Arthritis, Juvenile
Conditions
Keywords
Methotrexate, Anti-TNFα Antibody, Golimumab, Pediatric Participants
Brief summary
The purpose of this study is to evaluate the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of golimumab administered intravenously (IV) to pediatric participants with polyarticular (affects 5 or more joints) juvenile (an onset before age 16) idiopathic (of unknown cause) arthritis (joint pain) (pJIA) manifested by greater than or equal to (\>=) 5 joints with active arthritis despite methotrexate (MTX) therapy for \>= 2 months.
Detailed description
This is a single arm, Open-label (all people know the identity of the intervention), multi-center (when more than one hospital or medical school team work on a medical research study) study to determine the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), efficacy (effectiveness) and safety of intravenous golimumab in participants with pJIA despite current treatment with methotrexate (MTX). The study will consist of 3 parts: Screening Phase (6 weeks); an Open-label Treatment Phase (consists of golimumab and MTX treatment for 52 weeks, wherein after Week 28, MTX dose change is allowed); Long-term Extension Phase (after Week 52 through Week 252) and Extended Treatment Period (after week 252). The maximal study duration for a participant will not exceed 832 weeks. All the eligible participants will be administered golimumab IV infusion and commercial MTX. Blood samples will be collected for evaluation of pharmacokinetics of study treatment. Participants' safety will be monitored throughout the study.
Interventions
DRUGGolimumab
Golimumab 80 mg/m\^2 IV infusion at Weeks 0, 4, and every 8 weeks through Week 244. At Week 252, participants who meet the criteria for the optional Extended Treatment Period (ETP) may continue treatment with golimumab 80 mg/m\^2 every 8 weeks after completion of the Week 252 assessments.
DRUGMethotrexate
Methotrexate BSA-based dose (10 to 30 mg/m\^2 per week for participants with BSA \<1.67 m\^2, or minimum of 15 mg/week for participants with BSA \>=1.67 m\^2) weekly at least through Week 28.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis must be made per Juvenile Idiopathic Arthritis (JIA) International League of Associations for Rheumatology (ILAR) diagnostic criteria and the onset of disease must have been before the participant's 16th birthday * Failure or inadequate response to at least a 2 month course of methotrexate (MTX) before screening * Participants must have greater than or equal to (\>=) 5 joints with active arthritis at screening and at Week 0 as defined by American College of Rheumatology (ACR) criteria (that is, a joint with either swelling, or in the absence of swelling, limited range of motion associated with pain on motion or tenderness) * Participants must have a screening C-reactive protein (CRP) of \>=0.1 milligram (mg)/deciliter (dL) with the exception of approximately 30 percent (%) of the study population * Participants must have active polyarticular juvenile idiopathic arthritis (pJIA) despite current use of oral, intramuscular, or subcutaneous MTX for \>=2 months before screening. For participants with body surface area (BSA) less than (\<)1.67 meter square (m\^2), the MTX dose must be between 10 to 30 milligram per meter square (mg/m\^2) per week and stable for \>=4 weeks before screening. For participants with BSA \>=1.67 m\^2, the MTX dose must be a minimum of 15 mg/week and must be stable for \>=4 weeks before screening. In situations where there is documented intolerance of doses greater than (\>)10 mg/m\^2 weekly (for participants with BSA \<1.67 m\^2) or \>=15 mg/week (for participants with BSA \>=1.67 m\^2); or where documented country or site regulations prohibit use of \>=15 mg of MTX per week in participants with BSA \>=1.67 m\^2, participants may be entered into the trial on a lower dose of MTX
Exclusion criteria
* Participant has initiated disease-modifying antirheumatic drugs (DMARDs) and/or immunosuppressive therapy within 4 weeks prior to first study agent administration * Participant has been treated with intra-articular, intramuscular or intravenous corticosteroids (including intramuscular corticotropin) during the 4 weeks before first study agent administration * Participant has been treated with any therapeutic agent targeted at reducing Interleukin (IL)-12 or IL 23, including but not limited to ustekinumab and ABT-874, within 3 months before first study agent administration * Participant has been treated with natalizumab, efalizumab, or therapeutic agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) during the 12 months before first study agent administration, or have evidence at screening of persistent depletion of the targeted lymphocyte after receiving any of these agents * Participant has been treated with alefacept within 3 months before first study agent administration * If a participant has been previously treated with an anti-tumor necrosis factor alpha (TNF alpha) agent, the reason for discontinuation of the anti-TNF alpha agent cannot have been a severe or serious adverse event consistent with the class of anti-TNF alpha agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Trough Concentration (C-trough) of Golimumab | Week 28 | Serum golimumab trough concentration at Week 28 was reported. |
| Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28 | Week 28 | AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Trough Concentration (C-trough) at Week 52 | Week 52 | Serum golimumab trough concentration at Week 52 was reported. |
| Baysesian Area Under Curve at Steady State (AUCss) at Week 52 | Week 52 | AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling). |
Countries
Argentina, Brazil, Canada, Chile, Israel, Mexico, Russia, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Golimumab Participants received 80 milligrams per meter square (mg/m\^2) golimumab as an intravenous (IV) infusion at Weeks 0, 4, and then every 8 weeks (q8w) till Week 52. Participants also received commercial methotrexate (MTX) weekly through Week 28 at the same body surface area (BSA)-based dosage (10 to 30 mg/m\^2 per week for participants with BSA less than \[\<\] 1.67 meter square \[m\^2\], or minimum of 15 mg/week for participants with BSA greater than or equal to \[\>=\] 1.67 m\^2) as at time of study entry. After Week 28, changes in MTX administration were permitted. Participants who completed Week 52 had the option to enter into the long-term extension (LTE) phase. Participants who opted not to enter the LTE completed an additional 8-week safety follow-up visit following the last administration of the study agent. Participants who entered LTE continued to receive 80 mg/m\^2 IV golimumab q8w through Week 244. All participants who completed Week 244 were followed for safety through Week 252. Participants who met the inclusion criteria entered the extended treatment period (ETP) and continued to receive 80 mg/m\^2 IV golimumab q8w from Week 252 to Week 420. | 127 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| ETP Period (Week 252 to Week 420) | Adverse Event | 1 |
| ETP Period (Week 252 to Week 420) | Other | 8 |
| ETP Period (Week 252 to Week 420) | Physician Decision | 3 |
| ETP Period (Week 252 to Week 420) | Withdrawal by Subject | 2 |
| LTE Period (Week 52 to Week 252) | Other | 43 |
| Treatment Period (Week 0-52) | Adverse Event | 11 |
| Treatment Period (Week 0-52) | Enrolled and not Treated | 3 |
| Treatment Period (Week 0-52) | Other | 1 |
| Treatment Period (Week 0-52) | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Golimumab |
|---|---|
| Age, Continuous | 11.6 years STANDARD_DEVIATION 3.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized More than one race | 4 Participants |
| Race/Ethnicity, Customized Other | 28 Participants |
| Race/Ethnicity, Customized White | 85 Participants |
| Region of Enrollment ARGENTINA | 18 Participants |
| Region of Enrollment BRAZIL | 16 Participants |
| Region of Enrollment CANADA | 7 Participants |
| Region of Enrollment CHILE | 7 Participants |
| Region of Enrollment ISRAEL | 2 Participants |
| Region of Enrollment MEXICO | 25 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 14 Participants |
| Region of Enrollment SOUTH AFRICA | 15 Participants |
| Region of Enrollment UNITED STATES | 23 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 127 | 1 / 127 | 0 / 32 |
| other Total, other adverse events | 74 / 127 | 57 / 127 | 8 / 32 |
| serious Total, serious adverse events | 9 / 127 | 18 / 127 | 3 / 32 |
Outcome results
Primary
Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28
AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).
Time frame: Week 28
Population: The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Golimumab | Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28 | 399 micrograms*day/milliliter (mcg*day/mL) |
Primary
Serum Trough Concentration (C-trough) of Golimumab
Serum golimumab trough concentration at Week 28 was reported.
Time frame: Week 28
Population: The pharmacokinetic (PK) analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Golimumab | Serum Trough Concentration (C-trough) of Golimumab | 0.50 micrograms per milliliter (mcg/mL) | Standard Deviation 0.427 |
Secondary
Baysesian Area Under Curve at Steady State (AUCss) at Week 52
AUCss was defined as area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).
Time frame: Week 52
Population: The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Golimumab | Baysesian Area Under Curve at Steady State (AUCss) at Week 52 | 421 mcg*day/mL |
Secondary
Serum Trough Concentration (C-trough) at Week 52
Serum golimumab trough concentration at Week 52 was reported.
Time frame: Week 52
Population: The PK analysis set included all treated participants (who received at least 1 infusion) who have sufficient PK samples for analysis. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Golimumab | Serum Trough Concentration (C-trough) at Week 52 | 0.52 mcg/mL | Standard Deviation 0.475 |