set variables improving by more than 30% at the time of the flare. The 6 variables are: physicians global assessment of disease, participants/parent global assessment of overall well-being, number of active joints (defined as either swelling, or in absence of swelling, limited range of motion associated with pain on motion or tenderness), number of joints with limited range of motion, physical function by childhood health assessment questionnaire, and erythrocyte sedimentation rate. |
| Percentage of Participants With American College of Rheumatology (ACR) 30 Response Who Had Inactive Disease at Week 48 | Week 16 through Week 48 | Inactive disease is indicated by the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to juvenile idiopathic arthritis; no active uveitis (eye disease), normal erythrocyte sedimentation rate or C-reactive protein; physician global assessment of disease activity indicating no active disease; and duration of morning stiffness less than 15 minutes. |
| Percentage of Participants Who Achieved Clinical Remission While on Medication for Juvenile Idiopathic Arthritis (JIA) at Week 48 | Week 16 through Week 48 | Clinical remission while on medication for JIA is defined as inactive disease at each visit for a period of 6 months or more while on medication. Inactive disease is indicated by the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to juvenile idiopathic arthritis; no active uveitis (eye disease), normal erythrocyte sedimentation rate or C-reactive protein; physician global assessment of disease activity indicating no active disease; and duration of morning stiffness less than 15 minutes. |
Countries
Austria, Belgium, Brazil, Canada, Finland, Germany, Lithuania, Mexico, Netherlands, Poland, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group I: Participants Who Did Not Enter RW Period Enrolled participants who did not enter randomized withdrawal (RW) period, including those who discontinued prior Week 16, and those who were non-responders (did not achieve an American College of Rheumatology \[ACR\] Ped 30 response) at Week 16. | 19 |
| Group II: Placebo Subcutaneously (SC) + MTX Participants who were treated with golimumab 30 milligram per square meter (mg/m\^2) through Week 12 and were treated with placebo + Methotrexate (MTX) at Week 16 and continued on placebo + MTX through Week 48. | 11 |
| Group III: Placebo + MTX -> Golimumab 30 mg/m^2 + MTX Participants who were treated with golimumab 30 mg/m\^2 through Week 12 and were treated with placebo + MTX at Week 16 and switched to golimumab 30 mg/m\^2 + MTX at anytime during the study through Week 48. Adverse events are reported for participants who switched to golimumab 30 mg/m\^2 + MTX at anytime during the study through Week 48. | 65 |
| Group IV: Golimumab + MTX Participants were treated with golimumab 30 mg/m\^2 through Week 12 and who were treated with golimumab 30 mg/m\^2 + MTX at Week 16 and continued on golimumab 30 mg/m\^2 + MTX through Week 48. | 78 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 3 | 7 |
| Overall Study | Lack of Efficacy | 14 | 1 | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 3 |
| Overall Study | Recovery | 0 | 6 | 0 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 2 | 56 | 63 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Group I: Participants Who Did Not Enter RW Period | Group II: Placebo Subcutaneously (SC) + MTX | Group III: Placebo + MTX -> Golimumab 30 mg/m^2 + MTX | Group IV: Golimumab + MTX | Total |
|---|---|---|---|---|---|
| Age, Continuous | 11.8 years STANDARD_DEVIATION 4.4 | 13.6 years STANDARD_DEVIATION 2.2 | 10.7 years STANDARD_DEVIATION 4.66 | 11.1 years STANDARD_DEVIATION 4.43 | 11.2 years STANDARD_DEVIATION 4.44 |
| Region of Enrollment Austria | 1 participants | 0 participants | 2 participants | 2 participants | 5 participants |
| Region of Enrollment Belgium | 2 participants | 1 participants | 5 participants | 2 participants | 10 participants |
| Region of Enrollment Brazil | 1 participants | 0 participants | 3 participants | 4 participants | 8 participants |
| Region of Enrollment Canada | 2 participants | 0 participants | 0 participants | 5 participants | 7 participants |
| Region of Enrollment Finland | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Germany | 4 participants | 7 participants | 14 participants | 24 participants | 49 participants |
| Region of Enrollment Lithuania | 0 participants | 0 participants | 6 participants | 4 participants | 10 participants |
| Region of Enrollment Mexico | 2 participants | 1 participants | 8 participants | 11 participants | 22 participants |
| Region of Enrollment Netherlands | 0 participants | 0 participants | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Poland | 2 participants | 0 participants | 1 participants | 4 participants | 7 participants |
| Region of Enrollment Russian Federation | 4 participants | 1 participants | 12 participants | 12 participants | 29 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 12 participants | 7 participants | 21 participants |
| Sex: Female, Male Female | 15 Participants | 6 Participants | 51 Participants | 59 Participants | 131 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 14 Participants | 19 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 19 | 9 / 10 | 60 / 66 | 68 / 78 |
| serious Total, serious adverse events | 4 / 19 | 2 / 10 | 15 / 66 | 18 / 78 |
Outcome results
Primary
Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 16 Who Did Not Experienced a Flare of Disease Through Week 48
Percentage of participants with American College of Rheumatology (ACR) Ped 30 responders at Week 16 who did not experience a flare of disease between Week 16 and Week 48 calculated as number of participants with response and who did not experience flare divided by number of participants randomized. Flare of disease was defined as the worsening from Week 16 by 30% or more in 3 of the 6 ACR Pediatric (Ped) Core Set Variables with no more than 1 of the 6 ACR Ped Core Set variables improving by more than 30% at the time of the flare. The 6 variables are: physicians global assessment of disease, participants/parent global assessment of overall well-being, number of active joints (defined as either swelling, or in absence of swelling, limited range of motion associated with pain on motion or tenderness), number of joints with limited range of motion, physical function by childhood health assessment questionnaire, and erythrocyte sedimentation rate.
Time frame: Week 16 through Week 48
Population: Intent-to-treat (ITT) population included all participants achieving American College of Rheumatology (ACR) Pediatric (Ped) 30 response who were randomized at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 16 Who Did Not Experienced a Flare of Disease Through Week 48 | 52.6 Percentage of Participants |
| CNTO 148 (Golimumab) | Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 16 Who Did Not Experienced a Flare of Disease Through Week 48 | 59.0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Clinical Remission While on Medication for Juvenile Idiopathic Arthritis (JIA) at Week 48
Clinical remission while on medication for JIA is defined as inactive disease at each visit for a period of 6 months or more while on medication. Inactive disease is indicated by the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to juvenile idiopathic arthritis; no active uveitis (eye disease), normal erythrocyte sedimentation rate or C-reactive protein; physician global assessment of disease activity indicating no active disease; and duration of morning stiffness less than 15 minutes.
Time frame: Week 16 through Week 48
Population: ITT population included all participants achieving ACR Ped 30 response who were randomized at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Remission While on Medication for Juvenile Idiopathic Arthritis (JIA) at Week 48 | 11.8 Percentage of Participants |
| CNTO 148 (Golimumab) | Percentage of Participants Who Achieved Clinical Remission While on Medication for Juvenile Idiopathic Arthritis (JIA) at Week 48 | 12.8 Percentage of Participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 48
Percentage of participants with ACR 30 response at Week 48 was calculated as number of participants with ACR 30 response at Week 48 divided by number of participants randomized. ACR Ped 30 response was defined as the worsening from Week 16 by 30% or more in 3 of the 6 ACR Pediatric (Ped) Core Set Variables with no more than 1 of the 6 ACR Ped Core Set variables improving by more than 30% at the time of the flare. The 6 variables are: physicians global assessment of disease, participants/parent global assessment of overall well-being, number of active joints (defined as either swelling, or in absence of swelling, limited range of motion associated with pain on motion or tenderness), number of joints with limited range of motion, physical function by childhood health assessment questionnaire, and erythrocyte sedimentation rate.
Time frame: Week 16 through Week 48
Population: Intent-to-treat (ITT) population included all participants achieving American College of Rheumatology (ACR) Pediatric (Ped) 30 response who were randomized at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 48 | 55.3 Percentage of Participants |
| CNTO 148 (Golimumab) | Percentage of Participants With American College of Rheumatology (ACR) 30 Response at Week 48 | 52.6 Percentage of Participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 30 Response Who Had Inactive Disease at Week 48
Inactive disease is indicated by the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to juvenile idiopathic arthritis; no active uveitis (eye disease), normal erythrocyte sedimentation rate or C-reactive protein; physician global assessment of disease activity indicating no active disease; and duration of morning stiffness less than 15 minutes.
Time frame: Week 16 through Week 48
Population: ITT population included all participants achieving ACR Ped 30 response who were randomized at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 30 Response Who Had Inactive Disease at Week 48 | 27.6 Percentage of Participants |
| CNTO 148 (Golimumab) | Percentage of Participants With American College of Rheumatology (ACR) 30 Response Who Had Inactive Disease at Week 48 | 39.7 Percentage of Participants |