Clinical trial NCT02277444
Conditions: Arthritis, Juvenile
Keywords: Methotrexate Anti-TNFα Antibody Golimumab Pediatric Participants
Sponsor: Janssen Research & Development, LLC
Start date: 2014-12-22; Completion date: 2024-09-27
Enrollment: 130 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Participants will receive 80 milligram per meter square (mg/m\^2) as an intravenous (IV) infusion at Weeks 0, 4, and every 8 weeks thereafter up to Week 244, along with 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 the time of study entry. 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.
Interventions: intervention 1: Golimumab intervention 2: Methotrexate
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents:
Prot_000.pdf: 
1
Status: Approved, Date: 16 December 2019
Janssen Research & Development*
Clinical Protocol
A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα 
Antibody, in Pediatric Subjects With Active Polyarticular Course Juvenile Idiopathic 
Arthritis Despite Methotrexate Therapy
GO-VIVA
Protocol CNTO148JIA3003; Phase 3
Amendment INT-4
SIMPONI® (golimumab) for Intravenous Use
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity acting as the Sponsor for Janssen Research & Development 
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen 
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Infectious Diseases BVBA; Janssen 
R&D Ireland; or Janssen Research & Development, LLC. The term “Sponsor” is used throughout the 
protocol to represent these various legal entities; the Sponsor is identified on the Contact Information 
page that accompanies the protocol.
This study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
Status:
Approved
Date:
16 December 2019
Prepared by:
Janssen Research & Development, LLC
EDMS No:
EDMS-ERI-71227414, 6.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
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SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 64
TIME AND EVENTS SCHEDULES ............................................................................................................ 69
ABBREVIATIONS ...................................................................................................................................... 77
1.
INTRODUCTION................................................................................................................................ 79
1.1.
Background .................................................................................................................................... 79
1.1.1.
Juvenile Idiopathic Arthritis......................................................................................................... 79
1.1.2.
Golimumab Clinical Studies in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis............... 80
1.1.2.1.
Intravenous Golimumab in Adult Rheumatoid Arthritis ........................................................... 81
1.1.2.2.
Subcutaneous Golimumab in Juvenile Idiopathic Arthritis ...................................................... 84
1.2.
Overall Rationale for the Study...................................................................................................... 86
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 87
2.1.
Objectives ...................................................................................................................................... 87
2.2.
Hypothesis ..................................................................................................................................... 87
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 87
3.1.
Overview of Study Design.............................................................................................................. 87
3.1.1.
Week 0 Through Week 28.......................................................................................................... 89
3.1.2.
Week 28 Through Week 52........................................................................................................ 89
3.1.3.
Week 52 Through Week 252 (Long-term Extension) ................................................................. 89
3.1.4.
After Week 252 (Extended Treatment Period) ........................................................................... 90
3.1.5.
End of Study Definition ............................................................................................................... 90
3.2.
Study Design Rationale.................................................................................................................. 90
3.2.1.
Blinding, Control, Study Phase/Periods, Treatment Groups ...................................................... 90
3.2.2.
Dose Selection............................................................................................................................ 90
3.2.3.
Rationale..................................................................................................................................... 91
4.
SUBJECT POPULATION.................................................................................................................. 91
4.1.
Inclusion Criteria ............................................................................................................................ 92
4.2.
Exclusion Criteria ........................................................................................................................... 97
4.3.
Prohibitions and Restrictions ....................................................................................................... 100
5.
TREATMENT ALLOCATION AND BLINDING............................................................................... 101
6.
DOSAGE AND ADMINISTRATION ................................................................................................ 101
6.1.
Golimumab................................................................................................................................... 101
6.2.
Methotrexate ................................................................................................................................ 102
7.
TREATMENT COMPLIANCE.......................................................................................................... 102
8.
PRESTUDY AND CONCOMITANT THERAPY .............................................................................. 102
9.
STUDY EVALUATIONS .................................................................................................................. 104
9.1.
Study Procedures......................................................................................................................... 104
9.1.1.
Overview................................................................................................................................... 104
9.1.2.
Screening Phase ...................................................................................................................... 105
9.1.3.
Treatment Phase: Week 0 Through Week 28 .......................................................................... 106
9.1.4.
Treatment Phase: After Week 28 Through Week 52 ............................................................... 107
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SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
9.1.5.
Long-Term Extension Phase: After Week 52 Through Week 252 ........................................... 107
9.1.6.
Extended Treatment Period...................................................................................................... 108
9.2.
Efficacy......................................................................................................................................... 108
9.2.1.
Evaluations ............................................................................................................................... 108
9.2.1.1.
Joint Evaluation ..................................................................................................................... 108
9.2.1.2.
American College of Rheumatology Pediatric Response ..................................................... 109
9.2.1.3.
Physician Global Assessment of Disease Activity................................................................. 110
9.2.1.4.
Childhood Health Assessment Questionnaire....................................................................... 110
9.2.1.5.
C-reactive Protein.................................................................................................................. 111
9.2.1.6.
Juvenile Arthritis Disease Activity Score (JADAS) ................................................................ 111
9.2.2.
Endpoints.................................................................................................................................. 111
9.3.
Pharmacokinetics and Immunogenicity ....................................................................................... 112
9.3.1.
Evaluations ............................................................................................................................... 112
9.3.2.
Analytical Procedures............................................................................................................... 112
9.3.3.
Pharmacokinetic Parameters ................................................................................................... 113
9.3.4.
Immunogenicity Assessments (Antibodies to Golimumab) ...................................................... 113
9.4.
Safety Evaluations ....................................................................................................................... 113
9.5.
Sample Collection and Handling.................................................................................................. 117
10.
SUBJECT COMPLETION/WITHDRAWAL..................................................................................... 118
10.1.
Completion ................................................................................................................................... 118
10.2.
Discontinuation of Study Treatment............................................................................................. 118
10.3.
Withdrawal from the Study........................................................................................................... 120
11.
STATISTICAL METHODS............................................................................................................... 120
11.1.
Subject Information ...................................................................................................................... 120
11.2.
Sample Size Determination ......................................................................................................... 121
11.3.
Efficacy Analyses ......................................................................................................................... 121
11.4.
Pharmacokinetic Analyses........................................................................................................... 122
11.5.
Immunogenicity Analyses ............................................................................................................ 122
11.6.
Pharmacokinetic/Pharmacodynamic Analyses............................................................................ 122
11.7.
Safety Analyses ........................................................................................................................... 122
11.8.
Interim Analysis............................................................................................................................ 123
11.9.
Data Monitoring Committee ......................................................................................................... 123
12.
ADVERSE EVENT REPORTING .................................................................................................... 123
12.1.
Definitions .................................................................................................................................... 124
12.1.1.
Adverse Event Definitions and Classifications ......................................................................... 124
12.1.2.
Attribution Definitions................................................................................................................ 125
12.1.3.
Severity Criteria ........................................................................................................................ 126
12.2.
Special Reporting Situations........................................................................................................ 126
12.3.
Procedures................................................................................................................................... 126
12.3.1.
All Adverse Events.................................................................................................................... 126
12.3.2.
Serious Adverse Events ........................................................................................................... 127
12.3.3.
Pregnancy................................................................................................................................. 128
12.4.
Events of Special Interest ............................................................................................................ 129
12.5.
Contacting Sponsor Regarding Safety......................................................................................... 129
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 129
13.1.
Procedures................................................................................................................................... 129
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 129
14.
STUDY DRUG INFORMATION....................................................................................................... 129
14.1.
Physical Description of Study Drug.............................................................................................. 129
14.2.
Packaging .................................................................................................................................... 130
14.3.
Labeling........................................................................................................................................ 130
14.4.
Preparation, Handling, and Storage............................................................................................. 130
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SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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14.5.
Drug Accountability ...................................................................................................................... 130
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 131
16.
ETHICAL ASPECTS ....................................................................................................................... 131
16.1.
Study-Specific Design Considerations......................................................................................... 131
16.2.
Regulatory Ethics Compliance..................................................................................................... 132
16.2.1.
Investigator Responsibilities ..................................................................................................... 132
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 132
16.2.3.
Informed Consent ..................................................................................................................... 134
16.2.4.
Privacy of Personal Data .......................................................................................................... 135
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 135
16.2.6.
Country Selection ..................................................................................................................... 135
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 136
17.1.
Protocol Amendments.................................................................................................................. 136
17.2.
Regulatory Documentation .......................................................................................................... 136
17.2.1.
Regulatory Approval/Notification .............................................................................................. 136
17.2.2.
Required Prestudy Documentation........................................................................................... 136
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 137
17.4.
Source Documentation................................................................................................................. 137
17.5.
Case Report Form Completion .................................................................................................... 138
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 139
17.7.
Record Retention ......................................................................................................................... 139
17.8.
Monitoring .................................................................................................................................... 140
17.9.
Study Completion/Termination..................................................................................................... 141
17.9.1.
Study Completion ..................................................................................................................... 141
17.9.2.
Study Termination..................................................................................................................... 141
17.10.
On-Site Audits .............................................................................................................................. 141
17.11.
Use of Information and Publication.............................................................................................. 141
REFERENCES.......................................................................................................................................... 144
ATTACHMENT 1 QUANTIFERON®-TB GOLD TESTING....................................................................... 146
ATTACHMENT 2 TUBERCULIN SKIN TESTING ................................................................................... 149
ATTACHMENT 3 HEPATITIS B VIRUS (HBV) SCREENING................................................................. 151
ATTACHMENT 4: ANTICIPATED EVENTS ............................................................................................ 152
ATTACHMENT 5: SLIT LAMP EVALUATIONS...................................................................................... 153
ATTACHMENT 6: EXTENDED TREATMENT PERIOD .......................................................................... 154
INVESTIGATOR AGREEMENT ............................................................................................................... 161
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SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Screening Through Week 52.................................................................................................... 69
Table 2:
From Week 60 Through Week 156 (Long-term Extension)...................................................... 73
Table 3:
From Week 164 Through Week 252 (Continuation of Long-term Extension) .......................... 75
Table 4:
Approximate Volume of Blood to be Collected From Each Subject Through Week 252 ....... 105
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 88
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
10 March 2014
Amendment 1
12 August 2014
Amendment 2
11 July 2016
Amendment 3
28 February 2017
Amendment 4
16 December 2019
Amendments below are listed beginning with the most recent amendment.
Amendment 4 (16 December 2019)
The overall reason for the amendment: The overall reasons for this amendment are: 1) to allow continued 
treatment of subjects in the long-term extension (LTE) phase of the study (Week 52 through Week 252) that more 
closely resembles a real-world setting, collects critical safety information, and reduces the burden to subjects, and 2) 
to add details regarding an Extended Treatment Period (ETP) which allows subjects who are <18 years of age who 
are benefiting from treatment to continue to receive golimumab after Week 252 if the drug is not commercially 
available.
Applicable Section(s)
Description of Change(s)
Rationale: To change the collection of concomitant medications during the LTE to review and documentation of 
concomitant medications in source with update to the concomitant medications case report form (CRF) page to 
include only those medications that are associated with adverse events (AEs) and serious adverse events (SAEs).
Corresponding text was updated in Section 8 (Prestudy and Concomitant Therapy).
Time and Events 
Schedules
Table 2 and 3
Concomitant medication collection has been updated to indicate that during the LTE, 
collection of concomitant medications is limited to only those medications associated with 
AEs and SAEs.
Footnote c.
c. Review concomitant medications with subject and document in source; update 
concomitant medication CRF page to include only those medications that are 
associated with AEs and SAEs (ie, used to treat event or suspected in causing event).
8. Prestudy and 
Concomitant Therapy
Prestudy JIA medications administered before the first dose of study agent must be 
recorded at screening. All concomitant therapies must be recorded throughout through
Week 52 of the study beginning with the administration of the first dose of the study drug. 
After Week 52, the investigator will review concomitant medications with the subject 
and document in source, and record on the CRF page only those concomitant 
medications that are associated with AEs and SAEs (ie, used to treat event or 
suspected in causing event).
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, 
herbal supplements; non-pharmacologic therapies such as electrical stimulation and 
acupuncture) different from the study drug must be recorded in the CRF through 
Week 52. Recorded information will include a description of the type of the drug, 
treatment period, dosing regimen, route of administration, and its indication. Modification 
of an effective pre-existing therapy should not be made for the explicit purpose of entering 
a subject into the study.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: To change the frequency of review of systems, QuantiFERON®-TB Gold test, and the collection of vital 
signs before, during, and after an infusion in the LTE to at the discretion of the investigator to more closely follow 
standard medical practice. Corresponding text was updated in Section 9.4 (Safety Evaluations).
Time and Events 
Schedules
Table 2 and 3
Review of systems, QuantiFERON®-TB Gold test, and requirement for collection of vital 
signs before, during, and after the infusion have been updated to indicate that they are to 
be performed at the discretion of the investigator during the LTE.
Footnote d.
d. Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute intervals 
during the infusion); and at 60 and 90 minutes (during the 1-hour observation period 
following the infusion).
Footnote f.
f. Testing is not required for subjects with a history of latent TB and ongoing treatment for 
latent TB or documentation of having completed adequate treatment
Time and Events 
Schedules
Table 2
Footnote d.
d. Perform at the discretion of the investigator.
Time and Events 
Schedules
Table 3
Footnote e.
e. Perform at the discretion of the investigator.
9.4. Safety 
Evaluations 
(Vital Signs)
Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute intervals during 
the infusion); and at 60 and 90 minutes (during the 1-hour observation period following 
the infusion) through Week 52. After Week 52, vital signs should be taken at the 
discretion of the investigator.
9.4. Safety 
Evaluations 
(Physical 
Examination)
Physical examinations, including a skin exam at every physical examination and Tanner 
staging at least every 6 months for sexual maturity will be performed (through Week 52 
only) according to the Time and Events Schedule. Review of systems will be performed at 
all visits through Week 52 to evaluate for new symptomatology and if necessary, full 
physical examination may be performed at investigator discretion. After Week 52, review 
of systems will be performed at investigator discretion. Any clinically significant 
abnormalities persisting at the end of the study will be followed by the investigator until 
resolution or until reaching a clinically stable endpoint.
9.4. Safety 
Evaluations
(Early Detection of 
Active Tuberculosis)
To aid in the early detection of TB, reactivation, or new TB infection during study 
participation, subjects must be evaluated for signs and symptoms of active TB at scheduled 
visits (refer to Time and Events Schedule) or by telephone contact approximately every 8 
to 12 weeks through Week 252. After Week 252, TB evaluation will be carried out at 
investigator discretion and according to local and country guidelines for 
immunosuppressed patients. The following series of questions is suggested for use 
during the evaluation.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
9.4. Safety 
Evaluations 
(Early Detection of 
Active Tuberculosis)
Annual QuantiFERON®-TB Gold (and tuberculin skin) testing at Week 52 is not required 
for subjects with a history of latent TB, and ongoing treatment for latent TB, or 
documentation of having completed adequate treatment for TB. After Week 52, testing 
for latent TB should be performed at the discretion of the investigator and according 
to local and country guidelines.
Subjects who experience close contact with an individual with active TB during the 
conduct of the study must should have a repeat chest radiograph, a repeat 
QuantiFERON®-TB Gold test, a repeat tuberculin skin test in countries in which the 
QuantiFERON®-TB Gold test is not approved/registered, and, if possible, referral to a 
physician specializing in TB to determine the subject’s risk of developing active TB and 
whether treatment for latent TB is warranted. The QuantiFERON®-TB Gold test (and 
tuberculin skin test) does not need to be repeated for subjects with a history of latent TB, 
and ongoing treatment for latent TB, or documentation of having completed adequate 
treatment for TB. If the QuantiFERON®-TB Gold test result is indeterminate, the test 
should be repeated as outlined in Section 9.1.2. Subjects should be encouraged to return 
for all subsequent scheduled study visits according to the protocol.
Rationale: To remove Tanner staging during the LTE since this exam may place investigators and subjects in an 
unnecessary uncomfortable situation, may be particularly burdensome for subjects, and no safety concerns have 
been identified.
Time and Events 
Schedules
Table 2
Footnote e.
e. c. Includes skin examination at every physical examination and Tanner staging 
approximately every 6 months.
Time and Events 
Schedules
Table 3
Footnote f.
f. c. Includes skin exam and Tanner staging.
Rationale: To decrease the frequency of routine laboratory analyses and antinuclear antibodies (ANA)/anti-dsDNA 
antibodies collected during the LTE. With decreased laboratory sampling, Footnote c. was added to Table 4 to 
indicate that the total volume of blood to be collected from each subject is decreased with the implementation of 
Protocol Amendment 4.
Time and Events 
Schedules
Table 2 and 3
The frequency of collection of routine laboratory analyses during the LTE has been 
decreased from every 24 weeks to once yearly. The collection of ANA/anti-dsDNA 
antibodies has been changed from occurring every 24 weeks to occurring only at the end of 
the LTE and at the final safety follow-up visit.
Table 4. Approximate 
Volume of Blood to 
be Collected From 
Each Subject Through 
Week 252
Footnote c.
c. The approximate total volume is the maximum volume of blood collected from a 
subject during the study; with implementation of Protocol Amendment 4, the volume 
of blood collected will be decreased.
Rationale: To change the frequency of collection of chest x-rays during the LTE to at the discretion of the 
investigator.
Time and Events 
Schedules
Table 2
Footnote g.
g. Chest x-ray screening should be performed at the discretion of the investigator and
as per local and country regulations for initiation of children with JIA who are receiving
immunosuppressive agents in children with JIA and who are at risk of TB.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Time and Events 
Schedules
Table 3
Footnote h.
h. g. Chest x-ray screening should be performed at the discretion of the investigator 
and as per local and country regulations for initiation of children with JIA who are 
receiving immunosuppressive agents in children with JIA and who are at risk of TB.
Rationale: To change the frequency of uveitis and slit lamp evaluations during the LTE to at the discretion of the 
investigator and per standard of care. Corresponding text was updated in Section 9.4 (Safety Evaluations) and 
Attachment 5 (Slit Lamp Evaluations).
Time and Events 
Schedules
Table 2 and 3
Evaluation of uveitis has been updated to indicate that the evaluation is to be performed at 
the discretion of the investigator during the LTE.
Time and Events 
Schedules
Table 2
Footnote h.
h. Evaluations (based on physical examination and interview) should be performed by at 
the discretion of the investigator at least every 6 months in all subjects. In addition, all 
subjects are required to have sSlit lamp evaluations performed by an 
ophthalmologist/optometrist during the study at the discretion of the investigator and 
per standard of care intervals (based on JIA subtype, ANA test results, age at JIA onset, 
and JIA duration) as specified in Attachment 5.
Time and Events 
Schedules
Table 3
Footnote i.
i. h. Evaluations (based on physical examination and interview) should be performed by at 
the discretion of the investigator at least every 6 months in all subjects. In addition, all 
subjects are required to have sSlit lamp evaluations performed by an 
ophthalmologist/optometrist during the study at the discretion of the investigator and 
per standard of care intervals (based on JIA subtype, ANA test results, age at JIA onset, 
and JIA duration) as specified in Attachment 5.
9.4. Safety 
Evaluations (Uveitis 
Evaluations)
All subjects will be assessed for new-onset uveitis at screening and at least every 6 months 
thereafter through Week 52 by the investigator based on physical examination and 
interview. After Week 52, uveitis evaluations will be performed at investigator 
discretion. This consists of an assessment of signs and symptoms of uveitis, including, but 
not limited to, eye redness, light sensitivity, changes in vision, and floaters. Based upon 
changing clinical standards, examinations may be more frequent.
In addition, all subjects are required to have slit lamp evaluations performed by an 
ophthalmologist/optometrist during the study through Week 52 at intervals (based on JIA 
subtype, ANA test results, age at JIA onset, and JIA duration) as specified in 
Attachment 5. After Week 52, slit lamp evaluations will be performed at the discretion 
of the investigator and per standard of care.
Attachment 5: Slit 
Lamp Evaluations
Through Week 52, aAll subjects are required to have slit lamp evaluations performed by
an ophthalmologist/optometrist during the study at intervals (based on JIA subtype, ANA 
test results, age at JIA onset, and JIA duration) as specified in the table below. After 
Week 52, slit lamp evaluations will be performed at the discretion of the investigator 
and per standard of care. The date of the screening visit and the ANA test results during 
screening (as applicable depending on the JIA subtype) should be used to determine when 
the first slit lamp evaluation should be performed during the study. The interval for the slit 
lamp evaluations may be adjusted thereafter based on the subject’s ANA test results and 
JIA disease duration after screening. However, once a subject tests positive for ANA at 
any time during the study (and regardless if the subject subsequently tests negative for 
ANA), the subject should be considered ANA positive when determining the frequency of 
slit lamp evaluations.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: To change the length of infusion reaction evaluation from at least 60 minutes to at the discretion of the 
investigator. Corresponding text was updated in Section 9.4 (Safety Evaluations).
Time and Event 
Schedules
Table 2
Footnote j.
j. Subjects will be observed at the discretion of the investigator for at least 60 minutes
after the administration of study agent for symptoms of an infusion reaction.
Time and Event 
Schedules
Table 3
Footnote k.
k. j. Subjects will be observed at the discretion of the investigator for at least 60 minutes
after the administration of study agent for symptoms of an infusion reaction.
9.4. Safety 
Evaluations (Infusion 
Reaction Evaluations)
An infusion reaction is any unfavorable or unintended sign that occurs during the infusion 
or within 1 hour of completion of the infusion. All subjects must be carefully observed for 
symptoms of an infusion reaction. Through Week 52, sSubjects will be observed for at 
least 60 minutes after completion of the IV administration of study agent for symptoms of 
an infusion reaction. After Week 52, subjects will be observed at the discretion of the 
investigator after completion of the IV administration of study agent for symptoms of 
an infusion reaction. If an infusion reaction is observed, the subject should be treated at 
the investigator’s discretion.
9.4 Safety 
Evaluations (Allergic 
Reactions)
Throughout the studyWeek 52, all subjects must be observed carefully for symptoms of an 
allergic reaction (eg, urticaria, itching, hives) for at least 60 minutes after the completion 
of the infusion. After Week 52, subjects must be observed carefully for symptoms of 
an allergic reaction at the discretion of the investigator after completion of the 
infusion. If mild or moderate allergic reaction is observed, acetaminophen or NSAIDs and 
diphenhydramine at approved pediatric doses may be administered.
Rationale: To remove efficacy assessments from the LTE and add requirement for investigators to sign an annual 
attestation form regarding subject’s receipt of continued benefit of treatment. The attestation form will be 
maintained in the subject’s source documents. As no efficacy assessments will be collected during the LTE, 
instructions regarding Childhood Health Assessment Questionnaire (CHAQ) collection are no longer needed.
Time and Event 
Schedules
Table 2 and 3
All efficacy assessments have been removed from visits during the LTE.
Time and Event 
Schedules
Table 2 
Footnote k.
k. JIA assessments include the following:  Physician Global Assessment of Disease 
Activity, Childhood Health Assessment Questionnaire (CHAQ), and duration of morning 
stiffness.  CHAQ should be completed before any tests, procedures, or other 
consultations for that visit to prevent influencing subjects’ perceptions. Investigator 
will complete an annual attestation form to document that subject is benefiting from 
treatment.
Time and Event 
Schedules
Table 3
Footnote l.
l. k. JIA assessments include the following:  Physician Global Assessment of Disease 
Activity, Childhood Health Assessment Questionnaire (CHAQ), and duration of morning 
stiffness.  CHAQ should be completed before any tests, procedures, or other 
consultations for that visit to prevent influencing subjects’ perceptions. Investigator 
will complete an annual attestation form to document that subject is benefiting from 
treatment.
Time and Event 
Schedules
Table 2 and 3
Footnote l.
l. CHAQ to be completed by the parent or caregiver; preferably the same parent or 
caregiver should complete at every visit. Subjects who are 15 to <18 years of age at study 
entry may complete the assessment jointly with the parent/caregiver.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
11
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
3.1.3. Week 52 
through Week 252 
(Long-term 
Extension)
During the LTE, all subjects will continue to receive golimumab q8w (±1 week) through 
Week 244. For children who have completed the full trial period of 252 weeks and for 
whom drug is proven beneficial but is not commercially available for pJIA indication (or 
patient does not qualify for insurance to pay for the drug) IV golimumab will continue to 
be provided by the Sponsor, as described in Section 3.1.4. Between Week 52 and 
Week 252, disease activity will be monitored and assessed by investigators, and benefit 
of treatment will be documented in the subject’s source documents by investigators 
on a yearly basis via an attestation form documented in the CRF every 16 weeks; 
infusions and safety measurements will be done every 8 weeks at the investigative site 
according to the Time and Events Schedule.
9.1.5. Long-Term 
Extension Phase: 
After Week 52 
through Week 252
Subjects will have safety, efficacy, PK, and immunogenicity evaluations performed 
according to the Time and Events Schedules (Table 2 and Table 3). After Week 52, 
disease activity will be monitored and assessed by investigators. Investigators will fill 
out an annual attestation form to document that a subject is benefiting from 
treatment. Subjects who discontinue study agent administration prior to Week 244 
without withdrawing consent should return for a final safety follow-up visit approximately 
8 weeks after their last study agent infusion (Section 10.2).
9.2.1. Evaluations
The Time and Events Schedule summarizes the frequency and timing of efficacy 
measurements applicable to this study (Table 1, Table 2, and Table 3). After Week 52, 
investigators will complete an attestation form annually to document that the subject 
is benefiting from treatment.
9.2.1.1. Evaluations 
(Joint Evaluation)
It is preferable that the consistent joint assessor who performs the baseline joint 
assessments for a subject also performs the joint assessments for that subject for all 
subsequent visits through the final efficacy assessment at Week 244 52.
Rationale: To update the instructions regarding visits outside the recommended acceptable visit window after 
Week 52 in order to more closely resemble a real-world setting and reduce the burden to subjects.
9.1.1. Overview
The Time and Events Schedules summarize the frequency and timing of efficacy, PK, 
immunogenicity, and safety measurements applicable to this study (Table 1, Table 2, and 
Table 3). All scheduled study visits should occur within ±3 days of the intended visit
through Week 28 and ±1 week from Week 28 through Week 244. Through Week 52, iIf 
the recommended acceptable window cannot be observed, the Sponsor must be contacted 
before scheduling a visit. After Week 52, if the recommended acceptable window 
cannot be observed, the reason for the deviation must be recorded in source 
documents. After Week 252, study procedures will be performed as described in 
Attachment 6.
Rationale: To update the assessments performed at unscheduled visits based on the changes to Time and Events 
Schedule.
9.1.1. Overview
At every unscheduled visit, the investigator will perform the following evaluations:

Review of systems (after Week 52, at the discretion of the investigator)

Vital signs (after Week 52, at the discretion of the investigator)

TB questionnaire

Adverse events

Review of concomitant medications (after Week 52, medications should be 
reviewed and documented in source; medications used to treat or associated with 
AEs and SAEs should be recorded on the CRF)

Safety laboratory evaluations (after Week 52, at the discretion of the investigator)
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
12
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: To clarify the responsibilities of the investigator during the LTE based on the changes to Time and 
Events Schedule.
9.1.5. Long-Term 
Extension Phase: 
After Week 52 
through Week 252
Review of systems, collection of vital signs, QuantiFERON®-TB Gold testing, uveitis 
evaluations (including slit lamp evaluations), and chest x-ray screening will be 
performed at the discretion of the investigator, refer to the Time and Events 
Schedules (Table 2 and Table 3). It is the responsibility of the investigator to carry 
out all assessments per standard of practice and to update the CRF with all 
information related to AEs and SAEs (eg, concomitant medications).
Rationale: To update the assessments performed at the final safety follow-up visit based on the changes to Time 
and Events Schedule.
Time and Events 
Schedules
Table 2 
Footnote b.
b. All subjects who discontinue study agent administration before Week 156 but do not 
withdraw consent must return to the study site for a final safety visit approximately 
8 weeks after the last infusion (Section 10.2). Collection of vital signs, review of
symptoms, and uveitis evaluation are performed at the final safety follow-up visit at 
the discretion of the investigator.
Time and Events 
Schedules
Table 3
Footnote b.
b. All subjects who discontinue study agent administration before Week 244 but do not 
withdraw consent must return to the study site for a final safety visit approximately 
8 weeks after the last infusion (Section 10.2). Collection of vital signs, review of 
symptoms, and uveitis evaluation are performed at the final safety follow-up visit at
the discretion of the investigator.
10.2. Discontinuation 
of Study Treatment
Subjects who discontinue study agent infusions but do not terminate study participation 
will have the following assessments performed at the final safety follow-up visit:
•
Safety evaluations including (vital signs, review of systems, AE review, TB 
evaluation, uveitis evaluation and the collection of a blood sample for routine laboratory 
analyses, and determination of the presence of ANA/anti-double-stranded 
deoxyribonucleic acid (dsDNA) antibodies, and antibodies to golimumab).; after 
Week 52, other safety evaluations are performed at the discretion of the investigator 
(vital signs, review of systems, uveitis evaluation).
•
Concomitant medication review (after Week 52, medications should be reviewed 
and documented in subject’s source records; medications used to treat or associated 
with AEs and SAEs should be recorded in the source document as well as the CRF).
•
Efficacy evaluations (joint assessments, JIA assessments, and collection of blood 
sample for CRP) through Week 52 only.
•
Blood samples drawn for measurement of golimumab concentration for all subjects at 
the final safety follow-up visit.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
13
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: To add an ETP in order to allow subjects <18 years of age who are demonstrating benefit from treatment 
with golimumab to continue treatment after Week 252 if the drug is not commercially available. An additional 
database lock at the end of the ETP is planned, which will be the final database lock for the study.
Synopsis (Overview 
of Study Design)
All subjects will receive 80 mg/m2 golimumab as an IV infusion (over 30±10 minutes) at 
Weeks 0, 4, and q8w (±3 days) through Week 28 and q8w (±1 week) thereafter (maximum 
single dose 240 mg [maximum body surface area (BSA) 3.0 m2 x 80 mg/m2]). Commercial 
MTX is to be administered at a stable dose of 10-30 mg/m2/week in subjects with BSA 
<1.67 m2 or a stable minimum dose of 15 mg/week in subjects with BSA ≥1.67 m2 through 
Week 28 (unless lower doses of MTX are administered for documented safety reasons or 
unless documented country or site regulations prohibit dose of 15 mg/week or above in 
subjects with BSA ≥1.67 m2). Subjects who complete the study at Week 52 will have the 
option to enter into the long-term extension (LTE) phase of the study. During the LTE, all 
subjects will continue to receive 80 mg/m2 IV golimumab q8w (±1 week; maximum single 
dose 240 mg) through Week 244. All subjects who complete the Week 244 visit are 
expected to participate in the safety follow-up visit at Week 252. Subjects <18 years of 
age who have completed the study through Week 252 and are benefiting from 
treatment, but for whom golimumab is not commercially available for the treatment 
of pJIA, will have the option to continue to receive golimumab (80 mg/m2 q8w) in the 
Extended Treatment Period (ETP). The first dose of golimumab in the ETP is 
administered at Week 252 after all assessments have been completed. Golimumab 
after Week 252 (for subjects who have completed the full 252-week study before drug 
commercialization for pJIA indication has taken place) will be provided in the Extended 
Treatment Period until the drug will be is approved and marketed for use in pJIA in the 
country of the subject or for as long as proven beneficial to the child (in cases where 
commercial drug is not accessible to the subject).
Since this is an open-label study with all subjects receiving the same BSA-based dose of 
IV golimumab, an external Data Monitoring Committee will not be established.
The end of the study is defined as the last follow-up assessment for the last subject in the
LTEETP.
Synopsis (Dosage and 
Administration, 
Golimumab)
During the ETP, subjects will continue to receive 80 mg/m2 golimumab IV infusions 
q8w starting at Week 252.
Time and Events 
Schedule
Table 3
Footnote d.
d. The ETP starts at Week 252. These procedures should only be completed for 
subjects who enter the ETP.
3.1. Overview of 
Study Design
All subjects will receive 80 mg/m2 golimumab (maximum single dose 240 mg) as an IV 
infusion given over 30±10 minutes at Weeks 0, 4, and every 8 weeks (q8w; ±3 days) 
through Week 28 and then q8w (±1 week) thereafter through Week 244. Body surface area 
will be calculated based on the subject’s height and body weight measured at each visit, 
and the BSA-based dose of golimumab will be adjusted as needed to maintain the dose at 
80 mg/m2. Subjects will also receive commercial MTX weekly through Week 28 at the 
same BSA-based dosage (10 to 30 mg/m2 per week of MTX in subjects with BSA 
<1.67 m2, or a minimum of 15 mg/week in subjects with BSA ≥1.67 m2) as at time of 
study entry as outlined in Section 6.2. At Week 252, subjects who meet the inclusion 
criteria for the optional Extended Treatment Period (ETP) may continue treatment 
with golimumab (80 mg/m2 q8w) after completion of the Week 252 assessments.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
14
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
3.1.1. Week 0 through 
Week 28
After all subjects complete the Week 28 visit, the database will be locked to assess PK, 
safety and efficacy. An additional safety, efficacy, and PK database lock is currently 
planned for Week 52. Final A database lock will be performed at Week 252, and a final 
database lock will be performed at the end of study.
3.1.3. Week 52 
through Week 252 
(Long-term 
Extension)
The final A database lock will occur be at Week 252.
3.1.4. After Week 252 
(Extended Treatment 
Period)
Subjects <18 years of age who complete the study through Week 252, and for whom 
drug is proven beneficial but is not commercially available for pJIA, will have the 
option to enter the ETP at Week 252, as described in Attachment 6. 
The final database lock will occur at the end of the ETP, as described in 
Attachment 6.
3.1.5 End of Study 
Definition
The end of the study is defined as the last follow-up assessment for the last subject in the
long-term extension ETP.
3.2.1. Blinding, 
Control, Study 
Phase/Periods, 
Treatment Groups
This is a single-arm, open-label study to evaluate the PK of IV golimumab in subjects with 
pJIA, with all subjects receiving the same BSA-based dose of IV golimumab through 
Week 52. Subjects who complete the study at Week 52 will have the option to enter into 
the LTE phase of this study through Week 252. After Week 252, subjects who meet 
specific criteria (see Attachment 6) will have the opportunity to continue treatment 
with golimumab in the ETP.
5. Treatment 
Allocation and 
Blinding
This is an open-label study. All subjects will receive golimumab 80 mg/m2 at Week 0, 
Week 4, and q8w (± 3 days) through Week 28 and q8w (± 1 week) up to Week 244 after 
Week 28.
4. Subject Population
Eligibility criteria for the ETP are provided in Attachment 6. Prohibitions and 
restrictions during the ETP are also provided in Attachment 6.
6.1. Golimumab
During the ETP, golimumab will be administered as described in Attachment 6. The 
first dose of golimumab during the ETP will be at Week 252 after the subject has 
completed the Week 252 assessments.
8. Prestudy and 
Concomitant Therapy
After Week 252, concomitant medications are documented as described in 
Attachment 6.
9.1.1. Overview
The Time and Events Schedules summarize the frequency and timing of efficacy, PK, 
immunogenicity, and safety measurements applicable to this study (Table 1, Table 2, and 
Table 3). All scheduled study visits should occur within ±3 days of the intended visit
through Week 28 and ±1 week from Week 28 through Week 244. Through Week 52, if the 
recommended acceptable window cannot be observed, the Sponsor must be contacted 
before scheduling a visit. After Week 52, if the recommended acceptable window cannot 
be observed, the reason for the deviation must be recorded in source documents. After 
Week 252, study procedures will be performed as described in Attachment 6.
9.1.6. Extended 
Treatment Period
9.1.6. Extended Treatment Period
Subjects who enter the ETP after completion of the Week 252 assessments will 
continue to receive 80 mg/m2 golimumab IV q8w.
The frequency and timing of assessments during the ETP are provided in 
Attachment 6.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
15
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
10. Subject 
Completion/
Withdrawal
Subject completion/withdrawal during the ETP is described in Attachment 6.
14.4. Preparation, 
Handling, and Storage
Preparation, handling, and storage of study agent during the ETP is described in 
Attachment 6.
14.5 Drug 
Accountability
Drug accountability during the ETP is described in Attachment 6.
Attachment 6. 
Extended Treatment 
Period
With the addition of the Extended Treatment Period, information was added to the 
protocol to detail the eligibility, requirements, and procedures of the Extended Treatment 
Period.
Rationale: To remove the use of a Data Review Committee as the study is open-label, golimumab has been 
marketed since 2009, and an internal Sponsor safety monitoring team reviews safety concerns in addition to routine 
medical monitoring. 
11.9. Data Monitoring 
Committee
This is an open-label study, with all subjects receiving the same dosage of IV golimumab. 
Therefore, an external Data Monitoring Committee will not be utilized. Safety data will be 
routinely evaluated by the study’s medical monitor and Sponsor’s internal Safety 
Management Team as needed and an internal Data Review Committee as defined in the 
DRC charter. In addition, the data may be reviewed by the Steering Committee.
Rationale: Minor errors were noted
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
16
Status: Approved, Date: 16 December 2019
Amendment INT-3 (28 February 2017)
The overall reason for the amendment: 1) to change the inclusion criterion regarding C-reactive protein (CRP); 
2) to provide clarification on the methotrexate (MTX) dose to be used during the study; 3) to modify the 
requirements and intervals for slit lamp evaluations; 4) to remove the term “emancipated” to describe a juvenile; 
5) to remove unnecessary wording regarding blinding; 6) to indicate that a local laboratory may be used for the 
QuantiFERON®-TB Gold test.
Applicable Section(s)
Description of Change(s)
Rationale: With approximately half the planned number of subjects enrolled in the study to date, the study 
population exhibits a range of C-reactive protein (CRP) levels that would support the planned population 
pharmacokinetics (PK) analysis. At the same time, the Sponsor has received consistent feedback from the Steering 
Committee and investigators that otherwise qualified subjects have failed screening because their CRP 
was<0.1 mg/dL. Given these facts, the inclusion criterion has been revised to allow approximately 30% of the study 
population to have a screening CRP of <0.1 mg/dL in order to enhance enrollment in the study without affecting the 
Sponsor’s ability to fulfill the objectives of the study.
Synopsis, Objectives
The primary objective of this study is to assess the pharmacokinetics (PK) following 
intravenously administered golimumab in subjects (ages 2 to less than 18 years) with pJIA 
manifested by ≥5 joints with active arthritis and C-reactive protein (CRP) of ≥0.1 mg/dL
despite methotrexate (MTX) therapy for ≥2 months.
Synopsis, Subject 
Population
Subjects must have ≥5 joints with active arthritis as defined by American College of 
Rheumatology (ACR) criteria at screening and enrollment.and must have a screening CRP 
of ≥0.1 mg/dL.
2.1 Objectives
The primary objective of this study is to assess the PK following intravenously 
administered golimumab in subjects (ages 2 to less than 18 years) with pJIA manifested by 
≥5 joints with active arthritis and CRP of ≥0.1 mg/dL despite MTX therapy for ≥2 months.
4.1 Inclusion Criteria
6. Subjects must have a screening CRP of ≥0.1 mg/dL with the exception of 
approximately 30% of the study population.
Rationale:  Text has been revised to clarify the appropriate MTX dose for subjects according to their body surface 
area (BSA) measurement.
Synopsis, Overview
of Study Design
Commercial MTX is to be administered at a stable dose of 10-30 mg/m2/week in subjects 
with BSA <1.67 m2 or a stable minimum dose of 15 mg/week in subjects with BSA 
≥1.67 m2 through Week 28 (unless lower doses of MTX are administered for 
documented safety reasons or unless documented country or site regulations prohibit 
dose of 15 mg/week or above in subjects with BSA ≥1.67 m2), lower doses of MTX are 
administered) through Week 28. For patients with BSA greater than 1.67 m2, a minimum 
fixed dose of 15 mg/week is required.
Synopsis, Dosage and 
Administration
Subjects will receive commercial MTX at least through Week 28 at the same BSA-based 
dose (10 to 30 mg/m2 per week for subjects with BSA <1.67 m2 or at least 15 mg/week 
for subjects with BSA ≥1.67 m2) as at time of study entry at least through Week 28.
3.1 Overview of 
Study Design
Subjects will also receive commercial MTX weekly through Week 28 at the same BSA-
based dosage (10 to 30 mg/m2 per week of MTX in subjects with BSA <1.67 m2, with or
a minimum of 15 mg/week in subjects with BSA ≥1.67 m2) as at time of study entry 
through Week 28 as outlined in Section 6.2.
…………………………………………………………………………………………….
(Legend for Figure 1)
All subjects receive 80 mg/m2 golimumab IV infusion at Weeks 0, 4, and every 8 weeks 
thereafter through Week 244. Subjects will receive and 10 to 30 mg/m2 per week of
commercial methotrexate at the same weekly dose as at time of study entry at least
through Week 28.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
17
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
4.1 Inclusion
7. Subjects must have active pJIA despite current use of oral, intramuscular, or 
subcutaneous MTX for ≥2 months before screening at a weekly dose of ≥10 mg/m2. 
Subjects currently on MTX must receive a stable dose (between 10 to 30 mg/m2 per week) 
of MTX for ≥4 weeks before screening. For subjects with BSA <1.67 m2, the MTX dose 
must be between 10 to 30 mg/m2 per week and stable for ≥4 weeks before screening.
For sSubjects with BSA ≥1.67 m2, the MTX dose must receive a be a minimum of 15 
mg/week and must be stable for ≥4 weeks before screening. of MTX unless documented 
country or site regulations prohibit use of 15 mg of MTX per week in subjects with BSA 
≥1.67 m2. In situations where there is documented intolerance of doses >10 mg/m2 weekly 
(for subjects with BSA <1.67 m2) or ≥15 mg/week (for subjects with BSA ≥1.67 m2); or 
where documented country or site regulations prohibit use of ≥15 mg of MTX per 
week in subjects with BSA ≥1.67 m2, subjects may be entered into the trial on a lower 
dose of MTX.
6.2 Methotrexate
Subjects will receive commercial MTX through Week 28 at the same BSA-based dose 
(10 to 30 mg/m2 per week for subjects with BSA <1.67 m2 or at least 15 mg/week for 
subjects with BSA ≥1.67 m2)(10 to 30 mg/m2 per week) as at time of study entrythrough 
Week 28. Absolute dose should remain stable from baseline through Week 28.
………………………………………………………………………………
After Week 28, changes in MTX administration are permitted (eg, increase or 
decrease in dosage, change in route of administration, or discontinuation).
8. Prestudy and 
Concomitant Therapy
Subjects must have received MTX at a weekly dose of ≥10 mg/m2 for ≥2 months before 
screening. For subjects with BSA <1.67 m2, the MTX dose must be between 10 to 
30 mg/m2 per week and stable for ≥4 weeks before screening. For sSubjects with BSA 
≥1.67 m2 the MTX dose must be a minimum of 15 mg/week of MTX and must be stable 
for ≥4 weeks before screening. The dose must have been stable and between 10 to 30 
mg/m2 weekly (or at least 15 mg/week in subjects with BSA ≥1.67 m2) for ≥4 weeks 
before screening.
9.1.3. Treatment 
Phase: Week 0 
through Week 28
Subjects will also receive commercial MTX weekly at the same BSA-based dosage (10 to 
30 mg/m2 per week) as at time of study entry at least through Week 28 and commercial 
folic acid ≥5 mg weekly or folinic acid (at half the MTX dose) given the day after the 
MTX dose (Section 6.2). In children <12 years of age, the administration of folic acid or 
folinic acid will be at the discretion of the physician.
9.1.4. Treatment 
Phase: After Week 28 
through Week 52
Subjects may also receive commercial MTX weekly at the same BSA-based dosage (10 to 
30 mg/m2 per week) as at time of study entry and commercial folic acid ≥5 mg weekly or 
folinic acid if administered (at half the MTX dose; Section 6.2) given the day after the 
MTX dose; however, increases, decreases or discontinuations of MTX, other DMARDs, 
corticosteroids, and/or NSAIDs are permissible after Week 28.
Rationale:  Text has been revised to clarify the nature of uveitis examinations and that, in addition to uveitis 
examinations performed at least every 6 months by the investigator, all subjects are required to have slit lamp 
evaluations performed by an ophthalmologist/optometrist during the study based on current clinical 
recommendations as specified in Attachment 5.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
18
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Time & Events 
Schedules, Table 1
h. Evaluations (based on physical examination and interview) should be performed by 
the investigator at least every 6 months in all subjects. In addition, all subjects are 
required to have slit lamp evaluations performed by an ophthalmologist/ optometrist 
during the study at intervals (based on JIA subtype, ANA test results, age at JIA 
onset, and JIA duration) as specified in Attachment 5. Subjects who test ANA positive 
at screening will be required to undergo slit lamp evaluation by a qualified 
ophthalmologist to evaluate for subclinical uveitis in the screening period, before first 
study drug administration, as well as at least every 3 months subsequent.
Time & Events 
Schedules, Table 2 
and Table 3
h. Evaluations (based on physical examination and interview) should be performed by 
the investigator at least every 6 months in all subjects. In addition, all subjects are 
required to have slit lamp evaluations performed by an ophthalmologist/ optometrist 
during the study at intervals (based on JIA subtype, ANA test results, age at JIA 
onset, and JIA duration) as specified in Attachment 5.  Subjects who test ANA positive 
at screening will be required to undergo slit lamp evaluation by a qualified 
ophthalmologist at least every 3 months.
9.4 Safety 
Evaluations (Uveitis 
Evaluations)
All subjects will be formally assessed for new-onset uveitis at screening and at least every 
6 months thereafter by the investigator evaluation based on physical examination and 
interview. pertaining to new-onset uveitis on physical examination by the investigator and 
by interview. This consists of an assessment of signs and symptoms of uveitis, 
including, but not limited to, eye redness, light sensitivity, changes in vision, and 
floaters. Based upon changing clinical standards, examinations may be more frequent. 
In addition, all subjects are required to have slit lamp evaluations performed by an 
ophthalmologist/optometrist during the study at intervals (based on JIA subtype, 
ANA test results, age at JIA onset, and JIA duration) as specified in Attachment 5.  
Subjects who test antinuclear antibodies (ANA) positive at screening will be required to 
undergo slit lamp evaluation by a qualified ophthalmologist to evaluate for subclinical 
uveitis in screening period as well as at least every 3 months subsequent as specified in the 
Time and Events Schedules (Table 1, Table 2, and Table 3).
If a subject develops uveitis during the study, the subject’s continued participation in the 
study is at the discretion of the investigator and Sponsor. and a qualified ophthalmologist.
Attachment 5: Slit 
Lamp Evaluations
(Attachment added that outlines requirements and intervals for slit lamp evaluations based 
on JIA subtype, ANA test results, age at JIA onset, and JIA duration.)
Rationale:  The term “emancipated” to describe a juvenile has been deleted because it does not have global 
application and text has been added to indicate that the CHAQ may be completed jointly with the parent/caregiver.
Time & Events
Schedules, Table 1, 
Table 2, and Table 3
l.
CHAQ to be completed by the parent or caregiver; preferably the same parent or 
caregiver should complete at every visit. Subjects who are emancipated juveniles (ages 15 
to <18 years of age) at study entry may complete the assessments jointly with the 
parent/caregiverthemselves.
4.1 Inclusion Criteria
17. A parent or guardian must should accompany the subject to each study visit until the 
subjects reaches the age of 18 years. unless the subject is an emancipated juvenile.
9.2.1.4 Childhood 
Health Assessment 
Questionnaire 
(Parent/Subject 
Assessment of 
Overall Well-being)
Subjects who are emancipated juveniles (ages 15 to <18 years) of age at study entry may
complete all the CHAQ assessments jointly with the parent/caregiverthemselves. 
Preferably, the same individual (eg, parent, caregiver, or subject) who completes the 
assessments at the start of the study should complete the assessments throughout the study.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
19
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale:  Unnecessary text regarding blinding has been removed to avoid confusion. 
3.1 Overview of 
Study Design
Unblinded sSafety data will be routinely evaluated by the study’s medical monitor.
5. Treatment 
Allocation and 
Blinding
As this is an open-label study, blinding procedures are not applicable. Subjects and 
investigational study sites will remain unblinded. Sponsor personnel who will be involved 
with data analyses will be identified before the interim analyses.
11.9 Data Monitoring 
Committee
Unblinded sSafety data will be routinely evaluated by the study’s medical monitor and an 
internal Data Review Committee as defined in the DRC charter.
Rationale: Wording was added to indicate that of a local laboratory may be used for the QuantiFERON®-TB Gold 
test.
ATTACHMENT 1 
QUANTIFERON®-
TB GOLD TESTING
The central laboratory will analyze and report results for each subject, and sites will be 
informed of the results. Under certain circumstances as approved by the Sponsor, a 
local laboratory may be used to process the QuantiFERON®-TB Gold test sample 
and/or analyze the results. 
Rationale: Minor errors were noted
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
20
Status: Approved, Date: 16 December 2019
Amendment INT-2 (11 July 2016)
The overall reason for the amendment: The overall reasons for the amendment are: 1) to change the criteria used 
to determine subject eligibility to enhance enrollment in the study; 2) to provide clarification and additional details
regarding the efficacy and safety evaluations to be used during the study; 3) to clarify the timing of changes that can 
be made to background medications; 4) removal of the ultrasound substudy; and 5) inclusion of anticipated events 
due to progression of the disease in the overall safety analyses for the study.
Applicable Section(s)
Description of Change(s)
Rationale: Published Juvenile idiopathic arthritis (JIA) treatment guidelines such as the ACR guidelines 
(2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: 
Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features) 
recommend the initiation of treatment with a TNFα inhibitor after 3 months of methotrexate (MTX) treatment for 
patients with active JIA despite MTX treatment. However, the Sponsor has received consistent feedback from the 
Steering Committee and investigators that this duration of MTX treatment is too long and is inconsistent with typical 
clinical practice. JIA is a cause of serious functional disability, and the goal of treatment for pediatric patients with 
the disease is to gain disease control as quickly as possible. The required duration of MTX therapy before screening 
was shortened from ≥3 months to ≥2 months to still allow adequate time for patients to demonstrate failure or 
inadequate response to MTX therapy, but to also provide this vulnerable patient population with an opportunity to 
enroll in a clinical trial and receive treatment that may provide symptomatic relief of their disease.
Synopsis, Objectives and 
Hypothesis
The primary objective of this study is to assess the pharmacokinetics (PK) of following
intravenously administered golimumab in subjects (ages 2 to less than 18 years) with 
polyarticular JIA (pJIA) manifested by ≥5 joints with active arthritis and C-reactive 
(CRP) of ≥ 0.1 mg/dL despite methotrexate (MTX) therapy for ≥32 months.  
Synopsis, Subject 
Population
Subjects must have active pJIA despite current use of oral, intramuscular or 
subcutaneous MTX (for ≥32 months before screening) at a weekly dose of ≥10 mg/m2.
2.1. Objectives, Primary 
Objective
The primary objective of this study is to assess the PK following intravenously 
administered golimumab in subjects (ages 2 to less than 18 years) with pJIA manifested 
by ≥5 joints with active arthritis and CRP of ≥0.1 mg/dL despite MTX therapy for 
≥32 months.
4.1.Inclusion Criteria 
(Criterion #4)
Failure or inadequate response to at least a 32-month course of MTX before screening.
4.1.Inclusion Criteria 
(Criterion #7)
Subjects must have active pJIA despite current use of oral, intramuscular, or 
subcutaneous MTX (for ≥32 months before screening and on a stable dose for 4 weeks 
as noted in Section 8) at a weekly dose of ≥10 mg/m2. 
8.Prestudy and 
Concomitant Therapy
Subjects must have received MTX at a weekly dose of ≥10 mg/m2 for ≥32 months
before screening.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
21
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale:  The secondary objectives were corrected to include PK evaluations.
Synopsis, Objective and 
Hypothesis;
The secondary objectives of this study are to evaluate IV golimumab in subjects with 
pJIA with respect to PK, efficacy (relief of signs and symptoms, physical function, and
quality of life), safety (adverse events [AEs], serious AEs [SAEs], and assessment of 
laboratory parameters), and immunogenicity (antibodies to golimumab).
2.1 Objectives, 
Secondary Objectives
The secondary objectives of this study are to evaluate IV golimumab in subjects with 
pJIA with respect to PK, efficacy (relief of signs and symptoms, physical function, and
quality of life), safety (AEs, SAEs, and assessment of laboratory parameters) and 
immunogenicity (antibodies to golimumab).
Rationale:  To align the description of the study design in the Synopsis with that in the body of the document.
Synopsis, Overview of 
Study Design
This is a Phase 3, open-label, single-arm, multicenter study to evaluate the PK, safety, 
and efficacy of IV golimumab in subjects with active pJIA despite current treatment 
with MTX and/or corticosteroids and/or non-steroidal anti-inflammatory agents and/or 
prior use of anti-TNFα agents (up to 30% of total population).
Synopsis, Overview of 
Study Design
Approximately At least 120 subjects will be enrolled at Week 0 to ensure that 
approximately at least 100 subjects remain in the study at Week 52.
Rationale:  The Synopsis was revised to clarify the evaluations and endpoints of the study and to align the 
presentation of this information with that in the body of the document. 
Synopsis
The efficacy evaluations/endpoints were separated from the PK evaluations/endpoints 
and clarified.  The safety evaluations and analyses were moved and are now presented 
before the immunogenicity evaluations and analyses.
Rationale:  To clarify the stable dose of MTX that subjects should be receiving for ≥4 weeks before screening.
4.1.Inclusion Criteria 
(Criterion #7)
Subjects currently on MTX (weekly 10 to 30 mg/m2), must receive a stable dose 
(between 10 to 30 mg/m2) per week of MTX for ≥4 weeks before screening.
Rationale: To clarify that MTX is to be administered to subjects through Week 28 of the study.
Synopsis, Overview of 
Study Design
All subjects will receive 80 mg/m2 golimumab as an IV infusion (over 30 ±10 minutes) 
at Weeks 0, 4, and every 8 weeks (q8w; (± 3 days) through Week 28 and q8w (± 1 
week) thereafter (maximum single dose 240 mg [maximum body surface area (BSA)
3.0 m2 x 80 mg/m2]), along with c. Commercial MTX is to be administered at a dose 
of 10-30 mg/m2/week (unless for documented safety reasons, lower doses of MTX are 
administered) through Week 28.
Rationale: Clarification that the MTX dose and route of administration should remain stable through the Week 28 
“visit,” not the Week 28 “safety and efficacy database lock.”
Synopsis, Dosage and 
Administration
Methotrexate
Every effort should be made to ensure that subjects remain on the same dose and route 
of administration of MTX through the Week 28 visit safety and efficacy database lock, 
unless intolerance or AEs due to MTX occur. 
6.2. Methotrexate
Every effort should be made to ensure that subjects remain on the same dose and route 
of administration of MTX through the Week 28 visitsafety and efficacy database lock, 
unless intolerance or AEs due to MTX occur (Section 8).
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
22
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: JADAS has been deleted from Time &Events schedules, Tables 1, 2, and 3, because it is not a specific 
assessment that the physician performs rather it is a calculation based on the Physician Global Assessment, 
parent/child ratings of well-being and pain, joint assessments, and CRP.   
Time and Events 
Schedules, Tables 1, 2, 
and 3
JADAS was removed from the Time and Events Schedules.
Rationale: The JADAS physician assessed remission was deleted from the efficacy endpoints because it is 
considered to be exploratory in nature and not necessary for the evaluation of efficacy in this study.  
9.2.1.6 Juvenile Arthritis
Disease Activity Score 
(JADAS)
JADAS physician assessed remission is defined as a total JADAS score of ≤2.
9.2.2 Endpoints, Other 
Endpoints
11.3 Efficacy Analyses, 
Other Efficacy Endpoints
•
The proportion of subjects who achieve JADAS 10, 27, and 71 remission over time.
Rationale: It has been decided not to initiate the exploratory ultrasound substudy as a result of concerns over the 
feasibility of enrolling a sufficient number of subjects in the substudy due to the lack of interest from sites
participating in the substudy or the inability of sites to participate due to operational reasons.
Synopsis, Ultrasound 
Substudy
Power Doppler Sonography (PDUS) is a non-invasive ultrasound technique to assess 
inflammation at the joint level in rheumatoid arthritis (RA). At selected sites, subjects 
over the age of 4 years who have been enrolled in the study and are currently receiving 
study treatment may undergo PDUS and High Frequency gray scale Ultrasound 
(HFUS) of the 2nd and 3rd metacarpophalangeal joints, wrist, knee and ankle. Up to 5 
exams will be performed at Weeks 0, 4, 12, 24, and 52 using a standardized protocol, 
described in a separate manual. Reading of the PDUS and HFUS will be performed by 
a blinded independent central reader.
9.6 Ultrasound Substudy
At selected sites, a total of approximately 20 subjects over the age of 4 years who are 
enrolled in this study and are currently receiving study treatment may undergo power 
ultrasounds of their metacarpophalangeal 2 and 3 joints (examining dorsal and volar 
surfaces), wrist (dorsal long midline, tendons), knee (suprapatellar long and parapatellar 
images; entheseal evaluations), and ankle (tibula/talar, subtalar medial and lateral 
surfaces, tendon examinations). Up to 5 ultrasound assessments may be conducted at 
Weeks 0, 4, 12, 28, and 52. The primary objective of the substudy is to examine Power 
Doppler response measured as the Power Doppler Sum Score at 6 months compared 
with the score at baseline. Additional details will be presented in the ultrasound 
substudy Protocol.
15. Study-Specific 
Materials

Ultrasound substudy (only for sites participating in the ultrasound substudy)  
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
23
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: A footnote was added to the Time and Events schedules (Tables 1, 2, and 3) to describe when vital signs 
should be taken at visits when study agent infusion is administered. Corresponding text was added to Section 9.4 
(Safety Evaluations).  
Time and Events 
Schedules, Tables 1, 2, 
and 3
Footnote d
9.4 Safety Evaluations,
Vital Signs
d. Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute 
intervals during the infusion); and at 60 and 90 minutes (during the 1-hour 
observation period following the infusion).
Pulse/heart rate, respiratory rate, temperature, and blood pressure measurements will 
be performed according to the Time and Events Schedules (Table 1, Table 2, and 
Table 3).
Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute intervals 
during the infusion); and at 60 and 90 minutes (during the 1-hour observation 
period following the infusion).
Rationale: Patients are excluded from the study if they had been treated with therapeutic agents that deplete B or 
T cells during the 12 months before the first study agent administration or have evidence of persistent depletion of 
the targeted lymphocyte after receiving any of these agents. Lymphocyte subset analyses were included in the Time 
and Events Schedule for subjects who received these agents >12 months prior to study entry. However, since these
analyses are not performed by the central laboratory for this study, these have been removed from the Time and 
Events Schedule. If a subject is being considered for enrollment who previously received treatment with an agent 
that depletes B or T cells > 12 months before the first study agent administration, these tests can be performed at a 
local laboratory to confirm that the subject does not have persistent depletion. Footnote c was deleted accordingly.
Time and Events 
Schedules, Table 1
Footnote c.
c. For subjects who have been treated with natalizumab, efalizumab, or therapeutic 
agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) during 
the ≥12 months before the first study agent administration.
Rationale: Based on general knowledge about the tests for latent TB (QuantiFERON®-TB Gold and tuberculin skin 
tests), it is not recommended to repeat these tests in patients with a history of latent TB and ongoing treatment for 
latent TB or documentation of having completed adequate treatment. Therefore, a footnote has been added to 
Tables 1, 2, and 3 and text was added to Section 9.4 to indicate that QuantiFERON®-TB Gold (and tuberculin skin) 
testing does not need to be repeated during the study for subjects with a history of latent TB and ongoing treatment 
for latent TB or documentation of having completed adequate treatment. 
Time and Events 
Schedules, Tables 1, 2, 
and 3
Footnote f.
f. Testing is not required for subjects with a history of latent TB and ongoing 
treatment for latent TB, or documentation of having completed adequate 
treatment.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
24
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
9.4 Safety Evaluations,
Early Detection of Active 
Tuberculosis
Annual QuantiFERON®-TB Gold (and tuberculin skin) testing is not required for 
subjects with a history of latent TB and ongoing treatment for latent TB, or 
documentation of having completed adequate treatment for TB.
Subjects who experience close contact with an individual with active TB during the 
conduct of the study must have a repeat chest radiograph, a repeat QuantiFERON®-TB 
Gold test, a repeat tuberculin skin test in countries in which the QuantiFERON®-TB 
Gold test is not approved/registered, and, if possible, referral to a physician 
specializing in TB to determine the subject’s risk of developing active TB and whether 
treatment for latent TB is warranted. The QuantiFERON®-TB Gold test (and 
tuberculin skin test) does not need to be repeated for subjects with a history of 
latent TB and ongoing treatment for latent TB, or documentation of having 
completed adequate treatment for TB. If the QuantiFERON®-TB Gold test result is 
indeterminate, the test should be repeated as outlined in Section 9.1.2. Subjects should 
be encouraged to return for all subsequent scheduled study visits according to the 
protocol.
Rationale: The inclusion criterion for subjects who require a chest x-ray prior to the first administration of study 
agent has been modified to reflect that this is dependent on country or local guidelines rather than country and site 
guidelines.  Similarly, Footnote f. in Tables 1, 2, and 3, has been modified to clarify that chest x-ray screening for 
each subject is to be conducted per local and country regulations, not per site and country regulations.
Time and Events 
Schedules, Tables 1, 2, 
and 3
Footnote g.
g f. Chest x-ray screening as per site local and country regulations for initiation of 
immunosuppressive agents in children with JIA who are at risk of TB.
4.1 Inclusion Criteria,
Criterion 10.g.
g.
Unless country or sitelocal guidelines do not recommend a chest radiograph as a 
necessary screening process prior to initiation of anti-TNFα therapies, a chest 
radiograph (posterior-anterior view) must have been taken within 3 months prior 
to the first administration of study agent and read by a qualified radiologist, with 
no evidence of current active TB or old inactive TB.
Rationale: Visit windows were added to the Time and Events Schedules (Table 1, Table 2, and Table 3) to provide 
clarification of timing of study visits.  
Time and Events 
Schedules, Table 1, 
Table 2, and Table 3
In Table 1, -6 weeks was added to the Screening Period.  A footnote was added to 
Table 1, Table 2 and Table 3 to indicate that the visit window from Week 0 through 
Week 28 is  ±3 days of the intended visit and ±1 week after Week 28. 
Rationale:  A column was added to the Time and Events Schedules, Tables 1, 2, and 3, to specify the assessments 
that should be performed at the Final Safety Follow-up Visit.  
Time and Events 
Schedules, Table 1, 
Table 2, and Table 3
A final safety follow-up visit was added to each table and the following footnote was 
moved to the column:  
b. a. All subjects who discontinue study agent administration before Week 244 but do 
not withdraw consent must return to the study site for a final safety visit 
approximately 8 weeks after the last infusion (Section 10.2).
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
25
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale:  Clarifications were made to the Time and Events Schedules (Tables 1, 2, and 3), regarding the efficacy 
evaluations. Specifically, morning stiffness, the Physician Global Assessment of Disease Activity and CHAQ were
grouped under “JIA assessments”; the footnote regarding the timing of PRO assessments was revised to clarify that 
the CHAQ should be conducted prior to any tests, procedures, or other consultations for that visit; and the redundant 
sentence in the footnote for the CHAQ was deleted.  
Time 
and 
Events 
Schedules, Tables 1, 2, 
and 3
Joint assessments/morning stiffness
Physician Global Assessment of Disease Activity JIA assessments
CHAQ
Time 
and 
Events 
Schedules, Tables 1, 2, 
and 3
Footnote k
k.All visit-specific PRO assessments should be conducted before any tests, procedures, 
or other consultations for that visit to prevent influencing subjects’ perceptions.
k. JIA assessments include the following:  Physician Global Assessment of Disease 
Activity, Childhood Health Assessment Questionnaire (CHAQ), and duration of 
morning stiffness.  CHAQ should be completed before any tests, procedures, or 
other consultations for that visit to prevent influencing subjects’ perceptions.
Time 
and 
Events 
Schedules, Tables 1, 2, 
and 3
Footnote l
l.
i. CHAQ to be completed by the parent or caregiver; preferably the same parent 
or caregiver should complete at every visit. Subjects who are emancipated juveniles 
(ages 15 to <18 years) at study entry may complete the assessments themselves. Ideally 
the same individual (eg, parent, caregiver, or subject) who completes the assessments at 
the start of the study should complete the assessments throughout the study
Rationale: Change made to footnote o in Table 1 and text in Section 9.1.3 to clarify that the additional sample for 
evaluation of serum golimumab concentration must be collected at least 24 hours prior to or after study agent dosing 
and must not be collected at a regularly scheduled visit (eg. Week 8).
Table 1.
Footnote o
9.1.3 Treatment Phase:  
Week 0 through Week 28
o
m. One additional sample for serum golimumab concentration for population 
PK will be collected from all subjects at any time between Weeks 0 and 8 other than at 
the time of the Week 0, Week 4, and Week 8 visits; this sample must be collected at 
least 24 hours prior to or after a study agent administration and must not be collected
at a regularly scheduled visit (eg. Week 8).
In addition, 1One additional sample for serum golimumab concentration for 
population PK will be collected from all subjects at any time between Weeks 0 and 8 
other than at the time of the Week 0, Week 4, and Week 8 visits; this sample must be 
collected at least 24 hours prior to or after a study agent administration and must not 
be collected at a regularly scheduled visit (eg, Week 8).
Rationale: Figure 1 was revised to clarify that subjects will receive MTX through Week 28 instead of Week 52; 
after Week 28, changes in MTX are permitted.
3.1. Overview of Study 
Design
Figure 1: Schematic Overview of the Study
Rationale: To be consistent in listing the background medications that may be used by subjects during the study.
3.1.1. Week 0 through 
Week 28
No changes should be made to background medications (ie, MTX, other DMARDs, 
corticosteroids, and NSAIDs) in terms of increases or decreases in dosage beyond the 
parameters provided in Section 8 (eg, no more than 10 mg/day prednisone or no more 
than 0.20 mg/kg/day, whichever is lower) and/or route of administration between 
Weeks 0 and 28, unless there is a safety concern (eg, elevated liver function tests), 
which requires changes to background medications.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
26
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Editorial changes made to be consistent in listing the background medications that may be used by 
subjects during the study and to clarify that changes to these medications can be made after Week 28.
3.1.2. Week 28 through 
Week 52
As noted beginning atafter Week 28, subjects will be permitted to change/add MTX, 
other DMARDs, (including agents besides MTX), MTX corticosteroids, and NSAIDs
use as outlined in Section 8.
Rationale: To clarify when subjects will be permitted to make changes to background medications (ie, after 
Week 28) during the long-term extension phase of the study; editorial changes have been made to be consistent in 
listing the background medications that may be used by subjects during each phase of the study; "approximately"
has been added to indicate when the follow-up visit should occur (ie, approximately 8 weeks after the last 
administration of study agent to the subject).
3.1.3. Week 52 through 
Week 252 (Long-term 
Extension)
As noted above beginning at after Week 28, subjects will be permitted to change/add
MTX, other DMARDs, MTX, corticosteroids, and NSAIDs use, including increases or 
decreases in BSA-based dosing (where appropriate) for these classes of agents as 
outlined in Section 8.
Those subjects who discontinue study agent at any time before Week 244 are also 
expected to return for a safety follow-up visit approximately 8 weeks after the last 
administration of study agent.
Rationale: Clarification of how the PK and PD data collected during the study will be used. There are no changes to 
the primary endpoints/outcomes in this study.
3.2.3. Rationale
The Sponsor will utilize PK/PD data generated from the proposed open-label 
CNTO148JIA3003 study to extrapolate to adult PK and efficacy data from the 
CNTO148ART3001 study in RA, which was the pivotal study that served as the basis 
for approval of intravenousIV golimumab (SIMPONI ARIA/ and SIMPONI for 
Intravenous Use) for adult patients with RA. Additionally, efficacy (PD) data will be 
collected to explore the assessment of supportive exposure-response.
Rationale: Clarification of the definition of a joint with active arthritis when using ACR criteria to determine the 
number of joints with active arthritis.
4.1 Inclusion Criteria,
Criterion 5.
Subjects must have ≥5 joints with active arthritis at screening and at Week 0 as defined 
by ACR criteria (ie, a joint with either swelling, or in the absence of swelling, 
limited range of motion associated with pain on motion or tenderness).
Rationale: To correct the error in the stated inclusion criterion for the serum ALT upper limit of normal for the 
central laboratory for enrollment of boys 10 to 18 years of age.
4.1 Inclusion Criteria,
Criterion 15.e.
Serum transaminase levels not exceeding 1.2 x the upper limit of normal for the central 
laboratory:
– Alanine aminotransferase (ALT)
o
≤41 IU/L (girls, ages 2 to 18)
o
≤41 IU/L (boys, ages 2 to <10)
o
≤42 52 IU/L (boys, ages 10 to 18)
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
27
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Investigators have provided feedback that requiring subjects to present documentation of immunization 
may limit the opportunity for this vulnerable patient population to enroll in a clinical trial and receive treatment that 
may provide symptomatic relief of their disease.  Therefore, the inclusion criterion has been modified to permit 
subjects without documentation of their immunizations with an opportunity to enroll in the trial provided that the 
investigator has evaluated the subject to confirm that the subject is up to date with all immunizations per the current 
local immunization guidelines for immunocompromised subjects.
4.1 Inclusion Criteria,
Criterion 16.
Subjects must be up to date with all immunizations in agreement with current local 
immunization guidelines for immunosuppressed subjects prior to enrollment before 
Week 0., and must present documentation of immunizations (eg, medical record or 
vaccination card).
17.4 Source 
Documentation
•
Subject verified report of vaccination or vaccination card
Rationale: Patients with JIA treated with a biologic medication may need to switch to another medication. Ideally, 
the first medication would be washed out prior to starting the second medication, since overlapping these types of 
treatments may result in increased risk of adverse events, such as infections. The Sponsor has received consistent 
feedback from investigators that the biologics washout periods in the CNTO148JIA3003 study are too long and are a 
deterrent to enrollment. The Sponsor has carefully assessed the half-lives of biologic agents that subjects may have 
previously been treated and has shortened the washout periods (ie, Criterion 6, Criterion 11, and Criterion 14), while 
at the same time, maintaining a long enough period of time between different administered medications to protect 
subjects from exposure to overlapping biologics.
4.2 Exclusion Criteria,
Criterion 6.
Subject has been treated with abatacept within 3 months 8 weeks before first study 
agent administration.
4.2 Exclusion Criteria,
Criterion 11.
Subject has received IL-1ra (anakinra) within 4 weeks 1 week of the first study agent 
administration.
4.2 Exclusion Criteria,
Criterion 14.
Subject has received etanercept, adalimumab, or certolizumab pegol within 6 weeks or 
has received etanercept within 4 weeks of the first dose of study agent.
Rationale: The target patient population for this study is patients with polyarticular JIA who have active disease 
despite MTX treatment. Anti-TNFα agents are typically the first biologic agent of choice after conventional 
DMARDs, however, other biologics may be used to treat the disease.  The Sponsor has received consistent feedback 
that the prohibited medications are a deterrent to enrollment in the study.  The Sponsor has carefully assessed the 
half-lives of known IL-12 and IL-23 inhibitors that subjects may have been treated and has modified Exclusion 
Criterion 3 to exclude only those subjects who have received a IL-12 or IL-23 inhibitor within 3 months before the 
first administration of study agent, while at the same time, maintaining a long enough period of time between the 
administration of this type of medication to protect subjects from exposure to overlapping biologics and from the 
risk of AEs, such as infections
4.2 Exclusion Criteria,
Criterion 3.
Subject has been treated with any therapeutic agent targeted at reducing IL-12 or IL-23, 
including but not limited to ustekinumab and ABT-874 within 3 months before first 
study agent administration.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
28
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: The target patient population for this study is patients with polyarticular JIA who have active disease 
despite MTX treatment. Anti-TNFα agents are typically the first biologic agent of choice after conventional 
DMARDs, and published JIA treatment guidelines such as the ACR guidelines (2011 American College of 
Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety 
Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features) recommend switching to a 
second anti-TNFα agent for patients who continue to have active JIA despite treatment with the first anti-TNFα 
agent. Factors besides lack of efficacy (including inconvenience and pain with administration) may also result in 
changes in treatment. The Sponsor has received consistent feedback that excluding patients who have received 
>1 anti-TNFα from this study is a deterrent to enrollment. Juvenile idiopathic arthritis is a cause of serious 
functional disability, and the goal of treatment for pediatric patients with the disease is to gain disease control as 
quickly as possible. Criterion 12 and Criterion 13 were modified to exclude patients who have been previously 
treated with more than 2 anti-TNFα agents. This change will provide this vulnerable patient population an 
opportunity to enroll in a clinical trial and receive treatment that may provide symptomatic relief of their disease.
4.2 Exclusion Criteria,
Criterion 12.
Subjects has previously been treated with more than 12 therapeutic agents targeted at 
reducing TNFα, including, but not limited to, infliximab, etanercept, adalimumab, or 
certolizumab pegol.
4.2 Exclusion Criteria,
Criterion 13.
If a subject has been previously treated with 1an anti-TNFα agent, the reason for 
discontinuation of the anti-TNFα agent cannot have been a severe or serious adverse 
event consistent with the class of anti-TNFα agents.
8. Prestudy and 
Concomitant Therapy
Subjects may have been previously treated with no more than 12 therapeutic agents 
targeted at reducing TNFα prior to study entry per InclusionExclusion Criterion 1912
(Section 4.14.2). Subjects may not have initiated or been treated with prohibited 
therapeutic agents as outlined in Exclusion Criteria 1 through 20 (Section 4.2).
Rationale: Previously, patients who were treated with a JAK inhibitor were not eligible for enrollment in the study, 
and the Sponsor has received feedback that this is a deterrent to enrollment. Subjects with JIA treated with a 
biologic medication may need to switch to another medication to gain disease control to prevent serious functional 
disability. The Sponsor has carefully assessed the half-lives of JAK inhibitors with which subjects may have been 
treated and has modified Exclusion Criterion 17 to exclude only those patients who have received a JAK inhibitor 
within 2 weeks of the first dose of study agent, while at the same time, maintaining a long enough period of time 
between the administration of this type of medication to protect subjects from exposure to overlapping treatments
and from the risk of AEs, such as infections.
4.2 Exclusion Criteria,
Criterion 17.
Subject has ever received a Janus Kinase (JAK) inhibitor, including but not limited to 
tofacitinib, within 2 weeks of the first dose of study agent.
Rationale: Editorial changes were made to be consistent with the time period of prohibited sperm donation and 
pregnancy planning.
4.3. Prohibitions and
Restrictions,
#4
If sexually active with a girl of childbearing potential and has not had a vasectomy, 
boys must use a double barrier method of birth control during the study and for 
6 months after receiving the last administration of study agent, including the LTE 
phase of the study. Boys must not donate sperm and must agree not to plan a pregnancy 
or father a child during the study and within for 6 months following the last 
administration of study agent, including the LTE phase of the study.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
29
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale:  A clarification was made to the collection of prior medications beginning at screening and concomitant 
medication collection beginning with the first dose of study drug.
8. Prestudy and 
Concomitant Therapy
Concomitant therapies must be recorded throughout the study beginning with start of 
the first dose of study drug to 8 weeks after the last dose of study drug.
Prestudy JIA medications administered before the first dose of study agent must 
be recorded at screening. All concomitant therapies must be recorded throughout 
the study beginning with the administration of the first dose of the study drug. 
Rationale: Correction of the cross-reference made in text regarding the number of anti-TNFα agents that subjects 
are allowed to have been treated with prior to study entry which are in Exclusion Criterion 12 and Section 4.2.
8. Prestudy and 
Concomitant Therapy
If using corticosteroids or NSAIDS, subjects must have been on stable doses of these 
medications prior to study entry per Inclusion Criteria 8 and 9 (Section 4.1). Subjects 
may have been previously treated with no more than 12 therapeutic agents targeted at 
reducing TNFα prior to study entry per InclusionExclusion Criterion 1912
(Section 4.14.2). Subjects may not have initiated or been treated with prohibited 
therapeutic agents as outlined in Exclusion Criteria 1 through 20 (Section 4.2).
Rationale: For consistency, changes were made to list of background medications that may be adjusted and 
clarification added that these adjustments are allowed after Week 28.
8. Prestudy and 
Concomitant Therapy
No changes should be made to background medications (ie, MTX, other DMARDs, 
corticosteroids, and NSAIDs) in terms of increases or decreases in dosage (eg, no more 
than 10 mg/day prednisone or no more than 0.20 mg/kg/day, whichever is lower) and/or 
route of administration between Weeks 0 and 28, unless there is a safety concern (eg, 
elevated liver function tests), which requires changes to background medications. 
Beginning atAfter Week 28, subjects will be permitted to change/add MTX, a new
other DMARDs, MTX, corticosteroids and NSAIDs use, including increases or 
decreases in dosage, changes of route of administration, or discontinuations from these 
classes of agents.
Rationale: To clarify that the CHAQ is the PRO assessment that should be conducted prior to any tests, procedures, 
or other consultations for that visit
9.1.1. Overview
The Childhood Health Assessment Questionnaire All visit-specific PRO assessments
(CHAQ) should be conducted before any tests, procedures, or other consultations for 
that visit to prevent influencing subjects’ perceptions. For additional details, refer to the 
PRO user manual.
Rationale: Clarification of the total volume of blood to be collected from each subject through the course of the 
study.  The total blood volume that was reflected in Table 4 is the correct total blood volume. The total volume of 
blood in the text has been revised accordingly.
9.1.1. Overview
The total blood volume to be collected from each subject for the study is approximately 
146149.4 mL (Table 4). Repeat or unscheduled samples may be taken for safety 
reasons or for technical issues with the samples.
Rationale: Added a cross-reference to Section 4.1 which includes the TB screening requirements.  
9.1.2. Screening Phase
Subjects must undergo testing for TB (Attachment 1 and Attachment 2) at screening 
and their medical history assessment must include specific questions about a history of 
TB or known personal exposure to individuals with active TB.  The subject should be 
asked about past testing for TB, including chest radiograph results and responses to 
tuberculin skin or other TB testing (see Section 4.1).
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
30
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarification regarding permissible changes in, or discontinuations of, other anti-rheumatic medications 
after Week 28 in subjects who continue to receive study agent through Week 52; clarification as to when subjects 
who discontinue or withdraw from study participation before Week 52 should return for a final safety follow-up visit 
after the last infusion of study agent.
9.1.4. Treatment Phase: 
After Week 28 through 
Week 52
Beginning at After Week 28, eligible subjects will continue to receive 80 mg/m2 
golimumab administered as IV infusions over 30±10 minutes at Week 28 and q8w 
(±1 week) through Week 52 (Section 6.1). Subjects may also receive commercial MTX 
weekly at the same BSA-based dosage (10 to 30 mg/m2 per week) as at time of study 
entry through Week 28 and commercial folic acid ≥5 mg weekly or folinic acid if 
administered (at half the MTX dose; Section 6.2) given the day after the MTX dose, 
however, increases, decreases or discontinuations of MTX, other DMARDs,
corticosteroids and/or NSAIDs are permissible after Week 28. All changes and reasons 
for changes for these medications need to be documented in the eCRF.
Rationale: Clarification that end of treatment assessments should be obtained approximately 8 weeks after last 
infusion of study agent if a subject prematurely discontinues study treatment.
9.1.4 Treatment Phase: 
After Week 28 through 
Week 52,
End of Treatment/Early 
Withdrawal
If a subject discontinues study agent before Week 52, the subject should return 
approximately 8 weeks after the last administration of study agent for a final safety 
follow-up visit (Section 10.2). If a subject withdraws from study participation before 
Week 52, every effort should be made to obtain end-of-treatment assessments prior to 
the subject’s withdrawal of consent.
10.2 Discontinuation of 
Study Treatment
If a subject discontinues study treatment before the end of the study, assessments 
should be obtained approximately 8 weeks after the last infusion of study agent.
10.3 Withdrawal from 
the Study
If a subject discontinues study treatment before the end of the study, end-of-treatment 
assessments should be obtained approximately 8 weeks after the last infusion of study 
agent at the final safety follow-up visit.
Rationale: Clarification that during the long-term extension phase of the study, subjects who discontinue before the 
end of the study without withdrawing consent should return for final evaluations within approximately 8 weeks after 
the last infusion of study agent.
9.1.5. Long-Term 
Extension Phase: After 
Week 52 through Week 
252
Subjects who discontinue study agent administration prior to Week 244 without 
withdrawing consent should return for a final safety follow-up visit approximately 
8 weeks after their last study agent infusion (Section 10.2).
Rationale: Clarifications on the evaluations that should be performed at the Final Safety Follow-up visit.
10.2 Discontinuation of 
Study Treatment

Safety evaluations (vital signs, review of systems, AE review, study agent 
infusion reaction evaluation, TB evaluation, uveitis evaluation, and the collection 
of a blood sample for routine laboratory analyses and determination of the 
presence of ANA/anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies 
and antibodies to golimumab).

Efficacy evaluations (eg joint assessments, pain assessment, Parent/Subject 
Assessment of Overall Well-Being and Physician’s Global Assessments of 
Disease Activity, and CHAQ, JIA assessments, and collection of blood sample 
for CRP).
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
31
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Removed the subsection for the “Parent/Subject Assessment of Overall Well-being” in Section 9.2.1.2 
and included it in Section 9.2.1.4, Childhood Health Assessment Questionnaire, since the “Parent/Subject 
Assessment of Overall Well-being” is part of the Childhood Health Assessment Questionnaire.
9.2.1.2. American 
College of Rheumatology 
Pediatric Response
Parent/Subject 
Assessment of Overall 
Wellbeing
Parent/Subject Assessment of Overall Well-being
The Parent/Subject Assessment of Overall Well-being is a 10 cm visual analog scale 
(VAS).  Parents/subjects are to complete the VAS that asks them to consider all the 
ways arthritis impacts their child/themselves and then indicate how the child is doing.  
The anchors of the scale are “very well” to “very poor”.  Lower scores indicate better 
well-being.  The process for including this measure in the core set of variables for the 
assessment of children has been captured in the literature.5  
Subjects who are emancipated juveniles (ages 15 to <18 years) at study entry may 
complete the assessments themselves.  The same individual (eg, parent, caregiver, or 
subject) who completes the assessments at the start of the study should complete the 
assessments throughout the study.
Rationale: Correction of the number scale units for the Physician’s Global Assessment of disease activity for 
inactive disease.
9.2.1.2. American 
College of Rheumatology 
Pediatric Response,
Inactive Disease

Physician’s Global Assessment of dDisease aActivity indicating no active disease 
(<0.5 cm 5 mm)
Rationale: Correction of the number scale units for the visual analog scale (VAS) used in the Physician Global 
Assessment of Disease Activity.
9.2.1.3. Physician Global 
Assessment of Disease 
Activity
The Physician Global Assessment of dDisease aActivity is a 10 cm100 mm VAS.
Rationale: Clarification of the construct and ordinal scores to be used to assess functioning and task performance 
with the Childhood Health Assessment Questionnaire (CHAQ); correction of the number scale units for the VAS 
used to assess the subject’s pain and overall well-being; paragraph 1 of “Parent/Subject Assessment of Overall Well-
being” was removed from Section 9.2.1.2 and was included in Section 9.2.1.4 since this assessment is a component 
of the CHAQ; paragraph 3 of Section 9.2.1.4, Childhood Health Assessment Questionnaire, was deleted because it 
was redundant to paragraph 2 which is now part of the subsection, “Parent/Subject Assessment of Overall Well-
being.”
9.2.1.4. Childhood 
Health Assessment 
Questionnaire
Parent/Subject 
Assessment of Pain
Parent/Subject 
Assessment of Overall 
Well-being
The functional status of subjects will be assessed by the Childhood Health Assessment 
Questionnaire (CHAQ).19  Parents/subjects will are to complete this questionnaire
20-question instrument to that assesses the degree of difficulty the subject child has in 
accomplishing tasks in 8 functional areas (dressing and grooming, arising, eating, 
walking, hygiene, reaching, gripping, and activities of daily living).  Responses in each 
functional area are scored from as 0, indicating “ (Wwithout any ANY difficulty)”, 
1 (with some difficulty), 2 (with much difficulty), to 3 (unable to do), or 4 (not 
applicable). indicating “With MUCH Difficulty” to perform a task in that area (lower 
scores are indicative of better functioning) with an ‘unable to do’ and ‘not applicable’ 
response options as well.  Lower scores are indicative of improved functioning and 
task performance in specific functional areas.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
32
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Additionally, the CHAQ includes 2 VAS questions—one used to assess the 
subject’s level of pain, and one used to assess the subject’s overall well-being.
Properties of the CHAQmeasure have been evaluated and its validity assessed.19  The 
CHAQ has been shown to be responsive to disease change.19  A decrease of 0.188 has 
been determined to be a meaningful clinical improvement.1
Subjects who are emancipated juveniles (ages 15 to <18 years) at study entry may 
complete the assessments themselves.  The same individual (eg, parent, caregiver, or 
subject) who completes the assessments at the start of the study should complete the 
assessments throughout the study. 
Parent/Subject Assessment of Pain
Visual Analog Scale for pPain will be assessed as average pain experienced by the 
subject during the past week using on a VAS.  The scale that ranges from “no pain” 
(0 mmcm) to “very severe pain” (100 mmcm).  This assessment should be completed 
by the parents (caregiver)/subjects prior to the tender and swollen joint examination.  
Parent/Subject Assessment of Overall Well-being
The Parent/Subject Assessment of Overall Well-being is a 0-100 mm VAS. 
Parents/subjects will complete the VAS that asks them to consider all the ways 
arthritis impacts their child/themselves and then indicate how the subject is doing. 
The anchors of the scale are “very well” (0 mm) to “very poor (100 mm)”. Lower 
scores indicate better well-being. The process for including this measure in the 
core set of variables for the assessment of children has been captured in the 
literature.5
Subjects who are emancipated juveniles (ages 15 to <18 years) at study entry may 
complete all the CHAQ assessments themselves.  Preferably, the same individual 
(eg, parent, caregiver, or subject) who completes the assessments at the start of the 
study should complete the assessments throughout the study.
Rationale: To align the text in Section 9.3.4 regarding the evaluation of samples for antibodies to golimumab for 
consistency with the Time and Events Schedule (Tables 1, 2, and 3).
9.3.4. Immunogenicity 
Assessments (Antibodies 
to Golimumab)
Antibodies to golimumab will be evaluated in serum samples collected from all 
subjects according to the Time and Events Schedule (ie, Weeks 0, 4, 8, 12, 28, 52, 100, 
148, 196, and 244).
Rationale: Editorial changes only regarding subjects with severe infusion reactions that involve bronchospasms 
with wheezing and/or dyspnea.
9.4 Safety Evaluations,
Allergic Reactions
Subjects with severe reactions following an infusion resulting that result in 
bronchospasms with wheezing and/or dyspnea requiring and require ventilatory 
support, or symptomatic hypotension with a decrease in systolic blood pressure greater 
than 40 mm mercury (Hg), will not be permitted to receive any additional study agent 
infusions. In the case of such reactions, appropriate medical treatment should be 
administered.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
33
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Editorial changes made to clarify that the DRC charter defines how the DRC will review safety.  The 
DRC charter does not define the Steering Committee’s review of safety data.
11.9. Data Monitoring 
Committee
Unblinded safety data will be routinely evaluated by the study’s medical monitor and 
an internal Data Review Committee as defined in the DRC charter.  In addition, the 
data may be reviewed by as well as the Steering Committee as defined in DRC 
charter.
Rationale: Addition of language to clarify that events meeting the definition of a serious adverse event will be 
reported, as well as those events that are anticipated as related to the progression of the disease under study.
12.3.1. All Adverse 
Events
All events that meet the definition of a serious adverse event will be reported as serious 
adverse events, regardless of whether they are protocol-specific assessments. 
Anticipated events will be recorded and reported as described in Attachment 4.
Rationale: The Parent/Subject Assessment of Overall Well-being and the VAS for pain were removed from the list 
of assessments that are recorded into an electronic device because these are part of the CHAQ.  Duration of morning 
stiffness was added as one of the assessments that are recorded into an electronic device.  Text was added to clarify 
that these assessments should be not recorded on paper first.  
17.4. Source 
Documentation

The following parent/subject-
and investigator-completed scales and 
assessments designated by the Sponsor will be recorded directly into an 
electronic device and will be considered source data: joint assessments, 
CHAQ, parent/subject assessment of overall well-being, pPhysician gGlobal 
aAssessment of dDisease aActivity, and duration of morning stiffness.and 
visual analog scale for pain. These assessments should not be recorded on 
paper first. 
Rationale: Addition of language to include events that meet the definition of a serious adverse event, and 
anticipated events which may occur during the study as part of the safety analyses for the study; clarification of 
which anticipated events (drug or disease related) are to be captured in the Case Report Form (CRF), reported to the 
sponsor (serious or non-serious), may or may not be exempt for reporting to Health Authorities, the role of the 
Anticipated Event Review Committee, and analysis of anticipated events for safety evaluation and monitoring.
ATTACHMENT 4 
ANTICIPATED 
EVENTS
An anticipated event is an adverse event (serious or non-serious) that commonly 
occurs as a consequence of the underlying disease or condition under investigation 
(disease related) or background regimen.
For the purposes of this study, the following events will be considered anticipated 
events:
Events related to the progression of the disease under study.
These events will be captured on the CRF and in the database, and will be 
reported to the sponsor as described in Section 12.3.1, All Adverse Events. Any 
event that meets serious adverse event criteria will be reported to the sponsor 
within the appropriate timeline as described in Section 12.3.2, Serious Adverse 
Events. These anticipated events are exempt from expedited reporting as 
individual single cases to Health Authorities. However, if based on an aggregate 
review, it is determined that an anticipated event is possibly related to study drug, 
the sponsor will report these events in an expedited manner.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
34
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Anticipated Event Review Committee (ARC)
An ARC will be established to perform reviews of pre-specified events at an 
aggregate level. The ARC is a safety committee within the sponsor’s organization 
that is independent of the sponsor’s study team. The ARC will meet to aid in the 
recommendation to the sponsor’s study team as to whether there is a reasonable 
possibility that an anticipated event is related to the study drug.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of 
review and threshold to trigger an aggregate analysis of anticipated event will be 
provided in a separate Anticipated Events Safety Monitoring Plan (ASMP).
Rationale: Minor errors were noted and corrected.
Throughout the
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
35
Status: Approved, Date: 16 December 2019
Amendment INT-1 (12 August 2014)
The overall reason for the amendment: The protocol has been revised to add safety information from golimumab 
studies in adults and pediatric patients and to address recommendations from PRINTO and PRCSG.
Applicable Section(s)
Description of Change(s)
Rationale: Clarification of approved therapies for pJIA has been made.
Section 1.1.1 Juvenile 
Idiopathic Arthritis
Elevated levels of TNFα receptors have been found in the serum of JIA patients with 
systemic onset disease, and these levels correlate with disease state. 
Currently approved biologic therapies for the treatment of polyarticular JIA (pJIA)
include etanercept, adalimumab, abatacept, and tocilizumab; canakinumab has been 
approved for systemic JIA.
Rationale: Editorial changes were made.
Section 1.1.2 Golimumab 
Clinical Studies in 
Rheumatoid Arthritis and 
Juvenile Idiopathic 
Arthritis
The results of the CNTO148ART3001 study of IV golimumab in adults 
CNTO148JIA3001 study of SC golimumab in subjects with JIA and the results of the 
CNTO148JIA3001 study of SC golimumab in subjects with JIA CNTO148ART3001 
study of IV golimumab in adults are described below.
Rationale: Clarification of AEs and SAEs has been made
Section 1.1.2.1 
Intravenous Golimumab 
in Adult Rheumatoid 
Arthritis
Through Week 16 (the placebo-controlled period prior to early escape) in 
CNTO148ART3001, 43.7% of subjects in the placebo group and 47.3% in the 
golimumab group had an AE; the highest incidence of AEs was in the infections 
and infestations SOC, 20.8% and 24.3% in the placebo and golimumab groups, 
respectively with upper respiratory tract infection (URTI) being the most 
frequently reported AE (5.6% and 5.1% in the placebo and golimumab groups, 
respectively). Through Week 112, 79.1% of golimumab-treated subjects had an 
AE; the highest incidence of AEs was in the infections and infestations SOC 
(50.5%) and URTI was the most frequently reported AE (11.5%). 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
36
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
The proportion of subjects who reported an AE was comparable between the 
golimumab + MTX and placebo + MTX groups through Week 16 (47.3% compared 
with 43.7%, respectively) and Week 24 (52.9% compared with 49.2%, respectively). 
The most commonly reported system organ class AEs through Week 16 were Infections 
and infestations (24.3% and 20.8% in the golimumab + MTX and placebo + MTX 
groups, respectively), and were predominantly upper respiratory tract infection, urinary 
tract infection, and nasopharyngitis.
Through Week 16 in CNTO148ART3001, 1.0% of subjects in the placebo group 
and 3.8% of subjects in the golimumab group had an SAE. The incidence of SAEs 
within each SOC was < 1.0%, and no SAE occurred in more than 1 subject. 
Through Week 112, 18.2% of golimumab-treated subjects had an SAE; the 
highest incidence of SAEs occurred in the infections and infestations SOC (5.5%) 
and musculoskeletal and connective tissue disorders SOC (3.4%) and the most 
frequently reported SAE was RA (2.1%).
Serious adverse events (SAEs) through Week 24 in the golimumab + MTX group were 
higher (4.1%) compared with the placebo + MTX group (2.0%) and were 
predominantly serious infections (1.0% in the golimumab + MTX group and 0.0% in 
the placebo + MTX group).
One subject in the placebo + MTX group died through Week 24 (presumed stroke due 
to hypertensive crisis; no autopsy performed).
Through Week 24, 1 patient died in the CNTO148ART3001 study, this subject 
was randomized to treatment with placebo + MTX, had never received 
golimumab, and died of a presumed cerebrovascular accident (stroke). Through 
Week 112, an additional 5 subjects died in the CNTO148ART3001 study. Two 
subjects randomized to treatment with placebo + MTX died, both after switching 
to golimumab 2 mg/kg + MTX; cause of death was sudden death (n=1) and 
complications of severe dehydration, Clostridium difficile colitis, and atrial 
fibrillation (n=1). Three subjects randomized to treatment with 2 mg/kg 
golimumab + MTX died in the study; reported cause of death was acute 
abdominal syndrome (later diagnosed as peritoneal tuberculosis [TB], n=1), 
presumed myocardial infarction (MI, n=1), and septic shock secondary to a 
pyogenic lung abscess due to Acinetobacter baumanii (n=1).
No malignancies were reported through Week 16 in CNTO148ART3001. Though 
not included in the tables which include only treatment-emergent events or the 
calculations of malignancy rates, there was 1 case of nontreatment-emergent lung 
adenocarcinoma reported in the placebo + MTX group before Week 16. Through 
the placebo-controlled period (Week 24), 1 malignancy (breast cancer) was
reported in the golimumab group. Through Week 112, 5 additional malignancies 
basal cell carcinoma, chronic lymphocytic leukemia in a subject with a family 
history of chronic lymphocytic leukemia, cervix carcinoma in situ, Bowen’s 
Disease and basal cell carcinoma) were reported. No lymphomas were reported 
through Week 112.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
37
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Through Week 16 (the placebo-controlled period prior to early escape) in 
CNTO148ART3001, 43.7% of subjects in the placebo group and 47.3% in the 
golimumab group had an AE; the highest incidence of AEs was in the infections and 
infestations SOC, 20.8% and 24.3% in the placebo and golimumab groups, respectively 
with upper respiratory tract infection (URTI) being the most frequently reported AE 
(5.6% and 5.1% in the placebo and golimumab groups, respectively). Through 
Week 112, 79.1% of golimumab-treated subjects had an AE; the highest incidence of 
AEs was in the infections and infestations SOC (50.5%) and URTI was the most 
frequently reported AE (11.5%).
The proportion of subjects who reported an AE was comparable between the 
golimumab + MTX and placebo + MTX groups through Week 16 (47.3% compared 
with 43.7%, respectively) and Week 24 (52.9% compared with 49.2%, respectively). 
The most commonly reported system organ class AEs through Week 16 were Infections 
and infestations (24.3% and 20.8% in the golimumab + MTX and placebo + MTX 
groups, respectively), and were predominantly upper respiratory tract infection, urinary 
tract infection, and nasopharyngitis.
Serious adverse events (SAEs) through Week 24 in the golimumab + MTX group were 
higher (4.1%) compared with the placebo + MTX group (2.0%) and were 
predominantly serious infections (1.0% in the golimumab + MTX group and 0.0% in 
the placebo + MTX group).
No malignancies were reported through Week 16 in study CNTO148ART3001. 
There was 1 case of non-treatment-emergent lung adenocarcinoma reported in the 
placebo + MTX group prior to receiving study agent. Through the placebo-
controlled period (Week 24), 1 malignancy (breast cancer) was reported in the 
golimumab group. Through Week 112, 5 additional malignancies were reported, 
including basal cell carcinoma, chronic lymphocytic leukemia in a subject with a 
family history of chronic lymphocytic leukemia, cervix carcinoma in situ, Bowen’s 
Disease and basal cell carcinoma. No lymphomas were reported through 
Week 112.
Through Week 16 in CNTO148ART3001, 0.5% of subjects in the placebo group and 
2.5% of subjects in the golimumab group had an infusion reaction. Through Week 112, 
3.9% of golimumab-treated subjects had an infusion reaction and 0.4% of infusions 
were complicated by infusion reactions. It should be noted that all placebo infusions 
consisted of 0.9% normal saline alone rather than a true matched placebo. No serious 
infusion reactions requiring study agent discontinuation or anaphylaxis were noted. 
There was a case of anaphylaxis which was not associated with study drug.
For the most comprehensive nonclinical and clinical information regarding 
Simponi (golimumab), refer to the latest version of the Investigator's Brochure 
and Addenda for Simponi (golimumab). 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
38
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
The median peak serum golimumab concentration (ie, post-infusion golimumab 
concentration) of 41.56 µg/mL was observed at Week 4 following IV administration of 
2 mg/kg golimumab at Week 0, Week 4, followed by q8w (±1 week) administration. 
This peak is higher than that reported for SC golimumab administration of 50 mg every 
4 weeks (q4w). The median trough serum golimumab concentration in subjects 
receiving IV golimumab at 2 mg/kg q8w with MTX was 0.28 µg/mL at Week 12 and 
0.22 µg/mL at Week 20; these levels are similar to those reported with SC golimumab 
50 mg. Overall exposure to golimumab in approximately 3 times that for SC 
golimumab 50 mg over a similar period of exposure.
Rationale: Major endpoints were not met and the study has been terminated and duly noted. Additionally, AEs have 
been described.
Section 1.1.2.2 
Subcutaneous 
Golimumab in Juvenile 
Idiopathic Arthritis
The baseline disease characteristics of the 173 enrolled subjects constituted a 
population with moderate to severe JIA comparable with other clinical studies of anti-
TNFα agents in pJIA, with the exception of numerically lower mean and median 
CRP/ESR levels in CNTO148JIA3001.
The study did not meet its primary and major secondary endpoints as the proportion of 
subjects who were JIA ACR 30 responders at Week 16 and did not experience a flare 
of disease between Week 16 and Week 48 was not significantly different in subjects 
randomized to continued golimumab treatment between Weeks 16 and 48 as compared 
with subjects randomized to receive placebo between Weeks 16 and 48 (59% versus 
52.6%, p=0.41). All sensitivity analyses
and major secondary endpoints 
demonstrated the lack of statistically significant differences between treatment groups. 
The Sponsor terminated the long-term extension of the study early as pre-specified 
efficacy endpoints were not met.
With regards to immunogenicity, 40.1% of subjects developed antibodies to golimumab 
using the recently developed drug tolerant immunoassay analyses. The new drug 
tolerant immunoassay is more sensitive compared with assays used previously in adult 
golimumab RA studies and allows the detection of antibodies to golimumab despite 
detectable serum golimumab levels. Among subjects who were randomized and 
remained on golimumab 30 mg/m2 SC + MTX, 30.8% developed antibodies to 
golimumab; antibody titers tended to be low. When evaluating the effects of 
immunogenicity on PK, efficacy, and safety, it was found that positive anti-golimumab 
antibody status significantly decreased steady-state trough golimumab concentrations 
when the titer levels were >1:100. However, the effect of antibodies on efficacy was 
less sensitive, requiring higher titers >1:1000 in order to correlate with apparent 
reductions in efficacy. Since only approximately 5% of subjects with JIA developed 
anti-golimumab antibodies with titers >1:1000, it was determined that immunogenicity 
was not a contributing factor to not achieving lack of achievement of the primary 
endpoint in CNTO148JIA3001. Lastly,
Additionally,
positive anti-golimumab 
antibody status did not appear to be associated with a higher incidence of injection-site 
reactions.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
39
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
The proportion of subjects who reported an AE through Week 48 was 87.9%. The most 
commonly reported system organ class of AEs was Infections and infestations (67.1%), 
and were predominantly upper respiratory tract infections and nasopharyngitis. There 
was no marked difference in AEs reported between Week 16 and Week 48 for subjects 
randomized to placebo (82.9%) and those randomized to continued golimumab 
treatment (78.2%), however it needs to be noted that all subjects in randomized 
withdrawal portion of the study were exposed to golimumab for 16 weeks before 
re-randomization. Serious adverse events were reported by 13.3% of subjects. The 
most commonly reported SAE was worsening of JIA (6.4%). Serious infections were 
reported in 2.9% of subjects (pneumonia, urinary tract infection, herpes zoster, upper 
respiratory tract infection, and pyelonephritis), and there were no deaths, malignancies, 
or demyelination events through Week 48. There were no reports of active TB and no 
serious opportunistic infections. Through Week 48, the number of subjects with 
abnormal ALT measurements (and no concomitant treatment for latent TB, which 
may affect LFTs) and no TB prophylaxis was 29.5% (51/167), 39 of the 51 subjects 
had elevations < 3 X ULN.
There were two subjects with ALT elevation to > 8 X ULN but neither subject met 
the criteria for Hy’s Law consistent with hepatotoxicity. Subjects were not 
receiving TB prophylaxis; one of the subjects had baseline ALT which was already 
abnormal. All subjects with LFT abnormalities were managed conservatively with 
changes in MTX dosing but one subject was discontinued for elevated LFTs.
The incidence of injections with injection-site reactions through Week 48 was 
0.8%; there was one SAE report of serum sickness-like reaction in a patient 
randomized to placebo who resumed golimumab treatment.
Although the CNTO148JIA3001 study did not meet its endpoints, when JIA ACR 
response rates were presented analyzed as observed data through Week 48 (using 
Week 0 as baseline and comparing drug/placebo effect at each visit through Week 48) 
the study showed the potential for significant efficacy that could be attained with SC 
golimumab in children with pJIA. Therefore, it lends support to the study of IV 
golimumab in subjects with pJIA who have an inadequate response to MTX.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
40
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarification of the primary objective has been made. Additionally, clarification on the prior use of 
agents has also been made.
Section 1.2 Overall 
Rationale for the Study
The primary objective of this study is to characterize the PK of IV golimumab in pJIA, 
along with simultaneous evaluations of the safety and efficacy (reflected in proportion 
of subjects with JADAS minimal disease activity at Week 28) of IV golimumab in 
these subjects. This study will also include subjects with multiple subtypes of JIA, 
including juvenile PsA, as well as subjects with prior anti-TNFα experience (up to 20
30% of the study population).
The study is designed to obtain PK data in response to BSA-based (80 mg/m2, which is 
expected to be equivalent to the 2 mg/kg dose in adult RA patients weighing 70 kg) IV 
golimumab for subjects with pJIA who have inadequate response to MTX treatment as 
well as prior treatment with non-steroidal anti-
inflammatory agents, 
corticosteroids and/or anti-TNFα agents, with the intent to demonstrate its similarity 
to the response seen with weight-based (2 mg/kg) doses of IV golimumab in adult RA 
subjects who have inadequate response to MTX treatment. The 80 mg/m2 dose for 
subjects with pJIA is based on the 2 mg/kg dose studied in CNTO148ART3001 in the 
adult RA population.
Rationale: Clarification of the primary objective has been made
Section 2.1 Objectives
Primary Objective
The primary objective of this study is to assess the PK and JADAS minimal activity 
scores following intravenously administered golimumab in subjects (ages 2 to less than 
18 years) with pJIA manifested by ≥5 joints with active arthritis and CRP of 
≥0.1 mg/dL despite MTX therapy for ≥3 months at Week 28.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
41
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications of duration of disease for enrollment in study and maximum single dose have been made.
Section 3.1 Overview of 
Study Design
This is a Phase 3, open-label, single-arm, multicenter study to evaluate the PK, safety, 
and efficacy of IV golimumab in subjects with active pJIA despite current treatment 
with MTX. The study population will be comprised of subjects with pJIA receiving 
MTX, ages 2 to less than 18 years, with at least a 6 3-month history of pJIA, and active 
arthritis in ≥5 joints. Approximately 120 subjects will be enrolled at Week 0 to ensure 
that approximately 100 subjects remain in the study at Week 52. Enrollment patterns 
are expected to yield a subject population of approximately 10% aged 2 to up to 6 
years, approximately 20% aged 6 to up to 12 years, and approximately 70% aged 12 to 
less than 18 years.
All subjects will receive 80 mg/m2 golimumab (maximum single dose 240 mg) as an 
IV infusion given over 30±10 minutes at Weeks 0, 4, and every 8 weeks (q8w; ± 3 
days) through Week 28 and then q8w (± 1 week) thereafter through Week 244. Body 
surface area will be calculated based on the subject’s height and body weight measured 
at each visit, and the BSA-based dose of golimumab will be adjusted as needed to 
maintain the dose at 80 mg/m2. Subjects will also receive commercial MTX weekly at 
the same BSA-based dosage (10 to 30 mg/m2 per week of MTX, with a minimum of 
15 mg in subjects with BSA ≥1.67 m2) as at time of study entry through Week 28 as 
outlined in Section 6.2.
Every effort should be made to maintain subjects at a dose of 80 mg/m2 of golimumab
based upon BSA, and decreases below or increases above 80 mg/m2 or shortening of the 
dosing interval (eg, from 8 weeks to 6 weeks) will not be permitted at any visit.
The schematic overview of the study (Figure 1) has been revised to show the 
screening period (-6 Weeks to Week 0) and safety follow-up period (Week 244 to 
Week 252).
Rationale: This subsection has been reorganized [Week 0 through Week 58 28] for clarity and therefore the 
deletion.
Section 3.1.1 Week 0 
through Week 28
Through Week 28 subjects will be monitored and disease activity and safety will be 
assessed at the investigative site every 4 weeks. From Week 28 through Week 52, 
subjects will be monitored and disease activity and safety will be assessed at the 
investigative site every 8 weeks.
After all subjects complete the Week 28 visit, the database will be locked to assess PK, 
safety and efficacy. An additional safety, efficacy, and PK database lock is currently 
planned for Week 52. Final data base lock will be performed at Week 252.
No changes should be made to background medications (ie, DMARDs, corticosteroids, 
and NSAIDs) in terms of increases or decreases in BSA-based dosage beyond the 
parameters provided in Section 8 (eg, no more than 10 mg/day prednisone or no more 
than 0.20 mg/kg/day, whichever is lower) and/or route of administration between 
Weeks 0 and 28, unless there is a safety concern (eg, elevated liver function tests), 
which requires changes to background medications. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
42
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: An additional subsection has been introduced as subsection 3.1.1 was re-organized for clarity
Section 3.1.2 Week 28 
through Week 52
From Week 28 through Week 52, infusions will continue to be performed every 8 
weeks (± 1 week), however subjects will be actively monitored at the investigative 
site and disease activity and safety will be assessed at the investigative site every 8 
weeks rather than every 4 weeks as between Weeks 0 and 28. As noted beginning 
at Week 28, subjects will be permitted to change DMARD (including agents 
besides MTX), MTX, corticosteroid, and NSAID use as outlined in Section 8.
Rationale: Clarifications of the availability of study agent have been made
Section 3.1.3 Week 52 
through Week 252 
(Long-term extension)
During the long-term extension, all subjects will continue to receive golimumab q8w (± 
1 week) through Week 244. For children who have completed the full trial period of 
252 weeks and for whom drug is proven beneficial but the drug is not 
commercially available for JIA indication (or patient does not qualify for 
insurance to pay for drug) IV golimumab will continue to be provided by the 
Sponsor. Between Week 52 and Week 252, disease activity will be monitored and 
assessed, and documented in the CRF every 16 weeks; infusions and safety 
measurements will be done every 8 weeks at the investigative site.
As noted beginning at Week 28, subjects will be permitted to change DMARD, MTX, 
corticosteroid, and NSAID use, including increases or decreases in BSA-based dosing 
(where appropriate) for these classes of agents as outlined in Section 8.
Rationale: Clarification of the visit window through Week 24 has been made
Section 3.2.2 Dose 
Selection
In the CNTO148JIA3001 study, BSA-based dosage of SC golimumab was utilized. 
After subjects with pJIA received golimumab 30 mg/m2 SC q4w, median steady-state 
trough golimumab levels were similar across different age groups (median 0.73 µg/mL 
to 1.25 µg/mL at Week 48). The median steady-state concentrations in subjects with 
pJIA were also similar to or higher than those seen in adult subjects with RA who 
received golimumab 50 mg SC q4w (0.82 µg/mL at Week 76 and 1.17 µg/mL at Week 
104 in C0524T06 using the same MSD ECLIA assay); both study populations were 
receiving concomitant MTX. The study results confirmed that BSA-based doses 
achieved fairly even drug exposure in pediatric subjects at different ages and were 
comparable to the adult exposure.
Data from the Phase 3 IV study in adults with RA (CNTO148ART3001) through 24 
weeks have shown that golimumab 2 mg/kg at Week 0, Week 4, and q8w (±1 week) 
thereafter is the optimal dose regimen for the treatment of RA in most adults. For a 
child, golimumab 80 mg/m2 (2 mg/kg/1.73 m2) would be approximately equivalent to 2 
mg/kg for an adult subject weighing 70 kg (with a BSA of 1.73 m2). Thus, in the 
current study (CNTO148JIA3003), a dose of golimumab 80 mg/m2 has been chosen to 
evaluate the safety and efficacy of golimumab in the JIA population.
Rationale: Clarification of route of administration for Simponi Aria
Section 3.2.3 Rationale
The Sponsor will utilize PK/PD data generated from the proposed open-label 
CNTO148JIA3003 study to extrapolate to adult PK and efficacy data from the 
CNTO148ART3001 study in RA, which was the pivotal study that served as the basis 
for approval of intravenous golimumab (SIMPONI ARIA and SIMPONI for 
Intravenous Use) for adult patients with RA.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
43
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Several inclusion criteria were revised per PRINTO/PRCSG recommendations
Section 4.1
Inclusion criteria #1
Pediatric Subjects must be age 2 years to less than 18 years with a body weight >15 kg 
at the time of screening and at Week 0.
Section 4.1
Inclusion criteria #3
Active JIA of one of the following subtypes:
a.
Rheumatoid factor positive or negative pJIA for ≥3 months prior to 
screening, or
b.
Systemic JIA with no systemic symptoms for ≥3 months but with 
polyarthritis for ≥3 months prior to screening, or
c.
Extended oligoarticular JIA ≥3 months prior to screening, or
d.
Polyarticular juvenile psoriatic arthritis ≥3 months prior to screening, or,
e.
Enthesitis related arthritis ≥3 months prior to screening.
Inclusion criteria #4
Failure or inadequate response to at least a 3-month course of MTX before 
screening.
Inclusion criteria #7
Subjects must have active JIA despite current use of oral, intramuscular or 
subcutaneous MTX (for ≥3 months before screening and on a stable dose for 4 weeks 
as noted in Section 8) at a weekly dose of ≥10 mg/m2. Subjects currently on MTX 
(weekly 10 to 30 mg/m2), must receive a stable dose of MTX for ≥4 weeks before 
screening. Subjects with BSA ≥1.67 m2 must receive a minimum of 15 mg/week of 
MTX unless documented country or site regulations prohibit use of 15 mg of MTX per 
week in subjects with BSA ≥1.67 m2. In situations where there is documented 
intolerance of doses >10 mg/m2 weekly or for subjects with BSA ≥1.67 m2 who do not 
tolerate 15 mg/week for subjects with BSA ≥1.67 m2, subjects may be entered into the 
trial on a lower dose of MTX.
Inclusion criteria #8
If using corticosteroids, must be on a stable dose of ≤10 mg/day prednisone equivalent 
or 0.20 mg/kg/day (whichever is lower) for ≥ 2 weeks before first administration of 
study agent (In extreme circumstances, a subject may receive <0.20 mg/kg/day if there 
is documented intolerance or AEs due to higher doses of corticosteroids). If currently 
not using corticosteroids, the subject must have not received corticosteroids for at least 
2 weeks before the first dose administration. Subjects with systemic onset JIA but 
without systemic symptoms must be on a stable dose of corticosteroids for at least 3 
days screening.
Inclusion criteria #9
If using NSAIDs, must be on a stable dose for ≥2 weeks before the first administration 
of study agent screening. If not currently using NSAIDs, must not have taken them for 
at least 2 weeks before the first administration of study agent screening.
Rationale: Several exclusion criteria were revised per PRINTO/PRCSG recommendations
Section 4.2
Exclusion criteria #1
Subject has initiated DMARDs and/or immunosuppressive therapy (with the exception 
of MTX) within 4 weeks prior to first study agent administration. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
44
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Exclusion criteria #9
Subject has received or is expected to receive any live viral or live bacterial 
vaccinations from 3 months before first study agent administration and up to 3 months 
after the last study agent administration.
Exclusion criteria #10
Subject has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of 
screening or is planned to receive BCG vaccination within 12 months following last 
study drug administration.
Exclusion criteria #14
Subject has received infliximab, etanercept, adalimumab, or certolizumab pegol within 
6 weeks of the first dose of study agent.
Exclusion criteria #15
Subject has received infliximab or tocilizumab within 8 weeks of the first 
administration of study agent.
Exclusion criteria #18
Subject has received canakinumab within prior 4 months prior to first study dose 
administration.
Exclusion criteria #31
Subject has a history of lymphoproliferative disease, including lymphoma, or signs 
suggestive of possible lymphoproliferative disease, such as lymphadenopathy of 
unusual size or location, or clinically significant splenomegaly not consistent with 
pJIA or systemic onset JIA without systemic symptoms.
Exclusion criteria #35
Subject has a past history of macrophage activation syndrome.
Exclusion criteria #45
Active uveitis within 3 months prior to screening 
Exclusion criteria #46
Subject with BSA >3.0 m2
Rationale: Clarification of prohibitions and restrictions has been made.
Section 4.3
Prohibitions and 
Restrictions #1
Subjects must not receive a live virus or live bacterial vaccination 3 months prior to
screening, during the study, or within 3 months after the last administration of study 
agent.
Prohibitions and 
Restrictions #2
Subjects must not receive a BCG vaccination for 12 months before the study screening, 
during the study or within 12 months after the last administration of study agent.
Prohibitions and 
Restrictions #5
Intramuscular administration of corticosteroids for the treatment of pJIA is not allowed 
during the study. Corticosteroids administered by bronchial or nasal inhalation for 
treatment of conditions other than pJIA may be given as needed throughout the course 
of the study. For additional details, see Section 8.
Prohibitions and 
Restrictions #6
Subjects must not receive investigational drugs, other immunosuppressants (such 
as, but not exclusively, cyclophosphamide), or other biologics for pJIA during the 
study. 
Rationale: Clarification of the visit windows through Week 24 and through Week 244 has been made
Section 5 Treatment 
Allocation and Blinding
This is an open-label study. Beginning at Week 0, all subjects will receive golimumab 
80 mg/m2 at Week 0, Week 4 and q8w (± 3 days) through Week 28 and q8w (± 1 week) 
up to Week 244. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
45
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications on the maximum single dose have been made.
Section 6.1 Dosage and 
Administration
Golimumab
The study will have 1 active treatment group and all subjects will receive 80 mg/m2
golimumab (maximum single dose 240 mg) IV infusions at Week 0, Week 4, and q8w 
(±3 days) through Week 28 and q8w (±1 week) thereafter through Week 244. The 
golimumab infusions will be prepared by a pharmacist under sterile conditions using 
golimumab 50 mg/4 mL liquid in vials and a 100 mL infusion bag of 0.9% saline. 
Subjects will receive 80 mg/m2 golimumab IV infusions over 30±10 minutes. Infusions 
may be slowed down for evidence of infusion reactions as deemed appropriate by the 
investigator, and all changes in the infusion rate should be recorded in the CRF. Body 
surface area will be calculated at each visit and the dose of golimumab will be adjusted 
as needed to maintain the dose at 80 mg/m2. Body surface area will be calculated using 
the Mosteller equation: BSA (m2) = ([height (cm) x weight (kg)]/3600)1/2. For 
additional details, see the Site IP Manual.
Rationale: Clarification on the use of the MTX has been made.
Section 6.2 Dosage and 
Administration
Methotrexate
Subjects will receive commercial MTX at the same BSA-based dose (10 to 30 mg/m2
per week of MTX) as at time of study entry through Week 28. Body surface area will 
be calculated at each visit and the dose of MTX will be adjusted as needed to maintain 
the dose at the same mg/m2 per week dose as the subject was receiving at time of study 
entry. Absolute dose should remain stable from baseline through Week 28.
Every effort should be made to ensure that subjects remain on the same BSA-based 
dose and route of administration of MTX through the Week 28 safety and efficacy 
database lock, unless intolerance or AEs due to MTX occur (Section 8). Guidelines for 
adjusting MTX dosage in the event of MTX toxicity are provided in the Trial Center 
File.
Subjects will also receive a total dose of commercial folic acid ≥5 mg weekly or folinic 
acid (at half the MTX dose) given the day after the weekly MTX dose. In children 
< 12 years of age, the administration of folic acid or folinic acid will be at the 
discretion of the physician.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
46
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications on the use of corticosteroids during participation in this study have been made
Section 8
Prestudy and 
Concomitant Therapy
All therapies (prescription or over-the-counter medications, including vaccines, 
vitamins, herbal supplements; non-pharmacologic therapies such as electrical 
stimulation, and acupuncture special diets, exercise regimens) different from the study 
drug must be recorded in the CRF. Recorded information will include a description of 
the type of the drug, treatment period, dosing regimen, route of administration, and its 
indication. Modification of an effective pre-existing therapy should not be made for the 
explicit purpose of entering a subject into the study.
If using corticosteroids or NSAIDs, subjects must have been on stable doses of these 
medications prior to study entry per Inclusion Criteria 8 and 9 (Section 4.1). Subjects 
may have been previously treated with no more than 1 therapeutic agent targeted at 
reducing TNFα prior to study entry per Inclusion Criterion 19 (Section 4.1). Subjects 
may not have initiated or been treated with prohibited therapeutic agents as outlined in 
Exclusion Criteria 1 through 20 (Section 4.2).
Subjects must have received MTX at a weekly dose of ≥10 mg/m2 for ≥3 months before 
screening. Subjects with BSA ≥1.67 m2 must receive a minimum of 15 mg/week of 
MTX. The dose must have been stable and between 10 to 30 mg/m2 weekly (or at least 
15 mg/week in subjects with BSA ≥1.67 m2) for ≥4 weeks before screening. For 
exceptions to this rule, see Inclusion Criterion 7. Subjects (with the exception of those 
with sJIA) receiving corticosteroids at the time of study entry must have been 
receiving a stable dose for ≥2 weeks before screening, and that dose must have been 
≤10 mg/day prednisone or prednisone equivalent or 0.20 mg/kg/day (whichever is 
lower). Subjects with systemic onset JIA but without systemic symptoms for ≥3 
months must be on stable corticosteroids for 3 days before screening and not 
exhibit systemic symptoms. If receiving NSAID therapy, the dose must have been 
stable for ≥2 weeks before screening.
No changes should be made to background medications (ie, DMARDs, MTX, 
corticosteroids, and NSAIDs) in terms of increases or decreases in BSA-based dosage 
(eg, no more than 10 mg/day prednisone or no more than 0.20 mg/kg/day, whichever is 
lower) and/or route of administration between Weeks 0 and 28, unless there is a safety 
concern (eg, elevated liver function tests), which requires changes to background 
medications. Beginning at Week 28, subjects will be permitted to change/add new
DMARD, MTX, corticosteroid, and NSAID use, including increases or decreases in 
dosage, changes of route of administration, or discontinuations in BSA-based 
dosage (where appropriate) for these classes of agents.
Subjects may receive intra-articular injections of a corticosteroid, if clinically required, 
during the study up to Week 52. However, the number of intra-articular injections 
should be limited to 2 over any 24-week period. That is, if a subject has received 2 
intra-articular injections and more than 24 weeks has elapsed, the subject may receive 
up to 2 additional intra-articular injections over another 24-week period.
After Week 52, the number of injected joints is no longer limited to 2 injections 
per 24 weeks. The Sponsor must be notified in advance (or as soon as possible 
thereafter) of any instances in which prohibited therapies are administered 
(Section 4.3).
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
47
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications regarding visit-specific PRO assessments have been made.
Section 9.1.1
Overview
The Time and Events Schedules summarize the frequency and timing of efficacy, PK, 
immunogenicity, and safety measurements applicable to this study (Table 1, Table 2, 
and Table 3). All scheduled study visits should occur within ±3 days of the intended 
visit through Week 28 and ± 1 week from Week 28 through Week 244. If the 
recommended acceptable window cannot be observed, the Sponsor must be 
contacted before scheduling a visit.
All visit-specific PRO assessments should be conducted before any tests, 
procedures, or other consultations for that visit to prevent influencing subjects’ 
perceptions. For additional details, refer to the PRO user manual.
The total blood volume to be collected from each subject for the study is approximately 
146.4 mL (Table 4). Repeat or unscheduled samples may be taken for safety reasons or 
for technical issues with the samples.
Table 4:
Approximate Volume of Blood to be Collected From Each Subject 
Through Week 252
Type of Sample
Approximate
Volume per 
Sample 
(mL)
No. 
of 
Samples 
per 
Subject
Approximate
Total 
Volume 
of 
Blood 
(mL)a,b
Safety 
(including 
screening 
and 
posttreatment assessments)
- Hematology
1.2
18 17
21.6 20.4
- Serum chemistry
1.1
18 17
19.8 18.7
Serology (hepatitis B and hepatitis 
C)
2.0
1
2.0
Serum -hCG pregnancy tests
1.1
1
1.1
- QuantiFERON®-TB Gold test
3.0
5 6
15.0 18.0
- Rheumatoid factor
1.1
1 
1.1
- Anti-dsDNA antibody 
1.1
16 11
17.6 12.1
- ANA antibodies 
1.1
11
12.1
Efficacy (CRP)
1.1
24
26.4
PK and immunogenicity (antibodies to 
golimumab)
2.5
15
37.5
Approximate Total
154.2 149.4
a.
Calculated as the number of samples multiplied by amount of blood per sample.
b.
Repeat or unscheduled samples may be taken for safety reasons or technical issues with the samples.
Note: An indwelling intravenous cannula may be used for blood sample collection. 
Abbreviations: ANA = antinuclear antibodies; β-hCG = β-human chorionic gonadotropin; CRP = C-
reactive protein; dsDNA = double-stranded deoxyribonucleic acid; PK = pharmacokinetic; TB = 
tuberculosis. 
Rationale: 
Section 9.1.2 Screening 
Phase
Subjects must undergo testing for TB (Attachment 1 and Attachment 2) at screening 
and their medical history assessment must include specific questions about a history of 
TB or known occupational or other personal exposure to individuals with active TB. 
The subject should be asked about past testing for TB, including chest radiograph 
results and responses to tuberculin skin or other TB testing.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
48
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Reorganizations noted in Sections 3.1.1 and 3.1.2 resulted in the revisions in Sections 9.1.3 
Section 9.1.3
Treatment Phase: Week 0 
through Week 28
Beginning at Week 0, eligible subjects will receive 80 mg/m2 golimumab administered 
as IV infusions over 30±10 minutes at Weeks 0, 4 and q8w (±3 days) through Week 28 
(Section 6.1). Subjects will also receive commercial MTX weekly at the same BSA-
based dosage (10 to 30 mg/m2 per week of MTX) as at time of study entry at least
through Week 28 and commercial folic acid ≥5 mg weekly or folinic acid (at half the 
MTX dose) given the day after the MTX dose (Section 6.2). In children <12 years of 
age, the administration of folic acid or folinic acid will be at the discretion of the 
physician.
Rationale: Additional details have been as a result of reorganization noted in Sections 3.1.1 and 3.1.2
Section 9.1.4 Treatment 
Phase: Week 28 through 
Week 52
Beginning at Week 28, eligible subjects will receive 80 mg/m2 golimumab 
administered as IV infusions over 30±10 minutes at Week 28 and q8w (±1week) 
through Week 52 (Section 6.1). Subjects may also receive commercial MTX 
weekly at the same BSA-based dosage (10 to 30 mg/m2 per week of MTX) as at 
time of study entry through Week 28 and commercial folic acid ≥5 mg weekly or 
folinic acid (at half the MTX dose) given the day after the MTX dose, however, 
increases, decreases or discontinuations of MTX, corticosteroids and/or NSAIDs 
are permissible after Week 28. All changes and reasons for changes for these 
medications need to be documented in the eCRF.
Subjects will have safety, efficacy, PK, and immunogenicity evaluations performed 
according to the Time and Events Schedule (Table 1). 
Rationale: Clarification of the visit windows from Week 52 through Week 244 has been made.
Section 9.1.5
Long-Term Extension 
Phase: After Week 52 
through Week 252
Subjects who enter the long-term extension after the Week 52 visit will continue to 
receive 80 mg/m2 golimumab administered as IV infusions over 30±10 minutes q8w 
(±1 week) through Week 244. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
49
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications for joint evaluations have been made.
Section 9.2.1.1
Joint Evaluation
Each of 75 joints will be evaluated for tenderness, and 68 joints will be evaluated for 
swelling and pain and limitation on motion
according to the standard 
PRINTO/PRCSG joint evaluation. A consistent joint assessor, with at least 1 year of 
experience in performing joint assessment, will be designated at each study center to 
perform all joint assessments.
Training will be provided to a single consistent joint assessor from each site before the 
start of subject enrollment; the training is mandatory unless the site’s joint assessor has 
taken certified training provided by PRINTO or PRCSG. If a consistent joint assessor 
was trained by the Sponsor in a previous clinical study, he or she may receive a waiver 
for this training. Documentation of Sponsor or PRINTO/PRCSG training will be 
maintained in the Trial Center File. If possible, the consistent joint assessor for the 
study should not be changed during the study. However, the assessor from each site 
who attends the consistent joint assessor training provided by the Sponsor may train 1 
additional assessor at the site for coverage during their absences.
Nonevaluable Joints
While it may be reasonable in clinical practice to identify as “nonevaluable” any joint 
which in the past or during study participation has been surgically altered (ie, prosthesis 
placement) or medically treated (ie, intra-articular injection), the designation of 
“nonevaluable” for the purposes of this study is slightly different. Joints should only be 
designated as “nonevaluable” by the consistent joint assessor in the ePRO device. if it 
is physically impossible to assess the joint (ie, joint inaccessible due to a cast, joint not 
present due to an amputation, joint deformed so as to make it impossible to assess). 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
50
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: The definition of CRP has been revised
Section 9.2.1.2 American 
College of Rheumatology 
Pediatric Response
The JIA ACR 30 response criteria4 is defined as a 30% improvement (ie, a decrease 
in score) from baseline in at least 3 of the following 6 components, with worsening of 
30% or more in no more than 1 of the following components:

Physician’s Global Assessment of disease activity

Parent/Subject 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 (CHAQ)

CRP (Improvement in CRP occurs when the CRP value changes from abnormal to 
normal or to lower levels within the abnormal range. Conversely, a worsening 
occurs when the CRP value changes from normal to abnormal or worsens within 
the abnormal range. Changes within the normal range are not considered 
improvements or worsening.)
The JIA ACR 50 response, the JIA ACR 70 response, and the JIA ACR 90 response are 
defined as a 50% improvement, a 70% improvement, and a 90% improvement from 
baseline, respectively, in at least 3 of the above 6 components, with worsening of 30% 
or more in no more than 1 of the above components.
Inactive Disease
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 JIA

No active uveitis

Normal CRP (≤0.287 mg/dL for subjects without underlying inflammatory 
disease)

Physician Global Assessment of disease activity indicating no active disease 
(<0.5 cm)

Duration of morning stiffness <15 minutes
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: As the VAS for pain is included in the CHAQ assessment, Sections 9.2.1.4 and 9.2.15 were merged. 
Clarification of very severe pain has also been made. CHAQ scoring has been aligned with the CHAQ questionnaire
Section 9.2.1.4
Childhood Health 
Assessment 
Questionnaire
The functional status of subjects will be assessed by the Childhood Health Assessment 
Questionnaire.18 Parents/subjects are to complete this 20-question instrument that 
assesses the degree of difficulty the child has in accomplishing tasks in 8 functional 
areas (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and 
activities of daily living). Responses in each functional area are scored from 0, 
indicating no difficulty, to 3, indicating inability to perform a task in that area (lower 
scores are indicative of better functioning) with an unable to do and not applicable 
response options as well. Responses in each functional area are scored from 0, 
indicating “Without ANY difficulty”, to 3, indicating “With MUCH Difficulty” to 
perform a task in that area (lower scores are indicative of better functioning) with 
‘an unable to do’ and ‘not applicable’ response options as well. Properties of the 
measure have been evaluated and its validity assessed.18 The CHAQ has been shown to 
be responsive to disease change.18 A decrease of 0.188 has been determined to be a 
meaningful clinical improvement.1
Visual Analog Scale for pain will be assessed as average pain during the past week on a 
VAS. The scale ranges from “no pain” (0 cm) to “very severe pain” (10 cm). This 
assessment should be completed by the parents/subjects prior to the tender and swollen 
joint examination. 
Rationale: Clarifications on C-reactive protein evaluations has been made.
Section 9.2.1.5
C-reactive Protein
C-reactive protein has been demonstrated to be useful as a marker of inflammation in 
patients with pJIA and is part of the JIA ACR 30 core assessments. C-reactive protein 
will be assayed by a central laboratory using a validated, high-sensitivity CRP assay. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
52
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: An additional sectional on JADAS has been added.
Section 9.2.1.6 Juvenile 
Arthritis Disease Activity 
Score (JADAS)
Recently, a composite disease activity score for pJIA, the Juvenile Arthritis 
Disease Activity Score (JADAS), was developed; in validation analyses it was 
found to have good metrologic properties, including the ability to predict disease 
outcome. The JADAS (modified for using CRP) is computed by assessing the 
following variables: (1) physician global rating of overall disease activity, 
measured on a 10-cm horizontal visual analog scale (VAS) (0 no activity; 10 
maximum activity for both VAS); (2) parent/child ratings of well-being and pain, 
assessed on a 21-Numbered Circle and 10-Centimeter Horizontal Line Visual 
Analog Scales20; (3) number of active joints, assessed in 71, 27, or 10 joints 
(JADAS 71, JADAS 27, and JADAS 10, respectively); and (4) CRP was truncated 
to a 0 scale according to the following formula: (CRP [mg/L]-10/10), similar to the 
truncated ESR used in JADAS-ESR. Before calculation, CRP values <10 mg/L are 
converted to 10 and CRP values >110 mg/L are converted to 110.10
The JADAS is calculated as the sum of the scores of its 4 components, which yields 
a global score of 0–101, 0–57, and 0–40 for the JADAS 71, JADAS 27, and JADAS 
10, respectively.
The state of JADAS 10, 27, and 71 minimal disease activity2,8 was defined as the 
presence of all of the following: physician’s global assessment of disease activity of 
≤3.5, parent’s global rating of well-being of ≤2.5, and swollen joint count of ≤1 in 
patients with polyarthritis.
JADAS physician assessed remission is defined as a total JADAS score of ≤2.
The criteria for JADAS inactive disease is defined as a total JADAS score of ≤1. 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
53
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarification on major secondary and other endpoints have been made.
Section 9.2.2 Endpoints
Major Secondary Endpoints
Major secondary endpoints include:

PK exposure at Week 52 (the trough concentrations at Week 52) and the 
Baysesian AUCss at Week 52 (from population PK modeling and simulation)
Other endpoints
Other endpoints include:

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders over 
time

The change from baseline in CHAQ over time

CRP concentrations over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA over time

The improvement from baseline in the pJIA core set at each visit

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by 
disease subtype, and/or age over time through Week 52

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal 
disease activity over time

The proportion of subjects who achieve JADAS 10, 27, and 71 remission over 
time
Rationale: No biomarker analyses will be done in this study.
Section 9.3.1
Evaluations
Serum samples will be used to evaluate the PK, as well as the immunogenicity of 
golimumab (antibodies to golimumab). Venous blood samples will be collected and 
each serum sample will be divided into 3 aliquots (1 each for pharmacokinetics, 
antibodies to study drug, and a back-up). Sera collected for golimumab serum 
concentration and antibodies to golimumab analyses may additionally be used to 
evaluate biomarkers of safety or efficacy aspects that address concerns that arise during 
or after the study period. Subject confidentiality will be maintained. The sample should 
be drawn from a different arm than the IV line, or if using an IV line that is also being 
used to deliver medication, the line should be flushed and cleared of any residual 
medication that may be remaining prior to each PK sample being drawn. When using 
an IV line to draw PK samples, the first 1 mL of blood should be drawn and discarded 
prior to obtaining the sample. Intravenous line maintenance should be followed as per 
the standard of care. At visits where serum concentration and antibodies to golimumab 
will be evaluated, 1 blood draw of sufficient volume can be used.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
54
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications on safety evaluations (physical examination and uveitis evaluations) have been made.
Section 9.4
Safety Evaluations
Serum Chemistry Panel
cholesterol panel (total cholesterol and triglycerides)
Physical Examination
Physical examinations, including a skin exam at every physical examination and
Tanner staging at least every 6 months for sexual maturity and a skin examination, will 
be performed according to the Time and Events Schedule. Review of systems will be 
performed at all visits to evaluate for new symptomatology and if necessary, full 
physical examination may be performed at investigator discretion. Any clinically 
significant abnormalities persisting at the end of the study will be followed by the 
investigator until resolution or until reaching a clinically stable endpoint.
Uveitis Evaluations
All subjects will be formally assessed at screening and at least every 6 months 
thereafter by evaluations pertaining to new-onset uveitis on physical examination by the 
investigator and by interview. Based upon changing clinical standards, examinations 
may be more frequent. Subjects who test antinuclear antibodies (ANA) positive at 
screening will be required to undergo slit lamp evaluation by a qualified 
ophthalmologist to evaluate for subclinical uveitis in screening period as well as at 
least every 3 months subsequent (Table 1, Table 2, and Table 3).
If a subject develops uveitis during the study, the subjects’ continued participation in 
the study is at the discretion of the investigator and a qualified ophthalmologist.
Rationale: Revisions to the number and time for the ultrasound assessments have been made.
Section 9.6 Ultrasound 
Substudy
At selected sites, a total of approximately 20 subjects over the age of 4 years who are 
enrolled in this study and are currently receiving study treatment may undergo power 
ultrasounds of their metacarpophalangeal 2 and 3 joints (examining dorsal and volar
surfaces), wrist (dorsal long midline, tendons), knee (suprapatellar long and parapatellar 
images; entheseal evaluations), and ankle (tibula/talar, subtalar medial and lateral 
surfaces, tendon examinations). Up to 5 ultrasound assessments may be conducted, at 
Weeks 0, 4, 8, 12, 28, and 52. The primary objective of the substudy is to examine 
Power Doppler response measured as the Power Doppler Sum Score at 6 months 
compared with the score at baseline. Additional details will be presented in the 
Ultrasound Substudy Protocol.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
55
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Uveitis evaluation has been added to the assessment to be performed for each subject who discontinue 
study agent administration but does not discontinue study participation.
Section 10.2 
Discontinuation of Study 
Treatment
Subjects who discontinue study agent infusions but do not terminate study 
participation, will have the following assessments performed at the final safety follow-
up visit:

Safety evaluations (eg, vital signs, AE review, study agent infusion reaction 
evaluation, TB evaluation, uveitis evaluation, and the collection of a blood 
sample for routine laboratory analyses and determination of the presence of 
ANA/anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies and 
antibodies to golimumab).
Rationale: Clarification on major secondary and other endpoint analyses have been made.
Section 11.3
Efficacy Analyses
Primary Endpoint Analysis
No primary efficacy endpoint analysis is planned. As the co-primary objective of this 
study is PK analyses of IV golimumab, the co-primary clinical evaluation is the 
proportion of subjects meeting JADAS minimal disease activity criteria at Week 28 the 
primary endpoint is not an efficacy endpoint (Section 11.4).
Major Secondary Endpoints Analyses
No major secondary efficacy endpoints analyses are planned.
Other efficacy endpoints
The following will be summarized for all subjects enrolled in the study:

The proportion of subjects who are JIA ACR 30, 50, 70, and 90 responders 
over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for JIA (ACR 
criteria) over time

The improvement from baseline in the JIA core set over time

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by 
disease subtype, and/or age over time through Week 52

The change from baseline in CHAQ over time

CRP concentrations over time

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal 
disease activity over time

The proportion of subjects who achieve JADAS 10, 27, and 71 remission over 
time
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
56
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: An additional PK analysis has been added
Section 11.4
Pharmacokinetic 
Analyses
Summary golimumab concentrations will be summarized and PK exposure will be 
evaluated through Week 52 and through the LTE. 
Rationale: Clarification on the DMC has been made
Section 11.9
Data Monitoring 
Committee
This is an open-label study, with all subjects receiving the same dosage of IV 
golimumab. Therefore, an external Data Monitoring Committee will not be utilized. 
Unblinded safety data will be routinely evaluated by the study’s medical monitor and 
an internal Data Review Committee (DRC) as well as the Steering Committee as 
defined in DRC charter.
Rationale: Clarification of time period for the reporting of serious adverse events has been made
Section 12.3.1
All Adverse Events
All adverse events and special reporting situations, whether serious or non-serious, will 
be reported from the time a signed and dated ICF is obtained until completion of the 
subject's last study-related procedure (which may include contact for follow-up of 
safety). Serious adverse events, including those spontaneously reported to the 
investigator within 30 days after the last dose of study drug of the end of the study, 
must be reported using the Serious Adverse Event Form. The Sponsor will evaluate any 
safety information that is spontaneously reported by an investigator beyond the time 
frame specified in the protocol.
Rationale: The study-specific materials that will be provided to all study sites have been revised.
Section 15
Study-specific Materials
The investigator will be provided with at least the following supplies:

Investigator Brochure

Trial Center File

Investigational Product Manual

Laboratory manual and laboratory supplies

ePRO device and user manual

Interactive voice/web response system manual

Electronic data capture (eDC) Manual (including on-line access)

Sample ICF and sample assent form

Subject participation cards (ie, wallet cards)
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
57
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: The storage time for samples collected in this study has been reduced from 15 to 2 years
Section 16.2.5
Long-Term Retention of 
Samples for Additional 
Future Research 
Samples collected in this study may be stored for up to 2 years (or according to local 
regulations) for additional research. Samples will only be used to understand 
golimumab, to understand pJIA, to understand differential drug responders, and to 
develop tests/assays related to SIMPONI for IV use and pJIA. The research may begin 
at any time during the study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and 
will not be labeled with personal identifiers. Subjects may withdraw their consent for 
their samples to be stored for research. (refer to Section 10.3, Withdrawal From the 
Study (Withdrawal From the Use of Samples in Future Research). 
Rationale: An incorrect reference has been deleted.
Section 16.2.6
Country Selection
This study will only be conducted in those countries where the intent is to launch or 
otherwise help ensure access to the developed product. unless explicitly addressed as a 
specific ethical consideration in Section 16.1, Study-Specific Design Considerations.
Rationale: Data that will be entered into the CRF has been revised
Section 17.4
Source Documentation
The following data (at a minimum) will be recorded directly into the CRF and will be 
considered source data where allowed by country regulations:

Race

History of smoking and all nicotine use (eg, cigarettes, cigars, chewing tobacco, 
patch, gum)

Blood pressure, pulse/heart rate, temperature, and respiratory rate

Height and weight

Details of physical examination

Limited range of motion and active joints

PRO assessments: CHQ and CHAQ

The following parent/subject-
and investigator-completed scales and 
assessments designated by the Sponsor will be recorded into an electronic 
device and will be considered source data: joint assessments, CHAQ, 
parent/subject assessment of overall well-being, physician global assessment 
of disease activity, and visual analog scale for pain.
Subject and investigator-completed scales and assessments designated by the Sponsor 
will be recorded and will be considered source data.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
58
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Transmission of IWRS and ePRO data has been added.
Section 17.6
Data Quality 
Assurance/Quality 
Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate study sites, review of protocol procedures with 
the investigator and study site personnel before the study, and periodic monitoring 
visits by the Sponsor, and direct transmission of clinical laboratory data from a central 
laboratory, IWRS, and PRO data into the Sponsor's data base. Written instructions 
will be provided for collection, handling, storage, and shipment of samples. 
Section 17.11
Use of Information and 
Publication
The results of the study will be reported in a Clinical Study Report generated by the 
Sponsor and will contain CRF data from all study sites that participated in the study, 
and direct transmission of clinical laboratory data from a central laboratory, IWRS, 
and PRO data into the Sponsor's database. Recruitment performance or specific 
expertise related to the nature and the key assessment parameters of the study will be 
used to determine a coordinating investigator. Results of analyses performed after the 
Clinical Study Report has been issued will be reported in a separate report and will not 
require a revision of the Clinical Study Report. Study subject identifiers will not be 
used in publication of results. Any work created in connection with performance of the 
study and contained in the data that can benefit from copyright protection (except any 
publication by the investigator as provided for below) shall be the property of the 
Sponsor as author and owner of copyright in such work.
Rationale: Clarifications to the Table of Events (Tables 1, 2, and 3) have been made
Table 1:
Screening 
Through Week 52
JADAS assessment has been added at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 36, 44, and 52.
Antibodies to golimumab assessments have been added at Weeks 4 and 8
QuantiFERON TB Gold test has been added at Week 52
Uveitis evaluations were deleted at Weeks 24 and 52 and added to Weeks 20 and 44
Footnote b
Includes skin examination at every physical examination and Tanner staging every 6 
months and skin examination at every physical examination.
Footnote f
Evaluations should be performed at least every 6 months in all subjects. Subjects who 
test ANA positive at screening will be required to undergo slit lamp evaluation by a 
qualified ophthalmologist to evaluate for subclinical uveitis in the screening period, 
before first study drug administration as well as at least every 3 months subsequent.
Footnote i
To be completed by the parent or caregiver, preferably the same parent or caregiver 
should complete at every visit. Subjects who are emancipated juveniles (ages 15 to <18 
years) at study entry may complete the assessments themselves. Ideally the same 
individual (eg, parent, caregiver, or subject) who completes the assessments at the start 
of the study should complete the assessments throughout the study. at least
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
59
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Footnote j
All visit-specific PRO assessments should be conducted before any tests, 
procedures, or other consultations for that visit to prevent influencing subjects’ 
perceptions.
Parent/subject assessment of overall well-being has been deleted
Visual analog scale for pain has been deleted
CHQ assessments have been deleted.
Checks for the following assessments during the screening period have been deleted: 
Parent/subject assessment of overall well-being, Physician Global Assessment of 
disease activity, and Visual analog scale for pain
Table 2:
From Week 60 
Through Week 156 
(Long-term Extension)
JADAS assessment has been added at Weeks 68, 84, 100, 116, 132, and 148.
Antibodies to golimumab assessments have been added at Weeks 4 and 8
QuantiFERON TB Gold test was deleted at Weeks 60 and 108 and has been added at 
Weeks 100 and 148.
Uveitis evaluations were deleted at Weeks 76, 100, 124, and 148 and added to Weeks 
68, 92, 116, and 140.
Footnote b
Includes skin exam and Tanner staging every 6 months.
Footnote e
Evaluations should be performed at least every 6 months in all subjects. Subjects who 
test ANA positive at screening will be required to undergo slit lamp evaluation by a 
qualified ophthalmologist at least every 3 months.
Footnote h
To be completed by the parent or caregiver, preferably the same parent or caregiver 
should complete at every visit. Subjects who are emancipated juveniles (ages 15 to <18 
years) at study entry may complete the assessments themselves. Ideally the same 
individual (eg, parent, caregiver, or subject) who completes the assessments at the start 
of the study should complete the assessments throughout the study.
Footnote i
All visit-specific PRO assessments should be conducted before any tests, 
procedures, or other consultations for that visit to prevent influencing subjects’ 
perceptions.
Parent/subject assessment of overall well-being has been deleted
Visual analog scale for pain has been deleted
CHQ assessments have been deleted.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
60
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Table 3:
From 
Week 164 Through Week 
252 (Long-term 
Extension – Continued)
JADAS assessment has been added at Weeks 164, 180, 196, 212, 228, and 244.
Antibodies to golimumab assessments have been added at Weeks 4 and 8
QuantiFERON TB Gold test was deleted at Week 172 and has been added at Week 196
Uveitis evaluations were deleted at Weeks 172, 196, 220, and 244 and added to Weeks 
164, 188, 212, 236, and 252.
Footnote b
Includes skin exam and Tanner staging every 6 months.
Footnote e
Evaluations should be performed at least every 6 months in all subjects. Subjects who 
test ANA positive at screening will be required to undergo slit lamp evaluation by a 
qualified ophthalmologist at least every 3 months.
Footnote h
To be completed by the parent or caregiver, preferably the same parent or caregiver 
should complete at every visit. Subjects who are emancipated juveniles (ages 15 to <18 
years) at study entry may complete the assessments themselves. Ideally the same 
individual (eg, parent, caregiver, or subject) who completes the assessments at the start 
of the study should complete the assessments throughout the study.
Footnote i
All visit-specific PRO assessments should be conducted before any tests, 
procedures, or other consultations for that visit to prevent influencing subjects’ 
perceptions.
Parent/subject assessment of overall well-being has been deleted
Visual analog scale for pain has been deleted
CHQ assessments have been deleted.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
61
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Rationale: Revisions were made to several sections of the synopsis to reflect the changes made in the protocol
Synopsis
Overview of Study 
Design
This is a Phase 3, open-label, single-arm, multicenter study to evaluate the PK, safety, 
and efficacy of IV golimumab in subjects with active pJIA despite current treatment 
with MTX and/or corticosteroids and/or non-steroidal anti-inflammatory agents 
and/or prior use of anti-TNFα agents (up to 30% of total population). The study 
population will be comprised of subjects with pJIA receiving MTX, ages 2 to less than 
18 years, with at least a 3-month history of pJIA, and active arthritis in ≥5 joints. At 
least 120 subjects will be enrolled at Week 0 to ensure that at least 100 subjects remain 
in the study at Week 52. Enrollment patterns are expected to yield a subject population 
of approximately 10% aged 2 to up to 6 years, approximately 20% aged 6 to up to 12 
years, and approximately 70% aged 12 to less than 18 years.
All subjects will receive 80 mg/m2 golimumab as an IV infusion (over 30 ±10 
minutes) at Weeks 0, 4, and every 8 weeks (q8w; ± 3 days) through Week 28 and 
q8w (± 1 week) thereafter (maximum single dose 240 mg [maximum BSA 3.0m2 x 
80 mg/m2]), along with commercial MTX at a dose of 10-30 mg/m2/week (unless for 
documented safety reasons, lower doses of MTX are administered). For patients 
greater than 1.67m2, a minimum fixed dose of 15 mg/week is required. Subjects 
who complete the study at Week 52 will have the option to enter into the long-term 
extension phase of the study. During the long-term extension, all subjects will continue 
to receive 80 mg/m2 IV golimumab q8w (±1 week; maximum single dose 240 mg) 
through Week 244. All subjects who complete the Week 244 visit are expected to 
participate in the safety follow-up visit at Week 252. Golimumab after Week 252 (for 
subjects who have completed the full 252 week study before drug 
commercialization for JIA indication has taken place) will be provided until the 
drug will be approved and marketed for use in JIA in the country of the subject or 
for as long as proven beneficial to the child (in cases where commercial drug is not 
accessible to the subject.
Subject Population
The onset of disease must have been before the subject’s 16th birthday, must be at least 
3 months’ duration, and must have active pJIA of one of the following subtypes: 
rheumatoid factor positive or negative pJIA; systemic JIA with no systemic symptoms 
but with polyarthritis for ≥3 months but with polyarthritis for ≥3 months; extended 
oligoarticular JIA; enthesitis related arthritis or polyarticular juvenile psoriatic 
arthritis (PsA).
Subjects must have ≥5 joints with active arthritis as defined by American College of 
Rheumatology (ACR) criteria at screening and enrollment and must have a screening 
C-reactive protein (CRP) of ≥0.1 mg/dL. Subjects must have active pJIA despite 
current use of oral, intramuscular or subcutaneous MTX (for ≥3 months before 
screening) at a weekly dose of ≥10 mg/m2. 
Dosage and 
Administration
Golimumab
The study will have 1 active treatment group and all subjects will receive 80 mg/m2
golimumab IV infusions at Week 0, Week 4, and q8w ± 3days through Week 28 and 
q8w ± 1 week thereafter through Week 244. BSA will be calculated at each visit and 
the dose of golimumab will be adjusted as needed to maintain the dose at 80 mg/m2. 
BSA will be calculated using the Mosteller equation: BSA (m2) = ([height (cm) x 
weight (kg)]/3600).1/2 The maximum single dose will be golimumab 240 mg.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
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Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Methotrexate
Subjects will receive commercial MTX at the same BSA-based dose (10 to 30 mg/m2
per week of MTX) as at time of study entry at least through Week 28. BSA will be 
calculated at each visit and the dose of MTX will be adjusted as needed to maintain the 
dose at the same mg/m2 per week dose as the subject was receiving at time of study 
entry. Every effort should be made to ensure that subjects remain on the same 
BSA-based dose and route of administration of MTX at least through the Week 28
safety and efficacy database lock, unless intolerance or AEs due to MTX occur.
Subjects will also receive commercial folic acid ≥5 mg weekly or folinic acid (at half 
the MTX dose) given the day after the weekly MTX dose. In children <12 years of 
age, the administration of folic acid or folinic acid will be at the discretion of the 
physician.
Efficacy/Pharmacokinetic 
Evaluations and 
Endpoints
Efficacy evaluations include the following:

Joint evaluations (number of active joints and number of joints with limited range 
of motion)

Parent/Subject Assessment of Overall Well-being

Physician Global Assessment of disease activity

Visual Analog Scale for Pain

Childhood Health Assessment Questionnaire (CHAQ)

JADAS 10, 27, and 71

CRP
The primary endpoint in this study is PK exposure at Week 28 (the trough 
concentrations at Week 28) and the Bayesian steady-state area under the curve [AUCss] 
over one dosing interval of 8 weeks (from population PK modeling and simulation).
The major secondary endpoints are as follows:

PK exposure at Week 52 (the trough concentrations at Week 52) and the 
Baysesian AUCss at Week 52 (from population PK modeling and simulation)
Other efficacy endpoints include:

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders over 
time

The change from baseline in CHAQ over time

CRP concentrations over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA over time

The improvement from baseline in the pJIA core set at each visit

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by 
disease subtype, and/or age over time through Week 52

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease 
activity over time

The proportion of subjects who achieve JADAS 10, 27, and 71 remission over 
time
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
63
Status: Approved, Date: 16 December 2019
Applicable Section(s)
Description of Change(s)
Serum golimumab concentration and/or efficacy measures will be evaluated at 
Weeks 0, 4, 8, 12, 20, 28, 52, 100, 148, 196, and 244 and summarized over time. A 
population PK analysis with data through Week 28 will be performed to 
characterize the PK of golimumab as well as to identify important covariates of 
PK in the pediatric population with pJIA. 
Summary golimumab concentrations will be summarized and PK exposure will be 
evaluated through Week 52 and through the LTE.
Immunogenicity 
Evaluations
Antibodies to golimumab will be evaluated in serum samples collected from all 
subjects at Weeks 0, 4, 8, 12, 28, 52, 100, 148, 196, and 244.
Ultrasound substudy
Power Doppler Sonography (PDUS) is a non-invasive ultrasound technique to 
assess inflammation at the joint level in RA. At selected sites, subjects over the age 
of 4 years who have been enrolled in the study and are currently receiving study 
treatment may undergo PDUS and High Frequency gray scale Ultrasound (HFUS)
of the 2nd and 3rd metacarpophalangeal joints, wrist, knee and ankle. Up to 5 
exams will be performed at Weeks 0, 4, 12, 24, and 52 using a standardized 
protocol, described in a separate manual. Reading of the PDUS and HFUS will be 
performed by a blinded independent central reader.
Efficacy Analyses
The following will be summarized for all subjects enrolled in the study:

The proportion of subjects who are JIA ACR 30, 50, 70, and 90 responders over 
time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for JIA (ACR 
criteria) over time

The improvement from baseline in the JIA core set over time

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by 
disease subtype, and/or age over time through Week 52

The change from baseline in CHAQ over time

CRP concentrations over time

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease 
activity over time

The proportion of subjects who achieve JADAS 10, 27, and 71 remission over 
time
Rationale: Minor errors were noted and corrected.
Throughout the
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
64
Status: Approved, Date: 16 December 2019
SYNOPSIS
A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα Antibody, in 
Pediatric Subjects With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite 
Methotrexate Therapy
Protocol Number: CNTO148JIA3003
Golimumab is a fully human monoclonal antibody (mAb) which binds to human tumor necrosis factor 
alpha (TNFα) with high affinity and specificity and neutralizes TNFα bioactivity. TNFα is a key 
inflammatory mediator, with high levels of TNFα implicated in the pathophysiology of diseases such as 
rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). SIMPONI® (golimumab) for intravenous 
(IV) use is being developed by the Sponsor to offer an alternative route of administration (compared with 
other available anti-TNFα agents) and a convenient dose regimen (ie, every 8 week [q8w] administration)
for patients with polyarticular JIA (pJIA).
OBJECTIVES AND HYPOTHESIS
Primary Objective
The primary objective of this study is to assess the pharmacokinetics (PK) following intravenously 
administered golimumab in subjects (ages 2 to less than 18 years) with pJIA manifested by ≥5 joints with 
active arthritis despite methotrexate (MTX) therapy for ≥2 months.
Secondary Objectives
The secondary objectives of this study are to evaluate IV golimumab in subjects with pJIA with respect to 
PK, efficacy (relief of signs and symptoms, physical function, and quality of life), safety (adverse events 
[AEs], serious AEs [SAEs], and assessment of laboratory parameters), and immunogenicity (antibodies to 
golimumab).
Hypothesis
No formal hypothesis testing is planned in this study.
OVERVIEW OF STUDY DESIGN
This is a Phase 3, open-label, single-arm, multicenter study to evaluate the PK, safety, and efficacy of IV 
golimumab in subjects with active pJIA despite current treatment with MTX. The study population will 
comprise subjects with pJIA receiving MTX, ages 2 to less than 18 years, with at least a 3-month history 
of pJIA, and active arthritis in ≥5 joints. Approximately 120 subjects will be enrolled at Week 0 to ensure 
that approximately 100 subjects remain in the study at Week 52. Enrollment patterns are expected to yield
a subject population of approximately 10% aged 2 to up to 6 years, approximately 20% aged 6 to up to 
12 years, and approximately 70% aged 12 to less than 18 years.
All subjects will receive 80 mg/m2 golimumab as an IV infusion (over 30±10 minutes) at Weeks 0, 4, and 
q8w (±3 days) through Week 28 and q8w (±1 week) thereafter (maximum single dose 240 mg [maximum 
body surface area (BSA) 3.0 m2 x 80 mg/m2]). Commercial MTX is to be administered at a stable dose of 
10-30 mg/m2/week in subjects with BSA <1.67 m2 or a stable minimum dose of 15 mg/week in subjects 
with BSA ≥1.67 m2 through Week 28 (unless lower doses of MTX are administered for documented 
safety reasons or unless documented country or site regulations prohibit dose of 15 mg/week or above in 
subjects with BSA ≥1.67 m2). Subjects who complete the study at Week 52 will have the option to enter 
into the long-term extension (LTE) phase of the study. During the LTE, all subjects will continue to 
receive 80 mg/m2 IV golimumab q8w (±1 week; maximum single dose 240 mg) through Week 244. All
subjects who complete the Week 244 visit are expected to participate in the safety follow-up visit at 
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
65
Status: Approved, Date: 16 December 2019
Week 252. Subjects <18 years of age who have completed the study through Week 252 and are benefiting 
from treatment, but for whom golimumab is not commercially available for the treatment of pJIA, will 
have the option to continue to receive golimumab (80 mg/m2 q8w) in the Extended Treatment Period 
(ETP). The first dose of golimumab in the ETP is administered at Week 252 after all assessments have 
been completed.
Since this is an open-label study with all subjects receiving the same BSA-based dose of IV golimumab, 
an external Data Monitoring Committee will not be established.
The end of the study is defined as the last follow-up assessment for the last subject in the ETP.
SUBJECT POPULATION
Study subjects must be 2 to less than 18 years of age with a body weight >15 kg at the time of enrollment.
The onset of disease must have been before the subject’s 16th birthday, must be of at least 3 months’ 
duration, and must be active pJIA of one of the following subtypes: rheumatoid factor positive or negative 
pJIA; systemic JIA with no systemic symptoms for ≥3 months but with polyarthritis for ≥3 months; 
extended oligoarticular JIA; enthesitis-related arthritis or polyarticular juvenile psoriatic arthritis (PsA).
Subjects must have ≥5 joints with active arthritis as defined by American College of Rheumatology 
(ACR) criteria at screening and enrollment. Subjects must have active pJIA despite current use of oral, 
intramuscular, or subcutaneous MTX (for ≥2 months before screening) at a weekly dose of ≥10 mg/m2.
DOSAGE AND ADMINISTRATION
Golimumab
The study will have 1 active treatment group and all subjects will receive 80 mg/m2 golimumab IV 
infusions at Week 0, Week 4, and q8w (± 3 days) through Week 28 and q8w (±1 week) thereafter through 
Week 244. BSA will be calculated at each visit and the dose of golimumab will be adjusted as needed to 
maintain the dose at 80 mg/m2. BSA will be calculated using the Mosteller equation: BSA (m2) = ([height 
(cm) x weight (kg)]/3600)½. The maximum single dose will be golimumab 240 mg.
During the ETP, subjects will continue to receive 80 mg/m2 golimumab IV infusions q8w starting at 
Week 252. 
Methotrexate
Subjects will receive commercial MTX at least through Week 28 at the same BSA-based dose (10 to
30 mg/m2 per week for subjects with BSA <1.67 m2 or at least 15 mg/week for subjects with BSA 
≥1.67 m2) as at time of study entry. Every effort should be made to ensure that subjects remain on the 
same dose and route of administration of MTX through the Week 28 visit, unless intolerance or AEs due 
to MTX occur.
Subjects will also receive commercial folic acid ≥5 mg weekly or folinic acid (at half the MTX dose) 
given the day after the weekly MTX dose. In children <12 years of age, the administration of folic acid or 
folinic acid will be at the discretion of the physician.
EFFICACY EVALUATIONS AND ENDPOINTS
Efficacy evaluations include the following:

Joint evaluations (number of active joints and number of joints with limited range of motion)

Physician Global Assessment of Disease Activity
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
66
Status: Approved, Date: 16 December 2019

Childhood Health Assessment Questionnaire (CHAQ; includes the Parent/Subject Assessment of 
Overall Well-being and Parent/Subject Assessment of Pain)

CRP
No primary efficacy endpoint or major secondary endpoints are planned.  Other efficacy endpoints 
include:

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders over time

The change from baseline in CHAQ over time

CRP concentrations over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA over time

The improvement from baseline in the pJIA core set at each visit

The proportions of subjects who are JIA ACR 30, JIA ACR 50, JIA ACR 70 and JIA ACR 90 
responders by disease subtype, and/or age over time through Week 52

The change from baseline in Juvenile Arthritis Disease Activity Score (JADAS) 10, 27, and 
71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease activity over time
PHARMACOKINETIC EVALUATIONS AND ENDPOINTS
Serum golimumab concentration will be evaluated at Weeks 0, 4, 8, 12, 20, 28, 52, 100, 148, 196, and 
244 and summarized over time. A population PK analysis with data through Week 28 will be performed 
to characterize the PK of golimumab as well as to identify important covariates of PK in the pediatric 
population with pJIA.
Golimumab concentrations will be summarized and PK exposure will be evaluated through Week 52 and 
through the LTE.
The primary endpoint in this study is PK exposure at Week 28 (the trough concentrations at Week 28) and 
the Bayesian steady-state area under the curve [AUCss] over one dosing interval of 8 weeks (from 
population PK modeling and simulation).
The major secondary PK endpoints include:

PK exposure at Week 52 (the trough concentrations at Week 52) and Bayesian AUCss at Week 52 
(from population PK modeling and simulation).
SAFETY EVALUATIONS
Safety evaluations include assessments of the following: AEs; infusion reactions; allergic reactions; 
clinical laboratory tests (hematology, chemistry, and pregnancy testing); vital signs; physical 
examination; height and body weight; uveitis; and early detection of tuberculosis.
IMMUNOGENICITY EVALUATIONS
Antibodies to golimumab will be evaluated in serum samples collected from all subjects at Weeks 0, 4, 8, 
12, 28, 52, 100, 148, 196, and 244.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
67
Status: Approved, Date: 16 December 2019
STATISTICAL METHODS
Subject Information
Demographics and baseline disease characteristics and prior medication data will be summarized for all 
subjects enrolled in the study, whether or not they have received study agent administration. 
Pharmacokinetic data will be summarized for all subjects who had received at least 1 administration of 
study agent. Efficacy analyses will be summarized for all subjects enrolled in the study. Safety 
assessments will be summarized for all treated subjects.
Sample Size
The sample size determination is not based on statistical considerations. The goal is to have a sample size 
that will be sufficient to build a population PK model and, if feasible, an exposure-response model. 
Additionally, a sample size that will provide reasonable safety assessments was also taken into 
consideration. With these considerations, a sample size of approximately 120 subjects has been chosen 
assuming that if 20 subjects drop out or if they do not provide PK samples, a sample size of 
approximately 100 subjects will remain in the study at Week 52. This sample size is thought to be 
sufficient to build a population PK model, given the sparse sampling of PK time points, as well as provide 
1 year of safety data from approximately 100 subjects.
Efficacy Analyses
No primary efficacy endpoint analysis and no major secondary efficacy endpoint analyses are planned. 
The following will be summarized for all subjects enrolled in the study:

The proportion of subjects who are JIA ACR 30, 50, 70, and 90 responders over time

The change from baseline in CHAQ over time

CRP concentrations over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA (ACR criteria) over time

The improvement from baseline in the pJIA core set over time

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by disease subtype, 
and/or age over time through Week 52

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease activity over time
Pharmacokinetic Analyses
The primary objective of this study is to characterize golimumab PK exposure (the trough concentrations 
at Week 28 and the Bayesian AUCss over a dosage interval of 8 weeks from population PK modeling and 
simulation) in the JIA population.
Serum golimumab concentrations will be summarized over time.  In addition, a population PK analysis on 
data through Week 28 will be performed to characterize the PK of golimumab as well as to identify and 
quantify important covariates of PK in the pediatric population with JIA.  Clearance and volume of 
distribution will be estimated using a nonlinear mixed effects modeling (NONMEM) approach.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
68
Status: Approved, Date: 16 December 2019
Safety Analyses
Safety will be assessed by evaluating summaries of AEs, clinical laboratory tests, and vital signs findings 
through Week 252.
Immunogenicity Analyses
The occurrence and titers of antibodies to golimumab during the study will be summarized over time for 
all subjects who receive an administration of golimumab and have appropriate samples collected for 
detection of antibodies to golimumab (ie, subjects with at least 1 sample obtained after their first 
golimumab administration).
Pharmacokinetic/Pharmacodynamic Analyses
The relationships between serum golimumab concentration and efficacy will be explored. A suitable 
PK/pharmacodynamic (PD) model will be explored and developed to describe the exposure-response 
relationship.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
69
Status: Approved, Date: 16 December 2019
TIME AND EVENTS SCHEDULES
Table 1:
Screening Through Week 52
Screen-
ing 
Period
(-6 
weeks)
Week
0a
Week
4a
Week
8a
Week 
12a
Week 
16a
Week
20a
Week 
24a
Week 
28a
Week 
36a
Week
44a
Week
52a
Final 
Safety 
Follow-
up 
Visitb
Procedures and 
Evaluations
Administrative
Informed 
consent/Assent
X
Medical 
history/demographic 
data
X
Concomitant 
medications 
collection
X
X
X
X
X
X
X
X
X
X
X
X
X
Inclusion/exclusion 
criteria
X
X
Study Agent
IV administration of 
study agent
X
X
X
X
X
X
X
X
Safety
Review of systems
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examinationc
X
X
X
X
Body weight 
measurement
X
X
X
X
X
X
X
X
X
X
X
X
Height measurement
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
Xd
Xd
X
Xd
X
Xd
X
Xd
Xd
Xd
Xd
X
Routine laboratory 
analyses
X
X
X
X
X
X
X
X
X
X
Hepatitis B virus 
screening
X
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
70
Status: Approved, Date: 16 December 2019
Table 1:
Screening Through Week 52
Screen-
ing 
Period
(-6 
weeks)
Week
0a
Week
4a
Week
8a
Week 
12a
Week 
16a
Week
20a
Week 
24a
Week 
28a
Week 
36a
Week
44a
Week
52a
Final 
Safety 
Follow-
up 
Visitb
Hepatitis C virus 
screening
X
QuantiFERON-TB 
Gold teste
X
Xf
TB evaluation 
(questionnaire)
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest x-rayg
X
Uveitis evaluationsh
X
X
X
X
Rheumatoid factor
X
ANA/Anti-dsDNA 
antibodies 
X
X
X
X
Pregnancy test 
(serum)i
X
Pregnancy test 
(urine)i
X
X
X
X
X
X
X
X
Infusion reaction 
evaluation j
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
Efficacy
Joint assessments
X
X
X
X
X
X
X
X
X
X
X
X
X
JIA assessmentsk, l
X
X
X
X
X
X
X
X
X
X
X
X
CRP
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics
Golimumab 
concentrationm, n
2X
2X
X
2X
X
X
X
X
Population PKo
← Xo →
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
71
Status: Approved, Date: 16 December 2019
Table 1:
Screening Through Week 52
Screen-
ing 
Period
(-6 
weeks)
Week
0a
Week
4a
Week
8a
Week 
12a
Week 
16a
Week
20a
Week 
24a
Week 
28a
Week 
36a
Week
44a
Week
52a
Final 
Safety 
Follow-
up 
Visitb
Immunogenicity
Antibodies to 
golimumabn
X
X
X
X
X
X
X
a.
All scheduled visits should occur within ±3 days of the intended visit through Week 28 and ± 1 week after Week 28 through Week 52.
b.
All subjects who discontinue study agent administration before Week 52 but do not withdraw consent must return to the study site for a final safety visit 
approximately 8 weeks after the last infusion (Section 10.2).
c.
Includes skin examination at every physical examination and Tanner staging approximately every 6 months.
d.
Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute intervals during the infusion); and at 60 and 90 minutes (during the 1-hour 
observation period following the infusion).
e.
Tuberculin skin tests should also be performed in countries where the QuantiFERON-TB Gold test is not approved/registered in that country or the 
tuberculin skin test is mandated by local Health Authorities.
f.
Testing is not required for subjects with a history of latent TB and ongoing treatment for latent TB or documentation of having completed adequate 
treatment.
g.
Chest x-ray screening as per local and country regulations for initiation of immunosuppressive agents in children with JIA who are at risk of TB.
h.
Evaluations (based on physical examination and interview) should be performed by the investigator at least every 6 months in all subjects. In addition, all 
subjects are required to have slit lamp evaluations performed by an ophthalmologist/optometrist during the study at intervals (based on JIA subtype, ANA 
test results, age at JIA onset, and JIA duration) as specified in Attachment 5. 
i.
All female subjects of childbearing potential (ie, post-menarche) must test negative for pregnancy during screening and at all visits prior to study drug 
administration.
j.
Subjects will be observed for at least 60 minutes after the administration of study agent for symptoms of an infusion reaction.
k.
JIA assessments include the following:  Physician Global Assessment of Disease Activity, Childhood Health Assessment Questionnaire (CHAQ), and 
duration of morning stiffness.  CHAQ should be completed before any tests, procedures, or other consultations for that visit to prevent influencing 
subjects’ perceptions.
l.
CHAQ to be completed by the parent or caregiver; preferably the same parent or caregiver should complete at every visit. Subjects who are 15 to <18 years
of age at study entry may complete the assessment jointly with the parent/caregiver. 
m. At the Weeks 0, 4, and 12 visits, 2 samples for serum golimumab concentrations (indicated by “2X” in the schedule above) will be collected: 1 sample will 
be collected immediately prior to the infusion and the other collected approximately 1 hour (eg, ± 10 minutes) after the end of the infusion. For each of the 
remaining visits, only 1 sample for serum golimumab will be collected, which should be collected prior to the infusion if an infusion of the study agent is 
administered at that visit. Post-infusion samples should be drawn from a different arm than the IV infusion line, or the IV infusion line must be flushed and 
cleared of any residual medication that may be remaining and 1 mL of blood should be drawn and discarded prior to obtaining the sample if using the same 
access line as was used for drug administration.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
72
Status: Approved, Date: 16 December 2019
Table 1:
Screening Through Week 52
Screen-
ing 
Period
(-6 
weeks)
Week
0a
Week
4a
Week
8a
Week 
12a
Week 
16a
Week
20a
Week 
24a
Week 
28a
Week 
36a
Week
44a
Week
52a
Final 
Safety 
Follow-
up 
Visitb
n.
The same serum samples may be used for the measurement of golimumab concentration and detection of antibodies to golimumab. For visits with study 
agent administration, all blood samples for assessing golimumab concentration and antibodies to golimumab MUST be collected BEFORE the 
administration of the study agent.
o.
One additional sample for serum golimumab concentration for population PK will be collected from all subjects at any time between Weeks 0 and 8 other 
than at the time of the Week 0, Week 4, and Week 8 visits; this sample must be collected at least 24 hours prior to or after a study agent administration and 
must not be collected at a regularly scheduled visit (eg, Week 8).
Abbreviations: ANA = antinuclear antibodies; CHAQ = Childhood Health Assessment Questionnaire; CRP = C-reactive protein; dsDNA = double-stranded 
deoxyribonucleic acid; IV = intravenous; PK = pharmacokinetic; TB = tuberculosis.
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
73
Status: Approved, Date: 16 December 2019
Table 2:
From Week 60 Through Week 156 (Long-term Extension)
Week
60a
Week
68 a
Week
76 a
Week
84a
Week
92a
Week
100a
Week
108 a
Week
116a
Week
124a
Week
132a
Week
140a
Week
148a
Week
156a
Final 
Safety 
Follow-
up 
Visitb
Procedures and Evaluations
Administrative
Concomitant medications 
collection
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Study Agent
IV administration of study 
agent
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety
Review of systems
Xd
Physical examinatione
X
X
X
X
X
Body weight measurement
X
X
X
X
X
X
X
X
X
X
X
X
X
Height measurement
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
Xd
Routine laboratory analyses
X
X
X
ANA/Anti-dsDNA antibodies
X
QuantiFERON-TB Gold 
test
Xd,f
TB evaluation (questionnaire)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest x-ray
Xg
Uveitis evaluations
Xh
Pregnancy test (urine)i
X
X
X
X
X
X
X
X
X
X
X
X
X
Infusion reaction evaluationj
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Efficacy
Annual attestation form
Xk
NCT02277444


SIMPONI® (golimumab) for Intravenous Use
Clinical Protocol CNTO148JIA3003 Amendment INT-4
74
Status: Approved, Date: 16 December 2019
Table 2:
From Week 60 Through Week 156 (Long-term Extension)
Week
60a
Week
68 a
Week
76 a
Week
84a
Week
92a
Week
100a
Week
108 a
Week
116a
Week
124a
Week
132a
Week
140a
Week
148a
Week
156a
Final 
Safety 
Follow-
up 
Visitb
Pharmacokinetics
Golimumab concentrationl
X
X
X
Immunogenicity
Antibodies to golimumabl
X
X
X
Note: All assessments at each study visit must be completed prior to study drug administration, unless otherwise specified.
a.
All scheduled visits should occur ±1 week of the intended visit.  
b.
All subjects who discontinue study agent administration before Week 156 but do not withdraw consent must return to the study site for a final safety visit 
approximately 8 weeks after the last infusion (Section 10.2). Collection of vital signs, review of symptoms, and uveitis evaluation are performed at the final 
safety follow-up visit at the discretion of the investigator.
c.
Review concomitant medications with subject and document in source; update concomitant medication CRF page to include only those medications that are 
associated with AEs and SAEs (ie, used to treat event or suspected in causing event).
d.
Perform at the discretion of the investigator.
e.
Includes skin examination at every physical examination.
f.
Tuberculin skin tests should also be performed in countries where the QuantiFERON-TB Gold test is not approved/registered or the tuberculin skin test is 
mandated by local Health Authorities.
g.
Chest x-ray screening should be performed at the discretion of the investigator and per local and country regulations for children with JIA who are receiving
immunosuppressive agents and who are at risk of TB.
h.
Evaluations (based on physical examination and interview) should be performed at the discretion of the investigator. Slit lamp evaluations performed by an 
ophthalmologist/optometrist at the discretion of the investigator and per standard of care. 
i.
All female subjects of childbearing potential (ie, post-menarche) must test negative for pregnancy at all visits prior to study drug administration.
j.
Subjects will be observed at the discretion of the investigator after the administration of study agent for symptoms of an infusion reaction.
k.
Investigator will complete an annual attestation form to document that subject is benefiting from treatment.
l.
The same serum samples may be used for the measurement of golimumab concentration and detection of antibodies to golimumab. For visits with study agent 
administration, all blood samples for assessing golimumab concentration and antibodies to golimumab MUST be collected BEFORE the administration of 
the study agent.
Abbreviations: AE=adverse event; ANA=antinuclear antibodies; dsDNA=double-stranded deoxyribonucleic acid; IV=intravenous; SAE=serious adverse event; 
TB=tuberculosis.
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Table 3:
From Week 164 Through Week 252 (Continuation of Long-term Extension)
Week
164a
Week
172 a
Week
180a
Week
188a
Week
196a
Week
204a
Week
212a
Week
220a
Week
228a
Week
236a
Week
244a
Week
252a
Final 
Safety 
Follow
-up 
Visitb
Procedures and Evaluations
Administrative
Concomitant medications 
collection
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Study Agent
IV administration of study agent
X
X
X
X
X
X
X
X
X
X
X
Xd
Safety
Review of systems 
Xe
Physical examinationf
X
X
X
X
Body weight measurement
X
X
X
X
X
X
X
X
X
X
X
Xd
Height measurement
X
X
X
X
X
X
X
X
X
X
X
Xd
Vital signs
Xe
Routine laboratory analyses 
X
X
X
ANA/Anti-dsDNA antibodies 
X
X
QuantiFERON-TB Gold test
Xe,g
TB evaluation (questionnaire)
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest x-ray
Xh
Uveitis evaluations
Xi
Pregnancy test (urine)j
X
X
X
X
X
X
X
X
X
X
X
Xd
Infusion reaction evaluationk
X
X
X
X
X
X
X
X
X
X
X
Xd
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
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Table 3:
From Week 164 Through Week 252 (Continuation of Long-term Extension)
Week
164a
Week
172 a
Week
180a
Week
188a
Week
196a
Week
204a
Week
212a
Week
220a
Week
228a
Week
236a
Week
244a
Week
252a
Final 
Safety 
Follow
-up 
Visitb
Efficacy
Annual attestation form
Xl
Pharmacokinetics
Golimumab concentrationm
X
X
X
Immunogenicity 
Antibodies to golimumabm
X
X
X
Note: All assessments at each study visit must be completed prior to study drug administration, unless otherwise specified.
a.
All scheduled visits should occur ± 1 week of the intended visit.  
b.
All subjects who discontinue study agent administration before Week 244 but do not withdraw consent must return to the study site for a final safety visit 
approximately 8 weeks after the last infusion (Section 10.2). Collection of vital signs, review of symptoms, uveitis evaluation are performed at the final 
safety follow-up visit at the discretion of the investigator.
c.
Review concomitant medications with subject and document in source; update concomitant medication CRF page to include only those medications that are 
associated with AEs and SAEs (ie, used to treat event or suspected in causing event).
d.
The ETP starts at Week 252. These procedures should only be completed for subjects who enter the ETP.
e.
Perform at the discretion of the investigator.
f.
Includes skin exam.
g.
Tuberculin skin tests should also be performed in countries where the QuantiFERON-TB Gold test is not approved/registered or the tuberculin skin test is 
mandated by local Health Authorities.
h.
Chest x-ray screening should be performed at the discretion of the investigator and per local and country regulations for children with JIA who are receiving 
immunosuppressive agents and who are at risk of TB.
i.
Evaluations (based on physical examination and interview) should be performed at the discretion of the investigator. Slit lamp evaluations performed by an 
ophthalmologist/optometrist at the discretion of the investigator and per standard of care. 
j.
All female subjects of childbearing potential (ie, post-menarche) must test negative for pregnancy at all visits prior to study drug administration.
k.
Subjects will be observed at the discretion of the investigator after the administration of study agent for symptoms of an infusion reaction.
l.
Investigator will complete an annual attestation form to document that subject is benefiting from treatment.
m. The same serum samples may be used for the measurement of golimumab concentration and detection of antibodies to golimumab. For visits with study 
agent administration, all blood samples for assessing golimumab concentration and antibodies to golimumab MUST be collected BEFORE the 
administration of the study agent.
Abbreviations: AE=adverse event; ANA=antinuclear antibodies; dsDNA=double-stranded deoxyribonucleic acid; ETP=Extended Treatment Period; 
IV=intravenous; SAE=serious adverse event; TB=tuberculosis.
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ABBREVIATIONS
ACR
American College of Rheumatology
AE
adverse event
ALT
alanine aminotransferase
ANA
antinuclear antibodies
ARC
Anticipated Event Review Committee
AS
ankylosing spondylitis
AST
aspartate aminotransferase
BCG
Bacille Calmette-Guérin 
-hCG
-human chorionic gonadotropin 
BSA
body surface area 
CHAQ
Childhood Health Assessment Questionnaire
CL/BSA
body surface area-normalized drug clearance
CL/F
apparent total systemic clearance
CRF
case report form 
CRP
C-reactive protein
DAS
Disease Activity Index Score
DMARD
disease-modifying anti-rheumatic drug
DNA
deoxyribonucleic acid
dsDNA
double-stranded deoxyribonucleic acid
eDC
electronic data capture
ETP
Extended Treatment Period
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HAQ
Health Assessment Questionnaire
HAQ-DI
Health Assessment Questionnaire Disability Index
HBsAg
HBV surface antigen
HBV
hepatitis B virus
HIV
human immunodeficiency virus
HLA-B27
human leukocyte antigen B27
HLA-DR4
human leukocyte antigen DR4
HLA-DR5
human leukocyte antigen DR5
HLA-DR8
human leukocyte antigen DR8
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IL-1
Interleukin-1 beta
IL-6
interleukin-6 
IRB
Institutional Review Board
JADAS
Juvenile Arthritis Disease Activity Score
JIA
juvenile idiopathic arthritis
LFT
liver function test
LTE
long-term extension
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NSAID
non-steroidal anti-inflammatory drug
PD
pharmacodynamic(s)
PED
pediatric
pJIA
polyarticular juvenile idiopathic arthritis
PK
pharmacokinetic
PQC
Product Quality Complaint
PPD
purified protein derivative
PRCSG
The Pediatric Rheumatology Collaborative Study Group
PRINTO
Pediatric Rheumatology INternational Trials Organisation
PRO
patient-reported outcome(s)
PsA
psoriatic arthritis
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q4w
every 4 weeks
q8w
every 8 weeks
RA
rheumatoid arthritis
RBC
red blood cell
RF
rheumatoid factor
SAE
serious adverse event
SC
subcutaneous
SF-36
36-item short form health survey
SI
International System of Units
SOC
system organ class
TB
tuberculosis
TNFα
tumor necrosis factor alpha
URTI
upper respiratory tract infection
US
United States
VAS
visual analog scale
vdH-S
van der Heijde Modified Sharp
V/F
apparent volume of distribution
Vss
volume of distribution at steady-state
WBC
white blood cell
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1.
INTRODUCTION
Golimumab is a fully human monoclonal antibody (mAb) with an immunoglobulin G1 heavy 
chain isotype (G1m[z] allotype) and a kappa light chain isotype. The molecular weight of 
golimumab ranges from 149,802 to 151,064 daltons. Golimumab binds to human tumor necrosis 
factor alpha (TNFα) with high affinity and specificity and neutralizes TNFα bioactivity.
TNFα is a key inflammatory mediator, with high levels of TNFα implicated in the 
pathophysiology of diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis 
(JIA). Blocking TNFα activity, as demonstrated in clinical studies of anti-TNFα agents, can 
prevent the deleterious effects caused by excessive TNFα. SIMPONI® (golimumab) for 
intravenous (IV) use is being developed by the Sponsor to offer an alternative route of 
administration (compared with other available anti-TNFα agents) and a convenient dose regimen 
(ie, every 8 week [q8w] administration) for patients with polyarticular JIA (pJIA).
For the most comprehensive nonclinical and clinical information regarding SIMPONI® refer to 
the latest version of the Investigator's Brochure and Addenda for SIMPONI.
The term "Sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
1.1.
Background
1.1.1.
Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis is a diagnosis of exclusion that encompasses all forms of arthritis that 
begin before the age of 16 years, persist for more than 6 weeks and are of unknown cause.18 It is 
the most common chronic rheumatic disease in children and is categorized according to the 
International League of Associations for Rheumatology (ILAR) classification into 7 subtypes 
(systemic arthritis, oligoarthritis, rheumatoid factor [RF]-negative polyarthritis, RF-positive 
polyarthritis, 
enthesitis-related 
arthritis, 
psoriatic 
arthritis, 
undifferentiated 
arthritis) 
characterized by distinct clinical presentations and features.16
The heterogeneity of JIA indicates that multiple factors contribute to the etiology and 
pathogenesis of the disease, and both genetic and environmental factors have been implicated. 
These include implicating infection as a triggering mechanism, links between human leukocyte 
antigen (HLA) and non-HLA molecules and disease development, and immunological 
abnormalities leading to tissue inflammation and joint destruction. The role of infection in 
disease development is still unproven.18 However, in JIA, HLA-DR5 and HLA-DR8 locus 
antigens have been implicated as associated contributory elements in young girls with 
oligoarticular arthritis, whereas HLA-DR4 has been implicated in RF-positive polyarticular 
arthritis in older children, and HLA-B27 has been implicated in older boys with oligoarticular 
disease.15,17
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Although the etiology and pathogenesis of JIA are still unclear, the same cell types and 
underlying mechanisms that play a role in the progression of adult RA are probably involved.15
The cellular entities involved include macrophages that elaborate a number of inflammatory 
cytokines and mediators of inflammation. Macrophage-derived cytokines, such as TNFα, appear 
to play a critically important role in the induction and perpetuation of chronic inflammatory 
processes in the joints of patients with RA as well as in the systemic manifestations of this 
disease,6 though the role of TNFα in systemic JIA is less convincing.3
Some studies have shown that levels of inflammatory cytokines (eg, interleukin-1 beta [IL-1β], 
interleukin-6 [IL-6], and TNFα) elevated in adults with RA are also elevated in the synovial fluid 
and serum of patients with JIA.9,19,12,3,20 These studies have also found different cytokine profiles 
among patients with various JIA subgroups.
Juvenile idiopathic arthritis is an important cause of short-term and long-term disability in 
children,14 but new advances in therapy have demonstrated clinically important steps forward. In 
the past 10 years, studies have shown that 40% to 60% of patients have inactive disease or 
clinical remission while on medication for JIA at follow-up. Functional outcome has improved in 
the last decade, with 2.5% to 10% of patients with serious functional disability.18 However, 
particularly serious complications of JIA include linear growth suppression, osteoporosis, local 
growth disturbances, macrophage activation syndrome and iridocyclitis.18
The aim of treatment in JIA is to obtain complete control of the disease, to preserve the physical 
and psychological integrity of the child and to prevent any long-term consequence related to the 
disease or its therapy. The mainstays of treatment in JIA have been NSAIDs, intra-articular and 
systemic corticosteroids, methotrexate (MTX), and other DMARDs. The introduction of 
biological medications has provided an important new therapeutic option for the treatment of 
patients with JIA who are resistant to conventional anti-rheumatic agents.18 Currently approved 
biologic therapies for the treatment of pJIA include etanercept, adalimumab, abatacept, and 
tocilizumab; canakinumab and tocilizumab have been approved for systemic JIA.
1.1.2.
Golimumab Clinical Studies in Rheumatoid Arthritis and Juvenile 
Idiopathic Arthritis
Golimumab given as a SC injection has been demonstrated to be efficacious in adults with RA, 
PsA, ankylosing spondylitis (AS), and ulcerative colitis. Intravenous golimumab has also proven 
effective in adults with RA. Other anti-TNFα agents have been effective in the treatment of 
subjects with JIA. The Sponsor conducted a study of BSA-based dosages of SC golimumab 
(CNTO148JIA3001) to assess the benefits and risks associated with the use of SC golimumab in 
the treatment of multiple subtypes of JIA, including juvenile PsA.
The results of the CNTO148ART3001 study of IV golimumab in adults and the results of the 
CNTO148JIA3001 study of SC golimumab in subjects with JIA are described below.
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1.1.2.1.
Intravenous Golimumab in Adult Rheumatoid Arthritis
The primary objective of CNTO148ART3001, a randomized, placebo-controlled, multicenter, 
double-blind study, was to assess the clinical efficacy of IV administration of golimumab 
2 mg/kg + MTX compared with MTX alone in adult subjects with active RA despite MTX 
therapy. Approximately 564 subjects were planned, and 592 were randomized.
Subjects were men or women 18 years of age or older with a diagnosis of RA for at least 
3 months prior to screening who had active RA, defined as ≥6 tender and ≥6 swollen joints, at 
screening and at baseline, despite concurrent MTX therapy. At screening, subjects had to have 
C-reactive protein (CRP) measurement of ≥1.0 mg/dL (upper limit of normal=1.0 mg/dL) and be 
RF-positive.
Subjects randomized to golimumab received 2 mg/kg of golimumab intravenously over a 
30±10 minute infusion time. Additionally, subjects were maintained on their stable dose of 
commercial MTX (between 15 mg and 25 mg/week) throughout the study.
Randomization was stratified based upon a screening CRP of <1.5 mg/dL or ≥1.5 mg/dL. 
Subjects were randomized 2:1 to golimumab + MTX or placebo + MTX at Week 0, Week 4, and
every 8 weeks (q8w) thereafter. The duration of treatment for the entire study was 100 weeks 
with a 12 week safety follow-up period.
In total, 570 (96%) of 592 subjects completed the 24-week study. The remaining 22 (4%) 
subjects discontinued the study before Week 24. Most discontinuations were due to AEs: 
9 [2.3%] subjects in the golimumab + MTX group and 2 [1.0%] subjects in the placebo + MTX 
group).
A significantly greater proportion of subjects in the golimumab + MTX group (58.5%) achieved
the primary endpoint, an ACR 20 response at Week 14, compared with subjects in the placebo + 
MTX group (24.9%, p<0.001). The treatment effect was consistent in subjects with either a CRP 
≥1.5 mg/dL or <1.5 mg/dL at screening. A significant difference in the proportion of ACR 20 
responders between the golimumab + MTX and placebo + MTX groups was observed as early as 
Week 2. Major secondary efficacy endpoints were also achieved. A significantly greater 
proportion of subjects in the golimumab + MTX group had good or moderate Disease Activity 
Index Score (DAS)28 responses (using CRP) at Week 14 (81.3%) compared with subjects in the 
placebo + MTX group (40.1%, p<0.001).
There was a significantly greater improvement in Health Assessment Questionnaire Disability 
Index (HAQ-DI) disability scores at Week 14 in subjects in the golimumab + MTX group 
(0.500) compared with subjects in the placebo + MTX group (0.125, p<0.001). There was also a 
significant difference in clinically relevant improvements in HAQ-DI (≥0.25) in the golimumab 
+ MTX group compared with the placebo + MTX group both at Week 14 (68.4% compared with 
43.1%, respectively, p<0.001) and at Week 24 (67.6% compared with 45.2%, respectively, 
p<0.001). Subjects who received golimumab + MTX demonstrated significantly greater ACR 50 
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response rates at Week 24 (34.9%) compared with subjects who received placebo + MTX 
(13.2%, p<0.001).
A consistent treatment benefit was observed within subgroups of demography, baseline clinical 
characteristics, and prior exposure to medications for RA except for subgroups with small 
population size (ie, <15 subjects).
Statistically significant greater improvement in the mental and physical component summary 
scores of the 36-item short form health survey (SF-36) as well as all 8 scales of the SF-36 
instrument were observed in golimumab + MTX treatment relative to placebo + MTX treatment 
at Week 12 (p<0.001 for all comparisons). These improvements were maintained through 
Week 24.
Through Week 16 (the placebo-controlled period prior to early escape) in CNTO148ART3001, 
43.7% of subjects in the placebo group and 47.3% in the golimumab group had an AE; the 
highest incidence of AEs was in the Infections and infestations system organ class (SOC), 20.8% 
and 24.3% in the placebo and golimumab groups, respectively, with upper respiratory tract 
infection (URTI) being the most frequently reported AE (5.6% and 5.1% in the placebo and 
golimumab groups, respectively). Through Week 112, 79.1% of golimumab-treated subjects had 
an AE; the highest incidence of AEs was in the Infections and infestations SOC (50.5%) and 
URTI was the most frequently reported AE (11.5%).
Through Week 16 in CNTO148ART3001, 1.0% of subjects in the placebo group and 3.8% of 
subjects in the golimumab group had a serious adverse event (SAE). The incidence of SAEs 
within each SOC was <1.0%, and no SAE occurred in more than 1 subject. Through Week 112, 
18.2% of golimumab-treated subjects had an SAE; the highest incidence of SAEs occurred in the 
infections and infestations SOC (5.5%) and musculoskeletal and connective tissue disorders 
SOC (3.4%) and the most frequently reported SAE was RA (2.1%).
Through Week 24, 1 patient died in the CNTO148ART3001 study; this subject was randomized 
to treatment with placebo + MTX, had never received golimumab, and died of a presumed 
cerebrovascular accident (stroke). Through Week 112, an additional 5 subjects died in the 
CNTO148ART3001 study. Two subjects randomized to treatment with placebo + MTX died, 
both after switching to golimumab 2 mg/kg + MTX; cause of death was sudden death (n=1) and 
complications of severe dehydration, Clostridium difficile colitis, and atrial fibrillation (n=1). 
Three subjects randomized to treatment with 2 mg/kg golimumab + MTX died in the study; 
reported cause of death was acute abdominal syndrome (later diagnosed as peritoneal 
tuberculosis [TB], n=1), presumed myocardial infarction (MI, n=1), and septic shock secondary 
to a pyogenic lung abscess due to Acinetobacter baumannii (n=1).
No malignancies were reported through Week 16 in study CNTO148ART3001. There was 1 case 
of nontreatment-emergent lung adenocarcinoma reported in the placebo + MTX group prior to 
receiving study agent. Through the placebo-controlled period (Week 24), 1 malignancy (breast 
cancer) was reported in the golimumab group. Through Week 112, 5 additional malignancies
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were reported, including basal cell carcinoma, chronic lymphocytic leukemia in a subject with a 
family history of chronic lymphocytic leukemia, cervix carcinoma in situ, Bowen’s Disease, and 
basal cell carcinoma. No lymphomas were reported through Week 112.
Through Week 16 in CNTO148ART3001, 0.8% of subjects in the golimumab group had a 
serious infection, including appendicitis, bacteremia, and (complications of) interstitial lung 
disease. No subjects in the placebo group had a serious infection. Through Week 112, 6.2% of 
golimumab-treated subjects had a serious infection. Serious infections occurring in more than 
one subject were pneumonia (n=5), UTI (n=4), and erysipelas (n=2).
Through Week 16 in CNTO148ART3001, 0.5% of subjects in the placebo group and 2.5% of 
subjects in the golimumab group had an infusion reaction. Through Week 112, 3.9% of 
golimumab-treated subjects had an infusion reaction and 0.4% of infusions were complicated by 
infusion reactions. It should be noted that all placebo infusions consisted of 0.9% normal saline 
alone rather than a true matched placebo. No serious infusion reactions requiring study agent 
discontinuation were noted. There was a case of anaphylaxis, which was not associated with 
study drug.
For the most comprehensive nonclinical and clinical information regarding golimumab, refer to 
the latest version of the Investigator's Brochure and Addenda for SIMPONI (golimumab).
The median peak serum golimumab concentration (ie, post-infusion golimumab concentration) 
of 41.56 µg/mL was observed at Week 4 following IV administration of 2 mg/kg golimumab at 
Week 0, Week 4, followed by q8w (±1 week) administration. This peak is higher than that 
reported for SC golimumab administration of 50 mg every 4 weeks (q4w). The median trough 
serum golimumab concentration in subjects receiving IV golimumab at 2 mg/kg q8w with MTX 
was 0.28 µg/mL at Week 12 and 0.22 µg/mL at Week 20; these levels are similar to those 
reported with SC golimumab 50 mg. Overall exposure to golimumab is approximately 3 times 
that for SC golimumab 50 mg over a similar period of exposure.
Data from the IV golimumab program demonstrated less radiographic progression in subjects 
treated with golimumab compared with subjects who received placebo. There was a significant 
difference in change from baseline in total van der Heijde Modified Sharp (vdH-S) score at 
Week 24 (placebo + MTX: 1.09 3.194, golimumab 2 mg/kg + MTX: 0.03 1.899 [p<0.001]) 
between the golimumab + MTX treatment group and placebo + MTX. Significant differences in 
favor of IV golimumab were also observed in changes from baseline in erosion and joint space 
narrowing scores. The proportion of subjects with radiographic progression based on the smallest 
detectable change was significantly lower for subjects treated with golimumab + MTX when 
compared with placebo + MTX for the total vdH-S score (p<0.001) as well as both erosion 
(p=0.001) and joint space narrowing measurements (p=0.01).
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1.1.2.2.
Subcutaneous Golimumab in Juvenile Idiopathic Arthritis
CNTO148JIA3001 
was
a
randomized
withdrawal, 
double-blind, 
placebo-controlled, 
parallel-group, multicenter study of BSA-based 30 mg/m2 (up to a maximum 50 mg/dose) SC 
golimumab given every 4 weeks (q4w) in pediatric subjects with active pJIA despite current 
treatment with MTX. The study population comprised subjects with pJIA receiving MTX, ages 2 
to less than 18 years, with at least a 6-month history of pJIA, and active arthritis in ≥5 joints. All 
subjects received SC golimumab in the active treatment portion of the study from Week 0 
through Week 16. At Week 16, JIA ACR 30 responders were randomized to receive placebo or 
golimumab for 32 weeks; subjects randomized to placebo who experienced flares during this 
32-week period had golimumab therapy re-instituted. The placebo-controlled period was through 
Week 48, and the long-term extension (LTE) was planned from Week 48 through Week 248.
Approximately 170 subjects were planned, and 173 subjects were enrolled into the study. All of 
the 173 subjects were included in the Week 48 efficacy and safety analyses. Nineteen of the 
173 subjects discontinued study agent through Week 16 (due to: lack of efficacy [n = 14]; AEs
[n = 4]; withdrawal of consent [n = 1]), and 154 subjects entered randomized withdrawal (76 to 
placebo and 78 continued golimumab).
The baseline disease characteristics of the 173 enrolled subjects constituted a population with 
moderate to severe JIA comparable with other clinical studies of anti-TNFα agents in pJIA, with 
the exception of numerically lower mean and median CRP/ESR levels in CNTO148JIA3001.
The proportion of subjects who were JIA ACR 30 responders at Week 16 was 87.3%. 
Additionally, the proportion of JIA ACR 50, JIA ACR 70, and JIA ACR 90 responders at 
Week 16 were 79.2%, 65.9%, and 36.4%, respectively.
The study did not meet its primary and major secondary endpoints as the proportion of subjects 
who were JIA ACR 30 responders at Week 16 and did not experience a flare of disease between 
Week 16 and Week 48 was not significantly different in subjects randomized to continued 
golimumab treatment between Weeks 16 and 48 as compared with subjects randomized to 
receive placebo between Weeks 16 and 48 (59% versus 52.6%, p=0.41). All sensitivity analyses
and major secondary endpoints demonstrated the lack of statistically significant differences 
between treatment groups. The Sponsor terminated the LTE of the study early as pre-specified 
efficacy endpoints were not met.
Post-hoc analyses that evaluated flare rates based on Week 0 CRP levels ranging from 
0.1-1.0 mg/dL demonstrated that, in general, among subjects with higher baseline CRP levels, 
the subjects who received continued golimumab therapy had significantly fewer flare episodes 
than subjects who were randomized to placebo at Week 16.
When JIA ACR response rates were analyzed based on observed data through Week 48 (using 
Week 0 as baseline and comparing drug/placebo effect at each visit through Week 48), JIA 
ACR 30 response rates of 89% to 95.9% and JIA ACR 90 response rates of 53.4% to 56.2% 
were achieved at Week 48. Improvements in the core sets through Week 48 were similar at all 
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visits in subjects randomized to golimumab at Week 16 as compared with subjects randomized to 
placebo at Week 16 and all represented clinically meaningful improvement in disease,
eg, median percent improvement of 94.6% and 95.1% in Physician Global Assessment of 
Disease Activity, and median percent improvement of 90.9% and 100% in the number of active 
joints.
Pharmacokinetic (PK) and immunogenicity data were collected through Week 48 in 
CNTO148JIA3001. In subjects with pJIA who received golimumab 30 mg/m2 SC and were 
randomized to stay on active treatment, median trough golimumab concentrations at Week 12, 
Week 24, and Week 48 were 1.16 µg/mL, 1.12 µg/mL, and 0.95 µg/mL, respectively, indicating 
that steady-state levels were maintained though Week 48. Furthermore, steady-state trough 
golimumab concentrations were similar across different age groups, body weight quartiles, body 
mass index quartiles, and body weight categories in subjects with pJIA. Overall, these 
concentrations were similar to the PK exposure observed in the adult active RA population
(despite MTX) in C0524T06 treated with SC golimumab, and thus supported the hypothesis that 
the BSA-based golimumab regimen of 30 mg/m2 SC q4w was sufficient to produce 
concentrations comparable to that seen in the adult RA population who received golimumab 
50 mg SC q4w. Further, PK and efficacy analyses showed that similar efficacy (as measured by 
JIA ACR 30 response, and flare rates) were seen in subjects with pJIA in the 4 subgroups of 
steady-state trough golimumab concentration quartiles. Additionally, there were no apparent PK 
differences observed between subjects with and without flares.
With regards to immunogenicity, 40.1% of subjects developed antibodies to golimumab using 
the recently developed drug tolerant immunoassay analyses. The new drug tolerant immunoassay 
is more sensitive compared with assays used previously in adult golimumab RA studies and 
allows the detection of antibodies to golimumab despite detectable serum golimumab levels. 
Among subjects who were randomized and remained on golimumab 30 mg/m2 SC + MTX, 
30.8% developed antibodies to golimumab; antibody titers tended to be low. When evaluating 
the effects of immunogenicity on PK, efficacy, and safety, it was found that positive 
anti-golimumab antibody status decreased steady-state trough golimumab concentrations when 
the titer levels were >1:100. However, the effect of antibodies on efficacy was less sensitive,
requiring higher titers >1:1000 in order to correlate with apparent reductions in efficacy. Since 
only approximately 5% of subjects with JIA developed anti-golimumab antibodies with titers 
>1:1000, it was determined that immunogenicity was not a contributing factor to lack of 
achievement of the primary endpoint in CNTO148JIA3001. Additionally, positive 
anti-golimumab antibody status did not appear to be associated with a higher incidence of 
injection-site reactions.
The proportion of subjects who reported an AE through Week 48 was 87.9%. The most 
commonly reported SOC of AEs was Infections and infestations (67.1%), and were 
predominantly URTIs and nasopharyngitis. There was no marked difference in AEs reported 
between Week 16 and Week 48 for subjects randomized to placebo (82.9%) and those 
randomized to continued golimumab treatment (78.2%); however, it needs to be noted that all 
subjects in randomized withdrawal portion of the study were exposed to golimumab for 
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16 weeks before re-randomization. Serious adverse events were reported by 13.3% of subjects. 
The most commonly reported SAE was worsening of JIA (6.4%). Serious infections were 
reported in 2.9% of subjects (pneumonia, urinary tract infection, herpes zoster, URTI, and 
pyelonephritis), and there were no deaths, malignancies, or demyelination events through 
Week 48. There were no reports of active TB and no serious opportunistic infections. Through 
Week 48, the number of subjects with abnormal alanine aminotransferase (ALT) measurements 
(and no concomitant treatment for latent TB, which may affect liver function tests [LFTs]) was 
29.5% (51/167), 39 of the 51 subjects had elevations <3×ULN.
There were 2 subjects with ALT elevation to > 8×ULN but neither subject met the criteria for 
Hy’s Law consistent with hepatotoxicity. Subjects were not receiving TB prophylaxis; one of the 
subjects had baseline ALT which was already abnormal. All subjects with LFT abnormalities 
were managed conservatively with changes in MTX dosing but one subject was discontinued for 
elevated LFTs.
The incidence of injections with injection-site reactions through Week 48 was 0.8%; there was 
one SAE report of serum sickness-like reaction in a subject randomized to placebo who resumed 
golimumab treatment.
For the most comprehensive nonclinical and clinical information regarding golimumab, refer to 
the latest version of the Investigator's Brochure and Addenda for SIMPONI (golimumab).
Although the CNTO148JIA3001 study did not meet its endpoints, when JIA ACR response rates 
were analyzed as observed data through Week 48 (using Week 0 as baseline and comparing 
drug/placebo effect at each visit through Week 48) the study showed the potential for efficacy 
that could be attained with SC golimumab in children with pJIA. Therefore, it lends support to 
the study of IV golimumab in subjects with pJIA who have an inadequate response to MTX.
1.2.
Overall Rationale for the Study
Intravenous golimumab has been demonstrated to be efficacious in the treatment of adults with 
RA (Section 1.1.2.1). Other biologics, including anti-TNFα agents, have been shown to be 
effective in the treatment of subjects with pJIA. Though biologic infusion therapies are available 
for the treatment of pJIA, there are currently no approved intravenously administered anti-TNFα 
agents for this condition. The every 8 week, 30-minute infusion paradigm proposed in this study 
for children and studied in adults with RA may be appropriate for populations of patients where 
greater physician scrutiny of drug therapy may be needed or requested. Particularly in the 
pediatric population, the reduction in the number of drug administrations (ie, to an every 8 week 
maintenance schedule) could provide greater convenience and less pain (due to fewer IV 
administrations) compared with other biologic agents. In addition, switching to a different 
anti-TNFα agent in a patient in whom a previous anti-TNFα agent was not efficacious may 
provide further symptomatic relief of disease.
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The primary objective of this study is to characterize the PK of IV golimumab in pJIA, along 
with evaluations of the safety and efficacy of IV golimumab in these subjects. This study will
also include subjects with multiple subtypes of JIA, including juvenile PsA, as well as subjects
with prior anti-TNFα experience (up to 30% of the study population).
The study is designed to obtain PK data in response to BSA-based (80 mg/m2, which is expected 
to be equivalent to the 2 mg/kg dose in adult RA patients weighing 70 kg) IV golimumab for 
subjects with pJIA who have inadequate response to MTX treatment as well as prior treatment 
with non-steroidal anti- inflammatory agents, corticosteroids, and/or anti-TNFα agents, with the 
intent to demonstrate its similarity to the response seen with weight-based (2 mg/kg) doses of IV 
golimumab in adult RA subjects who have inadequate response to MTX treatment. The 
80 mg/m2
dose for subjects with pJIA is based on the 2 mg/kg dose
studied
in
CNTO148ART3001 in the adult RA population.
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objective
The primary objective of this study is to assess the PK following intravenously administered 
golimumab in subjects (ages 2 to less than 18 years) with pJIA manifested by ≥5 joints with 
active arthritis despite MTX therapy for ≥2 months.
Secondary Objectives
The secondary objectives of this study are to evaluate IV golimumab in subjects with pJIA with 
respect to PK, efficacy (relief of signs and symptoms, physical function, and quality of life), 
safety (AEs, SAEs, and assessment of laboratory parameters), and immunogenicity (antibodies to 
golimumab).
2.2.
Hypothesis
No formal hypothesis testing is planned in this study.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 3, open-label, single-arm, multicenter study to evaluate the PK, safety, and 
efficacy of IV golimumab in subjects with active pJIA despite current treatment with MTX. The 
study population will comprise subjects with pJIA receiving MTX, ages 2 to less than 18 years, 
with at least a 3-month history of pJIA, and active arthritis in ≥5 joints. Approximately 
120 subjects will be enrolled at Week 0 to ensure that approximately 100 subjects remain in the 
study at Week 52. Enrollment patterns are expected to yield a subject population of 
approximately 10% aged 2 to up to 6 years, approximately 20% aged 6 to up to 12 years, and 
approximately 70% aged 12 to less than 18 years.
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All subjects will receive 80 mg/m2 golimumab (maximum single dose 240 mg) as an IV infusion 
given over 30±10 minutes at Weeks 0, 4, and every 8 weeks (q8w; ±3 days) through Week 28 
and then q8w (±1 week) thereafter through Week 244. Body surface area will be calculated 
based on the subject’s height and body weight measured at each visit, and the BSA-based dose of
golimumab will be adjusted as needed to maintain the dose at 80 mg/m2. Subjects will also 
receive commercial MTX weekly through Week 28 at the same BSA-based dosage (10 to 
30 mg/m2 per week of MTX in subjects with BSA <1.67 m2, or a minimum of 15 mg/week in 
subjects with BSA ≥1.67 m2) as at time of study entry as outlined in Section 6.2. At Week 252, 
subjects who meet the inclusion criteria for the optional Extended Treatment Period (ETP) may 
continue treatment with golimumab (80 mg/m2 q8w) after completion of the Week 252 
assessments. 
Every effort should be made to maintain subjects at a dose of 80 mg/m 2 of golimumab based 
upon BSA, and decreases below or increases above 80 mg/m2 or shortening of the dosing 
interval (eg, from 8 weeks to 6 weeks) will not be permitted at any visit.
This is an open-label study, with all subjects receiving the same BSA-based dose of IV 
golimumab. Safety data will be routinely evaluated by the study’s medical monitor. Therefore, 
an external Data Monitoring Committee will not be established.
A diagram of the study design is provided in Figure 1.
Figure 1:
Schematic Overview of the Study
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3.1.1.
Week 0 Through Week 28
Through Week 28, subjects will be monitored and disease activity and safety will be assessed at 
the investigative site every 4 weeks.
If <50% of the study population achieves an adequate response to the treatment (American 
College of Rheumatology Pediatric 30% [JIA ACR 30] response) at Week 28, the study will be 
discontinued.
After all subjects complete the Week 28 visit, the database will be locked to assess PK, safety 
and efficacy. An additional safety, efficacy, and PK database lock is currently planned for
Week 52. A database lock will be performed at Week 252, and a final database lock will be 
performed at the end of study.
No changes should be made to background medications (ie, MTX, other DMARDs, 
corticosteroids, and NSAIDs) in terms of increases or decreases in dosage beyond the parameters 
provided in Section 8 (eg, no more than 10 mg/day prednisone or no more than 0.20 mg/kg/day,
whichever is lower) and/or route of administration between Weeks 0 and 28, unless there is a 
safety concern (eg, elevated LFTs), which requires changes to background medications.
If a subject is lost to follow-up, every possible effort must be made by the study site personnel to 
contact the subject and determine the reason for discontinuation/withdrawal. The measures taken 
to follow-up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study drug assigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw will not be replaced.
3.1.2.
Week 28 Through Week 52
From Week 28 through Week 52, infusions will continue to be performed every 8 weeks 
(±1 week); however, subjects will be actively monitored at the investigative site and disease 
activity and safety will be assessed at the investigative site every 8 weeks rather than every 
4 weeks as between Weeks 0 and 28. As noted above, after Week 28 subjects will be permitted 
to change/add MTX, other DMARDs, corticosteroids, and NSAIDs as outlined in Section 8.
3.1.3.
Week 52 Through Week 252 (Long-term Extension)
Subjects who complete the study at Week 52 will have the option to enter into the LTE phase of 
this study. Subjects who opt not to enter the LTE will be encouraged to complete an additional 
8-week safety follow-up visit following the last administration of study agent.
During the LTE, all subjects will continue to receive golimumab q8w (±1 week) through 
Week 244. For subjects who have completed the trial period of 252 weeks and for whom drug is 
proven beneficial but is not commercially available for pJIA indication (or patient does not 
qualify for insurance to pay for the drug) IV golimumab will continue to be provided by the 
Sponsor, as described in Section 3.1.4. Between Week 52 and Week 252, disease activity will be 
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monitored and assessed by investigators, and benefit of treatment will be documented in the 
subject’s source documents by investigators on a yearly basis via an attestation form; infusions 
and safety measurements will be done at the investigative site according to the Time and Events 
Schedule.
As noted above, after Week 28, subjects will be permitted to change/add MTX, other DMARDs, 
corticosteroids, and NSAIDs, including increases or decreases in BSA-based dosing (where 
appropriate) for these classes of agents as outlined in Section 8.
All subjects who complete the Week 244 visit are expected to participate in the safety follow-up 
visit at Week 252. Those subjects who discontinue study agent at any time before Week 244 are 
also expected to return for a safety follow-up visit approximately 8 weeks after the last 
administration of study agent.
A database lock will occur at Week 252.
3.1.4.
After Week 252 (Extended Treatment Period)
Subjects <18 years of age who complete the study through Week 252, and for whom drug is 
proven beneficial but is not commercially available for pJIA, will have the option to enter the 
ETP at Week 252, as described in Attachment 6. 
The final database lock will occur at the end of the ETP, as described in Attachment 6.
3.1.5.
End of Study Definition
The end of the study is defined as the last follow-up assessment for the last subject in the ETP.
3.2.
Study Design Rationale
3.2.1.
Blinding, Control, Study Phase/Periods, Treatment Groups
This is a single-arm, open-label study to evaluate the PK of IV golimumab in subjects with pJIA, 
with all subjects receiving the same BSA-based dose of IV golimumab through Week 52.
Subjects who complete the study at Week 52 will have the option to enter into the LTE phase of 
this study through Week 252. After Week 252, subjects who meet specific criteria (see 
Attachment 6) will have the opportunity to continue treatment with golimumab in the ETP.
3.2.2.
Dose Selection
Unlike adult drug doses, pediatric drug doses (parenteral) are commonly calculated individually 
as weight-based (mg/kg) or BSA-based (mg/m2) doses to manage the PK variability observed in 
children across different ages as changes occur in their maturing organ systems.10,22 The 
successful outcome of dose extrapolation from adults to pediatric subjects through weight-based 
or BSA-based dose normalization for other approved anti-TNFα agents (eg, adalimumab and 
etanercept) supports the assumption that clinical responses to anti-TNFα agents in rheumatoid 
disease would be similar between adults and children. That is, after the PK differences inherent 
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between adults and children are accounted for, similar drug responses would be expected with 
similar drug exposure in both adults and children.
Data from the Phase 3 IV study in adults with RA (CNTO148ART3001) through 24 weeks have 
shown that golimumab 2 mg/kg at Week 0, Week 4, and q8w (±1 week) thereafter is the optimal 
dose regimen for the treatment of RA in most adults. For a child, golimumab 80 mg/m2
(2 mg/kg/1.73 m2) would be approximately equivalent to 2 mg/kg for an adult subject weighing 
70 kg (with a BSA of 1.73 m2). Thus, in the current study (CNTO148JIA3003), a dose of 
golimumab 80 mg/m2 has been chosen to evaluate the safety and efficacy of golimumab in the 
pJIA population.
3.2.3.
Rationale
The open-label study design for IV golimumab in the pJIA population is based on data from
studies of other anti-TNFα agents in adult RA and pJIA, PK and efficacy data from the 
Sponsor’s study of IV golimumab in adult RA (CNTO148ART3001), the Sponsor’s experience 
with SC golimumab in pJIA (CNTO148JIA3001),
and
feedback from
the Pediatric 
Rheumatology International Trials Organisation (PRINTO) and The Pediatric Rheumatology 
Collaborative Study Group (PRCSG).
The Sponsor will utilize PK data generated from the proposed open-label CNTO148JIA3003 
study to extrapolate to adult PK data from the CNTO148ART3001 study in RA, which was the 
pivotal study that served as the basis for approval of IV golimumab (SIMPONI ARIA/SIMPONI 
for Intravenous Use) for adult patients with RA. Additionally, efficacy (PD) data will be 
collected to explore the assessment of supportive exposure-response.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 6 weeks before administration of the 
study drug.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the
investigator should consult with the appropriate Sponsor representative before enrolling a subject 
in the study.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2, 
Sample Size Determination.
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
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Approximately 120 subjects will be enrolled in this study. Enrolled subjects who discontinue 
study treatment or withdraw from study participation will not be replaced with new subjects.
Retesting of an abnormal screening value that leads to exclusion is allowed only once using an 
unscheduled visit during the screening period to reassess eligibility. This should be considered 
only if there is no anticipated impact on subject safety.
Eligibility criteria for the ETP are provided in Attachment 6. Prohibitions and restrictions during 
the ETP are also provided in Attachment 6.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1.
Subjects must be age 2 years to less than 18 years with a body weight >15 kg at the time 
of screening and at Week 0. 
2.
Diagnosis must be made per JIA ILAR diagnostic criteria and the onset of disease must 
have been before the subject’s 16th birthday.
3.
Active JIA of one of the following subtypes:
a.
Rheumatoid factor positive or negative pJIA for ≥3 months prior to screening, or
b.
Systemic JIA with no systemic symptoms for ≥3 months, but with polyarthritis for 
≥3 months prior to screening, or
c.
Extended oligoarticular JIA ≥3 months prior to screening, or
d.
Polyarticular juvenile psoriatic arthritis ≥3 months prior to screening, or,
e.
Enthesitis-related arthritis ≥3 months prior to screening.
4.
Failure or inadequate response to at least a 2-month course of MTX before screening.
5.
Subjects must have ≥5 joints with active arthritis at screening and at Week 0 as defined 
by ACR criteria (ie, a joint with either swelling, or in the absence of swelling, limited 
range of motion associated with pain on motion or tenderness).
6.
Subjects must have a screening CRP of ≥0.1 mg/dL with the exception of approximately 
30% of the study population.
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7.
Subjects must have active pJIA despite current use of oral, intramuscular, or 
subcutaneous MTX for ≥2 months before screening. For subjects with BSA <1.67 m2,
the MTX dose must be between 10 to 30 mg/m2 per week and stable for ≥4 weeks before 
screening. For subjects with BSA ≥1.67 m2, 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 >10 mg/m2 weekly (for subjects with BSA 
<1.67 m2) or ≥15 mg/week (for subjects with BSA ≥1.67 m2); or where documented 
country or site regulations prohibit use of ≥15 mg of MTX per week in subjects with 
BSA ≥1.67 m2, subjects may be entered into the trial on a lower dose of MTX. 
8.
If using corticosteroids, must be on a stable dose of ≤10 mg/day prednisone equivalent 
or 0.20 mg/kg/day (whichever is lower) for ≥2 weeks before first administration of study 
agent. If currently not using corticosteroids, the subject must have not received 
corticosteroids for at least 2 weeks before the first dose administration. Subjects with 
systemic onset JIA but without systemic symptoms must be on a stable dose of 
corticosteroids for at least 3 days prior to screening.
9.
If using NSAIDs, must be on a stable dose for ≥2 weeks before screening. If not 
currently using NSAIDs, must not have taken them for at least 2 weeks before 
screening.
10.
Subjects are considered eligible according to the following TB screening criteria:
a.
Have no history of latent or active TB prior to screening. An exception is made 
for subjects currently receiving treatment for latent TB with no evidence of 
active TB, or who have a history of latent TB and documentation of having 
completed appropriate treatment for latent TB within 3 years prior to the first
administration of study agent. It is the responsibility of the investigator to 
verify the adequacy of previous anti-tuberculous treatment and provide 
appropriate documentation.
b.
Have no signs or symptoms suggestive of active TB upon medical history 
and/or physical examination.
c.
Have had no recent close contact with a person with active TB or, if there has 
been such contact, will be referred to a physician specializing in TB to undergo 
additional evaluation and, if warranted, receive appropriate treatment for latent 
TB prior to the first administration of study agent.
d.
Within 6 weeks prior to the first administration of study agent, have a negative 
QuantiFERON®-TB Gold (Attachment 1) test result, or have a newly identified 
positive QuantiFERON®-TB Gold test result in which active TB has been ruled 
out and for which appropriate treatment for latent TB (Section 9.1.2) has been 
initiated prior to the first administration of study agent. Within 6 weeks prior to 
the first administration of study agent, a negative tuberculin skin test 
(Attachment 2), or a newly identified positive tuberculin skin test in which 
active TB has been ruled out and for which appropriate treatment for latent TB 
has been initiated prior to the first administration of study agent, is additionally 
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required if the QuantiFERON®-TB Gold test is not approved/registered in that 
country or the tuberculin skin test is mandated by local Health Authorities.
e.
Indeterminate results should be handled as outlined in Section 9.1.2. Subjects 
with persistently indeterminate QuantiFERON®-TB Gold test results may be 
enrolled without treatment for latent TB, if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB), 
and the subject has no additional risk factors for TB as determined by the 
investigator. This determination must be promptly reported to the Sponsor’s 
medical monitor and recorded in the subject's source documents and initialed 
by the investigator.
f.
The QuantiFERON®-TB Gold test and the tuberculin skin test are not required 
at screening for subjects with a history of latent TB and ongoing treatment for 
latent TB or documentation of having completed adequate treatment as 
described above; Subjects with documentation of having completed adequate 
treatment as described above are not required to initiate additional treatment 
for latent TB.
g.
Unless country or local guidelines do not recommend a chest radiograph as a 
necessary screening process prior to initiation of anti-TNFα therapies, a chest 
radiograph (posterior-anterior view) must have been taken within 3 months 
prior to the first administration of study agent and read by a qualified 
radiologist, with no evidence of current active TB or old inactive TB. Chest 
radiographs (both posterior-anterior and lateral views) must be performed as 
part of the screening process in all cases when either the tuberculin skin test 
and/or QuantiFERON®-TB Gold testing for TB is positive. 
11.
Subjects must be medically stable on the basis of physical examination, medical history, 
and vital signs performed at screening. If there are abnormalities, they must be 
consistent with the underlying illness in the study population.
12.
Girls must be either:

Not of childbearing potential: premenarchal; permanently sterilized (eg, tubal 
occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of 
pregnancy,
OR

Of childbearing potential, and if sexually active, practicing a highly effective 
method of birth control consistent with local regulations regarding the use of birth 
control methods for subjects participating in clinical studies: eg, established use of 
oral, injected or implanted hormonal methods of contraception; placement of an 
intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom 
with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner 
sterilization (the vasectomized partner should be the sole partner for that subject); 
true abstinence (when this is in line with the preferred and usual lifestyle of the 
subject and at the discretion of the investigator/per local regulations). Girls of 
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childbearing potential must agree not to donate eggs (ova, oocytes) for the purposes 
of assisted reproduction during the study and for 6 months after receiving the last 
dose of study drug.
Note: If the childbearing potential changes after start of the study (eg, girl who is 
not heterosexually active becomes active, premenarchal girl experiences menarche) 
a girl must begin a highly effective method of birth control, as described above.
13.
Girls of childbearing potential must have a negative serum -human chorionic 
gonadotropin (-hCG) test at screening and a negative urine pregnancy test at each 
study visit where golimumab infusion is to take place.
14.
Boys must practice abstinence, or if sexually active with a girl of childbearing potential 
and has not had a vasectomy must agree to use a barrier method of birth control eg, 
either condom with spermicidal foam/gel/film/cream/suppository or partner with 
occlusive 
cap 
(diaphragm 
or 
cervical/vault 
caps) 
with 
spermicidal 
foam/gel/film/cream/suppository, and all boys must also not donate sperm during the 
study and for 6 months after receiving the last dose of study drug.
15.
Subjects’ screening laboratory tests must meet the following criteria:
a.
Hemoglobin: ≥8.0 g/dL (SI: ≥80 g/L; girls and boys, ages 2 to 11)
≥8.5 g/dL (SI: ≥85 g/L; girls, ages 12 to 18)
≥9.0 g/dL (SI: ≥90 g/L; boys, ages 12 to 18)
b. White blood cells (WBCs) ≥3.0 x 103 cells/µL (SI: ≥3.0 x 109 cells/L)
c.
Neutrophils ≥1.5 x 103 cells/µL (SI: ≥1.5 x 109 cells/L)
d. Platelets ≥140 x 103 cells/µL (SI: ≥140 x 109 cells/L)
e.
Serum transaminase levels not exceeding 1.2 x the upper limit of normal for the 
central laboratory:
–
Aspartate aminotransferase (AST)
o
≤67 IU/L (girls, ages 2 to <4)
o
≤58 IU/L (girls, ages 4 to <7)
o
≤48 IU/L (girls, ages 7 to 18)
o
≤83 IU/L (boys, ages 2 to <4)
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o
≤71 IU/L (boys, ages 4 to <7)
o
≤48 IU/L (boys, ages 7 to 18)
–
Alanine aminotransferase (ALT)
o
≤41 IU/L (girls, ages 2 to 18)
o
≤41 IU/L (boys, ages 2 to <10)
o
≤52 IU/L (boys, ages 10 to 18)
f.
Serum creatinine not to exceed:
–
0.5 mg/dL (SI: 44 µmol/L; ages 2 to 5)
–
0.7 mg/dL (SI: 62 µmol/L; ages 6 to 10)
–
1.0 mg/dL (SI: 88 µmol/L; ages 11 to 12)
–
1.2 mg/dL (SI: 106 µmol/L; ages ≥13)
16.
Subjects must be up to date with all immunizations in agreement with current local 
immunization guidelines for immunosuppressed subjects before Week 0.
17.
A parent or guardian should accompany the subject to each study visit until the subject 
reaches the age of 18 years.
18.
The subject and his/her parent (if applicable) must be able to adhere to the study visit 
schedule, and understand and comply with other protocol requirements.
19.
Subject must be willing and able to adhere to the prohibitions and restrictions specified 
in this protocol.
20.
Each subject (or their legally acceptable representative) must sign an ICF indicating that 
he or she understands the purpose of and procedures required for the study and are 
willing to participate in the study. Assent is also required of children capable of 
understanding the nature of the study (typically 7 years of age and older and per local 
regulations) as described in Section 16.2.3, Informed Consent.
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4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study.
Concomitant or previous medical therapies received:
1.
Subject has initiated DMARDs and/or immunosuppressive therapy within 4 weeks 
prior to first study agent administration. 
2.
Subject has been treated with intra-articular, intramuscular or intravenous 
corticosteroids (including intramuscular corticotropin) during the 4 weeks before 
first study agent administration.
3.
Subject has been treated with any therapeutic agent targeted at reducing IL-12 or 
IL-23, including but not limited to ustekinumab and ABT-874 within 3 months
before first study agent administration.
4.
Subject 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 has evidence at screening of 
persistent depletion of the targeted lymphocyte after receiving any of these agents.
5.
Subject has been treated with alefacept within 3 months before first study agent 
administration.
6.
Subject has been treated with abatacept within 8 weeks before first study agent 
administration.
7.
Subject has been treated with leflunomide within 4 weeks before first study agent 
administration (irrespective of undergoing a drug elimination procedure), or have 
received leflunomide from 4 to 12 weeks before first study agent administration and 
have not undergone a drug elimination procedure. 
8.
Subject has been treated with cytotoxic agents, including cyclophosphamide, 
nitrogen mustard, chlorambucil, or other alkylating agents.
9.
Subject has received or is expected to receive any live viral or live bacterial 
vaccinations from 3 months before first study agent administration and up to 
3 months after the last study agent administration.
10.
Subject has had a BCG vaccination within 12 months of screening or is planned to 
receive BCG vaccination within 12 months following last study drug administration.
11.
Subject has received IL-1ra (anakinra) within 1 week of the first study agent 
administration.
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12.
Subject has previously been treated with more than 2 therapeutic agents targeted at 
reducing TNFα, including, but not limited to, infliximab, etanercept, adalimumab, or 
certolizumab pegol.
13.
If a subject has been previously treated with an anti-TNFα agent, the reason for 
discontinuation of the anti-TNFα agent cannot have been a severe or serious adverse 
event consistent with the class of anti-TNFα agents. 
14.
Subject has received adalimumab or certolizumab pegol within 6 weeks or has 
received etanercept within 4 weeks of the first dose of study agent.
15.
Subject has received infliximab or tocilizumab within 8 weeks of the first 
administration of study agent.
16.
Subject has ever received IV or SC golimumab. 
17.
Subject has received a Janus kinase (JAK) inhibitor, including but not limited to 
tofacitinib, within 2 weeks of the first dose of study agent.
18.
Subject has received canakinumab within 4 months prior to first study dose 
administration.
19.
Subject has current side effects related to MTX or conditions that would preclude 
treatment with MTX, including but not limited to liver cirrhosis, liver fibrosis, 
persistent elevations of ALT and AST (more than 3 of 5 tests elevated within 
6-months period), MTX pneumonitis, severe mucosal ulcers, intractable nausea, 
vomiting/diarrhea, evidence of clinically significant bone marrow suppression, 
severe headaches, severe bone pain, or traumatic fractures.
20.
Subject has received an investigational drug (including investigational vaccines) or 
used an invasive investigational medical device within 3 months or 5 half-lives, 
whichever is longer, before the planned first dose of study drug or is currently 
enrolled in an investigational study.
Infections or predisposition to infections:
21.
Subject has a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, prior to screening. Refer to inclusion criterion (Section 4.1) for 
information regarding eligibility with a history of latent TB.
22.
Subject tests positive for hepatitis B virus (Attachment 3).
23.
Subject is seropositive for antibodies to hepatitis C virus (HCV).
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24.
Subject has a known history of infection with human immunodeficiency virus 
(HIV).
25.
Subject has had a nontuberculous mycobacterial infection or opportunistic infection 
(eg, cytomegalovirus, pneumocystis, or aspergillosis) within 6 months prior to 
screening. 
26.
Subject has a history of an infected joint prosthesis or has received antibiotics for a 
suspected infection of a joint prosthesis unless that prosthesis has been removed or 
replaced.
27.
Subject has or has had a serious infection (including but not limited to hepatitis, 
pneumonia, or pyelonephritis), or have been hospitalized or received IV antibiotics 
for an infection during the 2 months before first study agent administration.
28.
Subject has a history of or ongoing chronic or recurrent infectious disease, including, 
but not limited to, chronic renal infection, chronic chest infection (eg, 
bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent 
pyelonephritis), open, draining, or infected skin wound, or ulcer.
29.
Subject has a chest radiograph within 3 months prior to the first administration of 
study agent that shows an abnormality suggestive of a malignancy or current active 
infection, including TB (if applicable).
Malignancy or increased potential for malignancy:
30.
Subject has a known malignancy or a history of malignancy.
31.
Subject has a history of lymphoproliferative disease, including lymphoma, or signs 
suggestive of possible lymphoproliferative disease, such as lymphadenopathy of 
unusual size or location, or clinically significant splenomegaly not consistent with 
pJIA or systemic onset JIA without systemic symptoms.
Coexisting medical conditions or past medical history:
32.
Subject has a history of severe progressive or uncontrolled liver or renal 
insufficiency; or significant cardiac, vascular, pulmonary, gastrointestinal, 
endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances.
33.
Subject has known allergies, hypersensitivity, or intolerance to golimumab or its 
excipients (refer to Investigator's Brochure) or subject has known allergies, 
hypersensitivity, or intolerance to immunoglobulins. 
34.
Subject has or has had a substance abuse (drug or alcohol) problem.
35.
Subject has a history of macrophage activation syndrome.
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36.
Subject has another inflammatory disease that might confound the evaluation of 
benefit from golimumab therapy, including but not limited to systemic lupus 
erythematosus or Lyme disease.
37.
Subject is incapacitated, largely or wholly bedridden, or confined to a wheelchair, or 
has little or no ability for age-appropriate self-care.
38.
Subject has a known history of demyelinating diseases such as multiple sclerosis.
39.
Subject has a history of, or concomitant diagnosis of, congestive heart failure.
Other: 
40.
Subject has any condition for which, in the opinion of the investigator, participation 
would not be in the best interest of the subject (eg, compromise the well-being) or 
that could prevent, limit, or confound the protocol-specified assessments.
41.
Subject is a girl who is pregnant, or breast-feeding, or planning to become pregnant 
while enrolled in this study or within 6 months after the last dose of study drug.
42.
Subject is a boy who plans to father a child while enrolled in this study or within
6 months after the last dose of study drug.
43.
Subject is unable or unwilling to undergo multiple venipunctures because of poor 
tolerability or lack of easy access.
44.
Subject is an employee of the investigator or study site, with direct involvement in 
the proposed study or other studies under the direction of that investigator or study 
site, as well as family members of the employees or the investigator.
45.
Subject has active uveitis within 3 months prior to screening.
46.
Subject with BSA >3.0 m2.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a subject's status changes (including laboratory results or receipt of additional medical records) 
after screening but before the first dose of study drug is given such that he or she no longer meets
all eligibility criteria, then the subject should be excluded from participation in the study. 
Section 17.4, Source Documentation, describes the required documentation to support meeting 
the enrollment criteria.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
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1.
Subjects must not receive a live virus or live bacterial vaccination 3 months prior to 
screening, during the study, or within 3 months after the last administration of study 
agent.
2.
Subjects must not receive a BCG vaccination for 12 months before screening, during the 
study or within 12 months after the last administration of study agent.
3.
If sexually active and of childbearing potential, girls must remain on a highly effective 
method of birth control during the study and for 6 months after receiving the last 
administration of study agent, including the LTE phase of the study. Girls must not 
donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study 
and for 6 months after receiving the last dose of study agent, including the LTE phase of 
the study.
4.
If sexually active with a girl of childbearing potential and has not had a vasectomy, boys 
must use a double barrier method of birth control during the study and for 6 months 
after receiving the last administration of study agent, including the LTE phase of the 
study. Boys must not donate sperm and must agree not to plan a pregnancy or father a 
child during the study and for 6 months following the last administration of study agent, 
including the LTE phase of the study. 
5.
Intramuscular administration of corticosteroids for the treatment of pJIA is not allowed 
during the study. Corticosteroids administered by bronchial or nasal inhalation for
treatment of conditions other than pJIA may be given as needed throughout the course 
of the study. For additional details, see Section 8.
6. 
Subjects must not receive investigational drugs, other immunosuppressants (such as, but 
not exclusively, cyclophosphamide), or other biologics for pJIA during the study. 
5.
TREATMENT ALLOCATION AND BLINDING
This is an open-label study. All subjects will receive golimumab 80 mg/m2 at Week 0, Week 4,
and q8w (± 3 days) through Week 28 and q8w (± 1 week) after Week 28.
As this is an open-label study, blinding procedures are not applicable.
6.
DOSAGE AND ADMINISTRATION
6.1.
Golimumab
The study will have 1 active treatment group and all subjects will receive 80 mg/m2 golimumab 
(maximum single dose 240 mg) IV infusions at Week 0, Week 4, and q8w (±3 days) through 
Week 28 and q8w (±1 week) thereafter through Week 244. The golimumab infusions will be 
prepared by a pharmacist under sterile conditions using golimumab 50 mg/4 mL liquid in vials 
and a 100 mL infusion bag of 0.9% saline. Subjects will receive 80 mg/m2 golimumab IV 
infusions over 30±10 minutes. Infusions may be slowed down for evidence of infusion reactions 
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as deemed appropriate by the investigator, and all changes in the infusion rate should be recorded 
in the CRF. Body surface area will be calculated at each visit and the dose of golimumab will be 
adjusted as needed to maintain the dose at 80 mg/m2. Body surface area will be calculated using 
the Mosteller equation: BSA (m2) = ([height (cm) x weight (kg)]/3600)1/2. For additional details, 
see the Site IP Manual.
During the ETP, golimumab will be administered as described in Attachment 6. The first dose of 
golimumab during the ETP will be at Week 252 after the subject has completed the Week 252 
assessments.
6.2.
Methotrexate
Subjects will receive commercial MTX through Week 28 at the same BSA-based dose (10 to 
30 mg/m2 per week for subjects with BSA <1.67 m2 or at least 15 mg/week for subjects with 
BSA ≥1.67 m2) as at time of study entry. Absolute dose should remain stable from baseline 
through Week 28.
Every effort should be made to ensure that subjects remain on the same dose and route of 
administration of MTX through the Week 28 visit, unless intolerance or AEs due to MTX occur
(Section 8). Guidelines for adjusting MTX dosage in the event of MTX toxicity are provided in 
the Trial Center File.
Subjects will also receive a total dose of commercial folic acid ≥5 mg weekly or folinic acid 
(at half the MTX dose) given the day after the weekly MTX dose. In children <12 years of age, 
the administration of folic acid or folinic acid will be at the discretion of the physician.
After Week 28, changes in MTX administration are permitted (eg, increase or decrease in 
dosage, change in route of administration, or discontinuation).
7.
TREATMENT COMPLIANCE
The study site personnel will ensure compliance with the treatment assignments. Site personnel 
will administer the study infusion at each visit and record the amount of infusion given.
All subject CRFs will be monitored by a site monitor designated by the Sponsor. During these 
monitoring visits, all procedures will be evaluated for compliance with the protocol. Treatments 
that are administered outside of the scheduled windows, as well as missed visits, will be recorded 
on the CRF. Subject charts will be reviewed and compared with the data entries on the CRFs to 
ensure accuracy.
8.
PRESTUDY AND CONCOMITANT THERAPY
Prestudy JIA medications administered before the first dose of study agent must be recorded at 
screening. All concomitant therapies must be recorded through Week 52 of the study beginning 
with the administration of the first dose of the study drug. After Week 52, the investigator will 
review concomitant medications with the subject and document in source, and record on the CRF 
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page only those concomitant medications that are associated with AEs and SAEs (ie, used to 
treat event or suspected in causing event).
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation and acupuncture) 
different from the study drug must be recorded in the CRF through Week 52. Recorded 
information will include a description of the type of the drug, treatment period, dosing regimen,
route of administration, and its indication. Modification of an effective pre-existing therapy 
should not be made for the explicit purpose of entering a subject into the study.
If using corticosteroids or NSAIDS, subjects must have been on stable doses of these 
medications prior to study entry per Inclusion Criterion 8 and 9 (Section 4.1). Subjects may have 
been previously treated with no more than 2 therapeutic agents targeted at reducing TNFα prior 
to study entry per Exclusion Criterion 12 (Section 4.2). Subjects may not have initiated or been 
treated with prohibited therapeutic agents as outlined in Exclusion Criteria 1 through 20
(Section 4.2).
Subjects must have received MTX for ≥2 months before screening. For subjects with BSA 
<1.67 m2, the MTX dose must be between 10 to 30 mg/m2 per week and stable for ≥4 weeks 
before screening. For subjects with BSA ≥1.67 m2
, the MTX dose must be a minimum of 
15 mg/week of MTX and must be stable for ≥4 weeks before screening. For exceptions to this 
rule, see Inclusion Criterion 7. Subjects (with the exception of those with sJIA) receiving 
corticosteroids at the time of study entry must have been receiving a stable dose for ≥2 weeks 
before screening, and that dose must have been ≤10 mg/day prednisone or prednisone equivalent 
or 0.20 mg/kg/day (whichever is lower). Subjects with systemic onset JIA but without systemic 
symptoms for ≥3 months must be on stable corticosteroids for 3 days before screening and not 
exhibit systemic symptoms. If receiving NSAID therapy, the dose must have been stable for 
≥2 weeks before screening.
No changes should be made to background medications (ie, MTX, other DMARDs, 
corticosteroids, and NSAIDs) in terms of increases or decreases in dosage (eg, no more than 
10 mg/day prednisone or no more than 0.20 mg/kg/day, whichever is lower) and/or route of 
administration between Weeks 0 and 28, unless there is a safety concern (eg, elevated LFTs), 
which requires changes to background medications. After Week 28, subjects will be permitted to 
change/add MTX, other DMARDs, corticosteroids, and NSAIDs, including increases or 
decreases in dosage, changes of route of administration, or discontinuations from these classes of 
agents.
Intramuscular administration of corticosteroids for the treatment of pJIA is not allowed during 
the study. Corticosteroids administered by bronchial or nasal inhalation for treatment of 
conditions other than pJIA may be given as needed throughout the course of the study.
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Every attempt should be made to avoid the use of IV corticosteroids. For subjects requiring short 
courses (2 weeks or less) of oral or IV corticosteroids for reasons such as prophylactic therapy 
prior to surgery (stress-dose corticosteroids) or therapy for limited infections, exacerbation of 
asthma, or for any condition other than pJIA, corticosteroid therapy should be limited to 
situations in which, in the opinion of the treating physician, there are no adequate alternatives 
and should be documented in the CRF.
Subjects may receive intra-articular injections of a corticosteroid, if clinically required, during 
the study up to Week 52. However, the number of intra-articular injections should be limited to 
2 over any 24-week period. That is, if a subject has received 2 intra-articular injections and more 
than 24 weeks has elapsed, the subject may receive up to 2 additional intra-articular injections
over another 24-week period.
After Week 52, the number of injected joints is no longer limited to 2 injections per 24 weeks. 
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered (Section 4.3).
After Week 252, concomitant medications are documented as described in Attachment 6.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedules summarize the frequency and timing of efficacy, PK, 
immunogenicity, and safety measurements applicable to this study (Table 1, Table 2, and 
Table 3). All scheduled study visits should occur within ±3 days of the intended visit through 
Week 28 and ±1 week from Week 28 through Week 244. Through Week 52, if the recommended 
acceptable window cannot be observed, the Sponsor must be contacted before scheduling a visit.
After Week 52, if the recommended acceptable window cannot be observed, the reason for the 
deviation must be recorded in source documents. After Week 252, study procedures will be 
performed as described in Attachment 6.
The Childhood Health Assessment Questionnaire (CHAQ) should be conducted before any tests,
procedures, or other consultations for that visit to prevent influencing subjects’ perceptions. For 
additional details, refer to the PRO user manual.  
At every unscheduled visit, the investigator will perform the following evaluations:

Review of systems (after Week 52, at the discretion of the investigator)

Vital signs (after Week 52, at the discretion of the investigator)

TB questionnaire

Adverse events
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
Review of concomitant medications (after Week 52, medications should be reviewed and 
documented in source; medications used to treat or associated with AEs and SAEs should be 
recorded on the CRF)

Safety laboratory evaluations (after Week 52, at the discretion of the investigator)
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's participation in the study.
The total blood volume to be collected from each subject for the study is approximately
149.4 mL (Table 4). Repeat or unscheduled samples may be taken for safety reasons or for 
technical issues with the samples.
Table 4:
Approximate Volume of Blood to be Collected From Each Subject Through Week 252
Type of Sample
Approximate
Volume per 
Sample (mL)
No. of Samples 
per Subject
Approximate
Total Volume of 
Blood (mL)a,b
Safety (including screening and posttreatment 
assessments)
- Hematology
1.2
17
20.4
- Serum chemistry
1.1
17
18.7
Serology (hepatitis B and hepatitis C)
2.0
1
2.0
Serum -hCG pregnancy tests
1.1
1
1.1
- QuantiFERON®-TB Gold test
3.0
6
18.0
- Rheumatoid factor
1.1
1
1.1
- Anti-dsDNA antibody 
1.1
11
12.1
- ANA antibodies 
1.1
11
12.1
Efficacy (CRP)
1.1
24
26.4
PK and immunogenicity (antibodies to golimumab)
2.5
15
37.5
Approximate Totalc
149.4
a. Calculated as the number of samples multiplied by amount of blood per sample.
b. Repeat or unscheduled samples may be taken for safety reasons or technical issues with the samples.
c. The approximate total volume is the maximum volume of blood collected from a subject during the study; with 
implementation of Protocol Amendment 4, the volume of blood collected will be decreased. 
Note: An indwelling intravenous cannula may be used for blood sample collection.
Abbreviations: ANA = antinuclear antibodies; β-hCG = β-human chorionic gonadotropin; CRP = C-reactive protein; 
dsDNA = double-stranded deoxyribonucleic acid; PK = pharmacokinetic; TB = tuberculosis. 
9.1.2.
Screening Phase
After written informed consent/assent has been obtained (Section 16.2.3), and within a period of 
6 weeks before Week 0, all screening evaluations establishing subject eligibility will be 
performed. Subjects who meet all of the inclusion and none of the exclusion criteria will be 
enrolled in the study. Every effort should be made to adhere to the study Time and Events 
Schedule for each subject (Table 1).
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Girls of childbearing potential must have a negative serum β-hCG pregnancy test at screening 
and a negative urine pregnancy test prior to each administration of study agent. Sexually active
subjects must consent to use a highly effective method of contraception and continue to use 
contraception for the duration of the study and for 6 months after receiving the last dose of study 
agent. The method(s) of contraception used by each subject must be documented.
Subjects must undergo testing for TB (Attachment 1 and Attachment 2) at screening and their 
medical history assessment must include specific questions about a history of TB or known 
personal exposure to individuals with active TB. The subject should be asked about past testing 
for TB, including chest radiograph results and responses to tuberculin skin or other TB testing 
(Section 4.1).
Subjects with a negative QuantiFERON®-TB Gold test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON®-TB Gold test is not approved/registered or the 
tuberculin skin is mandated by local Health Authorities) are eligible to continue with screening 
procedures. Subjects with a newly identified positive QuantiFERON®-TB Gold (and/or 
tuberculin skin test) result must undergo an evaluation to rule out active TB and initiate 
appropriate treatment for latent TB. Appropriate treatment for latent TB is defined according to 
local country guidelines for immunocompromised patients. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed, or the subject will be 
excluded from the study.
A subject whose first QuantiFERON®-TB Gold test result is indeterminate must have the test 
repeated. In the event that the second QuantiFERON®-TB Gold test result is also indeterminate, 
the subject may be enrolled without treatment for latent TB if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB), and the subject 
has no additional risk factors for TB as determined by the investigator. This determination must 
be promptly reported to the Sponsor’s medical monitor and recorded in the subject's source 
documents and initialed by the investigator.
Retesting of an abnormal screening value that leads to exclusion is allowed only once using an 
unscheduled visit during the screening period to reassess eligibility. This should only be 
considered if there is no anticipated impact on subject safety.
9.1.3.
Treatment Phase: Week 0 Through Week 28
Beginning at Week 0, eligible subjects will receive 80 mg/m2 golimumab administered as IV 
infusions over 30±10 minutes at Weeks 0, 4 and q8w (±3 days) through Week 28 (Section 6.1). 
Subjects will also receive commercial MTX weekly at least through Week 28 at the same 
BSA-based dosage as at time of study entry and commercial folic acid ≥5 mg weekly or folinic 
acid (at half the MTX dose) given the day after the MTX dose (Section 6.2). In children 
<12 years of age, the administration of folic acid or folinic acid will be at the discretion of the 
physician.
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Subjects will have safety, efficacy, PK, and immunogenicity evaluations performed according to 
the Time and Events Schedule (Table 1). One additional sample for serum golimumab 
concentration for population PK will be collected from all subjects at any time between Weeks 0 
and 8 other than at the time of the Week 0, Week 4, and Week 8 visits; this sample must be 
collected at least 24 hours prior to or after a study agent administration and must not be collected 
at a regularly scheduled visit (eg, Week 8).
9.1.4.
Treatment Phase: After Week 28 Through Week 52
After Week 28, subjects will continue to receive 80 mg/m2 golimumab administered as IV 
infusions over 30±10 minutes q8w (±1 week) through Week 52 (Section 6.1). Subjects may also 
receive commercial MTX weekly at the same BSA-based dosage as at time of study entry and 
commercial folic acid ≥5 mg weekly or folinic acid if administered (at half the MTX dose; 
Section 6.2) given the day after the MTX dose; however, increases, decreases or discontinuations 
of MTX, other DMARDs, corticosteroids, and/or NSAIDs are permissible after Week 28. All 
changes and reasons for changes for these medications need to be documented in the eCRF.
Subjects will have safety, efficacy, PK, and immunogenicity evaluations performed according to 
the Time and Events Schedule (Table 1).
End of Treatment/Early Withdrawal
If a subject discontinues study agent before Week 52, the subject should return approximately
8 weeks after the last administration of study agent for a final safety follow-up visit
(Section 10.2). If a subject withdraws from study participation before Week 52, every effort 
should be made to obtain end-of-treatment assessments prior to the subject’s withdrawal of 
consent.
9.1.5.
Long-Term Extension Phase: After Week 52 Through Week 252
Subjects who enter the LTE after the Week 52 visit will continue to receive 80 mg/m2
golimumab administered as IV infusions over 30±10 minutes q8w (±1 week) through Week 244.
Subjects will have safety, PK, and immunogenicity evaluations performed according to the Time 
and Events Schedules (Table 2 and Table 3). After Week 52, disease activity will be monitored 
and assessed by investigators. Investigators will fill out an annual attestation form to document 
that a subject is benefiting from treatment. Subjects who discontinue study agent administration 
prior to Week 244 without withdrawing consent should return for a final safety follow-up visit
approximately 8 weeks after their last study agent infusion (Section 10.2).
Review of systems, collection of vital signs, QuantiFERON®-TB Gold testing, uveitis 
evaluations (including slit lamp evaluations), and chest x-ray screening will be performed at the 
discretion of the investigator; refer to the Time and Events Schedules (Table 2 and Table 3). It is 
the responsibility of the investigator to carry out all assessments per standard of practice and to 
update the CRF with all information related to AEs and SAEs (eg, concomitant medications).
Subjects should continue to be evaluated for signs and symptoms of TB (Section 9.4).
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9.1.6.
Extended Treatment Period
Subjects who enter the ETP after completion of the Week 252 assessments will continue to 
receive 80 mg/m2 golimumab IV q8w.
The frequency and timing of assessments during the ETP are provided in Attachment 6.
9.2.
Efficacy
9.2.1.
Evaluations
The Time and Events Schedule summarizes the frequency and timing of efficacy measurements 
applicable to this study (Table 1). After Week 52, investigators will complete an attestation form 
annually to document that the subject is benefiting from treatment.
9.2.1.1.
Joint Evaluation
Each of 75 joints will be evaluated for tenderness, and 68 joints will be evaluated for swelling 
and pain and limitation on motion according to the standard PRINTO/PRCSG joint evaluation. A 
consistent joint assessor, with at least 1 year of experience in performing joint assessment, will 
be designated at each study center to perform all joint assessments.
Training will be provided to a single consistent joint assessor from each site before the start of 
subject enrollment; the training is mandatory unless the site’s joint assessor has taken certified 
training provided by PRINTO or PRCSG. If a consistent joint assessor was trained by the 
Sponsor in a previous clinical study, he or she may receive a waiver for this training. 
Documentation of Sponsor or PRINTO/PRCSG training will be maintained in the Trial Center 
File. If possible, the consistent joint assessor for the study should not be changed during the 
study. However, the assessor from each site who attends the consistent joint assessor training 
provided by the Sponsor may train 1 additional assessor at the site for coverage during their 
absences.
It is expected that any additional consistent joint assessors who are trained will also have 1 or 
more years of experience as joint assessors or be approved by the Sponsor. If the designated 
consistent joint assessor from the site trains any additional assessors at the site, a letter 
documenting the training should be filed in the site’s Trial Center File. In addition, if more than 
1 consistent joint assessor at a site performs joint assessments during the study, the names of all 
consistent joint assessors performing the joint evaluation at the site at each visit must be listed in 
the Trial Center File and documented in the source document.
It is preferable that the consistent joint assessor who performs the baseline joint assessments for 
a subject also performs the joint assessments for that subject for all subsequent visits through the 
final efficacy assessment at Week 52.
Nonevaluable Joints
While it may be reasonable in clinical practice to identify as “nonevaluable” any joint which in 
the past or during study participation has been surgically altered (ie, prosthesis placement) or 
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medically treated (ie, intra-articular injection), the designation of “nonevaluable” for the 
purposes of this study is slightly different. Joints should only be designated as “nonevaluable” by 
the consistent joint assessor in the ePRO device if it is physically impossible to assess the joint 
(ie, joint inaccessible due to a cast, joint not present due to an amputation, joint deformed so as 
to make it impossible to assess).
9.2.1.2.
American College of Rheumatology Pediatric Response
The JIA ACR 30 response criteria5 is defined as a 30% improvement (ie, a decrease in score)
from baseline in at least 3 of the following 6 components, with worsening of 30% or more in no 
more than 1 of the following components:

Physician Global Assessment of Disease Activity

Parent/Subject 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 CHAQ

CRP
The JIA ACR 50 response, the JIA ACR 70 response, and the JIA ACR 90 response are defined 
as a 50% improvement, a 70% improvement, and a 90% improvement from baseline, 
respectively, in at least 3 of the above 6 components, with worsening of 30% or more in no more 
than 1 of the above components.
Inactive Disease
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 JIA

No active uveitis

Normal CRP (≤0.287 mg/dL for subjects without underlying inflammatory disease)

Physician Global Assessment of Disease Activity indicating no active disease (<5 mm)

Duration of morning stiffness <15 minutes
Clinical Remission While on Medication for JIA
Clinical remission while on medication for JIA is defined as inactive disease at each visit for a 
period of ≥6 months while on medication.
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9.2.1.3.
Physician Global Assessment of Disease Activity
The Physician Global Assessment of Disease Activity is a 100 mm VAS. Physicians are to 
complete the VAS that has them assess the patient’s current arthritis activity. The anchors of the 
scale are “no arthritis activity” to “extremely active arthritis.” Lower scores indicate less disease 
activity. The process for including this measure in the core set of variables for the assessment of 
children has been captured in the literature.5
9.2.1.4.
Childhood Health Assessment Questionnaire
The functional status of subjects will be assessed by the CHAQ.21 Parents/subjects will complete 
this questionnaire to assess the degree of difficulty the subject has in accomplishing tasks in 
8 functional areas (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, 
and activities of daily living).  Responses in each functional area are scored as 0 (without any 
difficulty), 1 (with some difficulty), 2 (with much difficulty), 3 (unable to do), or 4 (not 
applicable).  Lower scores are indicative of improved functioning and task performance in 
specific functional areas. 
Additionally, the CHAQ includes 2 VAS questions—one used to assess the subject’s level of 
pain, and one used to assess the subject’s overall well-being. Properties of the CHAQ have been 
evaluated and its validity assessed.21 The CHAQ has been shown to be responsive to disease 
change.21 A decrease of 0.188 has been determined to be a meaningful clinical improvement.1
Parent/Subject Assessment of Pain
Pain will be assessed as average pain experienced by the subject during the past week using a 
VAS scale that ranges from “no pain” (0 mm) to “very severe pain” (100 mm). This assessment 
should be completed by the parents (caregiver)/subjects prior to the tender and swollen joint 
examination.  
Parent/Subject Assessment of Overall Well-being
The Parent/Subject Assessment of Overall Well-being is a 0-100 mm VAS. Parents/subjects will 
complete the VAS that asks them to consider all the ways arthritis impacts their child/themselves 
and then indicate how the subject is doing. The anchors of the scale are “very well” (0 mm) to 
“very poor” (100 mm). Lower scores indicate better well-being. The process for including this 
measure in the core set of variables for the assessment of children has been captured in the 
literature.5
Subjects who are 15 to <18 years of age at study entry may complete the CHAQ jointly with the 
parent/caregiver. Preferably, the same individual (eg, parent, caregiver, or subject) who 
completes the assessment at the start of the study should complete the assessment throughout the 
study. 
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9.2.1.5.
C-reactive Protein
C-reactive protein has been demonstrated to be useful as a marker of inflammation in patients 
with pJIA and is part of the JIA ACR 30 core assessments. C-reactive protein will be assayed by 
a central laboratory using a validated, high-sensitivity CRP assay.
9.2.1.6.
Juvenile Arthritis Disease Activity Score (JADAS)
Recently, a composite disease activity score for pJIA, the Juvenile Arthritis Disease Activity 
Score (JADAS), was developed; in validation analyses it was found to have good metrologic 
properties, including the ability to predict disease outcome. The JADAS (modified for using 
CRP) is computed by assessing the following variables: (1) physician global rating of overall 
disease activity, measured on a 100-mm horizontal VAS (0 no activity; 100 maximum activity 
for both VAS); (2) parent/child ratings of well-being and pain, assessed on a 21-Numbered 
Circle and 100-Millimeter Horizontal Line Visual Analog Scales4; (3) number of active joints, 
assessed in 71, 27, or 10 joints (JADAS 71, JADAS 27, and JADAS 10, respectively); and 
(4) CRP was truncated to a 0 scale according to the following formula: (CRP [mg/L]-10/10), 
similar to the truncated ESR used in JADAS-ESR. Before calculation, CRP values <10 mg/L are
converted to 10 and CRP values >110 mg/L are converted to 110.13
The JADAS is calculated as the sum of the scores of its 4 components, which yields a global 
score of 0 to 101, 0 to 57, and 0 to 40 for the JADAS 71, and JADAS 27, and JADAS 10,
respectively.
The state of JADAS 10, 27, and 71 minimal disease activity2,11 was defined as the presence of all 
of the following: Physician Global Assessment of Disease Activity of ≤3.5, parent’s global rating 
of well-being of ≤2.5, and swollen joint count of ≤1 in patients with polyarthritis.
The criteria for JADAS inactive disease is defined as a total JADAS score of ≤1.
9.2.2.
Endpoints
Primary Endpoint
The primary endpoint in this study is PK exposure at Week 28 (the trough concentrations at 
Week 28) and the Bayesian AUCss over one dosing interval of 8 weeks (from population PK 
modeling and simulation).
Major Secondary Endpoints
Major secondary endpoints include:

PK exposure at Week 52 (the trough concentrations at Week 52) and the Bayesian AUCss at 
Week 52 (from population PK modeling and simulation)
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Other Endpoints
Other endpoints include:

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders over time

The change from baseline in CHAQ over time

CRP concentrations over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA over time

The improvement from baseline in the pJIA core set at each visit

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by disease 
subtype, and/or age over time through Week 52

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease activity over 
time
9.3.
Pharmacokinetics and Immunogenicity
9.3.1.
Evaluations
Serum samples will be used to evaluate the PK, as well as the immunogenicity of golimumab 
(antibodies to golimumab). Venous blood samples will be collected and each serum sample will 
be divided into 3 aliquots (1 each for pharmacokinetics, antibodies to study drug, and a back-up).
Subject confidentiality will be maintained. The sample should be drawn from a different arm 
than the IV line, or if using an IV line that is also being used to deliver medication, the line 
should be flushed and cleared of any residual medication that may be remaining prior to each PK 
sample being drawn. When using an IV line to draw PK samples, the first 1 mL of blood should 
be drawn and discarded prior to obtaining the sample. Intravenous line maintenance should be 
followed as per the standard of care. At visits where serum concentration and antibodies to 
golimumab will be evaluated, 1 blood draw of sufficient volume can be used.
9.3.2.
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of golimumab using a validated, 
specific, and sensitive method by or under the supervision of the Sponsor.
Immunogenicity
The detection and characterization of antibodies to golimumab will be performed using a 
validated assay method by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to golimumab will also be evaluated for golimumab serum concentration 
to enable interpretation of the antibody data.
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9.3.3.
Pharmacokinetic Parameters
Serum golimumab concentrations will be evaluated at Weeks 0, 4, 8, 12, 20, 28, 52, 100, 148, 
196, and 244 and summarized over time.
Pre-infusion (immediately before infusion) and post-infusion (1 hour after infusion) samples will 
be drawn at Weeks 0, 4, and 12, and an additional random population PK sample will be drawn 
at any time between Weeks 0 and 8 other than at the time of the Week 0, Week 4, and Week 8 
visits and collected at least 24 hours prior to or after study agent administration. For each of the 
remaining visits, only 1 sample for serum golimumab will be collected, which should be 
collected prior to the infusion if an infusion of the study agent is administered at that visit. 
Post-infusion samples should be drawn from a different arm than the IV infusion line, or the 
IV infusion line must be flushed and cleared of any residual medication that may be remaining 
and 1 mL of blood should be drawn and discarded prior to obtaining the sample if using the same 
access line as was used for drug administration.
A population PK analysis with data through Week 28 will be performed to characterize the PK of 
golimumab as well as to identify important covariates of PK in the pediatric population with 
pJIA. Additionally the population PK model will be used to assess the similarity of the PK in 
pediatrics and adults. The clearance and volume of distribution will be estimated using a 
NONMEM approach. In addition, an exposure-response analysis will be performed to explore 
and characterize the relationship between exposure and efficacy.
9.3.4.
Immunogenicity Assessments (Antibodies to Golimumab)
Antibodies to golimumab will be evaluated in serum samples collected from all subjects 
according to the Time and Events Schedule (ie, Weeks 0, 4, 8, 12, 28, 52, 100, 148, 196, and 
244). Additionally, serum samples should also be collected at the final visit from subjects who 
are discontinued from treatment or withdrawn from the study. These samples will be tested by 
the Sponsor or Sponsor's designee.
Serum samples will be screened for antibodies binding to golimumab and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to golimumab and/or further characterize the immunogenicity of golimumab.
The incidence of antibodies to golimumab during the study will be determined.
9.4.
Safety Evaluations
Any clinically relevant changes occurring during the study must be recorded on the Adverse 
Event section of the CRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator until resolution or until a clinically stable endpoint is reached.
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the Time and Events Schedules:
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Adverse Events
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the subject's legally acceptable representative) for the duration of the study. Adverse events 
will be followed by the investigator as specified in Section 12, Adverse Event Reporting.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory report, document this review, and record any clinically relevant changes 
occurring during the study in the adverse event section of the CRF. The laboratory reports must 
be filed with the source documents.
The following tests will be performed by the central laboratory:

Hematology Panel
-hemoglobin
-WBC (neutrophils, lymphocytes, monocytes, 
eosinophils, basophils [%, absolute])
-hematocrit
-platelet count
-RBC 
-mean corpuscular volume
-mean corpuscular hemoglobin 
-mean corpuscular hemoglobin concentration 
-RBC morphology
-WBC morphology (if present)

Serum Chemistry Panel
-sodium
-total bilirubin
-potassium
-bilirubin (direct and indirect)
-urea nitrogen 
-calcium
-creatinine
-phosphorous
-glucose 
-albumin
-AST 
-total protein
-ALT 
-alkaline phosphatase
-uric acid
-bicarbonate
-chloride

Serum pregnancy testing for girls of childbearing potential will be conducted at screening.

Urine pregnancy testing for girls of childbearing potential will be performed according to 
the Time and Events Schedules.

Additional serum or urine pregnancy tests may be performed, as determined necessary by 
the investigator or required by local regulation, to establish the absence of pregnancy 
throughout the study.

Serology for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), 
and hepatitis B core antibody (anti-HBc total) at screening.

Serology for HCV antibody at screening.
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Vital Signs
Pulse/heart rate, respiratory rate, temperature, and blood pressure measurements will be 
performed according to the Time and Events Schedules (Table 1, Table 2, and Table 3).
Vital signs should be taken pre-infusion; at 15 and 30 minutes (15-minute intervals during the 
infusion); and at 60 and 90 minutes (during the 1-hour observation period following the infusion)
through Week 52. After Week 52, vital signs should be taken at the discretion of the investigator.
Physical Examination
Physical examinations, including a skin exam at every physical examination and Tanner staging
for sexual maturity will be performed (through Week 52 only) according to the Time and Events 
Schedule. Review of systems will be performed at all visits through Week 52 to evaluate for new 
symptomatology and if necessary, full physical examination may be performed at investigator 
discretion. After Week 52, review of systems will be performed at investigator discretion. Any 
clinically significant abnormalities persisting at the end of the study will be followed by the 
investigator until resolution or until reaching a clinically stable endpoint.
Height and Body Weight
Height will be measured at screening, and all timepoints specified in the Time and Events 
Schedule. Weight will be measured at the timepoints specified in the Time and Events Schedule, 
using a calibrated scale at each weight measurement. Subjects will be instructed to remove shoes 
and outdoor apparel and gear.
Uveitis Evaluations
All subjects will be assessed for new-onset uveitis at screening and at least every 6 months 
through Week 52 by the investigator based on physical examination and interview. After
Week 52, uveitis evaluations will be performed at investigator discretion. This consists of an 
assessment of signs and symptoms of uveitis, including, but not limited to, eye redness, light 
sensitivity, changes in vision, and floaters. 
In addition, all subjects are required to have slit lamp evaluations performed by an 
ophthalmologist/optometrist through Week 52 at intervals (based on JIA subtype, ANA test 
results, age at JIA onset, and JIA duration) as specified in Attachment 5. After Week 52, slit 
lamp evaluations will be performed at the discretion of the investigator and per standard of care.
If a subject develops uveitis during the study, the subject’s continued participation in the study is 
at the discretion of the investigator and Sponsor.
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Infusion Reaction Evaluations
Before an infusion is started, the appropriate personnel, medications (eg, epinephrine, inhaled 
beta agonists, antihistamines and corticosteroids), and other requirements to treat anaphylaxis 
should be available. The subject may be premedicated with prophylactic drugs 
(eg, diphenhydramine) prior to starting the infusion based on investigator’s discretion but this is 
not mandatory. However, corticosteroids for prophylaxis are not allowed. Premedications should 
be recorded in the eCRF.
The investigator or qualified designee will evaluate the subject for infusion reactions according 
to the Time and Events Schedule.
An infusion reaction is any unfavorable or unintended sign that occurs during the infusion or 
within 1 hour of completion of the infusion. All subjects must be carefully observed for 
symptoms of an infusion reaction. Through Week 52, subjects will be observed for at least 
60 minutes after completion of the IV administration of study agent for symptoms of an infusion 
reaction. After Week 52, subjects will be observed at the discretion of the investigator after 
completion of the IV administration of study agent for symptoms of an infusion reaction. If an 
infusion reaction is observed, the subject should be treated at the investigator’s discretion.
The investigator will record the infusion reaction in the AE page. If no infusion reaction is 
observed, the investigator will note this in the subject’s medical records (source data).
Allergic Reactions
Through Week 52, all subjects must be observed carefully for symptoms of an allergic reaction 
(eg, urticaria, itching, hives) for at least 60 minutes after the completion of the infusion. After 
Week 52, subjects must be observed carefully for symptoms of an allergic reaction at the 
discretion of the investigator after completion of the infusion. If mild or moderate allergic 
reaction is observed, acetaminophen or NSAIDs and diphenhydramine at approved pediatric
doses may be administered.
Subjects with severe reactions following an infusion that result in bronchospasm with 
wheezing and/or dyspnea and require ventilatory support, or symptomatic hypotension 
with a decrease in systolic blood pressure greater than 40 mm mercury (Hg), will not be 
permitted to receive any additional study agent infusions. In the case of such reactions, 
appropriate medical treatment should be administered.
Early Detection of Active Tuberculosis
To aid in the early detection of TB, reactivation, or new TB infection during study participation, 
subjects must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
Time and Events Schedule) or by telephone contact approximately every 8 to 12 weeks through 
Week 252. After Week 252, TB evaluation will be carried out at investigator discretion and 
according to local and country guidelines for immunosuppressed patients. The following series 
of questions is suggested for use during the evaluation.
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
“Has your child had a new cough of >14 days’ duration or a change in a chronic cough?”

“Has your child had any of the following symptoms”:

Persistent fever?

Unintentional weight loss?

Night sweats?”

“Has your child had close contact with an individual with active TB?” (If there is 
uncertainty as to whether a contact should be considered “close,” a physician specializing in 
TB should be consulted.)
If the evaluation raises suspicion that a subject may have TB reactivation or new TB infection, 
study agent administration should be interrupted and an immediate and thorough investigation 
should be undertaken, including, where possible, consultation with a physician specializing in 
TB.
Investigators should be aware that TB reactivation in immunocompromised subjects may present 
as disseminated disease or with extrapulmonary features. Subjects with evidence of active TB 
must immediately discontinue study agent and should be referred for appropriate treatment.
QuantiFERON®-TB Gold (and tuberculin skin) testing at Week 52 is not required for subjects 
with a history of latent TB, and ongoing treatment for latent TB, or documentation of having 
completed adequate treatment for TB. After Week 52, testing for latent TB should be performed 
at the discretion of the investigator and according to local and country guidelines.
Subjects who experience close contact with an individual with active TB during the conduct of 
the study should have a repeat chest radiograph, a repeat QuantiFERON®-TB Gold test, a repeat 
tuberculin skin test in countries in which the QuantiFERON®-TB Gold test is not
approved/registered, and, if possible, referral to a physician specializing in TB to determine the 
subject’s risk of developing active TB and whether treatment for latent TB is warranted. The 
QuantiFERON®-TB Gold test (and tuberculin skin test) does not need to be repeated for subjects 
with a history of latent TB, and ongoing treatment for latent TB, or documentation of having 
completed adequate treatment for TB. If the QuantiFERON®-TB Gold test result is 
indeterminate, the test should be repeated as outlined in Section 9.1.2. Subjects should be 
encouraged to return for all subsequent scheduled study visits according to the protocol.
9.5.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory 
requisition form.
Refer to the Time and Events Schedule for the timing and frequency of all sample collections.
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Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
10.
SUBJECT COMPLETION/WITHDRAWAL
Subject completion/withdrawal during the ETP is described in Attachment 6.
10.1.
Completion
A subject will be considered to have completed the main study if he or she has completed 
assessments at Week 52. A subject will be considered to have completed the LTE if he or she has
completed assessments at Week 252.
10.2.
Discontinuation of Study Treatment
If a subject's study treatment must be discontinued before the end of the treatment regimen, this 
will not result in automatic withdrawal of the subject from the study.
A subject's study treatment should be permanently discontinued if any of the following occur:

The investigator believes that for safety reasons (eg, adverse event) it is in the best interest 
of the subject to discontinue study treatment.

The subject becomes pregnant.

Reaction resulting in bronchospasm (both new-onset study agent-related and severe 
exacerbation of pre-existing asthma) with and without wheezing, and/or dyspnea requiring 
ventilatory support, and/or symptomatic hypotension that occurs following a study agent 
administration.

Reaction resulting in myalgia and/or arthralgia with fever and/or rash (suggestive of serum 
sickness and not representative of signs and symptoms of other recognized clinical 
syndromes) occurring 1 to 14 days after an infusion of study agent. These may be 
accompanied by other events including pruritus, facial, hand, or lip edema, dysphagia, 
urticaria, sore throat, and/or headache.

Opportunistic infection.

Malignancy.

The subject develops congestive heart failure at any time during the trial.

Demyelinating disease.

The subject withdraws consent for administration of study agent.

The initiation of protocol-prohibited medications.
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
Subject is deemed ineligible according to the following TB screening criteria.

A diagnosis of active TB is made.

A subject has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination, or has had recent close contact with a person 
with active TB, and cannot or will not continue to undergo additional evaluation.

A subject undergoing evaluation has a chest radiograph with evidence of current active 
TB and/or a positive QuantiFERON®-TB Gold test result (or a positive tuberculin skin 
test result in countries in which the QuantiFERON®-TB Gold test is not 
approved/registered or the tuberculin skin test is mandated by local Health Authorities), 
unless active TB can be ruled out and appropriate treatment for latent TB can be 
initiated prior to the next administration of study agent and continued to completion. 
Indeterminate QuantiFERON®-TB Gold test results should be handled as in 
Section 9.1.2. Subjects with persistently indeterminate QuantiFERON®-TB Gold test 
results may continue without treatment for latent TB if active TB is ruled out, their 
chest radiograph shows no abnormality suggestive of TB (active or old, inactive TB) 
and the subject has no additional risk factors for TB as determined by the investigator. 
This determination must be promptly reported to the Sponsor’s medical monitor and 
recorded in the subject's source documents and initialed by the investigator.

A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliant with the therapy.
All subjects who discontinue study agent infusions during the study will be followed for 
approximately 8 weeks after the last infusion is administered.
Note: The visit that is approximately 8 weeks after the last study agent infusions is referred 
to as the “final safety follow-up visit,” which may occur at a scheduled or an unscheduled 
visit.
Subjects who discontinue study agent infusions but do not terminate study participation will have 
the following assessments performed at the final safety follow-up visit:

Safety evaluation including AE review, TB evaluation, and the collection of a blood sample 
for routine laboratory analyses, determination of the presence of ANA/anti-double-stranded 
deoxyribonucleic acid (dsDNA) antibodies, and antibodies to golimumab; after Week 52, 
other safety evaluations are performed at the discretion of the investigator (vital signs, 
review of systems, uveitis evaluation).

Concomitant medication review (after Week 52, medications should be reviewed and
documented in subject’s source records; medications used to treat or associated with AEs 
and SAEs should be recorded in the source document as well as the CRF).

Efficacy evaluations (joint assessments, JIA assessments, and collection of blood sample for 
CRP) through Week 52 only.

Blood samples drawn for measurement of golimumab concentration for all subjects at the 
final safety follow-up visit.
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If a subject discontinues study treatment before the end of the study, assessments should be 
obtained approximately 8 weeks after the last infusion of study agent.
10.3.
Withdrawal from the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death
If a subject discontinues study treatment before the end of the study, end-of-treatment 
assessments should be obtained approximately 8 weeks after the last infusion of study agent at 
the final safety follow-up visit.
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken to follow-up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study drug assigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw will not be replaced.
If a subject withdraws from the study before the end of the study, end-of-treatment assessments 
should be obtained prior to the withdrawal of consent.
11.
STATISTICAL METHODS
Statistical analysis will be done by the Sponsor or under the authority of the Sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan.
In general, descriptive statistics, such as mean, median, standard deviation, interquartile range, 
minimum and maximum for continuous variables, and counts and percentages for categorical 
variables will be used to summarize data.
11.1.
Subject Information
All subjects who are enrolled in the study will have baseline descriptive statistics provided.
Subject baseline data, demographic and baseline disease characteristics will be summarized. The 
baseline measurement is defined as the closest measurement taken before the time of the Week 0 
study agent administration.
Demographics and subject baseline disease characteristics and prior medication data will be 
summarized for all subjects who have been enrolled in the study, whether or not they have 
received study agent administration. Pharmacokinetic data will be summarized for all subjects 
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who had received at least 1 administration of study agent. Efficacy analyses will be summarized 
for all subjects enrolled in the study unless otherwise specified. Safety assessments will be 
summarized for all treated subjects.
11.2.
Sample Size Determination
The sample size determination is not based on statistical considerations. For the purpose of 
determining sample size of this study, the variability of PK in pediatric populations was 
considered. The goal is to have a sample size that will be sufficient to build a population PK and,
if feasible, an exposure-response model. Additionally, a sample size that will provide reasonable 
safety assessments was also taken into consideration. With these considerations, a sample size of 
approximately 120 subjects has been chosen assuming that if 20 subjects were to drop out or if 
they do not provide PK samples, a sample size of approximately 100 subjects is thought to be 
sufficient to build a population PK model, given the sparse sampling of PK time points, as well 
as provide 1 year of safety data from approximately 100 subjects.
11.3.
Efficacy Analyses
Primary Endpoint Analysis
No primary efficacy endpoint analysis is planned.
Major Secondary Endpoints Analyses
No major secondary efficacy endpoints analyses are planned.
Other Efficacy Endpoints
The following will be summarized for all subjects enrolled in the study:

The proportion of subjects who are JIA ACR 30, 50, 70, and 90 responders over time

The proportion of subjects who have inactive disease over time

The proportion of subjects in clinical remission on medication for pJIA (ACR criteria) over 
time

The improvement from baseline in the pJIA core set over time

The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by disease 
subtype, and/or age over time through Week 52

The change from baseline in CHAQ over time

CRP concentrations over time

The change from baseline in JADAS 10, 27, and 71 scores over time

The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease activity over 
time
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11.4.
Pharmacokinetic Analyses
The primary objective of this study is to characterize golimumab PK exposure (the trough 
concentrations at Weeks 28 and the Bayesian AUCss over a dosing interval of 8 weeks from 
population PK modeling and simulation) in the pJIA population.
Serum golimumab concentrations will be summarized over time. In addition, a population PK 
analysis on data through Week 28 will be performed to characterize the PK of golimumab as 
well as to identify and quantify important covariates of PK in the pediatric population with pJIA. 
Clearance and volume of distribution will be estimated using a NONMEM approach. Details will
be provided in a population PK analysis plan and the results of the analysis will be presented in a 
separate report.
Measures of PK exposure will be graphically evaluated in the pediatric populations after 
administration of IV golimumab (including but not limited to steady-state Cmax, Cmin and AUC) 
and compared to PK exposure from adults in CNTO148ART3001. Similarity between pediatric 
and adult subjects will be assessed by the generation of box plots from the population PK 
modeling via visual inspection in addition to the descriptive statistics of the observed 
concentrations.
Summary golimumab concentrations will be summarized and PK exposure will be evaluated 
through Week 52 and through the LTE.
11.5.
Immunogenicity Analyses
The occurrence and titers of antibodies to golimumab during the study will be summarized over 
time for all subjects who receive an administration of golimumab and have appropriate samples 
collected for detection of antibodies to golimumab (ie, subjects with at least 1 sample obtained 
after their first golimumab administration).
11.6.
Pharmacokinetic/Pharmacodynamic Analyses
The relationships between serum golimumab concentration and efficacy will be explored. A
suitable PK/PD model will be explored and developed to describe the exposure-response 
relationship.
11.7.
Safety Analyses
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). All reported adverse events 
with onset during the treatment phase (ie, treatment-emergent adverse events, and adverse events 
that have worsened since baseline) will be included in the analysis. For each adverse event, the 
percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group.
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Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue treatment due to an adverse event, or who experience a severe 
or a serious adverse event.
The following analyses will be used to assess the safety of subjects in this trial:

The occurrence and type of AEs

The occurrence and type of SAEs

The occurrence and type of reasonably related AEs

The occurrence of infusion reactions

The occurrence of ANA and anti-dsDNA antibodies

The occurrence of antibodies to golimumab

The occurrence of markedly abnormal laboratory (hematology and chemistry) parameters
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly 
abnormal results (specified in the Statistical Analysis Plan) will be used in the summary of 
laboratory data. Changes from baseline results will be presented in pre- versus posttreatment
cross-tabulations (with classes for below, within, and above normal ranges). Frequency 
tabulations of the abnormalities will be made. A listing of subjects with any markedly abnormal 
laboratory results will also be provided.
Vital Signs
Descriptive statistics of pulse/heart rate, respiratory rate, temperature, and blood pressure 
(systolic and diastolic) values and changes from baseline will be summarized at each scheduled 
time point in the Schedule of Events.
11.8.
Interim Analysis
No interim analysis is planned.
11.9.
Data Monitoring Committee
This is an open-label study, with all subjects receiving the same dosage of IV golimumab. 
Therefore, an external Data Monitoring Committee will not be utilized. Safety data will be 
routinely evaluated by the study’s medical monitor and Sponsor’s internal Safety Management 
Team as needed. In addition, the data may be reviewed by the Steering Committee.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the Sponsor, and are mandated by 
regulatory agencies worldwide. The Sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
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information; all clinical studies conducted by the Sponsor or its affiliates will be conducted in 
accordance with those procedures.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. An adverse event can therefore be any unfavorable
and unintended sign (including an abnormal finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational or non-investigational) product, whether or not 
related to that medicinal (investigational or non-investigational) product. (Definition per 
International Conference on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The Sponsor collects adverse events starting with the signing of the ICF (refer to 
Section 12.3.1, All Adverse Events, for time of last adverse event recording).
Serious Adverse Event
An SAE based on ICH and European Union Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life threatening (The subject was at risk of death at the time of the event. It does not refer 
to an event that hypothetically might have caused death if it were more severe)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious.
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If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study drug and the event (eg, death from anaphylaxis), the event must 
be reported as a serious and unexpected suspected adverse reaction even if it is a component of 
the study endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For golimumab, the expectedness of an adverse 
event will be determined by whether or not it is listed in the Investigator's Brochure.
For MTX, which has a marketing authorization, the expectedness of an adverse event will be 
determined by whether or not it is listed in the package label supplied by the drug’s manufacturer 
in that country.
Adverse Event Associated With the Use of the Drug
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable, or very likely by the definitions listed in Section 12.1.2.
12.1.2.
Attribution Definitions
Not Related
An adverse event that is not related to the use of the drug.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant drug(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An adverse event that might be due to the use of the drug. An alternative explanation, 
eg, concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the drug. The relationship in time is suggestive 
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant 
drug(s), concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship 
in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
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12.1.3.
Severity Criteria
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
12.2.
Special Reporting Situations
Safety events of interest on a Sponsor study drug that may require expedited reporting and/or 
safety evaluation include, but are not limited to:

Overdose of a Sponsor study drug

Suspected abuse/misuse of a Sponsor study drug

Inadvertent or accidental exposure to a Sponsor study drug

Any failure of expected pharmacologic action (ie, lack of effect) of a Sponsor study drug

Unexpected therapeutic or clinical benefit from use of a Sponsor study drug

Medication error involving a Sponsor product (with or without subject/patient exposure to 
the Sponsor study drug, eg, name confusion)
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the CRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All adverse events and special reporting situations, whether serious or non-serious, will be 
reported from the time a signed and dated ICF is obtained until completion of the subject's last 
study-related procedure (which may include contact for follow-up of safety). Serious adverse 
events, including those spontaneously reported to the investigator within 30 days of the end of 
the study, must be reported using the Serious Adverse Event Form. The Sponsor will evaluate 
any safety information that is spontaneously reported by an investigator beyond the time frame 
specified in the protocol.
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All events that meet the definition of a serious adverse event will be reported as serious adverse 
events, regardless of whether they are protocol-specific assessments. Anticipated events will be 
recorded and reported as described in Attachment 4.
All adverse events, regardless of seriousness, severity, or presumed relationship to study drug, 
must be recorded using medical terminology in the source document and the CRF. Whenever 
possible, diagnoses should be given when signs and symptoms are due to a common etiology 
(eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper 
respiratory infection"). Investigators must record in the CRF their opinion concerning the 
relationship of the adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to Sponsor
instructions.
The Sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory 
authorities. The Sponsor will also report to the investigator (and the head of the investigational
institute where required) all serious adverse events that are unlisted (unexpected) and associated 
with the use of the study drug. The investigator (or Sponsor where required) must report these 
events to the appropriate Independent Ethics Committee/Institutional Review Board (IEC/IRB) 
that approved the protocol unless otherwise required and documented by the IEC/IRB.
For all studies with an outpatient phase, including open-label studies, the subject must be 
provided with a "wallet (study) card" and instructed to carry this card with them for the duration 
of the study indicating the following:

Study number

Statement, in the local language(s), that the subject is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local Sponsor's name and 24-hour contact telephone number (for medical staff only)

Site number

Subject number

Any other information that is required to do an emergency breaking of the blind
12.3.2.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate 
Sponsor contact person by study site personnel within 24 hours of their knowledge of the event.
Information regarding serious adverse events will be transmitted to the Sponsor using the Serious 
Adverse Event Form, which must be completed and signed by a physician from the study site, 
and transmitted to the Sponsor within 24 hours. The initial and follow-up reports of a serious 
adverse event should be made by facsimile (fax).
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All serious adverse events that have not resolved by the end of the study, or that have not 
resolved upon discontinuation of the subject's participation in the study, must be followed until 
any of the following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study drug or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a 
serious adverse event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a subject's participation in a study must be reported as a serious 
adverse event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the CRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not 
be considered serious adverse events. Any adverse event that results in a prolongation of the 
originally planned hospitalization is to be reported as a new serious adverse event.
The cause of death of a subject in a study within 2 months of the last dose of study drug, whether 
or not the event is expected or associated with the study drug, is considered a serious adverse 
event.
12.3.3.
Pregnancy
All initial reports of pregnancy must be reported to the Sponsor by the study site personnel
within 24 hours of their knowledge of the event using the appropriate pregnancy notification 
form. Abnormal pregnancy outcomes (eg, spontaneous abortion, stillbirth, and congenital 
anomaly) are considered serious adverse events and must be reported using the Serious Adverse 
Event Form. Any subject who becomes pregnant during the study must discontinue further study 
treatment.
Because the effect of the study drug on sperm is unknown, pregnancies in partners of male subjects 
included in the study will be reported by the study site personnel within 24 hours of their 
knowledge of the event using the appropriate pregnancy notification form.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
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12.4.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of 
study agent(s) in subjects participating in this clinical study must be reported by the investigator 
according to the procedures in Section 12.3. Investigators are also advised that active TB is 
considered a reportable disease in most countries. These events are to be considered serious only 
if they meet the definition of a serious adverse event.
12.5.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed on the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of subjects, investigators, 
and the Sponsor, and are mandated by regulatory agencies worldwide. The Sponsor has 
established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the Sponsor or its affiliates 
will be conducted in accordance with those procedures.
13.1.
Procedures
All initial PQCs must be reported to the Sponsor by the study site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with a serious adverse event, the study site personnel must report the 
PQC to the Sponsor according to the serious adverse event reporting timelines (refer to 
Section 12.3.2, Serious Adverse Events). A sample of the suspected product should be
maintained for further investigation if requested by the Sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed on the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug
The test product, golimumab, will be supplied as a sterile liquid for IV infusion at a volume of 
4 mL (50 mg, 12.5 mg/mL) in single-use vials. Each vial will contain golimumab in an aqueous 
medium of histidine, sorbitol and polysorbate 80 at pH 5.5. No preservatives are present. It will 
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be manufactured and provided under the responsibility of the Sponsor. Refer to the Investigator's 
Brochure for a list of excipients.
MTX (oral or injectable) will not be supplied by the Sponsor but rather must be acquired from a 
commercial pharmacy.
14.2.
Packaging
The study drug will be packaged in individual subject kits. Each kit will consist of a single vial
packaged within a carton. The packaging is not child-resistant. Both vials and cartons will have a 
booklet label containing local language translations as required for participating countries.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage
Liquid study agent in glass vials will be supplied ready to use. At the study site, vials of 
golimumab solution must be stored in a secured refrigerator at controlled temperatures ranging 
from 2°C to 8°C (35.6°F to 46.4°F).
The study agent IV infusions will be prepared according to the subject’s BSA. Details on the 
preparation and storage of study material are provided in the Pharmacy Manual.
Preparation, handling, and storage of study agent during the ETP is described in Attachment 6.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. The study drug administered to the subject must be 
documented on the drug accountability form. All study drug will be stored and disposed of 
according to the Sponsor's instructions. Study site personnel must not combine contents of the 
study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study drug must be available for verification by the Sponsor's 
study site monitor during on-site monitoring visits. The return to the Sponsor of unused study 
drug will be documented on the drug return form. When the study site is an authorized 
destruction unit and study drug supplies are destroyed on-site, this must also be documented on 
the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes.
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Study drug should be dispensed under the supervision of the investigator or a qualified member 
of the study site personnel, or by a hospital/clinic pharmacist. Study drug will be supplied only to 
subjects participating in the study. Returned study drug must not be dispensed again, even to the 
same subject. Study drug may not be relabeled or reassigned for use by other subjects. The 
investigator agrees neither to dispense the study drug from, nor store it at, any site other than the 
study sites agreed upon with the Sponsor.
Drug accountability during the ETP is described in Attachment 6.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with at least the following supplies:

Investigator Brochure

Trial Center File

Investigational Product Manual

Laboratory manual and laboratory supplies

ePRO device and user manual

Interactive voice/web response system manual

Electronic data capture (eDC) Manual (including on-line access)

Sample ICF and sample assent form

Subject participation cards (ie, wallet cards)
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the 
study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits, and 
potential adverse events of the study, and provide their consent voluntarily will be enrolled.
When referring to the signing of the ICF, the terms legal guardian and legally acceptable 
representative refer to the legally appointed guardian of the child with authority to authorize 
participation in research. For each subject, his or her parent(s) (preferably both parents, if 
available) or a legally acceptable representative(s), as required by local regulations, must give 
written consent (permission) according to local requirements after the nature of the study has been 
fully explained and before the performance of any study-related assessments. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically subjects 
7 years of age and older, depending on the institutional policies. For the purposes of this study, all 
references to subjects who have provided consent (and assent as applicable) refers to the subjects 
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and his or her parent(s) or the subject's legal guardian(s) or legally acceptable representative(s) 
who have provided consent according to this process. Minors who assent to a study and later 
withdraw that assent should not be maintained in the study against their will, even if their parents 
still want them to participate.
The total blood volume to be collected is considered to be normal for this study population
(ie, pediatric subjects with >15kg body weight) and does not exceed >1% of the subject’s blood 
volume per visit.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or Sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the Sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the ICF, applicable recruiting materials, and 
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subject compensation programs, and the Sponsor has received a copy of this approval. This 
approval letter must be dated and must clearly identify the IEC/IRB and the documents being 
approved.
During the study the investigator (or Sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the Sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of adverse events that are serious, unlisted/unexpected, and associated with the 
study drug

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study. The 
reapproval should be documented in writing (excluding the ones that are purely administrative, 
with no consequences for subjects, data, or study conduct).
At the end of the study, the investigator (or Sponsor where required) will notify the IEC/IRB 
about the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
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16.2.3.
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF(s) and assent form that are used must 
be approved by both the Sponsor and by the reviewing IEC/IRB and be in a language that the 
subject can read and understand. The informed consent should be in accordance with principles 
that originated in the Declaration of Helsinki, current ICH and GCP guidelines, applicable 
regulatory requirements, and Sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed 
that choosing to not participate will not affect the care the subject will receive for the treatment 
of his or her disease. Subjects will be told that alternative treatments are available if they refuse 
to take part and that such refusal will not prejudice future treatment. Finally, they will be told 
that the investigator will maintain a subject identification register for the purposes of long-term 
follow-up if needed and that their records may be accessed by Health Authorities and authorized 
Sponsor personnel without violating the confidentiality of the subject, to the extent permitted by 
the applicable law(s) or regulations. By signing the ICF the subject or legally acceptable 
representative is authorizing such access, including permission to obtain information about his or
her survival status, and agrees to allow his or her study physician to recontact the subject for the 
purpose of obtaining consent for additional safety evaluations, if needed, and subsequent disease
related treatments, or to obtain information about his or her survival status.
The subject or legally acceptable representative will be given sufficient time to read the ICF and 
the opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
Children (minors) or subjects who are unable to comprehend the information provided can be 
enrolled only after obtaining consent of a legally acceptable representative. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically 
subjects 7 years of age and older, depending on the institutional policies. Written assent should 
be obtained from subjects who are able to write. A separate assent form written in language the 
subject can understand should be developed for adolescents. After having obtained the assent, a 
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copy of the assent form must be given to the subject, and to the subject's parent and/or legally 
acceptable representative.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative)
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for study-
related monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also 
addresses the transfer of the data to other entities and to other countries.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 2 years (or according to local regulations) 
for additional research. Samples will only be used to understand golimumab, to understand pJIA, 
to understand differential drug responders, and to develop tests/assays related to SIMPONI for 
IV use and pJIA. The research may begin at any time during the study or the post-study storage 
period.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for research.
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product.
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17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the Sponsor will modify this protocol without a formal amendment
by the Sponsor. All protocol amendments must be issued by the Sponsor, and signed and dated 
by the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
Sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IRB (and IEC where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate Sponsor
representative (see Contact Information page(s) provided separately). Except in emergency 
situations, this contact should be made before implementing any departure from the protocol. In 
all cases, contact with the Sponsor must be made as soon as possible to discuss the situation and 
agree on an appropriate course of action. The data recorded in the CRF and source documents 
will reflect any departure from the protocol, and the source documents will describe this 
departure and the circumstances requiring it.
17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the Sponsor before shipment of study drug to the 
study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approval must clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study site personnel is a member of the IEC/IRB, documentation must be 
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obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The following documents must be provided to the Sponsor before enrollment of the first subject:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable

Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable
17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
Sponsor study site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth. In cases where the subject is not enrolled into the study, the date seen and date 
of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
At a minimum, source documentation must be available for the following to confirm data 
collected in the CRF: subject identification, eligibility, and study identification; study discussion 
and date of signed informed consent; dates of visits; results of safety and efficacy parameters as 
required by the protocol; record of all adverse events and follow-up of adverse events; 
concomitant medication; drug receipt/dispensing/return records; study drug administration 
information; and date of study completion and reason for early discontinuation of study drug or 
withdrawal from the study, if applicable.
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In addition, the author of an entry in the source documents should be identifiable.
At a minimum, the type and level of detail of source data available for a subject should be 
consistent with that commonly recorded at the study site as a basis for standard medical care. 
Specific details required as source data for the study will be reviewed with the investigator 
before the study and will be described in the monitoring guidelines (or other equivalent 
document).
The following data (at a minimum) will be recorded directly into the CRF and will be considered 
source data where allowed by country regulations:

Race

History of smoking and all nicotine use (eg, cigarettes, cigars, chewing tobacco, patch, gum)

Blood pressure, pulse/heart rate, temperature, and respiratory rate

Height and weight

Details of physical examination

The following parent/subject- and investigator-completed scales and assessments designated 
by the Sponsor will be recorded directly into an electronic device and will be considered 
source data: joint assessments, CHAQ, Physician Global Assessment of Disease Activity, 
and duration of morning stiffness. These assessments should not be recorded on paper first.
The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
17.5.
Case Report Form Completion
Case report forms are provided for each subject in electronic format.
Electronic Data Capture (eDC) will be used for this study. The study data will be transcribed by 
study site personnel from the source documents onto an electronic CRF, and transmitted in a 
secure manner to the Sponsor within the timeframe agreed upon between the Sponsor and the 
study site. The electronic file will be considered to be the CRF.
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Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the subject's source documentation. All data relating to the 
study must be recorded in CRFs prepared by the Sponsor. Data must be entered into CRFs in 
English. Study site personnel must complete the CRF as soon as possible after a subject visit, and 
the forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever 
possible. The investigator must verify that all data entries in the CRFs are accurate and correct.
All CRF entries, corrections, and alterations must be made by the investigator or other authorized 
study site personnel. If necessary, queries will be generated in the eDC tool. The investigator or 
study site personnel must adjust the CRF (if applicable) and complete the query.
If corrections to a CRF are needed after the initial entry into the CRF, this can be done in 
3 different ways:

Study site personnel can make corrections in the eDC tool at their own initiative or as a 
response to an auto query (generated by the eDC tool).

Study site manager can generate a query for resolution by the study site personnel.

Clinical data manager can generate a query for resolution by the study site personnel.
17.6.
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study site personnel before the study, and periodic monitoring visits by the Sponsor, and direct 
transmission of clinical laboratory data from a central laboratory, IWRS, and PRO data into the 
Sponsor's data base. Written instructions will be provided for collection, handling, storage, and 
shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study site personnel before 
the start of the study.
The Sponsor will review CRFs for accuracy and completeness during on-site monitoring visits 
and after transmission to the Sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
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The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. It is the responsibility of the Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the Sponsor.
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.8.
Monitoring
The Sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the 
monitor will compare the data entered into the CRFs with the hospital or clinic records (source 
documents). The nature and location of all source documents will be identified to ensure that all 
sources of original data required to complete the CRF are known to the Sponsor and study site 
personnel and are accessible for verification by the Sponsor study site contact. If electronic 
records are maintained at the study site, the method of verification must be discussed with the 
study site personnel.
Direct access to source documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded in the CRF are consistent with the original source data. Findings 
from this review of CRFs and source documents will be discussed with the study site personnel. 
The Sponsor expects that, during monitoring visits, the relevant study site personnel will be 
available, the source documentation will be accessible, and a suitable environment will be 
provided for review of study-related documents. The monitor will meet with the investigator on a 
regular basis during the study to provide feedback on the study conduct.
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17.9.
Study Completion/Termination
17.9.1.
Study Completion
The study is considered completed with the last study assessment for the last subject 
participating in the study. The final data from the study site will be sent to the Sponsor
(or designee) after completion of the final subject assessment at that study site, in the time frame 
specified in the Clinical Trial Agreement.
17.9.2.
Study Termination
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been 
collected and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local Health Authorities, the Sponsor's procedures, or GCP guidelines

Inadequate recruitment of subjects by the investigator

Discontinuation of further study drug development
17.10. On-Site Audits
Representatives of the Sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection and comparison with the CRFs. Subject 
privacy must, however, be respected. The investigator and study site personnel are responsible 
for being present and available for consultation during routinely scheduled study site audit visits 
conducted by the Sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the Sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding golimumab or the Sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the Sponsor to the investigator and not 
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previously published, and any data, including research data, generated as a result of this study, 
are considered confidential and remain the sole property of the Sponsor. The investigator agrees 
to maintain this information in confidence and use this information only to accomplish this 
study, and will not use it for other purposes without the Sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
Sponsor in connection with the continued development of golimumab and thus may be disclosed 
as required to other clinical investigators or regulatory agencies. To permit the information 
derived from the clinical studies to be used, the investigator is obligated to provide the Sponsor
with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the Sponsor and 
will contain CRF data from all study sites that participated in the study, and direct transmission 
of clinical laboratory data from a central laboratory, IWRS, and PRO data into the Sponsor's 
database. Recruitment performance or specific expertise related to the nature and the key 
assessment parameters of the study will be used to determine a coordinating investigator. Results 
of analyses performed after the Clinical Study Report has been issued will be reported in a 
separate report and will not require a revision of the Clinical Study Report. Study subject 
identifiers will not be used in publication of results. Any work created in connection with 
performance of the study and contained in the data that can benefit from copyright protection 
(except any publication by the investigator as provided for below) shall be the property of the 
Sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the Sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the Sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the Sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the Sponsor will review these issues with the investigator. The Sponsor
will not mandate modifications to scientific content and does not have the right to suppress 
information. For multicenter study designs and substudy approaches, secondary results generally 
should not be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 12 months of the availability of the final data (tables, 
listings, graphs), or the Sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
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review of the paper, and given final approval of the final version. PRINTO and PRCSG 
guidelines available on their respective websites should be followed.
Registration of Clinical Studies and Disclosure of Results
The Sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law.
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ATTACHMENT 1 QUANTIFERON®-TB GOLD TESTING
The QuantiFERON®-TB Gold test is one of the interferon-(IFN-based blood assays for TB 
screening (Cellestis, 2009). It utilizes the recently identified M. tuberculosis-specific antigens 
ESAT-6 and CFP-10 in the standard format, as well as TB7.7 (p4) in the In-Tube format, to 
detect in vitro cell-mediated immune responses in infected individuals. The QuantiFERON®-TB 
Gold assay measures the amount of IFN-produced by sensitized T-cells when stimulated with 
the synthetic M. tuberculosis-specific antigens. In M. tuberculosis-infected persons, sensitized 
T lymphocytes will secrete IFN-in response to stimulation with the M. tuberculosis-specific 
antigens and, thus, the QuantiFERON®-TB Gold test should be positive. Because the antigens 
used in the test are specific to M. tuberculosis and not found in BCG, the test is not confounded 
by BCG vaccination, unlike the tuberculin skin test. However, there is some cross-reactivity with 
the 3 Mycobacterium species, M. kansasii, M. marinum, and M. szulgai. Thus, a positive test 
could be the result of infection with one of these 3 species of Mycobacterium, in the absence of 
M. tuberculosis infection.
In a study of the QuantiFERON®-TB Gold test (standard format) in subjects with active TB, 
sensitivity has been shown to be approximately 89% (Mori et al, 2004). Specificity of the test in 
healthy BCG-vaccinated individuals has been demonstrated to be more than 98%. In contrast, the 
sensitivity and specificity of the tuberculin skin test was noted to be only about 66% and 35% in 
a study of Japanese patients with active TB and healthy BCG-vaccinated young adults, 
respectively. However, sensitivity and specificity of the tuberculin skin test depend on the 
population being studied, and the tuberculin skin test performs best in healthy young adults who 
have not been BCG-vaccinated.
Data from a limited number of published studies examining the performance of the 
QuantiFERON®-TB Gold assay in immunosuppressed populations suggest that the sensitivity of 
the QuantiFERON®-TB Gold test is better than the tuberculin skin test even in 
immunosuppressed patients (Ferrara et al, 2005; Kobashi et al, 2007; Matulis et al, 2008). The 
ability of IFN--based tests to detect latent infection has been more difficult to study due to the 
lack of a gold standard diagnostic test; however, several TB outbreak studies have demonstrated 
that the tests correlated better than the tuberculin skin test with the degree of exposure that 
contacts had to the index TB case (Brock et al, 2004; Ewer et al, 2003). In addition, TB contact 
tracing studies have shown that patients who had a positive QuantiFERON®-TB Gold test result 
and were not treated for latent TB infection were much more likely to develop active TB during 
longitudinal follow-up than those who had a positive tuberculin skin test and a negative 
QuantiFERON®-TB Gold test result (Higuchi et al, 2007; Diel et al, 2008).
Although the performance of the new IFN--based blood tests for active or latent M. tuberculosis
infection have not been well validated in the immunosuppressed population, experts believe 
these new tests will be at least as, if not more, sensitive, and definitely more specific, than the 
tuberculin skin test (Barnes, 2004; personal communication, April, 2008 TB Advisory Board).
Performing the QuantiFERON®-TB Gold Test
The QuantiFERON®-TB Gold test In-Tube format will be provided for this study. The In-Tube 
format contains 1 additional M. tuberculosis-specific antigen, TB7.7 (p4), which is thought to 
increase the specificity of the test.
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To perform the test using the In-Tube format, blood is drawn through standard venipuncture into 
supplied tubes that already contain the M. tuberculosis-specific antigens. Approximately 3 tubes 
will be needed per subject, each requiring 1 mL of blood. One tube contains the M. tuberculosis-
specific antigens, while the remaining tubes contain positive and negative control reagents. 
Thorough mixing of the blood with the antigens is necessary prior to incubation. The blood is 
then incubated for 16 to 24 hours at 37°C, after which tubes are centrifuged for approximately 
15 minutes at 2000 to 3000 g. Following centrifugation, plasma is harvested from each tube, 
frozen, and shipped on dry ice to the central laboratory. The central laboratory will perform an 
ELISA to quantify the amount of IFN-present in the plasma using spectrophotometry and 
computer software analysis.
The central laboratory will analyze and report results for each subject, and sites will be informed 
of the results. Under certain circumstances as approved by the Sponsor, a local laboratory may 
be used to process the QuantiFERON®-TB Gold test sample and/or analyze the results.
Subjects who have an indeterminate result should have the test repeated.
Adherence to Local Guidelines
Local country guidelines for immunocompromised patients should be consulted for acceptable 
anti-tuberculous treatment regimens for latent TB. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
In countries in which the QuantiFERON®-TB Gold test is not considered approved/registered, a 
tuberculin skin test is additionally required.
References
Barnes PF. Diagnosing latent tuberculosis infection: Turning glitter to gold [editorial]. Amer J Respir Crit Care 
Med. 2004;170:5-6.
Brock I, Weldingh K, Lillebaek T, et al. Comparison of tuberculin skin test and new specific blood test in 
tuberculosis contacts. Am J Respir Crit Care Med. 2004;170:65-69.
Cellestis. QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube Method package insert. 
Downloaded from www.cellestis.com, February 2009.
Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood IFN-
assay for the development of active tuberculosis disease after recent infection with mycobacterium tuberculosis. Am 
J Respir Crit Care Med. 2008;177:1164-1170.
Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of 
Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet. 2003;361:1168-73.
Ferrara G, Losi M, Meacci M, et al. Routine hospital use of a new commercial whole blood interferon-assay for 
the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2005; 172:631-635.
Higuchi K, Nobuyuki H, Mori T, Sekiya Y. Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a 
high school. Respirology. 2007;12:88-92.
Kobashi Y, Mouri K, Obase Y, et al. Clinical evaluation of QuantiFERON TB-2G test for immunocompromised 
patients. Eur Respir J. 2007; 30:945-950.
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Matulis G, Jüni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with 
autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon assay. Ann 
Rheum Dis. 2008;67:84-90
Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection: An interferon--based assay 
using new antigens. Am J Respir Crit Care Med. 2004;170:59-64.
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ATTACHMENT 2 TUBERCULIN SKIN TESTING
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons 
infected with Mycobacterium tuberculosis. Multiple puncture tests (Tine and Heaf) should not be 
used to determine whether a person is infected because the amount of tuberculin injected 
intradermally cannot be precisely controlled. Tuberculin skin testing is both safe and reliable 
throughout the course of pregnancy. The Mantoux tuberculin test is performed by placing an 
intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm. The test must 
be performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) 
of standard purified protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as 
recommended by the World Health Organization. PPD strengths of 1 TU or 250 TU are not 
acceptable (Menzies, 2000). Using a disposable tuberculin syringe with the needle bevel facing 
upward, the injection should be made just beneath the surface of the skin. This should produce a 
discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter. To prevent needle-
stick injuries, needles should not be recapped, purposely bent or broken, removed from 
disposable syringes, or otherwise manipulated by hand. After they are used, disposable needles 
and syringes should be placed in puncture-resistant containers for disposal. Institutional 
guidelines regarding universal precautions for infection control (eg, the use of gloves) should be 
followed. A trained health care worker, preferably the investigator, should read the reaction to 
the Mantoux test 48 to 72 hours after the injection. Subjects should never be allowed to read their 
own tuberculin skin test results. If a subject fails to show up for the scheduled reading, a positive 
reaction may still be measurable up to 1 week after testing. However, if a subject who fails to 
return within 72 hours has a negative test, tuberculin testing should be repeated. The area of 
induration (palpable raised hardened area) around the site of injection is the reaction to 
tuberculin. For standardization, the diameter of the induration should be measured transversely 
(perpendicular) to the long axis of the forearm. Erythema (redness) should not be measured. All 
reactions should be recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the 
tuberculin skin test is reserved for immunocompromised patients, and this definition is to be 
applied in this study to maximize the likelihood of detecting latent TB, even though the subjects 
may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin 
skin test is considered to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised 
patients should be consulted for the interpretation of tuberculin skin test results. If no local 
country guidelines for immunocompromised patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable 
anti-tuberculous treatment regimens for latent TB. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
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References
Centers for Disease Control and Prevention. Core curriculum on tuberculosis: What the clinician should know 
(Fourth Edition). Atlanta, GA: Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86.
Menzies RI. Tuberculin skin testing. In: Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach. 2nd ed. New York, NY: Marcel Dekker, Inc; 2000:279-322.
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ATTACHMENT 3 HEPATITIS B VIRUS (HBV) SCREENING
Subjects must undergo screening for HBV. At a minimum, this includes testing for HBsAg 
(HBV surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core 
antibody total):

Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and 
anti-HBs-) are eligible for this study.

Subjects who test negative for surface antigen (HBsAg-) and test positive for core 
antibody (anti-HBc+) and surface antibody (anti-HBs+) are eligible for this study.

Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this 
study.

Subjects who test positive for surface antigen (HBsAg+) are NOT eligible for this study, 
regardless of the results of other hepatitis B tests.

Subjects who test positive only for core antibody (anti-HBc+) are NOT eligible for this 
study.
For subjects who are not eligible for this study due to HBV test results, consultation with a 
physician with expertise in the treatment of hepatitis B virus infection is recommended.
Eligibility based on hepatitis B virus test results
Hepatitis B test result
Action
Hepatitis B surface 
antigen
(HBsAg)
Hepatitis B surface 
antibody
(anti-HBs)
Hepatitis B core 
antibody
(anti-HBc total)
Include
—
—
—
—
+
+
—
+
—
Exclude
+
— or +
— or +
—
—
+
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ATTACHMENT 4: ANTICIPATED EVENTS
An anticipated event is an adverse event (serious or non-serious) that commonly occurs as a 
consequence of the underlying disease or condition under investigation (disease related) or 
background regimen.
For the purposes of this study, the following events will be considered anticipated events:

Events related to the progression of the disease under study.
These events will be captured on the CRF and in the database, and will be reported to the 
Sponsor as described in Section 12.3.1, All Adverse Events. Any event that meets serious 
adverse event criteria will be reported to the Sponsor within the appropriate timeline as described 
in Section 12.3.2, Serious Adverse Events. These anticipated events are exempt from expedited 
reporting as individual single cases to Health Authorities. However, if based on an aggregate 
review, it is determined that an anticipated event is possibly related to study drug, the Sponsor 
will report these events in an expedited manner.
Anticipated Event Review Committee (ARC)
An ARC will be established to perform reviews of pre-specified events at an aggregate level. The 
ARC is a safety committee within the Sponsor’s organization that is independent of the 
Sponsor’s study team. The ARC will meet to aid in the recommendation to the Sponsor’s study 
team as to whether there is a reasonable possibility that an anticipated event is related to the 
study drug.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and 
threshold to trigger an aggregate analysis of anticipated event will be provided in a separate 
Anticipated Events Safety Monitoring Plan (ASMP).
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ATTACHMENT 5: SLIT LAMP EVALUATIONS
Through Week 52, all subjects are required to have slit lamp evaluations performed by an
ophthalmologist/optometrist during the study at intervals (based on JIA subtype, ANA test 
results, age at JIA onset, and JIA duration) as specified in the table below. After Week 52, slit 
lamp evaluations will be performed at the discretion of the investigator and per standard of care. 
The date of the screening visit and the ANA test results during screening (as applicable
depending on the JIA subtype) should be used to determine when the first slit lamp evaluation 
should be performed during the study. The interval for the slit lamp evaluations may be adjusted 
thereafter based on the subject’s ANA test results and JIA disease duration after screening. 
However, once a subject tests positive for ANA at any time during the study (and regardless if 
the subject subsequently tests negative for ANA), the subject should be considered ANA positive 
when determining the frequency of slit lamp evaluations. 
If a subject develops uveitis during the study, the subject’s continued participation in the study is 
at the discretion of the investigator and Sponsor, and slit lamp evaluations should be performed 
according to disease course.  
Intervals for Slit Lamp Evaluations
JIA Subtype
ANA
Age at JIA 
onset (in years)
JIA duration
(in years)
Slit Lamp 
Evaluation
Interval
(in months)
OA extended
Polyarticular RF-negative 
Juvenile PSA
Positive (+)
≤6
≤4
≤3
>4 and <7
≤6
≥7
≤12
>6
≤2
≤6
>2
≤12
Negative (-)
≤6
≤4
≤6
>4
≤12
>6
N/A
≤12
ERA
N/A
N/A
N/A
≤12
Polyarticular RF-positive
Systemic with polyarticular course 
without systemic symptoms
N/A
N/A
N/A
≤12
ANA = antinuclear antibody; ERA = enthesitis-related arthritis; JIA=  juvenile idiopathic arthritis; N/A = not 
applicable; OA = oligoarticular; PSA = psoriatic arthritis; RF = rheumatoid factor
Adapted from: Heiligenhaus et al, 20078 and Heiligenhaus et at, 20157
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ATTACHMENT 6: EXTENDED TREATMENT PERIOD
INTRODUCTION
As indicated in Section 3.1.4, subjects who have completed the full trial period of 252 weeks and 
for whom drug is proven beneficial but is not commercially available for the pJIA indication (or 
subject does not qualify for insurance to pay for the drug), will continue to be provided with IV 
golimumab by the Sponsor. This attachment outlines the procedures and assessments that should 
be followed, for provision of golimumab to eligible subjects after completion of the main study, 
in the ETP. 
Eligible subjects are <18 years of age at the time of their Week 252 visit of the main study, have 
received the Week 244 infusion, and completed the Week 252 assessments. The investigator 
must confirm that the subject, in their opinion, will benefit from continued golimumab treatment, 
and it is not commercially available for the pJIA indication (or subject does not qualify for 
insurance to pay for the drug). The ETP begins at Week 252 of the main study and will continue 
until the subject either turns 18 years of age, is no longer benefiting from golimumab treatment, 
or marketing authorization is obtained for golimumab in the treatment of pJIA in the subject’s 
respective country and subject qualifies for insurance to pay for the drug. Subjects may decide to 
stop golimumab treatment (withdraw consent) at any time.
Subjects will receive the same golimumab treatment (80 mg/m2 every 8 weeks administered 
intravenously; maximum dose 240 mg) that they received prior to Week 252 in the main study. 
Subject visits and monitoring (eg, laboratory evaluation, TB evaluation) should occur at the 
investigator’s discretion and as per usual clinical practice for a subject with pJIA receiving a 
TNFα inhibitor. Physicians participating in this ETP must agree to take full responsibility for the 
use of this product.
Local regulations and guidelines related to participation in the ETP, including but not limited to 
period approvals, and re-approvals are the responsibility of the physician.
The physician must ensure that any local requirements for safety reporting to Health Authorities 
and/or Independent Ethics Committees/Institutional Review Boards, if appropriate, are met. 
During the ETP, concomitant medications including those for pJIA will be administered at the 
discretion of the investigator for all subjects. During the course of the ETP, in situations where a 
departure from the protocol or standard of care is unavoidable, the investigator or other physician 
in attendance will contact the appropriate Sponsor (see Contact Information page[s] provided 
separately). Except in emergency situations, this contact should be made before implementing 
any departure from the protocol or standard of care. In all cases, contact with the Sponsor must 
be made as soon as possible to discuss the situation and agree on an appropriate course of action. 
The data recorded in the subject’s medical records should reflect any departure from the 
protocol/standard of care.
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ELIGIBILITY CRITERIA
The investigator must confirm and document in subject’s medical records the necessity of 
continuing golimumab treatment in the ETP and that switching to another commercially 
available treatment is not in the best interest of the subject. Additionally, for subjects to be 
eligible for the ETP, the investigator must document that golimumab is not commercially 
available for the pJIA indication (and subject does not qualify for insurance to pay for the drug). 
Documentation should be done at the following timepoints:

At Week 252, after the subject has completed participation in the study (ie, the Week 252 
assessments have been completed)

At each subsequent year the subject participates in the ETP (via attestation form).
Each subject must continue to satisfy specified inclusion and exclusion criteria as well as 
prohibitions and restrictions as noted in Sections 4.1, 4.2, and 4.3, respectively. For questions 
related to eligibility, the investigator should contact the Sponsor for clarification.
In addition, specific criteria for the ETP are noted below.
Inclusion Criteria
Each potential subject must satisfy the following criteria to continue to receive golimumab as 
part of the ETP. Criteria from Section 4.1 that apply are referenced below.
1.
Subjects must be less than 18 years of age.  
2.
Subject has received the Week 244 infusion and completed the Week 252 assessments 
as outlined in Table 3 of the Time and Events Schedule of the Protocol. 
3.
Each subject (or their legally acceptable representative) must sign an ICF indicating that 
he or she understands the purpose of and the procedures required for the ETP. Assent is 
also required of children capable of understanding the nature of the study (typically 
7 years of age and older and per local regulations) as described in Section 16.2.3, 
Informed Consent.  
4.
Subjects must continue to have pJIA as specified in inclusion criterion #3 in Section 4.1. 
Subjects may remain in treatment if in remission, but if the diagnosis is thought to 
change from pJIA, treatment should be discontinued.
5.
Subjects must continue to meet eligibility criteria for TB (Inclusion criterion #10 in 
Section 4.1)
6.
Subjects must continue to avoid pregnancy (Inclusion criteria #12, #13, and #14 in 
Section 4.1).
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Exclusion Criteria
The specific exclusion criteria listed in Section 4.2 that apply are noted below with the numbers 
referring to that section. If a subject meets these criteria, he/she will be excluded from continued
participation in the ETP.
1.
Pregnancy (in a female) or plans for pregnancy (in females or males) are exclusionary 
(Exclusion criteria #41 and #42 in Section 4.2).
2.
Subjects with a BSA >3.0 m2 (Exclusion criterion #46 in Section 4.2).
Prohibitions and Restrictions
All subjects must continue to comply with all the prohibitions and restrictions as noted in 
Section 4.3, with the exception of the prohibition regarding intramuscular corticosteroids. 
Contrary to the main study, subjects may receive intramuscular administration of corticosteroids 
for the treatment of pJIA as deemed necessary by the investigator in the ETP. However, these 
occurrences should be limited. If needed for ongoing control of pJIA, thought should be given to 
the need to change to a different medication and the subject stopping participation in the ETP. 
PROCEDURES AND ACTIVITIES
Subjects who enter the ETP at the Week 252 visit will continue to receive 80 mg/m2 golimumab 
(maximum dose 240 mg) administered as IV infusions over 30±10 minutes q8w (±1 week) until 
discontinuation of golimumab treatment, as described below.
The following procedures and activities must be performed by the investigator during the ETP:

Completion of the attestation form to document that a subject is benefiting from treatment -
annually.

Record AEs considered to be related to golimumab, all SAEs (regardless of causality to 
golimumab), pregnancy, and events of special interest (ie, malignancy and TB) on the CRF. 
Refer to Section 12.3.1 for procedures for reporting these events.

Record concomitant medications associated with or used to treat AEs and SAEs on the CRF.
Subject visits and monitoring (eg, laboratory evaluation, TB evaluation) should occur at the 
investigator’s discretion and as per usual clinical practice for a subject with pJIA receiving a 
TNFα inhibitor. Physicians participating in this ETP must agree to take full responsibility for the 
use of this product.
GOLIMUMAB STORAGE, PREPARATION, DOSAGE, ADMINISTRATION, and 
ACCOUNTABILITY
Golimumab will be supplied by the Sponsor during the ETP. The first dose of golimumab in the 
ETP will be administered at Week 252 after completion of the Week 252 assessments. Subjects 
will receive 80 mg/m2 golimumab (maximum dose 240 mg) IV infusions q8w. The q8w
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(±1 week) dosing regimen should be adhered to and infusions may only be missed for safety 
reasons. Exceptions to the q8w (±1 week) dosing regimen should only be made if infusions are 
off-schedule for safety reasons. In these instances, the minimum time between infusions can be 
4 weeks to enable the subject to resume the q8w dosing regimen.
Refer to Sections 14.1, 14.2, and 14.3 for details about the physical description, packaging, and 
labeling of golimumab, respectively. 
Investigators will be responsible for ensuring that golimumab is stored according to the 
specifications outlined in Section 14.4. 
Investigators/site personnel will also be responsible for scheduling golimumab infusions and 
ensuring correct administration. 
Prior to preparing a dose for infusion, the subject’s current weight and height should be used to 
obtain the subject’s body surface area (BSA). The subject’s BSA will be calculated prior to each 
infusion using the Mosteller equation and the dose of golimumab adjusted as needed to maintain 
the dose at 80 mg/m2. A maximum dose of 240 mg cannot be exceeded in any circumstance, 
even if a subject’s BSA is large enough to yield a higher calculated dose.
The golimumab infusions should be prepared and administered by a healthcare professional as 
noted in the Golimumab Preparation and Administration Instructions.
The investigator is responsible for ensuring that all golimumab received at the site is inventoried 
and accounted for throughout the ETP. All study drug should be stored and disposed of
according to the Sponsor's instructions. Site personnel must not combine contents of the study 
drug containers.
Golimumab should be handled in strict accordance with the Golimumab Preparation and 
Administration Instructions and the container label and should be stored in a limited-access area 
or in a locked cabinet under appropriate environmental conditions. When the site is an authorized 
destruction unit and study drug supplies are destroyed on-site, this must also be documented on 
the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes.
Golimumab should be dispensed under the supervision of the investigator or a qualified member 
of the site personnel, or by a hospital/clinic pharmacist. Golimumab will be supplied only to 
subjects participating in the ETP. Golimumab returned to the site/IWRS stock must not be 
dispensed again, even to the same subject. Golimumab may not be relabeled or reassigned for 
use by other subjects.
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CONCOMITANT MEDICATIONS
Concomitant medications including medications for pJIA may be administered and adjusted at 
the discretion of the investigator but should not violate any prohibitions and restrictions noted in 
Section 4.3, Prohibitions and Restrictions, with the exception noted in Section 4.3 concerning IM
corticosteroids.
Concomitant medications associated with, or used to treat, AEs and SAEs should be recorded in 
the CRF.
Methotrexate will not be supplied by the Sponsor.
DISCONTINUATION OF GOLIMUMAB/TREATMENT WITHDRAWAL CRITERIA
The subjects may at any time withdraw consent and discontinue treatment with golimumab. If a 
subject’s golimumab treatment is discontinued, this will result in automatic permanent 
withdrawal of the subject from the ETP. A subject’s golimumab treatment provided via this ETP
will be permanently discontinued when any of the following occur:

The subject is no longer benefiting from golimumab treatment.

The subject turns 18 years of age.

Golimumab becomes commercially available in the subject’s respective country and the 
subject’s insurance will pay for the drug.
A subject’s golimumab treatment should also be permanently discontinued if any of the criteria 
in Section 10.2. Discontinuation of Study Treatment, are met. 
When a subject discontinues study treatment, a follow-up evaluation should occur approximately 
8 weeks after the last infusion of study agent to ensure that there are no safety concerns.
ADVERSE EVENT REPORTING
AEs considered by the investigator to be related to study drug (as defined in Section 12.3.1), 
SAEs (as defined in Section 12.1.1), pregnancy, and events of special interest (ie, malignancy 
and TB) are required to be reported in the ETP on the CRF. Refer to the following sections for 
procedures for reporting these events: Section 12.3.1 for AEs, Section 12.3.2 for SAEs, 
Section 12.3.3 for pregnancy, and Section 12.4 for events of special interest.
PRODUCT QUALITY COMPLAINTS
Refer to Section 13 for definition of PQCs during the ETP. If a defect is combined with an SAE 
during the ETP, the study site personnel must report the PQC to the Sponsor according to the 
timelines and procedures for an SAE.
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed on the Contact Information page(s), which will be 
provided as a separate document.
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ETHICAL ASPECTS
Refer to Section 16 for details regarding ethical aspects of the ETP.
Extended Treatment Period Considerations
Potential subjects will be fully informed of the risks and requirements of the ETP and, during the 
ETP, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the ETP is voluntary and may 
be withdrawn at any time with no reason given and without penalty or loss of benefits to which 
they would otherwise be entitled. Only subjects who are fully able to understand the risks, 
benefits, and potential adverse events of the ETP, and provide their consent voluntarily will be 
enrolled. For additional details regarding the ICF process, see Section 16.1.
ADMINISTRATIVE REQUIREMENTS
Protocol Amendments
If a modification to ETP is needed, a formal protocol amendment will be issued by the Sponsor. 
Refer to Section 17.1 for additional details about the procedures that will be followed for the 
implementation of a protocol amendment.
Documentation Required for Extended Treatment Period
At a minimum, the type and level of detail of subject’s medical records available for a subject
participating in the ETP should be consistent with that commonly recorded at the site as a basis 
for standard medical care. Subject records must be available for review of AEs considered to be 
related to study drug and SAEs. The author of an entry in the subject’s medical records should be 
identifiable.
Record Retention
Refer to Section 17.7 for details regarding record retention during the ETP. 
Monitoring
The Sponsor will perform on-site monitoring visits as necessary. The monitor will record dates 
of the visits in a site visit log that will be kept at the site. The nature and location of all subject’s 
medical records will be identified to ensure that all sources of original data are known to the 
Sponsor and site personnel and are accessible for verification by the Sponsor site contact. If 
electronic records are maintained at the site, the method of verification must be discussed with 
the site personnel.
Direct access to subject’s medical records must be allowed for the purpose of verification of the 
data reported to the Sponsor. Findings from this review of the subject’s medical records will be 
discussed with the site personnel. The Sponsor expects that, during monitoring visits, the 
relevant site personnel will be available, the subject’s medical records will be accessible, and a 
suitable environment will be provided for review of ETP-related documents. The monitor will 
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meet with the investigator as needed during the ETP to provide feedback on the administration of 
the ETP.
Extended Treatment Period Completion/Termination
Extended Treatment Period Completion
The ETP is considered completed when the youngest subject enrolled in the ETP is 18 years of 
age or the last subject participating in the ETP discontinues. 
Extended Treatment Period Termination
The Sponsor reserves the right to close the study site or terminate the ETP at any time for any 
reason at the sole discretion of the Sponsor. Study sites will be closed by the Sponsor upon ETP
completion. Refer to Section 17.9.2 for further details regarding site closure and reasons for early 
closure of a site by the Sponsor. 
Use of Information and Publication
Refer to Section 17.11 for details regarding the use of information and publication of data 
generated as a result of this ETP. 
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INVESTIGATOR AGREEMENT
NCT02277444
PPD

SAP_001.pdf: 
1
Approved, Date: 1 August 2018
Janssen Research & Development *
Statistical Analysis Plan
A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα Antibody, in 
Pediatric Subjects with Active Polyarticular Course Juvenile Idiopathic Arthritis Despite 
Methotrexate Therapy GO-VIVA
Protocol CNTO148JIA3003; Phase 3
Simponi® (golimumab)
Status:
Approved
Date:
1 August 2018
Prepared by:
Janssen Research & Development, LLC  
Document No.: EDMS-ERI-112318522; 2.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF TABLES ......................................................................................................................................... 3
LIST OF FIGURES ....................................................................................................................................... 3
AMENDMENT HISTORY.............................................................................................................................. 4
ABBREVIATIONS ........................................................................................................................................ 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Trial Objectives ................................................................................................................................ 5
1.2.
Trial Design ...................................................................................................................................... 5
1.2.1.
Subject Population........................................................................................................................ 6
1.2.2.
Dosage and Administration .......................................................................................................... 7
1.2.3.
Database Locks............................................................................................................................ 7
1.3.
Statistical Hypotheses for Trial Objectives....................................................................................... 7
1.4.
Sample Size Justification ................................................................................................................. 7
1.5.
Randomization and Blinding ............................................................................................................ 8
1.5.1.
Randomization.............................................................................................................................. 8
1.5.2.
Treatment Supply and Allocation.................................................................................................. 8
1.5.3.
Maintenance of the Blind .............................................................................................................. 8
2.
GENERAL ANALYSIS DEFINITIONS ................................................................................................ 8
2.1.
Visit Windows................................................................................................................................... 8
2.2.
Pooling Algorithm for Analysis Centers............................................................................................ 9
2.3.
Analysis Sets.................................................................................................................................... 9
2.3.1.
Pharmacokinetics Analysis Set .................................................................................................... 9
2.3.2.
Full Analysis Set ........................................................................................................................... 9
2.4.
Definition of Subgroups.................................................................................................................... 9
2.4.1.
Subgroups for the Summary of Concentrations ........................................................................... 9
2.4.2.
Subgroups for the Summary of Other Efficacy Endpoints.......................................................... 10
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 10
3.1.
Interim Analysis.............................................................................................................................. 10
3.2.
Data Review Committee ................................................................................................................ 10
4.
SUBJECT INFORMATION................................................................................................................ 11
4.1.
Demographics and Baseline Characteristics ................................................................................. 11
4.2.
Disposition Information................................................................................................................... 11
4.3.
Treatment Compliance................................................................................................................... 11
4.4.
Extent of Exposure......................................................................................................................... 11
4.5.
Protocol Deviations ........................................................................................................................ 12
4.6.
Prior and Concomitant Medications ............................................................................................... 12
5.
EFFICACY ......................................................................................................................................... 12
5.1.
Analysis Specifications................................................................................................................... 12
5.1.1.
Level of Significance................................................................................................................... 12
5.1.2.
Data Handling Rules................................................................................................................... 12
5.1.3.
Joint Evaluability......................................................................................................................... 12
5.1.4.
Adjusted Joint Counts Rules ...................................................................................................... 13
5.2.
Primary Efficacy Endpoint.............................................................................................................. 13
5.3.
Major Secondary Endpoints........................................................................................................... 13
5.4.
Other Efficacy Variable(s) .............................................................................................................. 13
5.4.1.
Definition of other efficacy endpoints.......................................................................................... 13
5.4.1.1.
JIA ACR Response.................................................................................................................. 13
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5.4.1.2.
Inactive Disease ...................................................................................................................... 14
5.4.1.3.
Clinical Remission While on Medication.................................................................................. 14
5.4.1.4.
Childhood Health Assessment Questionnaire (CHAQ)........................................................... 14
5.4.1.5.
Juvenile Arthritis Disease Activity Score (JADAS) .................................................................. 15
5.4.2.
Analysis Methods........................................................................................................................ 15
6.
SAFETY............................................................................................................................................. 16
6.1.
Safety Table(s) Presentation ......................................................................................................... 16
6.2.
Adverse Events .............................................................................................................................. 16
6.3.
Clinical Laboratory Tests................................................................................................................ 17
6.4.
Vital Signs and Physical Examination Findings ............................................................................. 18
6.5.
Electrocardiogram.......................................................................................................................... 18
6.6.
Antinuclear (ANA)/ Anti-dsDNA antibodies.................................................................................... 18
7.
PHARMACOKINETICS/PHARMACODYNAMICS AND IMMUNOGENICITY ................................. 18
7.1.
Pharmacokinetics........................................................................................................................... 18
7.1.1.
Primary PK Endpoints................................................................................................................. 18
7.1.1.1.
Definition.................................................................................................................................. 18
7.1.1.2.
Analyses Methods ................................................................................................................... 18
7.1.2.
Major Secondary PK Endpoints.................................................................................................. 19
7.1.2.1.
Definition.................................................................................................................................. 19
7.1.2.2.
Analyses Methods ................................................................................................................... 19
7.1.3.
General PK Summaries.............................................................................................................. 19
7.2.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 21
7.3.
Immunogenicity.............................................................................................................................. 21
8.
HEALTH ECONOMICS ..................................................................................................................... 21
REFERENCES............................................................................................................................................ 22
ATTACHMENT ........................................................................................................................................... 23
Attachment 1: Analytical considerations on joints with joint procedure/injection prior to study a................ 23
Attachment 2: Analytical considerations on joints with injection and/or joint surgery for reasons 
NOT related to JIA during the study a ............................................................................................ 24
Attachment 3: Markedly Abnormal Laboratory Parameter Criteria............................................................. 25
LIST OF TABLES
Table 1:
Length of 95% CI with Sample Size 100 Subjects ..................................................................... 8
LIST OF FIGURES
Figure 1:
Schematic overview of the study ................................................................................................ 6
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AMENDMENT HISTORY
SAP Version
Date
Original SAP
11 December 2017
Amendment 1
01 August 2018
ABBREVIATIONS
ACR
American College of Rheumatology
AE
adverse event
ALT
alanine aminotransferase
ANA
antinuclear antibodies
AST
aspartate aminotransferase
AUCss
steady state AUC
BMI
body mass index
BSA
body surface area
CHAQ
Childhood Health Assessment Questionnaire
CI
confidence interval
CRP
C-reactive protein
DBL
database lock
DMARD
disease-modifying antirheumatic drug
DNA
deoxyribonucleic acid
DRC
Data Review Committee
ECG
electrocardiogram
eCRF
electronic case report form
GCP
Good Clinical Practice
IV
intravenous
IWRS
interactive web response system
JADAS
Juvenile Arthritis Disease Activity Score
JIA
juvenile idiopathic arthritis
LLOQ
lower limit of quantification
LTE
long-term extension
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
NSAID
non-steroidal anti-inflammatory drug
pJIA
polyarticular JIA
PK
pharmacokinetics
PKE
pharmacokinetics evaluable
q8w
every 8 weeks  
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SOP
Standard Operating Procedure
TB
tuberculosis
TNFα
tumor necrosis factor alpha
VAS
visual analogue scale
WBC
white blood cell
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1.
INTRODUCTION
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and
statistical
methods for the analysis of pharmacokinetics (PK), efficacy,
safety, and 
immunogenicity in the CNTO148JIA3003 study.
1.1.
Trial Objectives
Primary Objective 
The primary objective of this study is to assess the PK following intravenously administered 
golimumab in subjects (ages 2 to less than 18 years) with polyarticular JIA (pJIA) manifested by 
≥5 joints with active arthritis despite methotrexate (MTX) therapy for ≥2 months. 
Secondary Objectives 
The secondary objectives of this study are to evaluate IV golimumab in subjects with pJIA with 
respect to PK, efficacy (relief of signs and symptoms, physical function, quality of life), safety 
(AEs, SAEs, and assessment of laboratory parameters), and immunogenicity (antibodies to 
golimumab).
1.2.
Trial Design
This is a Phase 3, open-label, single arm, multicenter study to evaluate the PK, safety, and 
efficacy of IV golimumab in subjects with active pJIA despite current treatment with MTX.   
Approximately 120 subjects will be enrolled at Week 0 to ensure that approximately 100 subjects 
remain in the study at Week 52.   
All subjects will receive 80 mg/m2 golimumab (maximum single dose 240 mg [maximum BSA 
3.0 m2 x 80 mg/m2]) as an IV infusion (over 30 ±10 minutes) at Weeks 0, 4, and q8w (± 3 days) 
through Week 28 and then q8w (± 1 week) thereafter through Week 52.
Subjects will also 
receive commercial MTX weekly through Week 28 at the same BSA-based dosage (10 to 
30 mg/m2 per week of MTX in subjects with BSA <1.67 m2, or a minimum of 15 mg/week in 
subjects with BSA ≥1.67 m2) as at time of study entry.  Subjects who complete the study at 
Week 52 will have the option to enter into the long-term extension phase of the study (from 
Week 52 to Week 252). All subjects who complete the Week 244 visit are expected to participate 
in the safety follow-up visit at Week 252. 
Since this is an open-label study with all subjects receiving the same BSA-based dose of 
IV golimumab, an external Data Monitoring Committee will not be established. Instead, an 
internal Janssen Data Review Committee (DRC) will be formed in its place.
The end of the study is defined as the last follow-up assessment for the last subject in the long-
term extension.
Database locks (DBL) are scheduled for Weeks 28, 52 and 252 (Section 1.2.3).  
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If <50% of the study population achieves an adequate response to the treatment (American 
College of Rheumatology Pediatric 30% [JIA ACR 30] response) at the Week 28 DBL, the study 
will be discontinued.
Figure 1 depicts the schematic overview of the study.
Figure 1:
Schematic overview of the study
1.2.1.
Subject Population
Subjects must meet the inclusion and exclusion criteria of the study.
Subjects must be 2 to less than 18 years of age with a body weight >15 kg at the time of enrollment.  
The onset of disease must have been before the subject’s 16th birthday, must be of at least 3 months’
duration, and must be active pJIA of one of the following subtypes: rheumatoid factor positive or 
negative pJIA; systemic JIA with no systemic symptoms for ≥3 months but with polyarthritis for 
≥3 months; extended oligoarticular JIA; enthesitis-related arthritis or polyarticular juvenile psoriatic 
arthritis (PsA).
Subjects must have ≥5 joints with active arthritis as defined by American College of Rheumatology
(ACR) criteria at screening and enrollment. Subjects must have active pJIA despite current use of 
oral, intramuscular, or subcutaneous MTX (for ≥2 months before screening) at a weekly dose of 
≥10 mg/m2.
Subjects must have a screening CRP of ≥0.1 mg/dL with the exception of approximately 30% of 
the study population.
Screening for eligible subjects will be performed within 6 weeks before administration of the
study agent.
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1.2.2.
Dosage and Administration 
The study will have 1 active treatment group.  
All subjects will receive 80 mg/m2 golimumab (maximum single dose 240 mg) IV infusions at 
Week 0, Week 4, and q8w (±3 days) through Week 28 and q8w (±1 week) thereafter through 
Week 244.  BSA will be calculated using the Mosteller equation: 
BSA (m2) = ([height (cm) x weight (kg)]/3600)1/2.
All infusions will be completed over 30±10 minutes.
In addition, subjects will receive commercial MTX at the same BSA-based dose (10 to 30 mg/m2
per week for subjects with BSA <1.67 m2 or at least 15 mg/week for subjects with
BSA ≥1.67 m2) as at time of study entry through Week 28. Absolute dose should remain stable 
from baseline through Week 28.
1.2.3.
Database Locks
Database locks are scheduled at Weeks 28, 52 and 252.  The Week 28 and Week 52 database 
locks will include all data collected up to the Week 28 and Week 52 visits, respectively.  The 
final database lock at Week 252 will include all data collected.
1.3.
Statistical Hypotheses for Trial Objectives
No formal hypothesis testing is planned for this study. 
1.4.
Sample Size Justification
The sample size determination is not based on statistical considerations. For the purpose of 
determining sample size of this study, the variability of PK in pediatric populations was 
considered. The goal is to have a sample size that will be sufficient to build a population PK and, 
if feasible, an exposure-response model. Additionally, a sample size that will provide 
information about the safety profile of golimumab IV in children was also taken into 
consideration. 
With these considerations, a sample size of approximately 120 subjects has been chosen 
assuming that if 20 subjects were to drop out or if they do not provide PK samples, a sample size 
of approximately 100 subjects is thought to be sufficient to build a population PK model, given
the sparse sampling of PK time points, as well as provide 1 year of safety data from 
approximately 100 subjects.
Assuming that inter-subject coefficient of variation (CV%) of concentration is about 50% 
(moderate – large variation), a sample size of 100 subjects will be able to provide a 95%
confidence interval (CI) with the length about 20% of the mean concentration, i.e., 95% CI 
Mean(110%). 
The table below provides the length of 95% CI of mean concentration using sample size of 
100 subjects with various CV% from 30% (small variation) to 70% (larger variation).
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Table 1:
Length of 95% CI with Sample Size 100 Subjects
CV %
95% CI
30%
Mean(15.9%)  
40%
Mean(17.8%)  
50%
Mean(19.8%)  
60%
Mean(111.8%)  
70%
Mean(113.7%)  
1.5.
Randomization and Blinding
1.5.1.
Randomization 
All subjects will receive 80 mg/m2 golimumab and commercial MTX, therefore randomization 
of subjects to treatment is not needed.   
1.5.2.
Treatment Supply and Allocation
Golimumab will be supplied as a sterile liquid for IV infusion at a volume of 4 mL (50 mg, 
12.5 mg/mL) in single-use vials. 
Normal saline will be supplied as a sterile liquid for 
IV infusion in single-use infusion bags. 
Treatment (golimumab vials) allocation will be performed by using a centralized, interactive web 
response system (IWRS) provided by Parexel International Corporation. After the informed
consent has been obtained and the subject has been successfully screened, sites will enroll a 
subject at Week 0 via the IWRS. Vial numbers will be assigned to the subject.  One or more
golimumab vials can be assigned at each visit. The assigned vial numbers will be provided via 
fax to the pharmacist and will be stored electronically in the IWRS database. The IV study agent 
for infusion will be prepared according to the subject’s BSA.
In the event that a vial of treatment is not available at the site or a problem with the vial or vial 
contents are noted, an alternate vial number will be provided via IWRS to the pharmacist. The 
sponsor will be alerted in order to promptly address the deficient clinical supply issue. The 
assignment of the new vial will be recorded in the electronic case report form.
1.5.3.
Maintenance of the Blind
This is an open label study with one treatment group, therefore maintenance of blinding is not 
necessary.
2.
GENERAL ANALYSIS DEFINITIONS
2.1.
Visit Windows
All scheduled study visits should occur within ±3 days of the intended visit through Week 28 and 1 
week from Week 28 through Week 244.
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Unless otherwise specified, actual scheduled visits will be used for the summaries and listings 
over time with no visit windows applied.
For PK analyses, if a subject has an infusion more than 3 days of the scheduled dosing date
through Week 28, the concentration data collected between such a dosing visit and the 
subsequent dosing visit will be excluded from the by-visit data analyses. For the visits after 
Week 28, if the PK sampling time deviates more than 7 days of the scheduled date, the PK 
concentration at this visit will be excluded from the by-visit data analyses.
2.2.
Pooling Algorithm for Analysis Centers
Data from all investigational centers/sites will be pooled for analyses.
2.3.
Analysis Sets
2.3.1.
Pharmacokinetics Analysis Set 
The pharmacokinetics evaluable (PKE) analysis set includes treated subjects (who received at 
least 1 infusion) who have sufficient PK samples for analysis.
Pharmacokinetics analyses will be performed using the PKE analysis set.
2.3.2.
Full Analysis Set
The full analysis set includes all enrolled subjects who received at least 1 infusion.
This analysis set will be used for efficacy analysis and safety analysis, unless otherwise 
specified. 
2.4.
Definition of Subgroups
2.4.1.
Subgroups for the Summary of Concentrations 
To evaluate the consistency in the concentrations over demographics, baseline characteristics.  The 
subgroups described below are for the concentrations.  
The following demographic subgroups will be used for concentration summary:
a.
Age: 2 years to <6 years, ≥6 years to <12 years, ≥12 years to <18 years
b. Baseline body weight: quartiles 
c.
Baseline BMI: quartiles
d. Baseline BSA: quartiles
e.
Baseline CRP quartiles, CRP categories (<1.0 mg/dL, ≥1.0 mg/dL) and CRP categories 
(<0.1 mg/dL, ≥0.1 mg/dL)
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2.4.2.
Subgroups for the Summary of Other Efficacy Endpoints
In addition to demographic subgroups of age, gender, race, geographic region, weight, BMI, and
BSA the following subgroups will also be used for the summary of JIA ACR30 (Section 5.4.1.1).
The subgroups for efficacy analyses include, but are not limited to, the following:  
Baseline disease characteristics subgroups
a.
ILAR classification of disease (Systemic onset with polyarticular course with no 
systemic symptoms, Polyarticular Rheumatoid Factor-negative, Polyarticular 
Rheumatoid Factor-positive, Oligoarticular extended, Juvenile Psoriatic Arthritis, and 
Enthesitis-related JIA)
b.
Number of active joints (<6, ≥6 to <10, ≥10)
c.
Number of joints with limited range of motion (<6, ≥6 to <10, ≥10)
d.
CHAQ (<1, ≥1 to <2, ≥2)
e.
CRP (<1.0 mg/dL, and ≥1.0 mg/dL at baseline (Week 0))
f.
CRP (<0.1 mg/dL, and ≥0.1 mg/dL at baseline (Week 0))
g.
Previous joint surgery (yes, no)
h.
Disease duration (<6 months, ≥6 months to <1 year, ≥1 year to <3 years, ≥3 years)
Medication use subgroups:
a.
Prior anti-TNF therapy (yes, no)
b.
Oral corticosteroids (yes, no) 
c.
NSAIDs (yes, no) 
d.
MTX dose: tertiles
e.
Duration of MTX therapy (<1 year, ≥1 year to <3 years, ≥3 years)
f.
Prior DMARDs excluding MTX (0, 1, 2, ≥3)
g.
Concomitant conventional DMARDs use at baseline, excluding MTX (0, 1, 2, ≥3)
h.
Prior biologics, excluding anti-TNFs (yes, no)
i.
Prior JAK inhibitors (yes, no)
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
3.1.
Interim Analysis
No interim analyses are planned for this study. 
3.2.
Data Review Committee
An internal DRC will periodically review and assess safety data during the study to ensure 
subject safety while participating in the study. DRC review will commence when 20 subjects 
have been enrolled into the study and then will meet at least once annually as well as on an ad 
hoc basis upon the request of the study team, until the Week 252 DBL.  The content of safety
summaries, DRC
roles and responsibilities, and the general procedures (including
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communications) are defined and documented in the DRC Charter. Statistical output will be 
provided by Parexel International Corporation.
The safety data summary package prepared by Parexel International Corporation includes
summaries and listings of all adverse event (AEs), SAEs, infections, infusion reactions, and lab
parameter data.  Following the review, the DRC will make a formal, written recommendation 
regarding the conduct of the study to the study team.
4.
SUBJECT INFORMATION
Subject information will be summarized for PKE analysis set unless otherwise specified.
4.1.
Demographics and Baseline Characteristics
The baseline measurement is defined as the closest measurement taken prior to the first study 
agent administration (Week 0) unless otherwise stated.
Subjects’ demographic data including age, race, gender, height, weight, BSA, and BMI at 
baseline will be summarized.  Baseline disease characteristics including duration of disease and 
baseline JIA efficacy assessments will be summarized.
Baseline TB information and medication usage will also be summarized.
The number of subjects will also be summarized by geographic region, country, and 
investigational site.
4.2.
Disposition Information
The number of subjects screened, enrolled, and treated will be summarized.  Subjects who 
discontinued study agent through Week 28, and 52, and 252, and the reasons for discontinuation
will also be summarized. Likewise, subjects who terminated study participation and the reasons 
for termination will also be summarized.  
4.3.
Treatment Compliance
Subjects will be summarized by the study agent lot(s) received. 
Treatment compliance will be assessed by summarizing the total number of infusions actually 
received, interrupted infusions, and incorrect (± 15% of calculated dose in mg) infusions.
4.4.
Extent of Exposure
The cumulative dose of golimumab (mg/m2) and MTX dose (mg and mg/week) received will be 
summarized through Week 28, 52 and 252. The length of infusions will be summarized and 
subjects with <20 and >40 minutes infusion durations will be listed.
The number of administrations will be summarized.  
The average follow-up time will also be summarized in the safety tables.
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4.5.
Protocol Deviations
Major protocol deviations will be tabulated separately and presented for the following categories: 

Subjects who entered the study but did not satisfy entry criteria, 

Subjects who received the incorrect dose

Subjects who received disallowed medication, and other. 
Besides these major deviations, other deviations may be summarized. Subjects with protocol 
deviations in study agent administration will be summarized by type of deviations. 
All protocol deviations will be summarized through Week 28, through Week 52, and through 
Week 252 for the full analysis set.
4.6.
Prior and Concomitant Medications
Medications taken by subjects prior to starting the study will be summarized. These include 
medications for JIA such as MTX, other DMARDs, oral corticosteroids, and NSAIDs.
Concomitant medications will be summarized through Week 28, 52 and 252 for all subjects who 
belong in the full analysis set.
5.
EFFICACY
5.1.
Analysis Specifications
5.1.1.
Level of Significance
No statistical testing will be performed.
5.1.2.
Data Handling Rules
No data handling rules will be applied to all individual endpoints and composite endpoints that 
are not dichotomous.  Observed data will be summarized.
For a dichotomous composite endpoint, subjects who have completely missing data (ie, all 
components of the composite endpoint are missing) will be assumed to be a non-responder. 
When at least 1 of the components is non-missing, last observation carried forward (LOCF) will 
be used for imputing the components with missing data.
5.1.3.
Joint Evaluability
For subjects who have a joint injection or surgical procedure prior to the date of enrollment, the
affected joints will be analyzed according to the impact of the joint injection or joint surgical 
procedure on the evaluability of the involved joints. See Attachment 1 for details. If a joint is
considered nonevaluable at baseline, then all post-baseline joint evaluations will also be 
considered as nonevaluable; furthermore, this nonevaluability overrides any other documented,
post baseline joint assessments. For subjects undergoing joint injections and/or procedures
during the study for reasons not related to JIA, joint evaluability is summarized in Attachment 2.
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For subjects undergoing a joint procedure/injection for the treatment of JIA, the corresponding
joint(s) will be counted as swollen, having active arthritis, and having limited range of motion 
from the date of procedure onward.
5.1.4.
Adjusted Joint Counts Rules
For subjects who have an incomplete set of evaluable joints, the joint count will be adjusted to a 
69 joint count for joints with limited range of motion and 73 joint count for active joints for JIA 
ACR endpoints. This is done by dividing the number of affected joints by the number of 
evaluable joints and multiplying by 69 and 73, respectively.
5.2.
Primary Efficacy Endpoint
No primary efficacy endpoint is planned.
5.3.
Major Secondary Endpoints
No major secondary efficacy endpoints are planned.
5.4.
Other Efficacy Variable(s)
5.4.1.
Definition of other efficacy endpoints
5.4.1.1.
JIA ACR Response
JIA ACR responses are composite endpoints measured by the 6 pediatric ACR categories. These 
are as follows:
1.
Physician’s global assessment of disease activity, (0 = No arthritis activity, 100 = 
Extremely arthritis activity) (0-100 mm VAS)
2.
Parent/subject assessment of overall well-being, (0 = Very well, 100 = Very poor) 
(0-100 mm VAS)
3.
Number of active joints (defined as either swelling, or in absence of swelling, limited 
range of motion associated with pain on motion or tenderness), (0-73)
4.
Number of joints with limited range of motion, (0-69)
5.
Physical function by Childhood Health Assessment Questionnaire, (0-3) (See 
Section 5.4.1.4 for details)
6.
CRP (unit = mg/dL)
JIA ACR 30 response4 is defined as ≥30% improvement from baseline in at least 3 of the 
6 components with worsening of 30% or more in no more than 1 of the above noted components. 
Improvement in each of the individual components is indicated by a decrease in score.
If a subject’s baseline value for a component is zero (ie, no disease activity as measured by that 
component), the subject should be considered as not achieving 30% improvement from baseline 
for that component since there is no room for improvement.
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JIA ACR 50, 70 and 90 responses are similarly defined using the corresponding threshold for 
improvement from baseline and with worsening of 30% or more in no more than 1 of the above 
noted components.
5.4.1.2.
Inactive Disease
Inactive disease is indicated by the presence of all of the following:
1.
No joints with active arthritis
2.
No fever, rash, serositis, splenomegaly, hepatomegaly or generalized lymphadenopathy
attributable to JIA
3.
No active uveitis
4.
Normal CRP (≤0.287 mg/dL for subjects without underlying inflammatory disease)
5.
Physician Global Assessment of disease activity indicating no active disease (≤5 mm 
VAS)
6.
Duration of morning stiffness <15 minutes
5.4.1.3.
Clinical Remission While on Medication
Clinical remission while on medication for JIA is defined as inactive disease (Section 5.4.1.2) at 
each non-missed visit for a period of ≥6 months (24 weeks) while on medication. All subjects are 
assumed to be on medication.
For a given visit, the determination of clinical remission while on mediation for JIA will be 
based on the period of 24 weeks prior to the visit. To be considered clinical remission, all the 
visits encompassing at least 24 weeks prior to the visit will have to meet the inactive disease 
criteria.
5.4.1.4.
Childhood Health Assessment Questionnaire (CHAQ)
The functional status of subjects will be assessed by the CHAQ. Parents are to complete this
questionnaire to assess the degree of difficulty the subject has in accomplishing tasks in 
8 functional areas (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, 
and activities of daily living). Responses in each functional area are scored as 0 = without
difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do, or 4 = not 
applicable response options. If aids or devices are used or assistance is required, the minimal 
score for the corresponding area is 2. The CHAQ has been shown to be responsive to disease 
change.1 A decrease of 0.188 has been determined to be a meaningful clinical improvement.6
The disability index is calculated as the mean of the 8 domains and yields a score between 0 
(no disability) and 3 (most severe disability). The disability index is not computed if the subject 
does not have scores for at least 6 categories.
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5.4.1.5.
Juvenile Arthritis Disease Activity Score (JADAS) 
The JADAS (modified for using CRP) is computed by assessing the following variables: 
(1) Physician global rating of overall disease activity, measured on a 100-mm horizontal VAS 
(0 no activity; 100 maximum activity); 
(2) Parent/child ratings of well-being and pain, assessed on a 100-mm Horizontal Line Visual 
Analog Scales,3
(3) Number of active joints, assessed in 71, 27, or 10 joints (JADAS 71, JADAS 27, and 
JADAS 10, respectively); and 
(4) CRP was truncated to a 0-10 scale according to the following formula: ((CRP [mg/L]-
10)/10), similar to the truncated ESR used in JADAS-ESR. Before calculation, CRP values 
<10 mg/L are converted to 10 and CRP values >110 mg/L are converted to 110.5
JADAS-71 includes the entire number of joints.  The JADAS-27 includes the following joints:  
cervical spine, elbows, wrists, meta-carpophalangeal joints (from first to third), proximal 
interphalangeal joints, hips, knees, and ankles.  JADAS-10 is based on the count of any active
joint, irrespective of its type, up to a maximum of 10 joints.
The JADAS is calculated as the sum of the scores of its 4 components, which yields a global score of 
0–101, 0–57, and 0–40 for the JADAS 71, JADAS 27, and JADAS 10, respectively. 
JADAS 10, 27, and 71 minimal disease activity2,5 is defined as the presence of all of the 
following:
(1) Physician’s global assessment of disease activity of ≤3.5, 
(2) Parent’s global rating of well-being of ≤2.5, and 
(3) Swollen joint count of ≤1 in patients with polyarthritis. 
JADAS inactive disease is defined as a total JADAS score of ≤1.
5.4.2.
Analysis Methods
Unless otherwise specified, the analysis population will be the full analyses set defined in 
Section 2.3.2.
Summaries over time will be for all visits data was collected through Week 28, 52, and 252, if 
the visit of the endpoint is not specified.  Simple descriptive summary statistics, such as n, mean, 
SD, median, IQ range, minimum, and maximum for continuous variables, and counts and 
percentages for discrete variables will be used to summarize most data. 
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The following endpoints will be summarized over time. 
1.
The proportion of subjects who are JIA ACR 30, 50, 70, and 90 responders 
2.
The proportion of subjects who have inactive disease  
3.
The proportion of subjects in clinical remission on medication for pJIA 
4.
The improvement from baseline in the JIA ACR core set of components  
5.
The proportions of subjects who are JIA ACR 30, 50, 70, and 90 responders by disease 
subtype, and/or age through Week 52 
6.
The change from baseline in CHAQ  
7.
CRP concentrations
8.
The change from baseline in JADAS 10, 27, and 71 scores  
9.
The proportion of subjects who achieve JADAS 10, 27, and 71 minimal disease activity 
6.
SAFETY
Safety will be assessed by summarizing the occurrences and type of AEs, and examining the 
changes in the laboratory parameters.  
Subjects who received at least 1 IV study agent administration will be included in the analysis
(full analysis set).
6.1.
Safety Table(s) Presentation
If a subject discontinues study participation, the follow-up time will stop at the day of study
participation discontinuation.
The safety summary tables will be presented through the following periods:
1.
Through Week 28
2.
Through Week 52
3.
Through Week 252
6.2.
Adverse Events
Treatment-emergent AEs will be summarized by system organ class and preferred term defined 
by MedDRA.
The following treatment-emergent AE summary tables will be provided for this study:

Any AEs

SAEs
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
AEs with severe intensity

AEs and SAEs that are reasonably related to study agent

AEs leading to discontinuation of study agent

Infusion reactions

Infections and infections requiring oral or parenteral anti-microbial treatment

Serious infections
In addition to the summary tables, a listing of subjects who died and listings of subjects with the 
following AEs will be presented: SAEs, AEs leading to discontinuation of study agent(s), 
anaphylactic reactions or serum sickness reactions, malignancy, tuberculosis, clinically important
hepatobiliary events (defined as ALT ≥ 3×ULN and either bilirubin ≥ 2×ULN or occurrence of a 
serious adverse event in the hepatobiliary system-organ class), and demyelination.
Infusion reactions and infection:

An infusion reaction is identified as any unfavorable or unintended sign that occurs 
during the infusion or within 1 hour of completion of the infusion. Infusion reactions 
are captured in the eCRF.

An infection is identified as any AE that was recorded as an infection by the
investigator on the eCRF.
Since safety should be assessed relative to exposure, the following summaries will be presented:

Proportion of subjects receiving scheduled IV study agent administrations at each study 
agent administration visit.

Summary of cumulative golimumab dose.
In addition, all AE summary tables will include average weeks of follow-up and average number
of IV infusions.
6.3.
Clinical Laboratory Tests
The laboratory parameters include but are not limited to the following:
Hematology: hemoglobin, hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, 
platelets, and WBC count.
Chemistry:
BUN/urea, creatinine, total bilirubin, alkaline phosphatase, ALT/SGPT, 
AST/SGOT, bicarbonate, sodium, potassium, calcium, albumin, chloride, phosphate, glucose, 
uric acid and total protein.
Laboratory results will be graded according to NCI-CTCAE version 4.03 or later. Note that 
toxicity grading for creatinine increase will be based on the NCI CTC v4.03 or later criteria, but 
limited only to the part based on the upper limit of normal (ULN), the other part, that is based on 
change from baseline, will not be used for toxicity grading. Generic normal ranges will be 
applied whenever reference ranges are not available. 
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NCI-CTCAE grades will be used in the summary of laboratory data (Grade 0 – 4). The 
proportion of subjects for select laboratory parameters with maximum Grades will be presented. 
In addition, the proportion of subjects with markedly abnormal laboratory results will also be 
provided. The subjects’ maximum post-baseline ALT and AST will also be summarized by TB 
prophylaxis (TB prophylaxis, or no TB prophylaxis).
Levels of laboratory values that are considered to be markedly abnormal have been defined for 
each laboratory parameter in Attachment 3.
Boxplots will be used to describe the selected laboratory analyte at baseline and at each 
scheduled time point. The selected laboratory analytes are:  WBC counts, neutrophils, 
hemoglobin, platelets, ALT, and AST.
6.4.
Vital Signs and Physical Examination Findings
Vital signs including heart rate, respiratory rate, temperature, and blood pressure (systolic and 
diastolic) values and changes from baseline will be summarized by visit.
6.5.
Electrocardiogram
This section does not apply to this study.
6.6.
Antinuclear (ANA)/ Anti-dsDNA antibodies
Blood samples will be collected at Weeks 0, 24, 52, 76, 100, 124, 148, 172, 196, 220 and 244 to 
determine the presence of antinuclear (ANA)/ anti-dsDNA antibodies.
Subjects’ baseline ANA and anti-dsDNA status and proportion of subjects who change ANA and 
anti-dsDNA status during the trial will be summarized.
7.
PHARMACOKINETICS/PHARMACODYNAMICS AND IMMUNOGENICITY
7.1.
Pharmacokinetics
7.1.1.
Primary PK Endpoints
The primary endpoints in this study are PK exposure at Week 28 (the trough concentrations at 
Week 28) and the Bayesian AUCss over one dosing interval of 8 weeks (from population PK 
modeling and simulation).
7.1.1.1.
Definition
Ctrough,wk28 :  Serum golimumab trough concentration at Week 28
AUCss:  Area under the curve at steady-state over a dosing interval
7.1.1.2.
Analyses Methods
Summary golimumab concentrations will be summarized and PK exposure will be evaluated 
through Week 52 and through the LTE (Week 252).
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A population PK analysis with data through Week 28 will be performed to characterize the PK of 
golimumab as well as to identify and quantify important covariates of PK in the pediatric 
population with JIA. Clearance and volume of distribution will be estimated using a nonlinear
mixed effects modeling (NONMEM) approach. Details will be provided in a population PK 
analysis plan and the results of the analysis will be presented in a separate report.
Measures of PK exposure will be graphically evaluated in the pediatric populations after 
administration of IV golimumab (including but not limited to steady-state Cmax, Cmin and AUC) 
and compared to PK exposure from adults in CNTO148ART3001. Similarity between pediatric 
and adult subjects will be assessed by the generation of box plots from the population PK 
modeling via visual inspection in addition to the descriptive statistics of the observed 
concentrations.
7.1.2.
Major Secondary PK Endpoints
Major secondary endpoints include PK exposure at Week 52 (the trough concentrations at 
Week 52) and the Bayesian AUCss at Week 52 (from population PK modeling and simulation).
7.1.2.1.
Definition
Ctrough,wk52 :  Serum golimumab concentration at Week 52.
7.1.2.2.
Analyses Methods
The analysis of the major secondary PK endpoint will be performed via population PK modeling 
using NONMEM as described in Section 7.1.1.2.  
7.1.3.
General PK Summaries
PK samples for measuring serum golimumab concentrations will be collected from all subjects at 
the specified visits as shown in the schedule of events of the protocol. Samples will be collected 
at Weeks 0, 4, 8, 12, 20, 28, 52, 100, 148, 196 and 244.  Two samples, one pre-infusion and 
another post-infusion, will be collected at Weeks 0, 4, and 12. An additional random PK sample 
for serum golimumab concentration will be collected from all subjects at any time between 
Weeks 0 and 8 other than at the time of the Week 0, 4 and 8 visits; this sample must be collected 
at least 24 hours before or after a study agent infusion.  
All PK evaluations will be based on the subjects who receive at least 1 infusion of golimumab
(PKE analysis set). 
No imputation for missing concentration data will be performed. Pre and post infusion serum 
concentrations will be summarized separately.
The data analysis of serum golimumab concentrations includes the following:

Summary of serum golimumab concentrations at each visit

Summary of serum golimumab concentrations at each visit by body weight quartiles.

Summary of serum golimumab concentrations at each visit by BMI quartiles.
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
Summary of serum golimumab concentrations at each visit by BSA quartiles.

Summary of serum golimumab concentrations at each visit by age (2 to <6 years, 6 to 
<12 years, 12 to <18 years).

Summary of serum golimumab concentrations at each visit by CRP quartiles and CRP 
categories (<0.1 mg/dL, ≥0.1 mg/dL; <1.0 mg/dL, ≥1.0 mg/dL).

Proportion of subjects without detectable serum golimumab concentration at each visit.

Summary of serum golimumab concentrations at each visit by antibodies to golimumab 
status.

Median serum golimumab concentrations plotted over time.
In addition, the relationship between serum golimumab concentrations and antibody to
golimumab status, safety and efficacy may be explored using graphical displays. Median serum 
golimumab concentrations will be plotted. Box plots of serum golimumab concentrations will be 
plotted by percentage subjects who achieved JIA ACR 30 responses.
For summary statistics of serum golimumab concentrations, concentration values below the 
lower limit of quantification will be treated as zero. Once a subject meets one of the following 
dosing deviation criteria, the subject’s data will be excluded from the by-visit data analyses from 
that point onwards.
Dosing deviation criteria:

Discontinue IV study agent administrations.

Skipped an IV administration.

Received an incomplete / incorrect IV dose.

Received an additional IV dose.
In addition, if a subject has an administration more than 7 days earlier or later than the scheduled
dosing date, the concentration data collected between such a dosing visit and the subsequent 
dosing visit will be excluded from the by-visit data analyses. For visits prior to Week 28, if the 
PK sampling time deviates more than 3 days earlier or later than the scheduled date, the PK 
concentration at this visit will be excluded from the by-visit data analyses.  Additional exclusions 
for incongruous PK data to be implemented based on Janssen SOP-07948v2.
Population PK analyses will be performed to characterize the population PK parameters based on 
the available golimumab concentration data obtained through the Week 28 visit. The population 
pharmacokinetic approach will also be used to identify and quantify any significant covariates 
such as demographic characteristics (including but not limited to body weight, sex, and age).
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PK analyses will be summarized through the following time periods:

Through Week 28

Through Week 52

Through Week 244
7.2.
Pharmacokinetic/Pharmacodynamic Analyses 
The relationship between serum golimumab concentrations and efficacy measures may be 
explored, and the results will be reported in a separate technical report.
7.3.
Immunogenicity
Blood samples will be collected to examine the formation of antibodies to golimumab at the 
specified visits as shown in the schedule of events of the protocol. For subjects who discontinue 
IV study agent administrations, samples will be collected at their safety follow-up visit.
The data analysis of antibodies to golimumab includes the following:

The antibody status (positive, negative) of subjects will be summarized. For subjects 
who discontinue IV study agent administrations and complete safety follow-up, a listing 
of their antibody status will be presented.

The relationship between antibody to golimumab status and efficacy and safety will be 
assessed at major assessment time points (Weeks 28, 52 and 252). JIA ACR 30
responses by antibody to golimumab status; infusion reactions by antibody to 
golimumab status.

The relationship between antibody to golimumab status at Week 28 and antibody to
golimumab status at Week 52 will be explored.

The onset of antibody to golimumab formation will be summarized

The duration of antibody to golimumab will be summarized.

The serum golimumab concentrations by antibody to golimumab status will be 
presented graphically.
8.
HEALTH ECONOMICS
This section does not apply to this study.
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REFERENCES
1.
Brunner HI, Klein-Gitelman MS, Miller MJ, et al. Minimal clinically important differences of the childhood 
health assessment questionnaire. J Rheumatol. 2005; 32(1):150-161.
2.
Consolaro A, Bracciolini G, Ruperto N, et al. Remission, minimal disease activity, and acceptable symptom 
state in juvenile idiopathic arthritis. Arthritis Rheum. 2012; 64(7):2366-2374.
3.
Filocamo G, Davì S, Pistorio A, et al. Evaluation of 21-numbered circle and 10-centimeter horizontal line 
visual analog scales for physician and parent subjective ratings in juvenile idiopathic arthritis. J Rheumatol. 
2010; 37(7):1534-1541.
4.
Giannini EH, Ruperto N Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in 
juvenile arthritis. Arthritis Rheum. 1997; 40:1202-1209.
5.
Magni-Manzoni S, Ruperto N, Pistorio A, et al. Development and validation of a preliminary definition of 
minimal disease activity in patients with juvenile idiopathic arthritis. Arthritis Rheum. 2008; 59(8):1120-1127.
6.
Nordal EB, Zak M, Aalto K, et al. Validity and predictive ability of the juvenile arthritis disease activity score 
based on CRP versus ESR in a Nordic population-based setting. Ann Rheum Dis. 2012; 71(7):1122-1127.
7.
Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile 
rheumatoid arthritis. Arthritis Rheum. 1994; 37(12):1761-1769.
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ATTACHMENT
Attachment 1: Analytical considerations on joints with joint procedure/injection 
prior to study a
Procedures/Injection
Impact on Joint Count Outcome
Synovectomy 
Not evaluable
Arthrodesis 
Not evaluable
Joint replacement 
Not evaluable
Amputation 
Not evaluable
Arthrocentesis 
Evaluable if happened > 3 months prior to baseline
Excision / Resection 
Not evaluable
Arthrotomy 
Not evaluable
Arthroscopy – surgical 
Evaluable if happened > 3 months prior to baseline
visit, otherwise not evaluable
Arthroscopy – diagnostic 
Evaluable if happened > 4 weeks prior to baseline
visit, otherwise not evaluable
Chondroplasty 
Evaluable if happened > 4 weeks prior to baseline
visit, otherwise not evaluable
Synovial cyst aspiration 
Evaluable if happened > 4 weeks prior to baseline
visit, otherwise not evaluable
Needle biopsy – synovium
Evaluable if happened > 3 months prior to baseline
visit, otherwise not evaluable
Osteotomy 
Not evaluable
Radio synovectomy 
Not evaluable
Tendon surgery 
Not evaluable
Bursal surgery 
Not evaluable
Fracture reduction 
Not evaluable
Steroid injection (IA, tendon,
sheath, bursa)
Evaluable if happened > 3 months prior to baseline
visit, otherwise not evaluable
Other injection
Not evaluable
a The joint assessors may mark a joint as not evaluable based on his clinical judgment, which is not
included in this table.
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Attachment 2: Analytical considerations on joints with injection and/or joint 
surgery for reasons NOT related to JIA during the study a
Procedures/Injection
Impact on Joint Count Outcome
Synovectomy 
Not evaluable from procedure date onward
Arthrodesis 
Not evaluable from procedure date onward
Joint replacement 
Not evaluable from procedure date onward
Amputation 
Not evaluable from procedure date onward
Arthrocentesis 
Not evaluable from procedure date onward
Excision / Resection 
Not evaluable from procedure date onward
Arthrotomy 
Not evaluable from procedure date onward
Arthroscopy – surgical 
Evaluable if happened > 3 months prior to evaluation, otherwise not 
evaluable
Arthroscopy – diagnostic 
Evaluable if happened > 4 weeks prior to evaluation, otherwise not evaluable
Chondroplasty 
Evaluable if happened > 4 weeks prior to evaluation, otherwise not evaluable
Synovial cyst aspiration 
Evaluable if happened > 4 weeks prior to evaluation, otherwise not evaluable
Needle biopsy – synovium
Evaluable if happened > 3 months prior to evaluation, otherwise not 
evaluable
Osteotomy 
Not evaluable from procedure date onward
Radio synovectomy 
Not evaluable from procedure date onward
Tendon surgery 
Not evaluable from procedure date onward
Bursal surgery 
Not evaluable from procedure date onward
Fracture reduction 
Not evaluable from procedure date onward
Steroid injection (IA, tendon,
sheath, bursa)
Evaluable if happened > 3 months prior to evaluation, otherwise not 
evaluable
Other injection
Not evaluable from procedure date onward
a The joint assessors may mark a joint as not evaluable based on his clinical judgment, which is not
included in this table.
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Attachment 3: Markedly Abnormal Laboratory Parameter Criteria
Table 3
Markedly abnormal criteria for laboratory parameters
Hematology Test 
Criteria for Markedly Abnormal Status
Hemoglobin (g/L)
Decrease > 20.0 AND Value < 100.0
Hematocrit (%) 
Value < 0.27
Total WBC (x109/L)
Value < 2.0 OR Value > 20.0
Neutrophils, absolute (x109/L)
Percent decrease 33 AND Value < 1.5
Lymphocytes, absolute (x109/L)
Percent decrease 33 AND Value < 1.5
Eosinophils, absolute (x109/L)
Percent increase 100 AND Value > 1.3
Platelet count (x109/L)
Percent decrease 50 AND Value < 75
Chemistry Test
Criteria for Markedly Abnormal Status
Alkaline phosphatase (U/L)
Percent increase 100 AND Value > 500
ALT (U/L)
Percent increase 100 AND Value > 150
AST (U/L) 
Percent increase 100 AND Value > 150
Total bilirubin
(umol/L)
Percent increase 100 AND Value > 51.3
Sodium (mmol/L) 
(Increase 10 AND Value > 150) OR (Decrease 10 AND Value < 120)
Potassium (mmol/L) 
(Increase 0.8 AND Value > 5.5) OR (Decrease 0.8 AND Value < 3.0)
Chloride (mmol/L)
Value < 85 OR Value > 120
BUN/Urea (mmol/L)
Percent increase 66 AND Value > 14.28
Creatinine (umol/L) 
Percent increase 66 AND Value > 132.6
Albumin (g/L) 
Decrease 10.0 AND Value < 30.0
Total protein (g/L) 
Value < 45 OR Value > 100
Calcium (mmol/L) 
(Increase 0.37 AND Value > 2.62) OR (Decrease 0.37 AND Value < 1.87)
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