SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Sponsor: Janssen Research & Development, LLC

1
Status: Approved, Date: 23 August 2019
Janssen Research & Development *
Clinical Protocol
SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
T1GER
Protocol CNTO148DML2001; Phase 2a
Amendment 3
SIMPONI® (golimumab)
*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 
Sciences Ireland UC; 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:
23 August 2019
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-ERI-113134249, 4.0
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.
NCT02846545

SIMPONI®  (golimumab)
Clinical Protocol CNTO148DML2001 Amendment 3
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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 6
SYNOPSIS.................................................................................................................................................. 12
TIME AND EVENTS SCHEDULE .............................................................................................................. 18
ABBREVIATIONS ...................................................................................................................................... 25
1.
INTRODUCTION................................................................................................................................ 27
1.1.
Background .................................................................................................................................... 31
1.2.
Rationale for the Study................................................................................................................... 32
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 32
2.1.
Objectives and Endpoints .............................................................................................................. 32
2.2.
Hypothesis ..................................................................................................................................... 33
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 33
3.1.
Overview of Study Design.............................................................................................................. 33
3.2.
Study Design Rationale.................................................................................................................. 38
3.2.1.
Blinding, Control, Study Periods, Treatment Groups ................................................................. 38
3.2.2.
Dose Rationale ........................................................................................................................... 39
4.
SUBJECT POPULATION.................................................................................................................. 42
4.1.
Inclusion Criteria ............................................................................................................................ 43
4.1.1.
Inclusion Criteria Applicable to All Subjects ............................................................................... 43
4.1.2.
Additional Inclusion Criteria for Responders .............................................................................. 45
4.2.
Exclusion Criteria ........................................................................................................................... 45
4.2.1.
Exclusion Criteria applicable to All Subjects .............................................................................. 45
4.2.2.
Additional Exclusion Criteria for Responders ............................................................................. 49
4.3.
Exceptions to Inclusion and Exclusion Criteria for Open-Label Extension Period ........................ 49
4.4.
Prohibitions and Restrictions ......................................................................................................... 49
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 50
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 52
6.1.
Dosage........................................................................................................................................... 52
6.2.
Dose Administration....................................................................................................................... 53
7.
TREATMENT COMPLIANCE............................................................................................................ 55
7.1.
STUDY AGENT DOSING COMPLIANCE: RECORDING AND WINDOWS ................................. 55
7.1.1.
Dosing Recording ....................................................................................................................... 55
7.1.2.
Dosing Windows ......................................................................................................................... 56
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 57
8.1.
Required Medications .................................................................................................................... 57
8.2.
Permitted Medications.................................................................................................................... 58
8.3.
Prohibited Medications................................................................................................................... 58
9.
STUDY EVALUATIONS .................................................................................................................... 59
9.1.
Study Procedures........................................................................................................................... 59
9.1.1.
Overview..................................................................................................................................... 59

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9.1.2.
Screening Period ........................................................................................................................ 60
9.1.3.
Randomization, Treatment Period, and Follow-up Period.......................................................... 62
9.1.4.
Optional Screening - Open-Label Extension .............................................................................. 64
9.1.5.
Open-Label Extension Period..................................................................................................... 64
9.1.6.
All Study Visits - Early Detection of Active Tuberculosis............................................................ 66
9.2.
Study Endpoints and Evaluations .................................................................................................. 67
9.2.1.
Efficacy Evaluations.................................................................................................................... 67
9.2.2.
Efficacy Endpoints ...................................................................................................................... 68
9.2.3.
Safety Endpoints......................................................................................................................... 69
9.2.4.
Exploratory Endpoints................................................................................................................. 69
9.3.
Clinical Pharmacology.................................................................................................................... 70
9.3.1.
Evaluations ................................................................................................................................. 70
9.3.2.
Analytical Procedures................................................................................................................. 70
9.3.3.
Pharmacokinetic Parameters ..................................................................................................... 70
9.3.4.
Immunogenicity Assessments (Antibodies to Golimumab) ........................................................ 70
9.3.5.
Clinical Pharmacology – Open-Label Extension Period............................................................. 71
9.4.
Biomarkers ..................................................................................................................................... 71
9.4.1.
Biomarkers – Open-Label Extension Period .............................................................................. 71
9.5.
Pharmacogenomic (DNA) Evaluations .......................................................................................... 72
9.5.1.
Pharmacogenomic (DNA) Evaluations – Open-Label Extension Period.................................... 72
9.6.
Safety Evaluations ......................................................................................................................... 72
9.6.1.
Safety Evaluations – Open-Label Extension Period................................................................... 75
9.7.
Sample Collection and Handling.................................................................................................... 78
9.8.
Data to be Collected by Subjects................................................................................................... 79
9.9.
Injection Site Reaction Monitoring ................................................................................................. 79
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 80
10.1.
Completion ..................................................................................................................................... 80
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study ................................................... 81
10.3.
Withdrawal From the Use of Research Samples........................................................................... 84
11.
STATISTICAL METHODS................................................................................................................. 85
11.1.
Subject Information ........................................................................................................................ 85
11.2.
Sample Size Determination ........................................................................................................... 85
11.3.
Efficacy Analyses ........................................................................................................................... 86
11.3.1.
Exploratory Efficacy Analyses – Open-Label Extension Period................................................. 87
11.4.
Pharmacokinetic Analyses............................................................................................................. 87
11.5.
Immunogenicity Analyses (Antibodies to Golimumab) .................................................................. 87
11.6.
Biomarker Analyses ....................................................................................................................... 88
11.7.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 88
11.8.
Pharmacogenomic Analyses ......................................................................................................... 88
11.9.
Safety Endpoints and Analyses ..................................................................................................... 88
11.10.
Interim Analysis.............................................................................................................................. 90
11.11.
Data Monitoring Committee ........................................................................................................... 90
12.
ADVERSE EVENT REPORTING ...................................................................................................... 90
12.1.
Definitions ...................................................................................................................................... 90
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 90
12.1.2.
Severity Criteria .......................................................................................................................... 92
12.2.
Hypoglycemia Definitions, Recording and Interpretation............................................................... 93
12.3.
Special Reporting Situations.......................................................................................................... 93
12.4.
Procedures..................................................................................................................................... 93
12.4.1.
All Adverse Events...................................................................................................................... 93
12.4.2.
Serious Adverse Events ............................................................................................................. 94
12.4.3.
Pregnancy................................................................................................................................... 95
12.4.4.
Events of Special Interest........................................................................................................... 96
12.5.
Contacting Sponsor Regarding Safety........................................................................................... 96

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13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 96
13.1.
Procedures..................................................................................................................................... 96
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 97
14.
STUDY DRUG INFORMATION......................................................................................................... 97
14.1.
Physical Description of Study Drug(s) ........................................................................................... 97
14.2.
Packaging ...................................................................................................................................... 97
14.3.
Labeling.......................................................................................................................................... 97
14.4.
Preparation, Handling, and Storage............................................................................................... 97
14.5.
Drug Accountability ........................................................................................................................ 98
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 98
16.
ETHICAL ASPECTS ......................................................................................................................... 99
16.1.
Study-Specific Design Considerations........................................................................................... 99
16.2.
Regulatory Ethics Compliance..................................................................................................... 100
16.2.1.
Investigator Responsibilities ..................................................................................................... 100
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 100
16.2.3.
Informed Consent and Assent Form......................................................................................... 101
16.2.4.
Privacy of Personal Data .......................................................................................................... 102
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 103
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 103
17.1.
Protocol Amendments.................................................................................................................. 103
17.2.
Regulatory Documentation .......................................................................................................... 104
17.2.1.
Regulatory Approval/Notification .............................................................................................. 104
17.2.2.
Required Prestudy Documentation........................................................................................... 104
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 105
17.4.
Source Documentation................................................................................................................. 105
17.5.
Case Report Form Completion .................................................................................................... 106
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 106
17.7.
Record Retention ......................................................................................................................... 107
17.8.
Monitoring .................................................................................................................................... 107
17.9.
Study Completion/Termination..................................................................................................... 108
17.9.1.
Study Completion/End of Study................................................................................................ 108
17.9.2.
Study Termination..................................................................................................................... 108
17.10.
On-Site Audits .............................................................................................................................. 109
17.11.
Use of Information and Publication.............................................................................................. 109
18.
PROTOCOL AMENDMENTS HISTORY......................................................................................... 111
REFERENCES.......................................................................................................................................... 117
INVESTIGATOR AGREEMENT ............................................................................................................... 134
LIST OF ATTACHMENTS
Attachment 1:
Quantiferon-TB Gold Testing.................................................................................... 121
Attachment 2:
Dose and Device Charts for Study CNTO148DML2001 in Subjects With 
Type 1 Diabetes ....................................................................................................... 124
Attachment 2-A:
Dosing Chart for Induction Doses at Week 0 and Week 2....................................... 124
Attachment 2-B:
Dosing Chart for Maintenance Dosing Regimens at Week 4 through Week 52 ...... 125
Attachment 2-C:
Device Selection Chart............................................................................................. 126
Attachment 3:
Procedures for Performing the Mixed-Meal Tolerance Test .................................... 127
Attachment 4:
Hepatitis B Virus (HBV) Screening........................................................................... 131
Attachment 5:
Study Defined AST and ALT Normal Ranges, 2x ULN, and 3x ULN....................... 132
Attachment 6:
Anticipated Events.................................................................................................... 133

SIMPONI®  (golimumab)
Clinical Protocol CNTO148DML2001 Amendment 3
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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Golimumab SC Dosing Regimens by Body Weight Cut-Off For Subjects Who Are 
Randomized to the Golimumab Treatment Group.................................................................... 52
Table 2:
Study Agent Dosing Window Table .......................................................................................... 56
Table 3:
Study Agent Dosing Window Table – Open-Label Extension Period....................................... 57
FIGURES
Figure 1:
Schematic Overview of the Double-Blind Period...................................................................... 34
Figure 2:
Overview of the Open-Label Extension Period......................................................................... 35
Figure 3:
Overlap of simulated golimumab exposure for dosing regimens in current T1D study 
compared to those in pJIA and pediatric UC studies................................................................ 41

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 3
22 Aug 2019
Amendment 2
09 May 2016
Amendment 1
02 Jun 2016
Original Protocol
26 Apr 2016
Amendment 3 (22 August 2019)
Overall Rationale for the Amendment: Subsequent to the granting of a single patient investigational 
new drug for a subject who had shown an increase in C-peptide at Week 52 and who had an insulin 
dose-adjusted HbA1c (IDAA1c) score less than 9, the Data Monitoring Committee recommended to 
re-start active treatment for other subjects showing a similar response profile.
Section number
and Name
Description of Change
Brief Rationale
Time and Events Schedule
Created the time and events schedule for 
open-label extension period and defined 
timepoints and study procedures for this 
period. The existing schedule was 
indicated for double-blind period.
Abbreviations used in the table were 
mentioned in the footnote.
To accommodate the open-label 
extension period of the study.
Synopsis;
2.1. Objectives, Endpoints, and 
Hypothesis;
9.2.2.4. Exploratory Efficacy 
Endpoints – Open-Label Extension 
Period;
9.2.3.1. Safety Endpoints – Open-
Label Extension Period;
11.3.1. Exploratory Efficacy 
Analyses – Open-Label Extension 
Period;
11.9. Safety Endpoints and 
Analyses
The endpoints for open-label extension 
period were defined.
6.2. Dose Administration
A reference to Section 9.1.5 in addition to 
the existing Section 9.1.3 was mentioned 
for the procedure where subjects were to 
be monitored for at least 30 minutes 
following dosing.
Synopsis;
3.1. Overview of Study Design;
4.1.2. Additional Inclusion Criteria 
for Responders
9.1.1. Overview;
9.2.1.1. Efficacy Evaluation
The requirement and timing of mixed-
meal tolerance test (MMTT) was 
differentiated for the double-blind and 
open-label extension periods.
To check for any changes in 
C-peptide AUC and to clarify 
the timing of 4-hour MMTT for 
the double-blind and open-label 
extension periods.
Synopsis;
3.1. Overview of Study Design;
4.1.2. Additional Inclusion Criteria 
for Responders;
9.1.1. Overview;
9.2.1.1. Efficacy Evaluation
The requirements for C-responders 
lacking IDAA1c score were mentioned.
To accommodate the 
C-responders without IDAA1c 
score.

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Section number
and Name
Description of Change
Brief Rationale
Synopsis;
3.1. Overview of Study Design
The study design was amended to indicate 
that responders would have an option to 
restart active therapy while non-
responders would continue to follow the 
originally planned study design. The 
definition and criteria for responders were 
defined.
The data monitoring committee 
(DMC) for the study 
recommended that responders 
should have an option to receive 
active therapy.
Synopsis;
3.2.1. Blinding, Control, Study 
Periods, Treatment Groups
The criteria for unblinding subjects after 
database lock of double-blind period was 
specified. Requirement of full renewed 
informed consent was mentioned. 
Additionally, the conditions under which 
the subjects can continue off-therapy 
follow-up period were stated.
Following an amendment in the 
study design, the 
blinding/unblinding 
requirements and a renewed 
informed consent process for 
the off-therapy follow-up period
required an update.
Synopsis;
3.2.1. Blinding, Control, Study 
Periods, Treatment Groups;
16.2.3. Informed Consent and 
Assent Form
Specified that signing of new ICF/assent 
forms will be required if subject meets the 
responder’s criteria and enters the 
open-label extension period.
To clarify the requirement of 
informed consent and assent 
forms for open-label extension 
period.
1. Introduction
The author reference ‘Lind M, 2014’ was 
removed since the reference number was 
cited.
To maintain consistency in 
citation of reference numbers 
instead of author names.
3.1. Overview of Study Design
The following text was modified as:
Following initial study screening, 
subjects must be randomized within 28 
days.
To indicate that the screening 
period mentioned within text 
belonged to double-blind 
period.
3.1. Overview of Study Design
The number of planned data base locks 
were modified for the study from 2 to 3 
and the timing of the third data base lock 
was defined.
Following an amendment in the 
study design, the data base lock 
due to inclusion of the open-
label extension period was 
defined.
4.1.1. Inclusion Criteria Applicable
to All Subjects Criterion 6;
4.4. Prohibitions and Restrictions 
Criteria 3, 4, and 6;
8.3. Prohibited Medications.
The criteria were updated to include open-
label extension period.
To indicate that the criteria were 
applicable for open-label 
extension period as well.
Synopsis;
4.1.2. Additional Inclusion Criteria 
for Responders
Additional inclusion criteria for 
“responders” who were to receive active 
drug in the open-label extension period 
was defined.
To identify patients eligible to 
continue receiving therapy in 
the open label extension period.
4.2.1. Exclusion Criteria applicable 
to All Subjects Criteria 22 and 23 
(General Restrictions)
The criteria were modified to indicate that 
they were not applicable for the 
CNTO148DML2001 trial.
To exclude 
CNTO148DML2001 trial from 
the exclusion criteria.
4.2.2 Additional Exclusion Criteria 
for Responders
Additional exclusion criteria for 
“responders” was defined.
Individuals who do not meet 
response criteria will not be 
eligible for open-label extension 
period.
4.3. Exceptions to Inclusion and 
Exclusion Criteria for Open-Label 
Extension Period
The exceptions to the initial inclusion and 
exclusion criteria for the subjects from 
open-label extension period were stated.
To include subjects who may be 
older than 21 years, may have 
become auto-antibody negative, 
and negative Epstein-Barr Virus 
(EBV) polymerase chain 
reaction (PCR) results.
4.4. Prohibitions and Restrictions 
Criteria 5 and 7
Modified the term ‘through Week 104’ to 
‘throughout the study’
To accommodate the open-label 
extension period of the study.

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Section number
and Name
Description of Change
Brief Rationale
5. Treatment Allocation and 
Blinding
Modified the following text: The Study 
Responsible Physician will remain blinded 
throughout the study double-blind period
to subject level treatment assignment and 
dosing regimen. 
To follow the amended study 
design and indicate that 
blinding is specific to double-
blind period.
5. Treatment Allocation and 
Blinding

Revised the following text to exclude 
the term ‘final’: Site investigators and 
personnel, and the subjects/caregivers 
will remain blinded until after the 
final Week 104 DBL (DBL 2) has 
occurred.

Added the following text: An 
exception to this rule will be made for 
those subjects who are meeting the 
responder criteria at Week 52 of the 
double-blind period. These will be 
unblinded to determine eligibility for 
re-starting active treatment during the 
open-label extension period.
To clarify that Week 104 DBL 
is not the final DBL and specify 
the condition for unblinding.
6.1. Dosage
The responders will not undergo an 
induction regimen but will start with the 
maintenance dose was specified. The 
reason for this was also specified.
To clarify that no induction 
regimen will be used to avoid 
risk for immunogenicity or 
hypersensitivity reactions.
7.1.1.1. Dosing Recording;
9.1.1. Overview;
9.1.2.1. Screening Period;
9.6.1. Safety Evaluations;
9.8. Data to be Collected by 
Subjects
Use of paper diary for open-label 
extension period was specified.
To clarify usage of paper diaries 
instead of eDiaries for the 
open-label extension period.
8.1. Required Medications
A reference to Section 9.8 was provided to 
indicate paper diary usage for open-label 
extension period.
Synopsis;
2. Objectives, Endpoints, and 
Hypothesis
Added objective and endpoint for open-
label extension period and clarified that 
the existing objectives and endpoints 
belonged to double-blind period.
To accommodate the open-label 
extension period and 
differentiate and provide clarity 
between the double-blind and 
open-label extension periods.
3.1. Overview of Study Design

Added schematic overview of the 
open-label extension period.

Renamed Figure 1 title from 
‘Schematic Overview of the Study’ to 
‘Schematic Overview of the Double-
Blind Period’.
6.1. Dosage;
Table 1
Study agent dosage and timings of dosage 
calculation for open-label extension 
period were mentioned. 
6.2. Dose Administration
Responsibility and timings of study agent 
administration for responders in the 
open-label extension period was added.
7.1.1.1. Dosing Recording – Open-
Label Extension Period
A separate section to define the dose 
recording for open-label extension period 
was added.
7.1.2.1. Dosing Windows - Open-
Label Extension Period
A separate section to define the dosing 
windows for open-label extension period 
was added.
8.1. Required Medications;
The timing of recording insulin use for 

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Section number
and Name
Description of Change
Brief Rationale
9.8. Data to be Collected by 
Subjects
open-label extension period was added.
9.1.1. Overview;
16.1. Study-Specific Design 
Considerations
Blood volume collection for open-label 
extension period was added.
9.1.2.1. Screening Period –
Open-Label Extension Period;
9.1.4. Optional Screening –
Open-Label Extension Period
A separate section to define the screening 
period for the open-label extension period 
was added.
9.2.1.1. Efficacy Evaluations –
Open-Label Extension Period;
9.3.5.Clinical Pharmacology –
Open-Label Extension Period;
9.4.1. Biomarkers – Open-Label 
Extension Period.;
9.5.1. Pharmacogenomic (DNA) 
Evaluations – Open-Label 
Extension Period;
9.6.1. Safety Evaluations – Open-
Label Extension Period
Separate sections for efficacy, clinical 
pharmacology, biomarkers, 
pharmacogenomic, and safety evaluations 
that pertain to open-label extension period 
were added. 
9.1.5. Open-Label Extension Period
The different periods, ie, active treatment, 
and post-treatment visit for the open-label 
extension period were described. The 
study agent self-administration and study 
procedures at different timepoints were 
also described.
9.1.6. All Study Visits – Early 
Detection of Active Tuberculosis
A reference to Section 9.1.2.1 was added 
to indicate the procedure to be followed if 
the QuantiFERON-TB Gold test is 
indeterminate. 
10.1. Completion
The study completion criteria for open-
label extension period was specified and 
the text was modified as: A subject will be 
considered to have completed the study if 
he or she has completed assessments at 
Week 104 of the study off-therapy 
follow-up period or Week 60 of the 
open-label extension period of the 
study.
10.2. Discontinuation of Study 
Treatment/Withdrawal from the 
Study
A reference to Section 9.1.2.1 was added 
under the TB screening criteria for subject 
to deem ineligible. 
11. Statistical Methods
The definition on baseline measurement 
for the open-label extension period was 
added and the existing definition was 
indicated for the double-blind period. 
11.3.1. Exploratory Efficacy 
Analyses – Open-Label Extension 
Period
The exploratory efficacy analyses for 
open-label extension period were added.
8. Prestudy and Concomitant 
Therapy
The recording of prestudy therapies in the 
CRF was indicated for double-blind 
period.
To clarify that the prestudy 
therapies belonged to double-
blind period.
9.8. Data to be Collected by 
Subjects
The criteria for transmitting BG readings 
from the glucometers was added for the 
double-blind period.
To specify the condition when 
the BG readings from 
glucometer be transmitted.

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Section number
and Name
Description of Change
Brief Rationale
Synopsis;
9.2.1.1. Efficacy Evaluations –
Open-Label Extension Period;
9.8. Data to be Collected by 
Subjects
The acceptable glucose monitoring 
techniques and recording and frequency of 
BG values for open-label extension period 
were defined.
To provide acceptable glucose 
monitoring techniques for open-
label extension period.
9.9. Injection Site Reaction 
Monitoring
Modified the following text: A physician 
must be immediately available at the site 
during the first 3 dose administrations of 
study agent for the double-blind period 
and open label treatment period.
To clearly define the 
availability of physician at the 
site during study agent dose 
administrations.
10.2. Discontinuation of Study 
Treatment/Withdrawal from the 
Study
Added the following text: Subjects who 
permanently discontinue active treatment 
during the open-label extension period 
will have their end-of-study visit followed 
by the post-treatment visit 10 weeks later.
To define that an end-of-study 
visit will be performed for the 
subjects who discontinue active 
treatment during open-label 
extension period.
10.2. Discontinuation of Study 
Treatment/Withdrawal from the 
Study
The withdrawal criteria for responders 
was specified. 
Withdrawal criteria are based 
on deterioration of C-peptide 
AUC and/or remission score, 
similar to eligibility criteria
Synopsis;
11. Statistical Methods
Specified that hypotheses testing for open-
label extension phase will not be 
performed and data generated will be 
summarized descriptively.
Provided for data analyses of 
open-label extension portion.
11.10. Statistical Methods
Added the following text: The DMC 
serves the IAC function.
To clarify that the DMC is also 
the IAC for the study.
11.4. Pharmacokinetic Analyses;
11.5. Immunogenicity Analyses 
(Antibodies to Golimumab);
11.6. Biomarker Analyses;
11.7. 
Pharmacokinetic/Pharmacodynamic 
Analyses;
11.9. Safety Endpoints and 
Analyses
A statement to indicate that the analyses 
performed for double-blind period were 
applicable for the open-label extension 
period was mentioned.
To specify the analyses for the 
open-label extension period.
11.8. Pharmacogenomic analyses
Added the pharmacogenomic analyses for 
the open-label extension period.
Abbreviations
New abbreviations, ie, C responders, C+R 
responders, IDAA1c, PCR, OL, and R 
responders were added.
To accommodate the new 
terms/abbreviations from the 
additions/revisions to the 
protocol.
References
Following literature references were 
added,

Fonolleda M, Murillo M, Vazquez F, 
Bel J, Vives-Pi M. Remission Phase 
in Paediatric Type 1 Diabetes: New 
Understanding and Emerging 
Biomarkers. Horm Res Paediatr 
2017;88:307–315

Max Andersen MLC et al. Partial 
remission definition: Validation based 
on the insulin dose-adjusted HbA1c 
(IDAA1C) in 129 Danish children 
with new-onset type 1 diabetes. 
Pediatr Diabetes. 2014;15(7):469–
476.
References added to support the 
updated study design

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Section number
and Name
Description of Change
Brief Rationale

Mortensen H. B., Hougaard P., Swift 
P., et al. New definition for the partial 
remission period in children and 
adolescents with type 1 diabetes. 
Diabetes Care. 2009;32(8):1384–
1390.

Nagl K, Hermann JM, Plamper M, et 
al. Factors contributing to partial 
remission in type 1 diabetes: analysis 
based on the insulin dose-adjusted 
HbA1c in 3657 children and 
adolescents from Germany and 
Austria. Pediatr Diabetes 
2017;18:428-434.
Throughout

Minor formatting, editorial, or spelling 
changes were made.

The term ‘participant’ was replaced 
with ‘subject’ across the protocol for 
consistency.
Minor, therefore have not been 
summarized.

Added ’OL’ before week numbers that 
pertained to the open-label extension 
period.

Added ‘double-blind’ against week 
numbers or periods that pertained to 
the double-blind period.
To differentiate between 
open-label extension and 
double-blind periods.

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SYNOPSIS
SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
SIMPONI® (golimumab) is a fully human monoclonal antibody which binds to human tumor necrosis 
factor alpha (TNFα) with high affinity and specificity and neutralizes TNFα bioactivity. Golimumab was 
first approved by the United States Food and Drug Administration (FDA) in 2009 and has been shown to 
be safe and efficacious in adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing 
spondylitis (AS), and ulcerative colitis (UC). Additionally, golimumab has been evaluated in studies 
conducted under an Investigational New Drug (IND) for the treatment of polyarticular juvenile idiopathic 
arthritis (pJIA; 2 up to 18 years of age), and pediatric UC (2 up to 18 years of age).
Similar to these above conditions, Type 1 diabetes (T1D) is an autoimmune disorder with severe 
sequelae, but there are no approved disease modifying therapies for those with T1D. Children and young 
adults are those that most frequently develop T1D and have the most urgent need for a disease modifying 
therapy to reduce the associated short- and long-term morbidity and mortality. This study will evaluate 
whether golimumab administered subcutaneously (SC) in this population with newly diagnosed T1D has 
the potential to maintain residual β-cell function and improve metabolic control.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS

Double-Blind Period
Objectives
Endpoints
Primary Objective and Endpoints

To determine if golimumab can preserve β-cell 
function in children and young adults with 
newly diagnosed T1D.

The Mixed-meal Tolerance Test (MMTT) -
stimulated 4-hour C-peptide area under the 
concentration-time curve (AUC) at Week 52.
Secondary Objectives and Endpoints: Efficacy 

To evaluate the impact of golimumab on 
measures of diabetes control in this subject 
population.

To evaluate the off-therapy durability of 
golimumab on measures of diabetes control in 
this subject population. 

Change from baseline in insulin use in units 
per kilogram body weight per day over time.

Change from baseline in HbA1c over time.

Hypoglycemic event rates (defined as blood 
glucose levels (BG) of ≤70, 55, and 
35 mg/dL or clinical sequelae in the absence 
of a BG reading) through Week 52, after 
Week 52 through Week 104, and the entire 
study.

MMTT-stimulated 4-hour C-peptide AUC 
over time.
Secondary Objective and Endpoints: Safety 

To determine the safety and tolerability of 
golimumab in children and young adults with 
T1D.

Proportion of subjects with treatment-
emergent adverse events (AEs) and severe 
AEs through Week 52 and 104.

Proportion of subjects with severe infections 
through Week 52 and 104.

Proportion of subjects with study agent 
injection site reactions through Week 52.

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Objectives
Endpoints
Secondary Objective and Endpoints: Pharmacokinetics (PK) and Immunogenicity 

To evaluate the PK and immunogenicity of 
golimumab in this specific subject population 
with T1D.

Summary 
of 
serum 
golimumab 
concentrations and the PK profile after 
induction and maintenance dosing.

Incidence 
and 
titers 
of 
antibodies 
to 
golimumab. 
Exploratory Objective and Endpoints: Immunologic and Metabolic

To 
evaluate 
how 
golimumab 
impacts 
immunologic profiles and indicators of β-cell 
stress, and the correlation with efficacy and 
safety endpoints in this study.

Correlation of cellular and serologic immune 
profiles with clinical metabolic outcomes on-
therapy (Weeks 12, 26, 38, and 52) and 
off-therapy (Weeks 78 and 104).

Relationship of exploratory markers of β-cell 
stress and survival with clinical metabolic 
outcomes on-therapy (Weeks 12, 26, 38, and 
52) and off-therapy (Weeks 78 and 104).

Open-Label Extension Period
Objective
Endpoint

To evaluate additional one year of safety and 
exploratory 
efficacy 
endpoints
in 
those 
participants that have shown a particular 
response in the double-blind period.

Continue to evaluate safety and exploratory
efficacy endpoints as per the Time and 
Events 
Schedule 
(open-label 
extension 
period) and no new efficacy hypotheses will 
be tested compared to the double-blind 
period.
Hypothesis
The primary hypothesis to be tested in this study is that golimumab is superior to placebo in maintaining 
β-cell function in children and young adults with newly diagnosed T1D as measured by mixed-meal 
tolerance test (MMTT)-stimulated 4-hour C-peptide AUC at Week 52.
OVERVIEW OF STUDY DESIGN
This is a Phase 2a randomized, double-blind, placebo-controlled, parallel-group, multicenter, study of 
golimumab in subjects with new-onset T1D.
The duration of study participation will be 108 weeks, including screening and post-randomization. 
Following screening, subjects must be randomized within 28 days. Following randomization there will be 
a 52-week treatment period with study agent followed by a 52-week off-therapy follow-up period.
Responders at Week 52 who are still in the follow-up period and who are determined to be in the active 
treatment group will have the option to restart active therapy while the non-responders will continue to 
follow the originally planned study design, ie, the off-therapy follow-up monitoring period.
There will be an open-label extension period of the study for responders. Responders are defined as 
subjects who have profile at Week 52 which includes:

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1.
C-peptide and Remission score* responders (C+R responders): either having an increase in 
C-peptide AUC versus baseline or having a stable C-peptide AUC, not decreasing more than 5% 
versus baseline and having a remission score ≤9.
OR
2.
C-peptide responders (C responders): either having an increase in C-peptide AUC versus baseline or 
having a stable C-peptide AUC, not decreasing more than 5% versus baseline but not meeting a 
remission score of ≤9. Their remission score, however, must be <12.
OR
3.
Remission score responders (R responders): having a remission score ≤9 but not meeting C-peptide 
response as defined above. However, their C-peptide AUC decline from baseline should be less than 
or equal to 30% compared to baseline.
*Insulin Dose Adjusted HbA1c: IDAA1c= A1C (percent) + [4 × insulin dose (units per kilogram per 
24 h)].
This study will enroll male and female subjects 6 through 21 years of age who have been recently 
diagnosed with T1D and are able to be randomized within 100 days of diagnosis. A target of 
approximately 81 subjects will be randomly assigned in a 2:1 ratio to receive golimumab or placebo, 
administered SC for 52 weeks and monitored for an additional 52 weeks. Subjects will be randomized to 
receive active therapy (golimumab) or placebo and be stratified based on C-peptide AUC levels of 
<0.66 pmol/mL or ≥0.66 pmol/mL from a 4-hour MMTT conducted at study screening. The protocol will 
give the option for study agent administration by the subject or caregiver outside of the study site, ie, 
self-administration, after proper training.
An independent Data Monitoring Committee will be commissioned to continually assess the safety of 
study subjects.
Following database lock for the double-blind treatment period (Week 52), subjects who are still in the 
off-therapy follow-up period (Week 52 to 104 visits), who were on active drug during the double-blind 
period and who meet the response criteria will be offered the option to participate in the open-label 
extension period if eligibility criteria are met. Prior to initiating open-label screening assessments, 
subjects and parents/legal guardians will sign updated informed consent form/assent forms.
Subjects who did not meet the response criteria at Week 52 will continue the off-therapy follow-up 
period.
Subjects who met the response criteria but either declined to participate in the open-label extension 
period, or were determined to be on placebo, will continue the off-therapy follow-up period as planned.
SUBJECT POPULATION
Male or female subjects 6 through 21 years of age who meet the American Diabetes Association (ADA)
standard T1D criteria within 100 days of randomization. Subjects must be positive for at least 1 of the 
following diabetes-related autoantibodies obtained at study screening:

Glutamic acid decarboxylase (GAD-65)

IA-2

ZnT8

ICA; or

Insulin (if obtained within 10 days of the onset of exogenous insulin therapy)

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Subjects must be medically stable on the basis of physical examination, medical history, and vital signs 
performed at screening and have a stimulated C-peptide level ≥0.2 pmol/mL following a 4-hour MMTT 
obtained at study screening.
The responders for open-label extension period must meet the MMTT criteria at Screening for the 
open-label extension period. If the most recent MMTT is <3 months ago, a repeat MMTT is not required. 
Subjects who had their most recent safety laboratory samples drawn within 1 month prior to screening do 
not need a repeat; eligibility will be assessed based on these most recent laboratory tests. For 
C-responders who are lacking the necessary information to calculate IDAA1c score, an HbA1c will be 
performed and 10 days of insulin dose information will be required.
DOSAGE AND ADMINISTRATION
All study agent (golimumab or placebo) will be administered subcutaneously using a sponsor-supplied, 
single-use administration device. This will be either the commercially available prefilled syringe with 
needle guard (the PFS-Ultrasafe [PFS-U]), designed to deliver a single, fixed dose of 50 mg, or the 
investigational VarioJect injection device (“VarioJect”) which delivers a single, variable dose of 10 to 
45 mg in 5 mg increments. Identical devices containing placebo will be used to deliver a volume 
equivalent to that of active treatment for subjects randomized to the placebo arm.
EFFICACY EVALUATIONS
The following efficacy evaluations will be assessed:

A 4-hour MMTT will be performed to assess C-peptide levels and the C-peptide AUC at screening
and Weeks 12, 26, 38, 52, 78, and 104 of the double-blind period. During the open-label extension 
period, a 4-hour MMTT will be performed at OL screening (unless performed <3 months ago), OL
Week 28, and OL Week 52. For C-responders who are lacking the necessary information to calculate 
IDAA1c score, an HbA1c will be performed and 10 days of insulin dose information will be 
required. For additional details, see the Time and Events Schedule.

Blood glucose levels between visits will be obtained by downloading home-glucometer readings.
During the open-label extension period, subjects may use either fingersticks or continuous glucose 
monitoring (CGM) at the discretion of the investigator and/or according to local practice. The 
subjects will not be required to download BG values from the eDiary.

Hemoglobin A1c (as % HbA1c) and insulin as U/kg body weight/day. An HbA1c measurement will 
be done at each study visit and subjects should record the type and amount of insulin they have used 
during the 7-day period immediately preceding each study visit. During the open-label extension 
period, subject will record insulin usage on paper diary for 10 days prior to each study visit.

Hypoglycemic events, defined as a BG level of ≤70 mg/dL or clinical sequelae consistent with 
hypoglycemia without a BG reading, will be documented throughout the study.

Records of glucose measurements, insulin use and hypoglycemic events and communication with the 
subject will be kept in source documentation, on the appropriate case report form, or in the patient 
diary.
CLINICAL PHARMACOLOGY EVALUATIONS
Serum samples will be used to evaluate the pharmacokinetics (PK), the immunogenicity of golimumab 
(antibodies to golimumab), and pharmacodynamics (PD; free/total TNF) at the timepoints presented in 
the Time and Events Schedule.
Serum golimumab concentrations will be summarized for each treatment group over time. If necessary, a 
population PK analysis will be performed to characterize the PK of golimumab as well as to identify and 
quantify important covariates of PK using a nonlinear mixed effects modeling approach. If visual trends 

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are observed, a suitable PK/pharmacodynamic model may be developed to describe the 
exposure-response relationship.
To assess the immunogenicity of golimumab, detection of antibodies to golimumab will be performed 
using a validated assay method. Serum samples will be evaluated for antibodies binding to golimumab 
and the titer of confirmed positive samples and the incidence of antibodies to golimumab will be reported. 
Other analyses may be performed to more fully characterize the immunogenicity of golimumab in this 
population.
BIOMARKER EVALUATIONS
Serum and cell-based biomarkers will be evaluated for inflammation-associated proteins, changes in 
immune cell subsets, and will be used to better understand the biology of T1D, to provide a biological 
assessment of the response of subjects to treatment with golimumab, to analyze differences between 
responders and nonresponders, and to determine if the markers can be used to classify patients as 
potential responders prior to treatment.
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenetics blood sample for molecular major histocompatibility complex (MHC) haplotyping 
will be collected from all subjects at the start of the study. Exploratory pharmacogenomic research may 
consist of the analysis of one or more genetic markers throughout the genome in relation to golimumab or 
T1D clinical endpoints. Participation in exploratory pharmacogenetics research is optional. Subjects will 
need to provide consent/assent to participate in the exploratory phase of the pharmacogenetics research.
Pharmacogenomic assessment of molecular MHC haplotype and insulin DNA methylation will not be 
performed for the open-label extension period. The open-label extension period will include PBMC 
sample collection and serum biomarker sample collection.
SAFETY EVALUATIONS
Monitoring and evaluation of subjects in this study will focus on study agent, device-related, and 
disease-related safety issues. Monitoring will include physical examinations, clinical laboratory tests, vital 
signs, concomitant medications, and adverse events, including injection site reactions.
STATISTICAL METHODS
Descriptive statistics (eg, mean, median, standard deviation [SD], minimum, and maximum) will be used 
to summarize continuous variables. Counts and percentages will be used to summarize categorical 
variables. Graphic data displays may also be used to summarize the data.
The sample size calculation is based on the primary endpoint, an MMTT 4-hour C-peptide AUC at 
Week 52. Due to skewed C-peptide AUC data, normalizing transformation of log (AUC +1) is applied for 
sample size assessment. The method has been well accepted and used in numerous clinical studies. Based 
on published data, a common SD of log (AUC+1) of 0.215 is assumed, and the back-transformed means 
for 4-hour C-peptide AUC are assumed to be 0.385 and 0.635 for the placebo and golimumab groups 
respectively, ie the expected treatment difference (back-transformed) is 0.25. With 81 subjects (54 on 
golimumab and 27 on placebo) and an alpha of 0.05 (2-sided), there is 90% power to detect the treatment 
difference through a two-sample t-test.
All efficacy analyses will be performed on the modified intent-to-treat (mITT) population unless 
otherwise specified. The mITT population includes all randomized subjects who have received at 1 dose 
of study agent. The primary efficacy endpoint will be analyzed by using a mixed model for repeated 
measures.

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Safety assessments will include the examination of the incidence rates of AEs, vital signs, clinical 
laboratory parameters, and physical examinations. Safety analyses will be conducted on the safety 
analysis set, which is defined as all subjects who have received at least 1 dose of study agent.
An interim analysis using the 4-hour C-peptide AUC in response to a MMTT is planned for the study 
after at least 60% of subjects complete their Week 26 MMTT assessment. The primary goal of this 
interim analysis is to obtain an early read on treatment effect to facilitate planning of future studies.
All the efficacy endpoints defined for the double-blind period will be exploratory for the open-label 
extension period and will be summarized descriptively; there will be no hypotheses testing during the 
open-label extension period. Disease progression will be compared between the double-blind period and 
the extension period in subjects who attended the open-label extension period if deemed reasonable.

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TIME AND EVENTS SCHEDULE
Double-Blind Period
Screening Through Off-therapy Follow-up
Study Designation
Screening
Active Treatmentb,c
Off-therapy Follow-
upd
Study Weeka
-4 to -1
0
2
4
8
12
18
26
33
38
45
52
78
104
(EOSV)r
Study Daya (visit window in 
days)
-28 to -1
1
15
(±1)
29
(±1)
57
(±3)
85
(±3)
127
(±3)
183
(±3)
232
(±7)
267
(±3)
316
(±7)
365
(±3)
547
(±10)
729
(±10)
Study Procedure
Screening/Administrative
Informed consent/assent 
(ICF)
X
Pharmacogenetics 
consent/assente
X
Inclusion/exclusion criteria 
evaluation/review
X
X
Dispense electronic diary 
(eDiary) and glucometer and 
trainingf
X
Clinical Assessments / Ongoing Review
Full Physical examination
X
X
Brief physical examination
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height & Body weight 
measurement
X
X
X
X
X
X
X
X
Medical history and 
demographics
X
Interval history and eDiary 
review
X
X
X
X
X
X
X
X
X
X
X
X
X
Previous/concomitant 
medication review
X
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
Tuberculosis (TB) exposure 
review 
X
X
X
X
X
X
X
X
X
X
X
X
X
X

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Screening Through Off-therapy Follow-up
Study Designation
Screening
Active Treatmentb,c
Off-therapy Follow-
upd
Study Weeka
-4 to -1
0
2
4
8
12
18
26
33
38
45
52
78
104
(EOSV)r
Study Daya (visit window in 
days)
-28 to -1
1
15
(±1)
29
(±1)
57
(±3)
85
(±3)
127
(±3)
183
(±3)
232
(±7)
267
(±3)
316
(±7)
365
(±3)
547
(±10)
729
(±10)
Study Procedure
Randomization and Study Agent Administration
Randomization
X
Dose determination and 
modification
X
X
X
X
Required study agent 
administration at study siteg
X
X
X
X
X
X
X
X
X
Subjects participating in self-administrationb
Injection training by site 
personnelb
X
X
X
Distribute study agent 
injection devices
X
X
X
X
X
Xg
X
Xg
Return study agent injection 
devices
X
X
X
X
X
X
X
X
Subject Reported Data / eDiary Review
Glucometer reading review
X
X
X
X
X
X
X
X
X
X
X
X
X
Insulin use report review
X
X
X
X
X
X
X
X
X
X
X
X
X
Hypoglycemia event review
X
X
X
X
X
X
X
X
X
X
X
X
X
Study agent self-
administration reviewb
X
X
X
X
X
X
X
X
Clinical Laboratory Assessments
4h - Mixed-meal tolerance 
test (MMTT)h
X
X
X
X
X
X
X
HbA1c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Type 1 diabetes 
autoantibodiesi
X
X
X
X
X
QuantiFERON-Gold test
X
Serum pregnancy testj
X
Urine pregnancy testj
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematologyk
X
X
X
X
X
X
X
X
X

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Screening Through Off-therapy Follow-up
Study Designation
Screening
Active Treatmentb,c
Off-therapy Follow-
upd
Study Weeka
-4 to -1
0
2
4
8
12
18
26
33
38
45
52
78
104
(EOSV)r
Study Daya (visit window in 
days)
-28 to -1
1
15
(±1)
29
(±1)
57
(±3)
85
(±3)
127
(±3)
183
(±3)
232
(±7)
267
(±3)
316
(±7)
365
(±3)
547
(±10)
729
(±10)
Study Procedure
Chemistryk
X
X
X
X
X
X
X
X
X
Viral serologyl
X
Polymerase chain reaction 
(PCR) Viral loadm
X
X
X
X
X
X
X
Clinical Pharmacology
Golimumab concentrationn
X
X
X
X
X
X
X
X
X
X
X
X
Antibodies to golimumabn
X
X
X
X
X
X
X
X
Free/total TNFαn
X
X
X
X
X
X
X
X
X
X
X
X
Biomarkers and Pharmacogenomicss
Major histocompatibility 
complex (MHC) haplotypeo
X
Peripheral blood 
mononuclear cell (PBMC) 
sample collectionp
X
X
X
X
X
X
X
Serum biomarker samplep
X
X
X
X
X
X
X
DNA methylation 
(Optional)q
X
X
X
X
X
X
X
Abbreviations: eDiary=electronic diary, EOSV=End of Study Visit, ICF=informed consent, IDAA1c=insulin dose-adjusted HbA1c, MHC=major histocompatibility 
complex, MMTT=mixed-meal tolerance test, PBMC=peripheral blood mononuclear cell, PCR=polymerase chain reaction, TB=tuberculosis, TNFα=tumor necrosis 
factor alpha
a.
The study visit Week and target study visit Day are indicated and calculated based on the day of randomization. Acceptable windows for study visits in days before 
(-) or after (+) target study visit day are indicated and based on if study agent dosing will be given at that visit and time enrolled in the study.
b.
Subjects/caregivers will be given the option for at home “self-administration” for study agent doses after Week 4, since the dosing schedule for subject is q2w 
through Week 52. Training on self-administration will be provided at Weeks 0, 2, and 4. (See Section 6.2 for details). These subjects will record data regarding self-
administration in an eDiary (See Section 7.1.1) or if self-administering at the site, the data will be recorded in the study site’s documents, not in the eDiary.
c.
Subjects not participating in self-administration will schedule study agent dosing-only visits every 2 weeks through Week 52 (see Section 9.1.3).
d.
The 52-week off-therapy follow-up phase of the study begins after the completion of all assessments and administration of study agent for Week 52.

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e.
All subjects must participate in pharmacogenomics evaluation of molecular MHC haplotyping at the start of the study. Subjects do have the option to participate in 
the additional pharmacogenomic (PG) evaluations in this study and to do so subjects/caregivers must sign the PG informed consent/assent form indicating 
willingness to participate. These optional PG samples will be collected only from subjects who sign the PG informed consent/assent.
f.
For those who do not meet study criteria or choose not to participate in this study, instructions on how to return the eDiary and glucometer will be given.
g.
This does not represent all study agent dosings. Study agent is to be administered every 2 weeks. At Weeks 0, 2, and 4, administration will occur during study visits. 
At week 8, 12, 18, 26, 38 and 52 study visits where study agent will be administered, either subjects/caregivers or study staff may administer the injection. At the 
required visits in this table, drawing of pharmacokinetic/immunogenicity (ie, golimumab concentration and antibodies to golimumab) samples must take place 
prior to study agent administration at visits where study agent dosing occurs. Following study agent administration subjects will be observed for 30 minutes for 
symptoms of injection reactions. At Week 33 and Week 45, pharmacokinetic samples will be drawn and resupply of study agent injection devices will occur; no 
dosing will occur at these 2 specific study visits.
h.
The MMTT will be a 4-hour assessment to be conducted in the morning after an overnight fast. All other blood samples should be drawn prior to the MMTT. When 
MMTT occurs on study agent dosing days, study agent should be administered after the MMTT.
i.
Type 1 diabetes autoantibodies including glutamic acid decarboxylase (GAD-65), insulin, IA-2, ZnT8 and ICA.
j.
Females of childbearing potential must have a negative serum pregnancy at screening and a negative urine pregnancy test prior to administration of study agent.
k.
Specifics tests are described in Section 9.6. Note: Fasting lipid panel only done at screening, Week 12, 26, 38, 52, 78 and 104. Coagulation panel (PT/PTT/INR) 
only done at screening.
l.
Viral serology panels to include: CMV, EBV, HepB, HepC, HIV.
m. Quantitative PCR testing for CMV and EBV.
n.
The same serum samples may be used for the measurement of golimumab concentration, detection of antibodies to golimumab and amounts of free/total TNF. 
Drawing of these samples must take place prior to study agent administration at visits where study agent dosing occurs. Priority of analysis depending on sample 
volume is: PK, ADA, NAB, total TNF, free TNF. Additional serum samples for golimumab concentration and Total/Free TNFα will be collected at Week 33 and 
Week 45.
o.
Required pharmacogenomic assessment of molecular MHC haplotype.
p.
Anticipated assessments may include T- and B-cell subset analysis by multicolor flow cytometry and serum protein/cytokine profiling.
q.
Optional pharmacogenomics assessments anticipated to include insulin DNA methylation.
r.
End of Study Visit assessments: May be used in instances where subjects withdraw early from the study, see Section 10.2.
s.
All biomarker and pharmacogenomics samples must be collected prior to study agent administration.
.

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Open-Label Extension Period
Open-Label Extension Period
Study Designation
Screeningq
Active Treatmentb,c
Post-Treatmentd
Study Weeka
OL 0
OL 2
OL 4
OL 12
OL 20
OL 28
OL 36
OL 44
OL 52 
(EOSV)n
OL 60 or 10 
weeks post last 
dose
Study Daya (visit window in days)
-14 to -1
1
15
(±1)
29
(±3)
85
(±3)
141
(±3)
197
(±3)
253
(±3)
309
(±3)
365
(±3)
421
(±7)
Study Procedure
Screening/Administrative
Informed consent/assent (ICF)
Xp
Inclusion/exclusion criteria 
evaluation/review
X
X
Dispense dosing, insulin and 
hypoglycemia paper diarye
X
X
X
X
X
X
X
X
X
Clinical Assessments / Ongoing Review
Full Physical examination
X
X
X
Brief physical examination
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
Height & Body weight measurement
X
X
X
X
X
Interval history and paper diary 
review
X
X
X
X
X
X
X
X
X
Previous/concomitant medication 
review
X
X
X
X
X
X
X
X
X
X
X
IDAA1c
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
Tuberculosis (TB) exposure review 
X
X
X
X
X
X
X
X
X
X
X
Randomization and Study Agent Administration
Dose determination and 
modification
X
X
X
X
Required study agent administration 
at study sitef
X
X
X
X
X
X
X
X
Subjects participating in self-administrationb
Injection training by site personnelb
X

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Open-Label Extension Period
Study Designation
Screeningq
Active Treatmentb,c
Post-Treatmentd
Study Weeka
OL 0
OL 2
OL 4
OL 12
OL 20
OL 28
OL 36
OL 44
OL 52 
(EOSV)n
OL 60 or 10 
weeks post last 
dose
Study Daya (visit window in days)
-14 to -1
1
15
(±1)
29
(±3)
85
(±3)
141
(±3)
197
(±3)
253
(±3)
309
(±3)
365
(±3)
421
(±7)
Study Procedure
Distribute study agent injection 
devices
X
X
X
X
X
X
Return study agent injection devices
X
X
X
X
X
X
Subject Reported Data / Paper Review
Insulin use report review
X
X
X
X
X
X
X
X
X
X
Hypoglycemia event review
X
X
X
X
X
X
X
X
X
X
Study agent self-administration 
reviewb
X
X
X
X
X
X
X
Clinical Laboratory Assessments
4h - Mixed-meal tolerance test 
(MMTT)g
X
X
X
HbA1c
X
X
X
X
X
X
X
X
X
X
X
QuantiFERON-Gold test
X
Serum pregnancy testh
X
Urine pregnancy testh
X
X
X
X
X
X
X
X
X
X
Hematologyi
X
X
X
X
X
X
X
Chemistryi
X
X
X
X
X
X
X
Viral serologyj
X
Polymerase chain reaction (PCR) 
Viral loadk
X
X
X
X
Clinical Pharmacology
Golimumab concentrationl
X
X
X
X
X
Antibodies to golimumabl
X
X
X
X
X
X
Free/total TNFαl
X
X
X
X
X
X
Biomarkers and Pharmacogenomicso
Peripheral blood mononuclear cell 
(PBMC) sample collectionm
X
X
Serum biomarker samplem
X
X
Abbreviations: EOSV=End of Study Visit, ICF=informed consent, IDAA1c=insulin dose-adjusted HbA1c, MHC=major histocompatibility complex, MMTT=mixed-
meal tolerance test, OL=open-label, PBMC=peripheral blood mononuclear cell, PCR=polymerase chain reaction, TB=tuberculosis, TNFα=tumor necrosis factor alpha

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a.
The study visit Week and target study visit Day are indicated and calculated based on the day of first dose. Acceptable windows for study visits in days before (-) or 
after (+) target study visit day are indicated and based on if study agent dosing will be given at that visit and time enrolled in the study.
b.
Subjects/caregivers will be given the option for at home “self-administration” for study agent doses after OL Week 4, since the dosing schedule for subject is q2w 
through OL Week 50. Training on self-administration will be provided at OL Week 0 (See Section 6.2 for details). These subjects will record data regarding self-
administration in the paper diary (See Section 7.1.1.1) or if self-administering at the site, the data will be recorded in the study site’s documents, not in the paper 
diary.
c.
Subjects not participating in self-administration will schedule study agent dosing-only visits every 2 weeks through OL Week 50 (see Section 9.1.39.1.5).
d.
The post-treatment visit will be conducted for all subjects at OL Week 60 or 10 weeks after the last dose of study agent to collect SAEs and AEs of interest since 
the last visit unless the subject has died, has been lost to follow-up, or has withdrawn consent.
e.
For those who do not meet study criteria or choose not to participate in this study, instructions on how to return the paper diary will be given.
f.
This does not represent all study agent dosings. At OL Weeks 0, 2, and 4, administration will occur during study visits. At OL Weeks 12, 20, 28, 36, 44, and 50
study visits where study agent will be administered, either subjects/caregivers or study staff may administer the injection. At the required visits in this table, 
drawing of pharmacokinetic/immunogenicity (ie, golimumab concentration and antibodies to golimumab) samples must take place prior to study agent 
administration at visits where study agent dosing occurs. Following study agent administration subjects will be observed for 30 minutes for symptoms of injection 
reactions. The last dose of study agent is to be administered at Week 50. See Section 6.1 and Section 9.1.5.3.
g.
The MMTT will be a 4-hour assessment to be conducted in the morning after an overnight fast. All other blood samples should be drawn prior to the MMTT. When 
MMTT occurs on study agent dosing days, study agent should be administered after the MMTT.
h.
Females of childbearing potential must have a negative serum pregnancy at screening and a negative urine pregnancy test prior to administration of study agent.
i.
Specifics tests are described in Section 9.6.1. Note: Lipids will not be measured during the open-label extension period. Coagulation panel (PT/PTT/INR) only done 
at screening.
j.
Viral serology panels to include: CMV, EBV, HepB, HepC, HIV.
k.
Quantitative PCR testing for CMV and EBV. For the open-label extension period, subjects may begin open-label study agent while EBV PCR results are pending 
and if he/she meets all other inclusion/exclusion criteria. If EBV PCR results come back positive, subject must immediately stop treatment and be withdrawn from 
the study.
l.
The same serum samples may be used for the measurement of golimumab concentration, detection of antibodies to golimumab and amounts of free/total TNF. 
Drawing of these samples must take place prior to study agent administration at visits where study agent dosing occurs. Priority of analysis depending on sample 
volume is: PK, ADA, NAB, total TNF, free TNF.
m. Anticipated assessments may include T- and B-cell subset analysis by multicolor flow cytometry and serum protein/cytokine profiling.
n.
End of Study Visit assessments: May be used in instances where subjects withdraw early from the study, see Section 10.2. Subjects who permanently discontinue 
active treatment during the open-label extension period will have their end-of-study visit followed by the post-treatment visit 10 weeks later.
o.
All biomarker and pharmacogenomics samples must be collected prior to study agent administration.
p.
The retreatment screening visit should occur within 4 weeks of site notification of responders.
q.
The optional screening visit should take place no later than 21 days after the subject has been offered the opportunity to enter open-label extension period and in any 
event must occur within 14 days prior to Week 104.

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ABBREVIATIONS
ADA
American Diabetes Association
ADR
adverse drug reaction 
AE
adverse event
ALT
alanine aminotransferase 
ANCOVA
analysis of covariance 
anti-HBc
hepatitis B core antibody
ARC
Anticipated Event Review Committee
AS
ankylosing spondylitis
AST
aspartate aminotransferase 
AUC
area under the concentration-time curve
BCG
Bacille Calmette-Guérin 
BG
blood glucose
BSA
body surface area
C responders
C-peptide responders
CD
Crohn’s Disease
CDC
Centers for Disease Control and Prevention
CDE
certified diabetes educator
CL/F
apparent total systemic clearance
CMV
Cytomegalovirus
CRF
case report form(s) (paper or electronic as appropriate for this study)
C+R 
responders
C-peptide and remission score responders
DBL
data base lock 
DKA
diabetic ketoacidosis 
DMC
Data Monitoring Committee
EBV
Epstein-Barr virus
eDC
electronic data capture
eDiary
electronic diary 
FDA
Food and Drug Administration
GAD-65
Glutamic acid decarboxylase 
GCP
Good Clinical Practice
HbA1c
hemoglobin A1c
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HPV
human papillomavirus 
IAC
Interim Analysis Committee
IDAA1c
insulin dose-adjusted HbA1c
IB
Investigator Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IFU
instructions for use
IL
interleukin-
IND
Investigational New Drug 
IRB
Institutional Review Board
IWRS
interactive web response system
LQC
lowest quantifiable concentration 
MedDRA
Medical Dictionary for Regulatory Activities
MHC
major histocompatibility complex
mITT
modified intent-to-treat
MMRM
mixed model for repeated measures 
MMTT
Mixed-meal Tolerance Test 
MS
multiple sclerosis 
MTX
methotrexate

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NAb
neutralizing antibody
NONMEM
NONlinear Mixed Effects Modeling 
NPH
Neutral Protamine Hagedorn 
OL
open-label
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
pharmacodynamic(s)
PE
physical examination
PFS-U
UltraSafe Passive® Delivery System assembled with PFS
pJIA
polyarticular juvenile idiopathic arthritis
PK
pharmacokinetic(s)
PQC
Product Quality Complaint
PsA
psoriatic arthritis
PsO
psoriasis
q2w
every 2 weeks 
q4w
every 4 weeks
R responders
remission score responders
RA
rheumatoid arthritis
SAE
serious adverse event 
SAP
Statistical Analysis Plan 
SC
subcutaneous
SD
standard deviation 
SIPPM
Study Site Investigational Product and Procedures Manual
SLE
systemic lupus erythematosus 
SUSAR
suspected unexpected serious adverse reaction
T1D
type 1 diabetes
TB
tuberculosis 
TE
target engagement
TNFα
tumor necrosis factor alpha 
UC
ulcerative colitis
ULN
upper limit of normal
V/F
apparent volume of distribution

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1.
INTRODUCTION
SIMPONI® (golimumab) is a fully human monoclonal antibody which binds to human tumor 
necrosis factor alpha (TNFα) with high affinity and specificity and neutralizes TNFα bioactivity. 
Golimumab was first approved by the United States Food and Drug Administration (FDA) in 
2009 and has been shown to be safe and efficacious in adults with rheumatoid arthritis (RA), 
psoriatic arthritis (PsA), ankylosing spondylitis (AS), and ulcerative colitis (UC). Additionally, 
golimumab has been evaluated in studies conducted under an Investigational New Drug (IND) 
for the treatment of polyarticular juvenile idiopathic arthritis (pJIA; 2 up to 18 years of age), and 
pediatric UC (2 up to 18 years of age).
Similar to these above conditions, Type 1 diabetes (T1D) is an autoimmune disorder with severe 
sequelae, but there are no approved disease modifying therapies for those with T1D. Children 
and young adults are those that most frequently develop T1D and have the most urgent need for 
a disease modifying therapy to reduce associated short- and long-term morbidity and mortality. 
This study will evaluate whether golimumab administered subcutaneously (SC) in this 
population with newly diagnosed T1D has the potential to maintain residual β-cell function and 
improve metabolic control.
For the most comprehensive nonclinical and clinical information regarding golimumab, refer to 
the latest version of the Investigator's Brochure and Addenda for golimumab.
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.
Type 1 Diabetes
Type 1 diabetes (T1D) is an autoimmune disease that results in the progressive destruction of 
pancreatic cells leading to an absolute insulin deficiency and life-long daily exogenous insulin 
therapy.14,17 There is no cure nor approved disease modifying therapy for T1D. Every day, those 
with T1D are impacted by this disease as they require insulin injections for survival which must 
be calculated based on regular blood glucose (BG) checks, diet and exercise. Those with T1D are 
at high risk of acute sequelae from hypo- and hyper-glycemic and in the longer-term severe 
renal, cardiac, and vascular disease.6,17,72 Those who develop T1D early in life are at increased 
risk for significant neurocognitive disorder including behavioral issues, lower intellectual 
performance and motor dysfunction, and associated structural changes in the brain.4,7,44,49 Recent 
data indicate that even adhering to the most current recommendations and using the most 
advanced approaches for glycemic control, mortality for those with T1D is 2-fold greater than 
age-matched controls.45 Even though outwardly those with T1D may appear healthy, they are at 
high risk for a number of severe short- and long-term life-impacting and threatening sequelae 
including sudden death.15,64 Most sequelae accumulate over time and do not appear to be 
“preventable” even with the most exacting attempts of exogenous glycemic control, and thus 
those who would most benefit from a disease modifying therapy are those who develop disease 
earlier in life.27,41,43,75

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In the United States, approximately 3 million people have this disease.17,71 It most often presents 
in children and adolescence and is one of the 3 most prevalent severe chronic diseases of 
childhood, along with asthma and cancer.46,71 The annual incidence is highest in children and 
young adults with ~20 to 25 cases/100,000/year in those younger than 20 years old and there is 
approximately 30,000 total new cases of T1D annually in North America.34,71 Due to its 
short- and long-term complications, T1D is both a daily and life-long burden for individuals and 
their families and also represents significant socioeconomic and societal-medical ramifications, 
which are only going to rise as the worldwide incidence of T1D increases approximately 3% to 
5% annually.34,71
Type 1 diabetes (T1D) is the result of immune destruction of the insulin producing β-cells 
located in the islets of Langerhans in the pancreas and eventual absolute insulin deficiency. It is 
believed that those with a certain genetic susceptibility encounter an environmental trigger that 
breaks self-tolerance to β-cells, and an autoimmune response to β-cells is initiated.21 Over time, 
which may be years in some cases, a critical mass of β-cells is destroyed and normal glycemic 
control cannot be supported. Individuals present with clinical signs and symptoms, including 
polydipsia, polyphagia, polyuria, and often with severe metabolic disturbances, including life-
threatening diabetic ketoacidosis (DKA). Despite there being some residual β-cells at the time of 
clinical diagnosis of T1D, the vast majority of these, if not all, will be eventually destroyed.6,72
Upon diagnosis, those with T1D require daily exogenous insulin for the rest of their lives. Even 
with the best glycemic control with newer forms of exogenous insulin and enhanced BG
monitoring, there continues to be significant disease and treatment-associated morbidity and
mortality, both in the short- and long-term. Current data support that maintaining at least a 
minimal amount of endogenous insulin production can substantially reduce or delay a number of 
these complications.19,41,43 There is an urgent need to develop therapeutics that can prevent or 
slow the rate of β-cell loss to improve outcomes with T1D, which would provide benefit to those 
with T1D and would be a critical step forward on the path to reverse or prevent this disease.
Trials of Other Immunomodulators in T1D
Over the past decades, a number of clinical studies have evaluated immune and non-immune 
based strategies to try to prevent ongoing destruction of β-cells that are present at the time of 
diagnosis in order to reverse insulin need or at least maintain clinically relevant amounts of 
endogenous β-cell function. Of these, it is studies which used immune modulators that have 
shown the most promise. Small scale trials in the late 1980s and early 1990s using non-specific 
immune suppressants (ie, cyclophosphamide and azathioprine) were able to subdue the 
autoimmune progression of T1D and in some cases reverse insulin needs.9,10,16 However, these 
were not considered viable therapies due to their significant immune- and non-immune toxicities.
Since the advent of more targeted, safer, and better tolerated immune modulators (ie, biologics), 
a number of Phase 2a new-onset T1D clinical studies have been conducted. Some of these have 
been 
unsuccessful 
(interleukin
[IL] 
1β antagonism, 
thymoglobulin, 
anti-IL2 
receptor/mycophenolate mofetil) while some have shown some ability to slow disease 
progression 
(abatacept, 
rituximab, 
anti-cluster 
of 
differentiation-3
variants, 
and 

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alefacept).25,26,31,52,55,57,60,61 However due to a variety of reasons, none have been successfully 
developed into an approved disease modifying therapy for T1D.
Role of TNFα in the Pathogenesis of T1D
Decades of fundamental research on the autoimmune pathogenesis of T1D have demonstrated 
that it results from a complex interplay of innate and adaptive immune injury to β-cells involving 
T cells, B cells, antigen-presenting cells, and pro-inflammatory cytokines.8,30,73 In addition, 
recent data indicate that the increases in β-cell damage from metabolic and pro-inflammatory 
stressors may play an important role in the initiation and propagation of the autoimmune 
response.5,6,73
TNFα is a pro-inflammatory cytokine that has important roles in the immunopathogenesis of a 
number of human autoimmune diseases and current evidence indicates it plays an integral role in 
T1D. As detailed below, it has both 1) activating effects on the T1D autoimmune response and 
2) important direct pro-diabetogenic metabolic effects.
TNFappears to promote diabetes autoimmunity by enhancing the recruitment of inflammatory 
cells to the islets, activating cells and enhancing autoantigen presentation.40,58,73 TNFα activates 
vascular endothelium, upregulating major histocompatibility complex (MHC) I and adhesion 
molecules.4 In murine models of T1D, some of the first cells to infiltrate islets are dendritic 
cells.58,73 Dendritic cells and other antigen-presenting cells, which are critical for β-cell antigen 
presentation to T cells, are activated by TNFα by up regulation of MHC I and II and 
costimulatory molecules.38,58 TNFalso directly increases MHC I, and synergizes with 
interferon gamma to upregulate MHC II, on β-cells, both of which appear to increase their 
susceptibility to T-cell killing.5 Rodent models of autoimmune diabetes show that antagonizing 
TNFcan delay, prevent or reverse disease whereas TNFα production in the pancreas can 
accelerate disease.13,39,58
There are important non-immune effects of TNFα that make blocking it attractive in T1D. TNFα 
has direct cytostatic effects and impairs insulin production and secretion, and it has cytocidal 
activity, killing β-cells directly.20,37,47,58 TNFα also impairs insulin signaling and increases 
peripheral insulin resistance, which in experimental models can be reversed by blocking 
TNFα.38,58 Patients with new-onset T1D have elevated serum TNFα levels compared with those 
with long-standing disease or healthy controls.13 There are case reports of patients with T1D, 
who were started on TNFα blockers for other autoimmune diseases, in whom insulin 
requirements dropped due to an apparent increase in insulin sensitivity.3,11,74,76 Therefore, TNFα 
also has potent metabolic effects that may contribute to T1D by increasing β-cell stress and 
death.
Likely the most convincing data of the role of TNFα in T1D pathogenesis in children and young 
adults comes from a randomized, controlled, pilot clinical trial of etanercept in newly diagnosed 
T1D conducted at the University of Buffalo.48 Eligibility included subjects aged 3 to 18 years of 
age with recently diagnosed T1D. Subjects received etanercept 0.4 mg/kg (maximum 25 mg) or 
placebo dosed SC twice weekly for 24 weeks. The study enrolled 18 subjects (range 7 to 

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18 years of age, mean ~12.5 years), 10 into the etanercept arm and 8 into the placebo arm. Over 
the treatment period, etanercept-treated subjects showed a 39% increase in C-peptide production 
(as a measure of endogenous β-cell function) from baseline assessed by C-peptide area under the 
concentration-time curve (AUC) from a 2-hour mixed-meal tolerance test (MMTT). In contrast, 
the placebo group had a 20% decrease in C-peptide production. In addition, subjects in the active 
arm had improved glycemic control (lower Hemoglobin A1c’s [HbA1c’s]) versus those in the 
placebo group, and a decrease of 18% in daily insulin requirements (units/kg/day) from baseline 
where the placebo subjects had a 23% increase in requirements. There were no unexpected 
severe AEs in either group. Even though there has not been further evaluation of these very 
impressive findings, they are some of the most promising to date on identifying an approach to 
modify T1D disease course. Specifically, these findings support further evaluation of this 
approach in the target population and provide critical “prospect of benefit” for TNFα-blockade in 
children and young adults with newly diagnosed T1D.
Differences in Natural History and Pathogenesis of Pediatric versus Adult T1D
Type 1 diabetes usually develops in childhood and adolescence, however it can present late in 
adulthood in the 5th and 6th decades of life, although much less frequently.51,71 In addition to 
being more prone to some short- and long-term complications, there are differences in the 
clinical course and response to immune therapies between children/young adults and older 
adults. This supports the well-accepted observations that children suffer from severe diabetes 
symptoms, including polydipsia, polyuria, and weight loss, days or weeks before initial 
diagnosis. Often diagnosis is accompanied by DKA and shock which requires hospitalization for 
treatment and monitoring for cerebral edema and herniation.6,14,21,23,33,56,62,75 Children and young 
adults with new-onset T1D usually have an immediate need for exogenous insulin.
This sharply contrasts with the experience of adults (mid-20s and above) who often have months 
or years of non-specific symptoms or present asymptomatically from routine glycemic screening 
and can often be managed for prolonged periods of time (months or years) with diet or oral 
hypoglycemic agents before a demonstrable insulin need. More definitive studies have shown a 
different rate of decline of -cells according to age.14,21 Data from the Diabetes Trial Net group 
has demonstrated that “age is the most important factor impacting the rate of decline of 
C-peptide post diagnosis” and with significantly more rapid rate of decline in those 21 years old 
and younger versus those 22 years and older with new-onset disease.27,75
These differences in disease pathophysiology between younger and older individuals with T1D 
are supported by the data from a number of recent new-onset T1D studies that have 
demonstrated differences in how younger and older individuals respond to immune interventions. 
Studies of abatacept, rituximab, alefacept, and teplizumab all appear to have a preferential effect 
on children and young adults; whereas thymoglobulin appeared to preferentially spare -cells in 
those older than 21, but not in those younger.25,31,55,57,61,75
Children and young adults are those at highest risk of developing disease and suffer most 
substantially from short- and long-term morbidity and mortality and have the most to benefit 
from a disease modifying therapy. The existing data suggest an age “cut-off” of approximately 

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21 years old as one that distinguishes many of the properties of T1D in younger and older adults 
and supports the older age threshold of this study. Clearly, there not only appears to be important 
clinical pathophysiologic differences in T1D in younger and older individuals, but efficacy data 
of immune interventions from one age group may not be extrapolated to the other. Doing so may 
result in making misinformed and inaccurate decisions for further development. It is the 
sponsor’s view that the prospect of benefit for TNFα-blockade in children with newly diagnosed 
T1D has been demonstrated, and conversely because of the aforementioned differences in T1D 
disease in younger and older individuals, the study of older adults (ie, >21 years of age) would 
not be supported. As such, the direct study of children and young adults with T1D is required to 
develop a disease modifying therapy for those are most afflicted with this disease and will 
benefit the most from such therapies.6,14,75
1.1.
Background
TNFα-blockers In Human Autoimmune Diseases
The family of TNFα-blockers that golimumab belongs to has some of the most extensive clinical 
experience and success of biologic immune modulators used in in a variety of adult and pediatric 
autoimmune diseases. This family, that also includes infliximab, etanercept, certolizumab pegol,
and adalimumab, cumulatively has years of demonstrated safety and efficacy for conditions that 
include adult RA, psoriasis (PsO), PsA, UC, Crohn’s disease (CD), AS, and pediatric (pJIA), 
CD, and UC. Specifically, golimumab is currently approved in adults 18 years and above with 
RA, PsA, AS and UC.22,32,59,68
The adverse effect profile of these TNFα blockers is well known. Treatment with 
TNFα-blockers, is associated with increased rates of serious infections including tuberculosis, 
bacterial sepsis, invasive fungal, and other opportunistic infections sometimes leading to 
hospitalization or death, lymphoma and other malignancies, and new or exacerbation of 
congestive heart failure, although with very low frequencies.22,32,59,68
Based upon their overall positive benefit:risk profile, TNFα-blockers have been studied and 
approved in the United States and elsewhere for a number of other pediatric autoimmune 
conditions that arguably have similar morbidity and mortality and impact on life as T1D. 
Specifically, etanercept has been FDA-approved in children 2 years old and above with pJIA 
since 1999. Infliximab was approved in children 6 years old and above with CD and UC in 2009 
and 2011, respectively. Adalimumab was FDA-approved for pJIA in those 2 years old and above 
in 2008 and CD in those 6 years old and above in 2014. As detailed in the next section, 
golimumab has recently been studied in over 200 children in pediatric indications. Polyarticular 
juvenile idiopathic arthritis includes experience in children age 2 years and above and is 
currently under review for registration in Europe (Eu), and pediatric UC includes experience in 
children 6 to 17 years of age.
Use of golimumab and other TNFα-blockers for both adults and children includes routine 
evaluation of safety. Subjects in this study will be extensively evaluated as occurs with the 
routine use of TNFα-blockers including golimumab in adults and children, (and detailed above), 
subjects in this study will be thoroughly assessed for and excluded from participation if they 

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have risk factors for serious infections (including but not limited to tuberculosis [TB]), 
immunosuppression, malignancy and cardiac disorders, to limit the chance of untoward and 
adverse effects in this study.
Clinical Studies of Golimumab in Children
A significant portion of the target population in this study is individuals who are less than 
18 years of age. Although it is not currently approved for use in pediatric subjects, golimumab 
has already been evaluated in studies enrolling over 200 children 2 through 17 years of age with 
other autoimmune disorders that have been conducted in the US, EU and other regions globally. 
Specifically, SC golimumab was evaluated in children with pJIA (CNTO148JIA3001), and a 
clinical development program with SC golimumab in pediatric UC is currently ongoing 
(CNTO148UCO1001). Thus far, golimumab has been well tolerated in both studies in pediatric 
subjects of 2 to <18 years of age. In general, the safety profile of golimumab in the pJIA and 
pediatric UC studies including the type and frequency of the adverse reactions seen is consistent 
with the known safety profile for the adult populations studied and consistent with other TNFα 
inhibitors. No new safety signals have been observed.
1.2.
Rationale for the Study
This study will evaluate whether subcutaneously administered golimumab can maintain residual 
β-cell function and improve metabolic control in children and young adults with newly 
diagnosed T1D.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints

Double-Blind Period
Objectives
Endpoints
Primary Objective and Endpoints

To determine if golimumab can preserve β-cell 
function in children and young adults with 
newly diagnosed T1D.

The Mixed-meal Tolerance Test (MMTT) -
stimulated 4-hour C-peptide area under the 
concentration-time curve (AUC) at Week 52.
Secondary Objectives and Endpoints: Efficacy 

To evaluate the impact of golimumab on 
measures of diabetes control in this subject 
population.

To evaluate the off-therapy durability of 
golimumab on measures of diabetes control in 
this subject population. 

Change from baseline in insulin use in units 
per kilogram body weight per day over time.

Change from baseline in HbA1c over time.

Hypoglycemic event rates (defined as BG of 
≤70, 55, and 35 mg/dL or clinical sequelae in 
the absence of a BG reading) through 
Week 52, after Week 52 through Week 104, 
and the entire study.

MMTT-stimulated 4-hour C-peptide AUC 
over time.

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Objectives
Endpoints
Secondary Objective and Endpoints: Safety

To determine the safety and tolerability of 
golimumab in children and young adults with 
T1D.

Proportion 
of 
participants 
with 
treatment-
emergent AEs and severe AEs through Weeks 52 
and 104.

Proportion 
of 
participants 
with 
severe 
infections through Weeks 52 and 104.

Proportion of participants with study agent 
injection site reactions through Week 52.
Secondary Objective and Endpoints: Pharmacokinetics (PK) and Immunogenicity 

To evaluate the PK and immunogenicity of 
golimumab in this specific subject population 
with T1D.

Summary 
of 
serum 
golimumab 
concentrations and the PK profile after 
induction and maintenance dosing.

Incidence 
and 
titers 
of 
antibodies 
to 
golimumab.
Exploratory Objective and Endpoints: Immunologic and Metabolic

To 
evaluate 
how 
golimumab 
impacts 
immunologic profiles and indicators of β-cell 
stress, and the correlation with efficacy and 
safety endpoints in this study.

Correlation of cellular and serologic immune 
profiles with clinical metabolic outcomes on-
therapy (Weeks 12, 26, 38, and 52) and 
off-therapy (Weeks 78 and 104)

Relationship of exploratory markers of β-cell 
stress and survival with clinical metabolic 
outcomes on-therapy (Weeks 12, 26, 38, and 
52) and off-therapy (Weeks 78 and 104).

Open-Label Extension Period
Objective
Endpoint

To evaluate additional one year of safety and 
exploratory 
efficacy 
endpoints
in 
those 
participants that have shown a particular 
response in the double-blind period.

Continue to evaluate safety and exploratory 
efficacy endpoints as per the Time and 
Events 
Schedule
(open-label 
extension 
period) and no new efficacy hypotheses will 
be tested compared to the double-blind 
period.
2.2.
Hypothesis
The primary hypothesis to be tested in this study is that golimumab is superior to placebo in 
maintaining β-cell function in children and young adults with newly diagnosed T1D as measured 
by MMTT-stimulated 4-hour C-peptide AUC at Week 52.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 2a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 
study of golimumab in subjects with new-onset T1D.

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The duration
of study participation will be
108 weeks, including screening and 
post-randomization. Following initial study screening, subjects must be randomized within 
28 days. Following randomization there will be a double-blind 52-week treatment period with 
study agent followed by a 52-week off-therapy follow-up period.
Responders as defined below will be provided the option to participate in the 52-week open-label 
(OL) extension period.
The period to enroll all 81 subjects is expected to last approximately 12 to 18 months.
Schematic overviews of the double-blind study design and open-label extension period are 
provided in Figure 1 and Figure 2, respectively.
Figure 1:
Schematic Overview of the Double-Blind Period

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Figure 2:
Overview of the Open-Label Extension Period
This study will enroll male and female subjects 6 through 21 years old who have been recently 
diagnosed with T1D. As described above (in Section 1) recent data indicate that the 
immunopathogenesis, disease progression and even response to immune therapies is different in 
younger population with T1D versus older adults. There is recent recognition by medical groups, 
diabetes experts and health authorities that it is important to conduct studies in children with 
T1D directly to best determine efficacy in T1D, as long as there is a known and acceptable safety 
profile.28,29,75 Additionally, the critical “prospect of benefit” of therapeutic TNF-blockade in 
these younger individuals with new-onset T1D exists based on the aforementioned pilot trial 
described above conducted in children and adolescents.48 The choice of the upper age cut-off of 
21 years is based on studies noted above showing a differentiating break in disease progression 
and response to therapy at this age.25,27,61,75 Age 6 has been an accepted lower age threshold for 
enrollment in immunotherapeutic new-onset T1D studies, including those of abatacept and 
canakinumab.52,55 In addition there is a substantial amount of efficacy and safety experience of 
golimumab and other TNFα-blockers in children with other autoimmune diseases, and most of 
this is in those at and above 6 years old. This study will not enroll adults over 21 years old due to 
the difference noted above, including that there is not currently a “prospect of benefit” of 
anti-TNFtherapy in this older population. Most importantly as the goal for the sponsor is to 
develop a therapy for those who will most benefit from it, if older adults were to have a poorer 
response to therapy than younger individuals due to some of the reasons discussed above, this 
may result in diluting or missing important findings necessary to support further development in 
children, adolescents and young adults with T1D who are clearly those who have the most to 
gain from a disease modifying therapy.

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Confirmation of the autoimmune nature of T1D in subjects will be determined by positivity of at 
least one T1D-associated autoantibody. Subjects must also show evidence of residual 
endogenous β-cell function, defined by a C-peptide level of ≥0.2 pmol/mL from a 4-hour MMTT 
at study screening, and be able to be randomized within 28 days of screening and 100 days of 
diagnosis.19,25,42,61
A target of approximately 81 subjects will be randomly assigned in a 2:1 ratio to receive 
golimumab or placebo, administered SC for 52 weeks and monitored for an additional 52 weeks. 
Subjects will be randomized to receive active therapy (golimumab) or placebo and be stratified 
based on a C-peptide AUC of <0.66 pmol/mL or ≥0.66 pmol/mL from a 4-hour MMTT 
conducted at study screening.
All randomized subjects will receive a total of 27 doses of study agent, either active treatment or 
matched placebo, administered SC every 2 weeks (q2w). Study subjects weighing <45 kg who 
are randomized to active treatment will receive an induction dose of golimumab 60 mg/m2 SC at 
Weeks 0 and 2 followed by a maintenance dose of 30 mg/m2 SC at Week 4 and q2w through 
Week 52. Study subjects weighing ≥45 kg who are randomized to the golimumab treatment 
group will receive an induction dose of golimumab 100 mg SC at Weeks 0 and 2 followed by a 
maintenance dose of golimumab 50 mg SC at Week 4 and q2w through Week 52. Subjects 
randomized to the placebo treatment group will receive a SC placebo injection q2w through 
Week 52 to match the active arm (Figure 1). The protocol will give the option for study agent 
administration by subject or caregiver outside of the study site, ie, self-administration, after 
proper training (see Section 6).
Following randomization and the 52-week treatment period, there will be a 52-week off-therapy 
follow-up period focused on determining the off-therapy durability of the effect of golimumab. 
Thus, the participation for each subject is 104 weeks.
There will be a number of study visits that will include extensive metabolic assessments 
including a 4-hour MMTT. These assessments will occur at screening, during the double-blind 
treatment period (Weeks 12, 26, 38, and 52), and the off-therapy monitoring period (Weeks 78 
and 104). The primary endpoint analysis will be derived from data obtained at the double-blind 
Week 52 visit (double-blind period). During the open-label extension period, a 4-hour MMTT 
will be performed during OL screening (unless performed <3 months ago), OL Week 28, and OL 
Week 52. For C-responders who are lacking the necessary information to calculate IDAA1c 
score, an HbA1c will be performed and 10 days of insulin dose information will be required. 
Data from these and other visits will contribute to other key efficacy and safety endpoints and 
provide pharmacokinetic and exploratory assessments.
Three data base locks (DBLs) are planned for the study. The first DBL will occur after all 
subjects complete their Week 52 assessments (double-blind period), the second DBL will occur 
after the last subject completes the off-therapy follow-up period (Week 104), and the third DBL
will occur after the last subject completes the open-label extension period.

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An interim analysis based on 4-hour C-peptide AUC in response to an MMTT is planned for the 
study after at least 60% of subjects complete their Week 26 MMTT assessment. The primary 
goal of this interim analysis is to obtain an early read on treatment effect to facilitate planning of 
future studies.
During the study, all subjects will receive intensive management of their diabetes with 
exogenous insulin according to the current recommendations of the American Diabetes 
Association (ADA). Subjects and, when applicable, their caregivers must agree to follow the 
current ADA recommendations of tight glycemic control with specific HbA1c targets. These 
current recommendations are intended to achieve glucose levels that appear to decrease some of 
the short- and long-term sequelae of T1D. This study will include adhering to the ADA’s 
recommended glycemic control guidelines with an HbA1c target of <7.5% in children 17 years 
old and younger and <7% in those 18 years old and above.67 Approaches to achieve these HbA1c 
goals will be the responsibility of the subject, their caregivers and their health care providers.
Responders at Week 52 who are still in the follow-up period and who are determined to be in the 
active treatment group will have the option to restart active therapy while the non-responders 
will continue to follow the originally planned study design, ie, the off-therapy follow-up 
monitoring period.
There will be an open-label extension period of the study for responders. Responders are defined 
as subjects who have profile at Week 52 which includes:
1.
C-peptide and Remission score* responders (C+R responders): either having an increase in 
C-peptide AUC versus baseline or having a stable C-peptide AUC, ie, not decreasing more 
than 5% versus baseline and having a remission score ≤9.
OR
2.
C-peptide responders (C responders): either having an increase in C-peptide AUC versus 
baseline or having a stable C-peptide AUC, not decreasing more than 5% versus baseline but 
not meeting a remission score of ≤9. Their remission score, however, must be <12.
OR
3.
Remission score responders (R responders): having a remission score ≤9 but not meeting 
C-peptide response as defined above. However, their C-peptide AUC decline from baseline 
should be less than or equal to 30% compared to baseline.
*Insulin Dose Adjusted HbA1c (IDAA1c) = A1C (percent) + [4 × insulin dose (units per 
kilogram per 24 h)].24,50,53,54
An independent Data Monitoring Committee will be commissioned to continually assess the 
safety of study subjects. Refer to Section 11.11, Data Monitoring Committee, for details.

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3.2.
Study Design Rationale
3.2.1.
Blinding, Control, Study Periods, Treatment Groups
Blinding and a placebo control will be used in this study since there is no established comparator 
therapy to prevent β-cell loss in T1D and to reduce potential bias during data collection and 
evaluation of clinical, safety, and exploratory endpoints.
There will be a 28-day screening period to allow for all assessments required for randomization 
to be conducted. The primary endpoint will occur at Week 52 (double-blind period). Due to the 
natural history of β-cell loss following diagnosis, documenting a statistically significant and 
meaningful effect of a β-cell sparing agent in a study of a reasonable size is best accomplished at 
Week 52 and allows for important comparisons with other recent immune intervention studies in 
T1D which have used a 52-week primary endpoint.25,26,31,52,55,57,61 Golimumab and other 
TNFα-blockers are usually prescribed as continual “chronic” therapies for their autoimmune 
indications; therefore, the 52-week treatment duration is consistent with these experiences and 
will allow the best opportunity for evaluating efficacy of golimumab and ensure robust and 
meaningful safety evaluations.22,32,59,68 Following the primary endpoint analysis at Week 52
(double-blind period), an off-therapy follow-up period for 52 weeks will allow for continued 
assessment of safety and understanding of the durability of effect after discontinuation of 
therapy. This will provide data to assist in developing dosing strategies of golimumab for T1D in 
future studies.
Randomization will be used to minimize bias in the assignment of subjects to treatment groups, 
to increase the likelihood that known and unknown subject attributes (eg, demographic and 
baseline characteristics and disease severity) are evenly balanced across treatment groups, and to 
enhance the validity of statistical comparisons across treatment groups.
Per inclusion criteria, all randomized subjects will have a C-peptide level of ≥0.2 pmol/mL from 
a 4-hour MMTT at screening. Stratification will be employed based on subjects baseline 
MMTT-stimulated C-peptide AUC level as previous interventional studies in new-onset T1D 
suggest the response to immune therapies in new-onset T1D studies may be influenced, at least 
in part, by subject’s baseline endogenous β-cell function.31,55 To achieve balanced populations in 
the 2 treatment groups, eligible subjects will be randomized based on 2:1 ratio to receive active 
study agent or placebo within each stratum (<0.66 pmol/mL or ≥0.66 pmol/mL). This
stratification threshold of 0.66 pmol/mL was chosen based on simulations and calculations 
derived from existing data that this level is expected to be close to the median of the baseline 
MMTT-stimulated 4-hour C-peptide AUC of the study population.27,60
Following database lock for the double-blind treatment period (Week 52), subjects who are still 
in the off-therapy follow-up period (Week 52 to 104 visits), who were on active drug during the 
double-blind period and who meet the response criteria will be offered the option to participate 
in the open-label extension period if eligibility criteria are met. Prior to initiating open-label 
screening assessments, subjects and parents/legal guardians will sign updated informed consent 
form (ICF)/assent forms.

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Subjects who did not meet the response criteria at Week 52 will continue the off-therapy 
follow-up period.
Subjects who met the response criteria but either declined to participate in the open-label 
extension period, or were determined to be on placebo, will continue the off-therapy follow-up 
period as planned.
3.2.2.
Dose Rationale
This study uses a dosing regimen designed specifically for T1D. It is accepted that different 
diseases may require unique dosing approaches of the same therapeutic to be most efficacious. In 
the case of the class of TNF-blockers, there are a variety of dosing regimens that are 
disease-specific such as a higher dose regimen of SC golimumab for the treatment of UC as 
compared to that for rheumatic diseases.
The choice of dose and regimen for this study is based upon 3 factors: 1) disease-specific 
considerations of T1D, 2) modeling based upon the reported efficacy of TNFα inhibition of 
etanercept in a pilot study in children with T1D, and 3) the sponsor’s safety and pharmacokinetic
(PK) the experience with golimumab in adults, adolescents and children.48 Although, the dose 
regimen of SC golimumab chosen for the present T1D study has not been studied before, the 
sponsor’s use of golimumab in adult and pediatric subjects with other indications indicate that 
the overall exposures in this study population are overlapping with previous experience and thus 
the existing safety profile of golimumab is applicable to this study.
1.
T1D Disease-Specific Considerations
In T1D, the destruction of β-cells is rapid at the time of diagnosis and is considered 
irreversible.6,69,73 For aggressive immune-mediated diseases, higher and/or more frequent 
induction doses of anti-inflammatory therapies followed by lower regular maintenance doses are 
often used to gain rapid control of rampant disease activity, and then keep it under control. For 
most autoimmune indications, including pediatric and adult UC and CD, psoriasis, and in some 
cases RA, TNFα–blockers are administered using an induction regimen followed by maintenance 
treatment dosing regimen.14,22,32,59,68 To preserve residual β-cells in newly diagnosed T1D, rapid 
neutralization of the inflammatory, anti-β-cell response is likely to be key for an effective 
therapy. Golimumab steady-state concentrations are only achieved after at least 3 months with 
routine dosing, and with such a regimen continued β-cell destruction may likely occur. It was 
determined that 2 SC induction doses spaced by 2 weeks would more rapidly achieve a 
steady-state level and giving the best opportunity to protect residual β-cells. The induction doses 
will be followed by a lower maintenance dosing in order to maintain steady-state concentrations 
and continue to prevent further β-cell loss.

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2.
Model-Based Prediction of TNFα Suppression in T1D Subjects
To date golimumab has been studied in 2 pediatric populations; pJIA and pediatric UC. In the 
study of golimumab in children 2 to 18 years old with pJIA who were being treated with 
concomitant methotrexate (MTX) the dose was 30 mg/m2 SC every 4 weeks (q4w). In the study 
of golimumab in children 6 to 18 years old with pediatric UC that dose was 90 mg/m2 SC at
Week 0 and 45 mg/m2 SC at Week 2, and 45 mg/m2 SC q4w for children <45 kg and 200 mg SC 
at Week 0 and 100 mg SC at Week 2, and 100 mg SC q4w in children ≥45 kg. The approved 
dose of golimumab in adults (those 18 years old and above) with RA, PsA, and AS is 50 mg SC 
q4w and for UC is 200 mg SC at Week 0, followed by 100 mg SC at Week 2 and then 100 mg 
SC q4w.
A mechanistic PK/target engagement (TE) model incorporated PK exposure from a previously 
established population PK model-based on the pJIA population was paired with a target-
mediated drug disposition model to assess the interaction between drug and target and to 
simulate the suppression of TNFα after TNFα–blocker administration. The PK/TE model was 
developed based on the assumption that the etanercept dosing regimen tested in T1D results in 
sufficient TNFα neutralization given the positive results observed in the pilot trial in children 
with new-onset T1D.48 The golimumab dosing regimen was designed to approximate the extent 
of TNFα suppression obtained using the etanercept dosing regimen in this study and accounting 
for the differences in PK and TNFα binding affinity between golimumab and etanercept. 
Concomitant use of MTX, which is standard of care in pJIA, reduces golimumab clearance in 
subjects with this disease, likely due to suppression of anti-drug antibodies.77 Subjects with T1D 
do not receive MTX, therefore, a 56% faster clearance of golimumab in subjects with T1D than 
pJIA subjects was assumed for predicting the PK profile in the T1D population.
The PK/TE model suggested that an induction dosing regimen of 60 mg/m2 SC (to a maximum 
of 100 mg) at Week 0 and Week 2 followed by a maintenance dosing regimen of 30 mg/m2 SC 
(to a maximum of 50 mg) q2w or 60 mg/m2 SC (to a maximum of 100 mg) q4w results in 
suppression of TNFα to a level approximating that of etanercept. This target would not be 
achieved with a 30 mg/m2 SC q4w dose. The 30 mg/m2 q2w and 60 mg/m2 q4w maintenance 
dosing regimens would have the same overall exposure (AUC) and similar TNFα suppression; 
however, the 60 mg/m2 q4w regimen would have higher peak/trough concentration fluctuations 
and thus more fluctuation on suppression of TNFα. It is known that TNFα has direct cytostatic 
and cytocidal effects on β-cells.2,58 Thus the TNFα elevations that would be expected to occur 
during the troughs with the higher, but less frequent dosing, may result in more damage to 
residual β-cells. As the overall exposure to golimumab with these dosing regimens may be 
considered equivalent, the 30 mg/m2 SC (to a maximum of 50 mg) q2w dosing regimens was 
preferred due to less peak/trough fluctuation.
3.
Comparison of Golimumab Dose Regimens Between the T1D Population with Other 
Disease Populations of Adults and Children
Population PK simulations were performed comparing the proposed T1D dosing regimen with 
dosing regimens that have previously been studied in the pediatric populations (pJIA and 
pediatric UC, Figure 3 Panels A and B, respectively). The simulations to develop this dosing

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strategy used demographics for subjects age 6 through 21 years based upon the U.S. Centers for 
Disease Control and Prevention growth charts.18
For a child, golimumab 30 mg/m2
(50 mg/1.67 m2) would be approximately equivalent to a 50 mg dose for an adult subject 
weighing 60 kg (with a body surface area [BSA] of 1.67 m2). Thus the 30 mg/m2 dose is 
expected to be similar to the 50 mg dose in adults and the 60 mg/m 2 dose to be similar to the 
100 mg dose in adults. In adults, golimumab 50 mg q4w was the minimum effective dosing 
regimen for the treatment of RA, PsA, or AS. Due to the absence of concomitant MTX in T1D 
subjects, it is expected that a 30 mg/m2 q4w dosing regimen that is the pediatric equivalent to the 
adult 50 mg q4w dose may not result in sufficient systemic exposure for suppressing TNFα in 
T1D subjects, therefore a higher dose or more frequent dosing interval should be studied. For the 
simulation, a 40 kg weight cut-off was included (Figure 3 Panel A: <40 kg: 30 mg/m2 q4w; 
≥40 kg: 50 mg q4w). For the pediatric UC simulations, a 45 kg weight cut-off was implemented
as previously studied, such that subjects <45 kg would receive 60 mg/m2 at Weeks 0 and 
2 followed by 30 mg/m2 q2w and subjects ≥45 kg would receive 100 mg at Week 0 and 
2 followed by 50 mg q2w. Based on the PK simulations, the proposed T1D dosing regimens 
(<45 kg and ≥45 kg) are expected to result in drug exposure (AUC) between that observed for 
the pJIA with MTX and pediatric UC populations without MTX (Figure 3, Panel A and B), 
although the 30 mg/m2 q2w maintenance dosing interval will produce slightly higher trough 
concentrations.
Figure 3:
Overlap of simulated golimumab exposure for dosing regimens in current T1D study compared 
to those in pJIA and pediatric UC studies.
The safety and efficacy of golimumab has been extensively characterized in adult subjects with
RA, PsA, AS, and UC. In a Phase 2 study in subjects with RA, 4 different dosing regimens were 

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evaluated (50 mg q2w or q4w and 100 mg q2w or q4w) of which all doses tested were generally 
well tolerated and effective in maintaining clinical response without dose-related safety events
through Week 52.35 In pJIA, a 30 mg/m2 q4w dosing regimen was studied up to a maximum of 
50 mg (the approved adult RA dose). In pediatric UC, a 45 kg weight cut-off was implemented 
such that subjects below 45 kg received BSA-adjusted doses and subjects at or above 45 kg 
received doses according to adult UC dosing regimens (details discussed above). To date, the 
dosing regimens studied in pediatric patients were well tolerated. Overall no new adverse drug 
reactions were identified. Further, the frequency, type, and severities of the events observed were
similar to those observed in the adult rheumatology and inflammatory bowel disease studies.
Since the dosing regimen for golimumab proposed for this study in T1D subjects is expected to 
result in drug exposures that overlap with those observed in previous pediatric studies with 
golimumab, it is appropriate to also expect that a similar safety profile will be demonstrated in 
the T1D population planned for enrollment in this trial as that seen in pediatric studies in pJIA 
and UC.
Considering the above-mentioned disease-specific issues of T1D, pharmacologic comparisons of 
golimumab and etanercept and specific experience with golimumab, an induction dosing regimen
of 60 mg/m2 SC (to a maximum of 100 mg) at Weeks 0 and 2, followed by a maintenance dosing 
regimen with 30 mg/m2 SC (to a maximum of 50 mg) q2w was selected as the recommended 
dosing regimen in this study. In addition, a weight cut-off (45 kg), which has been implemented 
in the clinical pediatric UC study of golimumab, will also be studied such that subjects at or over 
the 45 kg weight cut-off will receive golimumab using the already approved adult PFS-U
presentations.
4.
SUBJECT POPULATION
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following subsections. These criteria are consistent with those for recent interventional studies in 
newly diagnosed T1D, the targeted subject age range in this study, and recent studies of 
golimumab for other indications. If there is a question about the inclusion or exclusion criteria 
below, the investigator must consult with the appropriate sponsor representative and resolve any 
issues before enrolling a subject in the study. Waivers are not allowed. Deviations from the 
inclusion and exclusion criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, and subject safety. Therefore, adherence to the criteria as
specified in the protocol is essential.
Individuals who meet entry criteria but are not able to be randomized within the allotted time (ie, 
28 days from screening) may still participate in the study so long as they repeat study screening 
and again meet eligibility criteria. Subjects may only be rescreened once.
If a subject is a screen failure but at some point, in the future is expected to meet the subject 
eligibility criteria, the subject may be rescreened on 1 occasion only after consultation with the 
sponsor.
Subjects who are rescreened will be assigned a new subject number, undergo the informed 
consent/assent process, and then restart a new screening phase.

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Retesting of abnormal screening values that lead 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.
If a subject's status changes (including laboratory results or receipt of additional medical records) 
after screening but before the first dose of study agent is given such that they no longer meet all 
eligibility criteria, they should be excluded from participation in the study.
4.1.
Inclusion Criteria
4.1.1.
Inclusion Criteria Applicable to All Subjects
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1.
Male or female 6 through 21 years of age who are diagnosed with T1D within 100 days 
of randomization per the ADA standard T1D criteria.70
2.
Be positive for at least 1 of the following diabetes-related autoantibodies obtained at 
study screening:

Glutamic acid decarboxylase (GAD-65)

IA-2

ZnT8

ICA; or

Insulin (if obtained within 10 days of the onset of exogenous insulin therapy)
3.
Have a peak stimulated C-peptide level ≥0.2 pmol/mL following a 4-hour MMTT
obtained at study screening.
4.
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.
5.
Females of childbearing potential must have a negative serum (-human chorionic 
gonadotropin [-hCG]) test at screening and a negative urine pregnancy test at the 
Week 0 visit.
6.
Criterion modified per Amendment 3 – open-label extension period
6.1. Females must be either:

Not of childbearing potential: premenarchal; permanently sterilized (eg, tubal 
occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of 
pregnancy,
OR

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
Of childbearing potential, and if sexually active, practicing through Week 104 and 
open-label extension period of the study be 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.

Females of childbearing potential must agree not to donate eggs (ova, oocytes) for 
the purposes of assisted reproduction through Week 104 and open-label extension 
period.
Note: If the childbearing potential changes after start of the study (eg, female who is not 
heterosexually active becomes active, premenarchal female experiences menarche) she 
must begin a highly effective method contraception of birth control, as described 
throughout the inclusion criteria.

Agrees to remain on a highly effective method of birth control throughout the 
study. 
7.
During the treatment period of the study (from randomization through Week 52) and for
a minimum of 1 spermatogenesis cycle (defined as 90 days after receiving the last dose 
of study agent), all males must:

Agree to be sexually abstinent or (2) if sexually active with a non-pregnant female 
of childbearing potential must agree to use a barrier method of contraception (eg, 
condom with spermicidal foam/gel/film/cream/suppository) and if sexually active 
with a female who is pregnant must use a condom.

Agree not to donate sperm.
8.
Subjects (or their legally acceptable representatives) are willing and able to adhere to 
requirements, prohibitions, and restrictions specified in this protocol.
9.
Subjects (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 is 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) as described in Section 16.2.3, 
Informed Consent and Assent Form.

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10.
Subjects (or their legally acceptable representative) must sign a separate informed consent 
form if he or she agrees to provide an optional DNA sample for research. Refusal to give 
consent/assent for the optional DNA research sample does not exclude a subject from 
participation in the study. Assent is also required of children capable of understanding the 
nature of the study (typically 7 years of age and older) as described in Section 16.2.3, 
Informed Consent and Assent form.
11.
Prior to receiving the study agent, subjects must be up-to-date with and agree to receive 
routine age-appropriate immunizations according to current Centers for Disease Control 
and Prevention (CDC) guidelines and agree to comply with the guidelines for 
immunosuppressed individuals and those with chronic disease (diabetes mellitus). 
Specific to the human papillomavirus (HPV) vaccine, pneumococcal vaccine and any 
non-routine vaccines for immunosuppressed individuals or those with chronic diseases, 
subjects must have received these immunizations or initiated the recommended vaccine 
series and have a completion plan before the first administration of study agent. 
Documentation of required immunizations or proof of corresponding immunity (eg, 
vaccination card, medical record, or demonstration of protective antibody titers) must be 
provided to the study site.
4.1.2.
Additional Inclusion Criteria for Responders
Each responder must also satisfy the following criteria to be eligible to restart active treatment:
1.
Subjects must meet the MMTT criteria at Screening for the open-label extension period. If 
the most recent MMTT is <3 months ago, a repeat MMTT is not required. Subjects who had 
their most recent safety laboratory samples drawn within 1 month prior to screening do not 
need a repeat; eligibility will be assessed based on these most recent laboratory tests. For 
C-responders who are lacking the necessary information to calculate IDAA1c score, an 
HbA1c will be performed and 10 days of insulin dose information will be required.
4.2.
Exclusion Criteria
4.2.1.
Exclusion Criteria applicable to All Subjects
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
Coexisting medical conditions or past medical history:
1.
Has a history of significant renal, vascular, pulmonary, gastrointestinal, neurologic, 
hematologic, rheumatologic, or psychiatric disease.
2
Has significant cardiovascular disease, including history of myocardial infarction, 
congestive heart failure, angina, abnormal electrocardiogram or abnormal stress test.
3.
Has a disease associated with lymphopenia, malignancy, bone marrow or organ 
transplantation, lymphoproliferative disorder, immune deficiency syndrome (eg, 

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severe combined immunodeficiency syndrome, T-cell deficiency syndromes, B-cell 
deficiency syndromes, or chronic granulomatous disease).
4.
Has another autoimmune disease (eg, RA, pJIA, PsA, AS, MS, systemic lupus 
erythematosus [SLE], celiac disease [clinically symptomatic and antibody positive, ie, 
tissue transglutaminase IgA]). excluding clinically stable autoimmune thyroiditis 
whether treated or untreated.
5.
Has nervous system disorder including but not limited to Guillain-Barre Syndrome, 
multiple sclerosis (MS), or progressive multifocal leukoencephalopathy (PML). 
6.
Has known allergies, intolerance and/or hypersensitivity to human immunoglobulin 
proteins, golimumab or any of its components or its excipients, or a known allergy or 
severe sensitivity to latex (refer to the SIMPONI and VarioJect Investigator's 
Brochures).35,36
7.
Has any of the following hematologic abnormalities at screening, confirmed by repeat 
tests at least 1 week apart:

White blood count <3,500/μL or >14,000/μL;

Platelet count <100,000 /μL; or

Hemoglobin <10 g/dL.
8.
Has a diagnosis of liver insufficiency or disease or hepatic enzymes equal to or above 
the values below, which represent alanine aminotransferase (ALT) and aspartate 
aminotransferase (AST) ≥2 times the upper limit of the gender- and age-based upper 
limit of normal confirmed by a repeat test at least 1 week apart (These values are 
based on the Central Laboratory normal ranges of AST and ALT values 
(Attachment 5)
Aspartate aminotransferase (AST)
Females

96 U/L (age 6)

80 U/L (age 7 through 17)

68 U/L (age 18 and above)
Males

118 U/L (age 6)

80 U/L (age 7 through 17)

72 U/L (age 18 and above)

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Alanine aminotransferase (ALT)
Females

68 U/L (age 6 and above )
Males

68 U/L (age 6 through 9)

86 U/L (age 10 and above)
Infections or predispositions to infections
9.
Has active infections, is prone to infections or has chronic, recurrent or opportunistic 
infectious disease, including but not limited to, chronic renal infection, chronic chest 
infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent 
pyelonephritis, chronic cystitis), Pneumocystis carinii, aspergillosis, latent or active 
granulomatous infection, histoplasmosis, or coccidioidomycosis or an open, draining, 
or infected non-healing skin wound or ulcer.
10.
Has any of the following TB screening criteria:

A history of latent or active TB prior to screening.

Signs or symptoms suggestive of active TB upon medical history and/or physical 
examination.

Recent close contact with a person with known or suspected active TB.

A history of or a positive QuantiFERON®-TB Gold test result at screening (see
Attachment 1).
A subject whose first QuantiFERON-TB Gold test result is indeterminate should have 
the test repeated. In the event that the second QuantiFERON-TB Gold test result is 
also indeterminate, the subject should be excluded from the study. Subjects with a 
negative QuantiFERON-TB Gold test result are eligible to continue with 
pre-randomization procedures. 
11.
Has a clinically active infection with Epstein-Barr virus (EBV) or an EBV viral load 
≥10,000 copies per mL of plasma obtained at study screening. 
12.
Has a clinically active infection with cytomegalovirus (CMV) or a CMV viral load 
≥10,000 copies per mL of plasma obtained at study screening. 
13.
Is infected with human immunodeficiency virus (HIV), hepatitis B (HBV) or 
hepatitis C (HCV) or at screening tests positive for HIV, HBV (See Attachment 4 for 
guidance for HBV test interpretation), or HCV.

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Concomitant or previous medical therapies received:
14.
Current or prior (within 30 days of screening) treatment that is known to cause a 
significant, ongoing change in the course of T1D or immunologic status, including 
high-dose inhaled, extensive topical, or systemic glucocorticoids.
15.
Current or prior (within 30 days of screening) use of anti-hyperglycemic agents, 
including but not limited to metformin, sulfonylureas, glinides, thiazolidinediones, 
exenatide, liraglutide, DPP-IV inhibitors or amylin.
16.
Current or prior (within 30 days of screening) use of any medication known to 
influence glucose tolerance including but not limited to atypical antipsychotics, 
diphenylhydantoin, thiazide, or other potassium-depleting diuretics, β-adrenergic 
blockers, or niacin.
17.
Has ever received a systemic immunosuppression medicine or immune modulatory 
biologic therapy, including but not limited to T- or B-cell depleting therapy.
18.
Has received or is expected to receive any live viral or live bacterial vaccinations 
from 90 days before first study agent administration, during the treatment period, and 
up to 120 days after the last study agent administration.
19.
Has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening 
or is planned to receive BCG vaccination during the treatment period, and up to 
12 months following last study agent administration.
Reproductive
20.
If female, is pregnant, lactating, or breastfeeding, or planning to become pregnant 
while enrolled in this study.
21.
If male, plans to father a child while enrolled in this study.
General Restrictions
22.
Criterion modified per Amendment 3 – open-label extension period
22.1. Has participated in any interventional clinical study within the 6 months prior to 
enrollment or is currently enrolled in an investigational study (apart from 
CNTO148DML2001 trial).
23.
Criterion modified per Amendment 3 – open-label extension period
23.1. Has received an investigational drug (including investigational vaccines) or used 
an invasive investigational medical device within 90 days before the planned first 
dose of study agent or is currently enrolled in an investigational study (apart from 

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CNTO148DML2001 trial).
24.
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.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening
and, at randomization. If a subject's clinical status changes (including any available laboratory 
results or receipt of additional medical records) after screening but before randomization and the 
first dose of study agent 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 9.1.2, Screening Period, 
describes options for retesting. Section 17.4, Source Documentation, describes the required 
documentation to support meeting the enrollment criteria.
4.2.2.
Additional Exclusion Criteria for Responders
1.
Subjects having reported clinically significant AEs or serious adverse event (SAEs)
deemed to be related to the study agent during the double-blind period (e.g. severe 
infections or hypersensitivity reactions), precluding renewed exposure to golimumab.
2
Subjects who discontinued study agent administration prior to Week 52 or who have 
completed the Week 104 visit of the double-blind period or discontinued early from 
the study.
3
Subjects and/or caregivers who are unwilling or unable to administer study agent.
4.3.
Exceptions to Inclusion and Exclusion Criteria for Open-Label Extension 
Period
The responders must continue to meet the initial inclusion and exclusion criteria to be eligible for 
the open-label extension period with following exceptions:
1.
Autoantibody status will not be assessed (refer to criteria 2 under Section 4.1.1). 
2.
Subjects older than 21 years of age are eligible (refer to criteria 1 under Section 4.1.1).
3.
For the open-label extension period, subjects may begin open-label study agent while EBV 
polymerase chain reaction (PCR) results are pending and if he/she meets all other 
inclusion/exclusion criteria. If EBV PCR results come back positive, subject must 
immediately stop treatment and be withdrawn from the study.
4.4.
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:
1.
Refer to Section 8 for details regarding prohibited and restricted therapy during the 
study.

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2.
Agree to follow the contraceptive requirements as noted in the inclusion criteria.
3.
Criterion modified per Amendment 3 – open-label extension period
3.1. Will not receive a live virus or live bacterial vaccination 90 days before first study 
agent administration, during the 52-week treatment period and the open-label extension 
period of the study and up to 120 days after the last study agent administration.
4.
Criterion modified per Amendment 3 – open-label extension period
4.1. Will not receive a BCG vaccination within 12 months of screening, during the 
52-week treatment period and the open-label extension period of the study and up to 12 
months following last study agent administration.
5.
Criterion modified per Amendment 3
5.1. If sexually active and of childbearing potential, females will remain on a highly 
effective method of birth control and must not donate eggs (ova, oocytes) for the 
purposes of assisted reproduction throughout the study, or if she withdraws early from 
the study within 6 months of the last study agent administration.
6.
Criterion modified per Amendment 3 – open-label extension period
6.1. If sexually active with a female of childbearing potential and has not had a 
vasectomy, males must use a double barrier method of birth control during the study. 
Males must not donate sperm and must agree not to plan a pregnancy or father a child 
during the 52-week treatment period and the open-label extension period of the trial and 
for 90 days after the last study agent administration, or if he withdraws early from the 
study within 90 days of the last study agent administration.
7.
Criterion modified per Amendment 3
7.1. Must not receive investigational drugs, systemic immunosuppressants (including, 
but not limited to cyclophosphamide) or other biologics throughout the study.
5.
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Subjects will be randomly assigned to 
1 of 2 treatment groups based on a computer-generated randomization schedule prepared before 
the study by or under the supervision of the sponsor. The randomization will be balanced by 
using randomly permuted blocks and will be stratified on subjects’ baseline C-peptide AUC
(<0.66 pmol/mL, ≥0.66 pmol/mL) derived from the 4-hour MMTT conducted at screening. The 
interactive web response system (IWRS) will assign a unique treatment code, which will dictate 

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the treatment assignment and matching study agent kit for the subject. Members of the study site 
will have unique user and personal identification numbers to contact the IWRS and must provide
relevant subject details to uniquely identify the subject.
Blinding
This will be a randomized, double-blind, placebo-controlled study. To maintain the study blind, 
the study agent container will have a multipart label containing the study name, study agent 
number, reference number, and other information on each part. The label will not identify the 
study agent in the container. However, if it is necessary for a subject's safety, the study blind 
may be broken, and the identity of the study agent ascertained. The study agent number will be 
entered in the case report form (CRF) when the study agent is administered. The study agents 
will be identical in appearance and will be packaged in identical containers.
The investigative sites will not be provided with randomization codes. The codes will be 
maintained within the IWRS, which has the functionality to allow the investigator to break the 
blind for an individual subject.
Data that may potentially unblind the treatment assignment (ie, study agent serum 
concentrations, anti-golimumab antibodies, and treatment allocation) will be handled with 
special care to ensure that the integrity of the blind is maintained and the potential for bias is 
minimized. This can include making special provisions, such as segregating the data in question 
from view by the investigators, clinical team, or others as appropriate until the time of DBL and 
unblinding.
Under normal circumstances, the blind should not be broken until all subjects have completed 
the study and the database is finalized. Otherwise, the blind will be broken only if specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
subject. In such cases, the investigator may in an emergency determine the identity of the 
treatment by contacting the IWRS. It is recommended that the investigator contact the sponsor or 
its designee if possible, to discuss the particular situation, before breaking the blind. Telephone 
contact with the sponsor or its designee will be available 24 hours per day, 7 days per week. In 
the event the blind is broken, the sponsor must be informed as soon as possible. The date and 
reason for the unblinding must be documented by the IWRS, in the appropriate section of the 
CRF, and in the source document. The documentation received from the IWRS indicating the 
code break must be retained with the subject's source documents in a secure manner.
Subjects who have had their treatment assignment unblinded for a SAE will not continue to 
receive study agent but should continue to return for scheduled evaluations.
Summary level unblinded data will be made available to the sponsor at the Week 52 DBL 
(DBL 1). Subject level data will be unblinded to selected members of the sponsor’s data 
management, programming, pharmacology, clinical and biostatistics teams for analysis and 
reporting, while the subjects are still being followed in the study. Identification of sponsor 
personnel who will have access to the unblinded subject level data will be documented prior to 
unblinding. The Study Responsible Physician will remain blinded throughout the double-blind 

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period to subject level treatment assignment and dosing regimen. Site investigators and 
personnel, and the subjects/caregivers will remain blinded until after the Week 104 DBL 
(DBL 2) has occurred. An exception to this rule will be made for those subjects who are meeting 
the responder criteria at Week 52 of the double-blind period. These will be unblinded to
determine eligibility for re-starting active treatment during the open-label extension period.
Subject level data will be unblinded to Data Monitoring Committee (DMC) and Interim Analysis 
Committee (IAC). Please refer to Section 11.10 and Section 11.11 for details.
6.
DOSAGE AND ADMINISTRATION
6.1.
Dosage
All study agent (golimumab or placebo) will be administered SC using a sponsor-supplied, 
single-use administration device. This will be either the commercially available prefilled syringe 
with a needle guard (the PFS-Ultrasafe [PFS-U]), designed to deliver a single, fixed dose of 
50 mg, or the investigational VarioJect injection device (“VarioJect)” which delivers a single, 
variable dose of 10 to 45 mg in 5 mg increments. Identical devices containing placebo will be 
used to deliver a volume equivalent to that of active treatment for subjects randomized to the 
placebo arm.
Body surface area will be calculated at Week 0 for the induction and maintenance dose of 
golimumab (and will be adjusted as needed) based on weight cut-off according to Table 1. 
Detailed charts using height and weight for induction and maintenance doses according to weight 
cut-off are presented in Attachment 2-A and 2-B, respectively. Body surface area will be 
calculated using the Mosteller equation: BSA (m2) = ([height (cm) x weight (kg)]/3600)1/2. The 
dosage form (PFS-U or VarioJect) and volumes required for administration are presented in 
Attachment 2-C. For certain induction doses, 2 injections may be required for administration of 
1 induction dose.
Table 1:
Golimumab SC Dosing Regimens by Body Weight Cut-Off For Subjects Who Are Randomized 
to the Golimumab Treatment Group
Body weight*
Week 0 and 2
Week 4 through Week 52 
(Double-Blind) Period
Week 0 through Week 
50 (Open-Label 
Extension) Period
<45 kg
60 mg/m2
30 mg/m2 q2w
30 mg/m2 q2w
≥45 kg
100 mg
50 mg q2w
50 mg q2w
Number of injections/dose
1 or 2**
1**
1**
*Body weight to be evaluated approximately every 3 months with dose adjustment if necessary (below and see Time 
and Events Table).
**Refer to Attachment 2
During the 52-week dosing period, subjects may experience changes in their weight and/or 
height necessitating a change in the dose of the study agent. There will be 4 opportunities to
calculate the study agent dose during the 52-week dosing period. Study agent dose for the first 
12 weeks will be based on height and weight obtained at the Week 0 visit. At the Week 12 visit, 
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will be calculated. Similarly, at the Week 26 and 38 visits, the dose for the subsequent 12 and 
14-week intervals, respectively, will be calculated (see Time and Events Schedule).
The same procedure will be applied for the responders during the open-label extension period. 
Study agent dose will be calculated at the OL Week 0, 12, 28, 44, and 50 visits. The last dose of 
study agent is to be administered at Week 50. Detailed charts using height and weight for 
open-label extension period according to weight cut-off is presented in Attachment 2-B.
Responders being restarted on active drug will not undergo an induction regimen but will 
immediately be started on the maintenance dose. A new induction dose may entail an increased 
risk for immunogenicity and/or hypersensitivity reactions and there is no clear rationale for 
reaching steady state as quickly as possible given the longer delay after diagnosis of T1D.
Details on dose preparation and administration can be found in the Study Site Investigational 
Product and Procedures Manual (SIPPM).
For the most comprehensive information regarding the VarioJect, refer to the current version of 
the VarioJect IB.
6.2.
Dose Administration
Study agent dosing will be administered using the PFS-U or VarioJect. It will be injected 
subcutaneously by trained study-site staff and for some dosings, subjects/caregivers will be given 
the option of "self-administration" after appropriate training (described below). For purposes of 
this study, the term “self-administration” is defined as study agent administered either by subject 
or caregiver and can occur at home and/or at study sites. In cases where subjects/caregivers do 
not want or are unable to participate in self-administration of study agent, subjects will receive 
all doses of study agent at study sites.
For responders in the open-label extension period, study agent administration will be performed 
by site personnel at all site visits. In-between visit doses will be administered either by the 
subject or by the caregiver. In cases where subjects/caregivers do not want or are unable to 
participate in self-administration of study agent, subjects will receive all doses of study agent at 
study sites.
Study staff and those subjects/caregivers who will participate in self-administration will receive 
training on study agent administration at the investigative site under the supervision of a trained 
health care professional, which must be documented. This will include education regarding 
instructions for use (IFU), proper handling and storage of devices, guidance on study agent 
injection, and proper handing and accounting for used devices. Required storage conditions and 
expiration date are indicated on the label.
Injection sites include the front of thighs (which is recommended), the lower abdomen (avoiding 
the 2-inch area around the navel), or the back of the upper arms. Different sites should be used 
for consecutive injections. Sites that are tender for any reason should be avoided. Study agent 
and insulin injections should be given at different anatomic sites.

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Study agent dosing should be held during the course of a febrile episode and other conditions as 
detailed Section 10.2. If the febrile episode is mild and transient and the subject does not meet 
any criteria in Section 10.2, that dose may still be administered as long as it is in the current 
dosing window (See Section 7.1) otherwise dosing should resume with the next planned dose. 
Refer to Section 10.2 for dose holding and dosing resumption for other conditions. If 
subjects/caregivers have a question about the subject status and their ability to be dosed, they are 
to consult with the study-site investigational team. If subjects/caregivers have a question about 
the subject status and their ability to be dosed, they are to consult with the study-site 
investigational team.
Administration of the first 3 doses will occur during study visits (Week 0, 2, and 4). For 
subjects/caregivers who will be participating in self-administration, training will take place at 
these visits. It is possible that the device required for induction doses differs from the device 
required for maintenance doses. Training should be provided on the device intended for 
maintenance dosing. Prior to allowing at home self-administration, at least 1 successful injection 
by the subject/caregiver using the device to be used for at home self-administration, must be 
witnessed by study staff. At the Week 8, 12, 18, 26, 38, and 52 study visits of the double-blind 
period and Week 12, 20, 28, 36, 44, and 50 study visits of the open-label extension period where 
study agent will be administered, either subjects/caregivers or study staff may administer the 
injection.
Following dosing, subjects are to be monitored for at least 30 minutes as detailed in Section 9.1.3
and Section 9.1.5. All data regarding study agent administration including date, time, and 
anatomic location of injection, study agent dosing device and if there are AEs, reactions or 
device complications will be recorded. During self-administration, subjects/caregivers are to 
contact the study-site team in the event of problems or complication including but not limited to 
signs of immediate or delayed local or systemic reaction (Section 9.9).
At any time, if subjects/caregivers are uncertain about how to administer the study agent or has 
questions regarding self-administration, the sponsor recommends a review of the IFU with the 
study staff along with practice injections with a training device if necessary. If at any time during 
one of the 3 opportunities for dose adjustment, there is a change in the device required for 
dosing, the subject/caregiver must return to the study site for training and the subject/caregiver 
using the device must be witnessed by study staff self-administering a successful injection prior 
to performing at home self-administration.
For subjects/caregivers unwilling or unable to self-administer the study agent outside of the 
study site, subsequent doses will be administered at the study site by qualified personnel on the 
appropriate dosing schedule per the Time and Events Schedule. During the dosing period these 
subjects/caregivers can be trained for self-administration of subsequent dosing per the above 
guidelines.

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7.
TREATMENT COMPLIANCE
7.1.
STUDY AGENT DOSING COMPLIANCE: RECORDING AND WINDOWS
7.1.1.
Dosing Recording
Details on the specifics of the study agent including study agent dosing device type, date, time, 
anatomic location of injection, and person administering the dose, will be documented in the 
CRF or recorded in the electronic diary (eDiary). Study-site personnel will record this 
information for study agent administrations conducted at the study visits (see Time and Events 
schedule). For subjects/caregivers participating in self-administration, this data will be entered
into an eDiary unless self-administration is done on-site where this information will be recorded 
in the study site’s documents, not in the eDiary. All information related to self-administration 
will be reviewed and verified with subjects/caregivers at subsequent study visits.
Subjects are to receive dosing with study agent every 2 weeks following randomization through 
Week 52, for a total of 27 doses (Table 2). The “target dosing day” for the study will be at 
14-day intervals and calculated based on the day of randomization. The target dosing day 
schedule will not be readjusted due to missed or off schedule dosing.
The investigator or designated study-site personnel will maintain a log of all study agent 
dispensed and returned both from and to the study site and the sponsor and, in cases of subject 
self-administration, to and from the study site and subject/caregiver. Drug supplies for each 
subject will be inventoried and accounted for throughout the study.
Study sites are expected to keep in close contact with subjects/caregivers and encourage dosing 
and study visit compliance, whether or not they are participating in self-administration. This may 
occur proactively via telephone or electronic communication, sending automated dosing 
reminders, and through monitoring eDiaries which will be obtaining regular (ie, daily) subject 
data entry updates.
7.1.1.1.
Dosing Recording – Open-Label Extension Period
Details on the specifics of the study agent including study agent dosing device type, date, time, 
anatomic location of injection, and person administering the dose, will be documented in the 
CRF or recorded in the or paper diary. Study-site personnel will record this information for study 
agent administrations conducted at the study visits (see Time and Events schedule). For 
subjects/caregivers participating in self-administration, this data will be entered into the paper 
diary unless self-administration is done on-site where this information will be recorded in the 
study site’s documents, not in the paper diary. All information related to self-administration will 
be reviewed and verified with subjects/caregivers at subsequent study visits.
Subjects are to receive dosing with study agent every 2 weeks based on Week 0 of the open-label 
extension period, for a total of 27 doses (Table 3). The “target dosing day” for the study will be 
at 14-day intervals and calculated based on the day of randomization. The target dosing day 
schedule will not be readjusted due to missed or off schedule dosing.

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The investigator or designated study-site personnel will maintain a log of all study agent 
dispensed and returned both from and to the study site and the sponsor and, in cases of subject 
self-administration, to and from the study site and subject/caregiver. Drug supplies for each 
subject will be inventoried and accounted for throughout the study.
Study sites are expected to keep in close contact with subjects/caregivers and encourage dosing 
and study visit compliance, whether or not they are participating in self-administration. This may 
occur proactively via telephone or electronic communication, sending automated dosing 
reminders, and through or paper diaries during the open-label extension period which will be 
obtaining regular (ie, daily) subject data entry updates.
7.1.2.
Dosing Windows
All attempts should be made to dose on the scheduled target dosing day, yet it is recognized 
that due to schedules and other events this may not be possible.
Weeks 2 and 4: Study agent dosing for Week 2 and 4 is to occur ± 1 day of the target-dosing
day.
Weeks 6 through 52: For study agent dosed from Weeks 6 through 52, every effort should be 
made to administer the study agent on the target dosing day or at least should be given ± 3 days 
of the target day, regardless of whether subjects are participating in self-administration or being 
dosed at study sites. In situations where subjects cannot dose within this window, the dose can be 
administered up to 7 days after the targeted dosing day. If the dose cannot be administered within 
this period, that dose should not be given, and subjects should resume dosing at the next 
scheduled dosing interval.
Entire study: Throughout the study, administration of sequential study agent dosing’s must 
occur no less than 7 days apart.
Table 2:
Study Agent Dosing Window Table
Time
Dose Administration Window Around Target Dosing Day*
Required Administration at the Study Site
Randomization Visit Week 0
N/A
Visits Week 2 and 4
± 1 day
Visits and Dosing Weeks 6 through 52
± 3 days
*Calculated based on 14-day intervals from randomization day. Subjects/caregivers will schedule dosing-only visits 
to comply with dosing schedule.
7.1.2.1.
Dosing Windows - Open-Label Extension Period
Week 2: Study agent dosing for Week 2 is to occur ± 1 day of the target-dosing day.
Weeks 4 through 50: For study agent dosed from Weeks 4 through 50, every effort should be 
made to administer the study agent on the target dosing day or at least should be given ± 3 days 
of the target day, regardless of whether subjects are participating in self-administration or being 
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Entire study: Throughout the study, administration of sequential study agent dosing’s must 
occur no less than 3 days apart.
Table 3:
Study Agent Dosing Window Table – Open-Label Extension Period
Time
Dose Administration Window Around Target Dosing Day*
Required Administration at the Study Site
Visit Week 2
± 1 day
Visits and Dosing Weeks 4 through 50
± 3 days
*Calculated based on Week 0 of open-label extension period. Subjects/caregivers will schedule dosing-only visits to 
comply with dosing schedule.
8.
PRESTUDY AND CONCOMITANT THERAPY
During the double-blind period, prestudy therapies administered up to 28 days before screening 
and between screening and randomization must be recorded in the CRF.
Concomitant therapies must be recorded throughout the study beginning at randomization 
through completion of the study.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements) different from the study agent 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.
8.1.
Required Medications
Insulin preparations as advised by the principal investigator and/or the subject’s primary 
physician or endocrinologist to target current glycemic control recommendations by the ADA 
specifically with a HbA1c target of <7.5% in children 17 years old and younger and <7% in 
those 18 years old and above.67
All subjects will be expected to take a sufficient number of daily insulin injections to meet the 
above glycemic targets. In general, the expectation is that all subjects will receive at least 
3 injections of insulin daily, including short- and long-acting insulin preparations, or will utilize 
a continuous subcutaneous insulin infusion/pump. Glucose levels should be checked at least 
4 times daily. HbA1c will be recorded regularly as part of the study and subjects may have 
HbA1c conducted by their physician who is managing their diabetes.
During the double-blind period, subjects will record insulin use for the 7-days preceding each 
study visit and hypoglycemic events occurring at any time during the study will be captured 
using an eDiary. Subjects will also be loading daily glucometer readings into their eDiary. This 
information will be reviewed at each study visit and recorded using CRFs. Please also refer to 
Section 9.8.
During the open-label extension period, subjects will record insulin use for the 10-days 
preceding each study visit and hypoglycemic events occurring at any time during the study will 
be captured using the paper diary.

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If subjects are not meeting the above goals, the study team should contact the subject’s primary 
clinical-care team about possible adjustments in the insulin regimen, referral to a registered 
dietitian, or other approaches that the diabetes management team believes would improve the 
glucose control if necessary.
8.2.
Permitted Medications
There are no medications specifically contraindicated for use with golimumab, so subjects may 
continue to receive medications as needed for existing medical conditions. Please see Section 8.3
for a list of medications that should not be taken in conjunction with the study agent during the 
study. Specific permitted medications that subjects may need during the study include, but are 
not limited to:

Low-dose estrogen oral contraception.

Acetaminophen and NSAIDs (eg, ibuprofen and naproxen).

Diphenhydramine (or equivalent antihistamines).

Non-infectious 
(ie, 
recombinant, 
inactivated 
or 
otherwise 
“non-live”) 
vaccines 
recommended by the CDC in individuals 6 years old and above (including the HPV vaccine) 
and those recommended for immunosuppressed individuals or those with chronic diseases 
(diabetes mellitus). For these immunizations, if required and applicable, subjects should 
receive recommended one-time vaccinations prior to first study agent administration. If a 
subject has started a recommended vaccination series, the next administration in the series 
should be given before first dosing of study agent, if consistent with recommended 
administration schedule. If needed, the series may be completed during the study according 
to the recommenced schedule. If a subject has not received the first dose of a required 
vaccination series, they should receive this before the first study agent administration and 
continue to receive vaccinations in this series during the study as recommended. Subjects 
are to receive non-infectious vaccines during the recommended time frame if they meet 
specific criterion during the study, ie, becoming age-eligible, while participating in the 
study. Documentation of all vaccines given during screening and post-randomization
participation in the study must be provided to the study site.
8.3.
Prohibited Medications
The concomitant use of the following drugs is not permitted during the study:

Live vaccines (eg, varicella, measles, mumps, rubella, cold-attenuated intranasal influenza 
vaccine, and smallpox) in the 90 days before enrollment, during the treatment periods, and 
for 120 days after completing study treatment. In addition, household contacts should be 
encouraged not to receive small pox or oral polio vaccine due to the risk of viral shedding.

BCG vaccination during the study or for 12 months after the last administration of study 
agent.

Agents that influence insulin sensitivity or secretion, which include but are not limited to 
MTX, sulfonylureas, metformin, diphenylhydantoin, thiazide, or other potassium-depleting 
diuretics, beta-adrenergic blockers, or niacin through Week 104 including the open-label 
extension period.

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
Agents that may result in immunosuppression or immunomodulation through Week 104 and 
the open-label extension period. This includes initiation of long- or chronic-dosing of 
high-dose inhaled, extensive topical or systemic glucocorticoids. This also includes biologic 
immune modulators including but not limited to abatacept and anakinra. Note: A short 
course of corticosteroids may be used for treatment of a transient condition.
If a subject receives, or if the principal investigator believes that a subject needs a prohibited 
medication, the case must be immediately discussed with sponsor Study Responsible Physician 
to determine whether study treatment should continue or be discontinued.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview

The Time and Events Schedule summarizes the frequency and timing of efficacy, PK,
immunogenicity, Pharmacodynamics, biomarker, pharmacogenomic, and safety assessments 
applicable to this study.

During the double-blind period, a 4-hour MMTT will be performed during screening, and at 
Weeks 12, 26, 38, 52, 78, and 10412. During the open-label extension period, a 4-hour 
MMTT will be performed to establish eligibility criteria unless the previous MMTT was 
<3 months ago and will also be performed at OL Screening and OL Weeks 28 and 52. For 
C-responders who are lacking the necessary information to calculate IDAA1c score, an 
HbA1c will be performed and 10 days of insulin dose information will be required. This test 
is to be performed in the morning after an overnight fast. Subjects are to follow the dietary 
and insulin use guidelines as described in Attachment 3 to perform the MMTT.

Subjects/caregivers will collect data related to diabetes management, hypoglycemic events, 
and study agent dosing using sponsor-supplied eDiary and glucometer (for the double-blind 
period) and paper diary (for the open-label extension period).

PK and Immunogenicity samples must be collected before study agent administration.

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.

Blood collection:

The total blood volume to be collected from each subject, including during screening, 
the 52-week treatment period and 52-week off-therapy follow-up period is 
approximately 436 mL for subjects <35 kg and 505 mL in subjects ≥35 kg. During the 
open-label extension period, approximately 210 mL for subjects <35 kg and 234 mL for 
subjects ≥35 kg will be drawn.

It is recognized that the amount of blood that may be drawn for research purposes in 
adults and children may not exceed certain limits, both at a single visit and over a set 
amount of time. Guidance for blood drawing in this study is:

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Adult Subjects (18 years of age and older)
The amount of blood that may be drawn for research purposes shall not exceed 10.5 mL/kg or 
550 mL, whichever is smaller, over any 8-week period.
Pediatric Subjects (6 Through 17 Years of Age):
The amount of blood that may be drawn for research purposes shall not exceed more than 
5 mL/kg in a single day and shall not exceed more than 9.5 mL/kg over any 8-week period.
In any subject whose clinical condition might be adversely affected by removal of the blood 
volumes stated above, for example, a subject with significant anemia or compromised cardiac 
output, investigators should consider further limiting the volume of blood withdrawn for research 
purposes.
In instances of medical need, it is the responsibility of the site investigator and/or subject’s 
healthcare providers to determine if blood draws in excess of the above limits should occur.
Because blood sampling in excess of those mandated by the protocol may be taken in the course 
of providing patient care during this study, sites must ensure that all instances of blood collection 
in excess of permitted volumes are recorded and justified in the subject’s record.
9.1.2.
Screening Period
For all subjects participating in this study, the screening visit must occur within 28 days of study 
agent administration and may occur over more than 1 day. Prior to screening, the investigator (or 
designee) will explain the study’s rationale, procedures, and risks, and ask each potential 
subject/caregiver to consent/assent to participate. The start of the screening period of the study 
will be defined as the day written informed consent/assent is obtained. Subjects may participate 
in optional pharmacogenomic assessments which will require a separate consent/assent. 
Subjects will be assigned a unique subject number and evaluation for inclusion/exclusion criteria 
(Section 4) will be performed, which will include clinical and laboratory evaluations and the
4-hour MMTT.
An eDiary and glucometer will be issued to subjects during screening for training on how 
subjects/caregivers are to collect data between study visits related to: including insulin use, BG
levels, hypoglycemic events, and study agent administration. Subject data collected using 
eDiaries will be reviewed and verified at subsequent study visits, including the randomization 
visit (see Time and Events Schedule). In cases where subjects are not enrolled in the study, they 
will be directed on how to return the devices.
The measurements collected and procedures performed during the screening visit for all subjects 
are identified in the Time and Events Schedule. In anticipation of successful screening and 
continued interest in the study, study personnel should discuss the optimal timing for and even 
tentatively schedule study randomization at the screening visit. This is due to the limited window 
between screening and randomization and recognizing that all future dosing and study visits for 
2 years will be based on that randomization date.

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Subjects must undergo testing for TB (see Attachment 1) 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 or suspected TB. The subject should be asked about past 
testing for TB, including responses to tuberculin skin or other TB testing.
Subjects with a negative QuantiFERON-TB Gold test result are eligible to continue with 
randomization procedures. Subjects with a positive QuantiFERON-TB Gold test result must be 
excluded from the study.
A subject whose first QuantiFERON-TB Gold test result is indeterminate should have the test 
repeated. In the event that the second QuantiFERON-TB Gold test result is also indeterminate, 
the subject should be excluded from the study.
Retesting
If subjects screen but do not meet all study participation criteria (See Section 4.1 and 
Section 4.2.1), they may be eligible for retesting that may lead to randomization. Retesting of 
laboratory tests will be allowed once and will take place during an unscheduled visit within 
28 days of initial screening phase.
Rescreening
If subjects are eligible to participate in the study but do not randomize within 28 days of signing 
the consent/assent form or do not meet specific enrollment criteria that may change to allow 
enrollment (ie, development of T1D autoantibodies), subjects may be rescreened and be 
randomized as long as inclusion and exclusion criteria are met and the subject is able to be 
randomized within 100 days of T1D diagnosis. Rescreening is allowed only once. Subjects who 
are rescreened will receive a new subject number, repeat the informed consent process, and then 
restart a new screening phase.
9.1.2.1.
Screening Period - Open-Label Extension Period
For the open-label extension period, the optional screening visit should occur within 21 days 
after the subject has been offered the opportunity to enter open-label extension period and in any 
event must occur within 14 days prior to Week 104. Prior to screening, the investigator (or 
designee) will explain the study’s rationale, procedures, and risks, and ask each potential 
subject/caregiver to consent/assent to participate. The start of the screening period of the study 
will be defined as the day written informed consent/assent is obtained. Rules for MMTT have 
been described in Attachment 3.
Subjects will be assigned a unique subject number and evaluation for inclusion/exclusion criteria 
(Section 4) will be performed, which will include clinical and laboratory evaluations and the 
4-hour MMTT.
A paper diary will be issued to subjects during screening for training on how subjects/caregivers
are to collect data between study visits related to: including insulin use, hypoglycemic events, 

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and study agent administration. Subject data collected using paper diaries will be reviewed and 
verified at subsequent study visits (see Time and Events Schedule).
Subjects must undergo testing for TB (see Attachment 1) 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 or suspected TB. The subject should be asked about past 
testing for TB, including responses to tuberculin skin or other TB testing.
Subjects with a negative QuantiFERON-TB Gold test result are eligible to continue with 
randomization procedures. Subjects with a positive QuantiFERON-TB Gold test result must be 
excluded from the study.
A subject whose first QuantiFERON-TB Gold test result is indeterminate should have the test 
repeated. In the event that the second QuantiFERON-TB Gold test result is also indeterminate, 
the subject should be excluded from the study.
9.1.3.
Randomization, Treatment Period, and Follow-up Period
9.1.3.1.
Active Treatment Period: Weeks 0 To 52
Randomization: Week 0
Randomization will occur no later than 28 days after screening is initiated and will be designated 
as Week 0 and Day 1 of the study. At this visit, inclusion and exclusion criteria, concomitant 
medications, and laboratory evaluations should be reviewed and documented to determine that a 
subject remains eligible for participation in the study. All eDiary data collected since screening
will be reviewed by clinic staff. Subjects must have at least 5 days of daily insulin use recorded
within the 7 days immediately preceding randomization. If not, subjects/caregivers should be 
instructed to reschedule this visit to have at least 5 days of daily insulin usage recorded prior to 
the rescheduled randomization visit. Subjects will be randomly assigned as described in 
Section 3.1 to receive study agent (golimumab or placebo). Subject weight and height will be 
obtained to determine dose and device.
After the predose PK/immunogenicity sample is drawn, the dose of study agent (golimumab or 
placebo) will be administered at the study site. Subjects should be monitored for at least 30 
minutes following injection and be observed for any adverse reactions, including injection site 
reactions (See Section 9.9). Subjects/caregivers who want to participate in study agent 
administration “self-administration” outside of some study visits begin training on using the 
sponsor-supplied single-use injection devices (See details Section 6.2). Additional training on the 
eDiary and glucometer will be given as needed.
Future target dosing and study visit days will be calculated based on the day of initial dosing at 
randomization (Week 0) and will not be redefined later during the study. Therefore, the study 
staff are encouraged to discuss the study visit days with subjects/caregivers and consider this 
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study visits. Specific study visits and study agent treatment windows and impact on study 
compliance is detailed in Section 7.
At this visit, subjects/caregivers will be supplied with a calendar with target dosing days and 
target study visit days that show dosing and visit windows (See Section 7.1.2).
Study Visits: Weeks 2 and 4
At these visits, subjects will have medical and eDiary review and other assessments per the Time 
and Events Schedule. Subjects will receive study agent by study staff and should be monitored 
for at least 30 minutes following injection and be observed for any adverse reactions, including 
injection site reaction (Section 9.9). In addition, for those who will be administering the injection
outside of study visits (“self-administration”), subjects and/or caregivers should continue and 
complete administration training, including conducting a successful injection by the subject or 
caregiver using the device to be used for self-injection. If the training was considered successful 
and the site staff considers that the subject or caregiver can successfully self-administer, the 
subject will be sent home with study agent injection devices at Week 4, with instructions for 
handling and storage of drug and used devices. The visit window for these visits is ±1 day from 
the target dosing day.
Study Visits Including Study Agent Dosing: Weeks 8, 12, 18, 26, 38, and 52
During Weeks 8 through 52, subjects will return to the site for their scheduled visit, have predose
PK/immunogenicity sample drawn, have safety and/or efficacy assessments performed, and 
receive study agent dosing by site staff according to the Time and Events Schedule. All subject 
required data, including that recorded via eDiary data, will be reviewed. During these visits, 
subjects/caregivers who are administering injections are to return used devices and receive 
additional devices and supplies per the Time and Events Schedule since the last visit. At these 
visits, subjects/caregivers will also receive additional device training as needed. During 
Weeks 12, 26, and 38, subjects are to have their weight and height reassessed to determine if 
dosing adjustments need to be made for the next interval as described in Section 6.1, with 
additional training as needed. The visit windows for these study visits are ± 3 days from the 
target dosing day.
Study Visits for PK Sampling and Clinical Review Only: Weeks 33 and 45
Visits on Weeks 33 and 45 are not dosing visits however in addition to clinical review and 
assessments, a random PK sample will be drawn. Subjects/caregivers who are participating in 
administering injections are to return used devices and receive additional injection devices and 
supplies, if needed, at these visits. The visit windows for these study visits are ± 7 days from the 
target dosing (visit) day.
9.1.3.2.
Study Agent Self-Administration or Dosing-Only Visits: Study Weeks 
6, 10, 14, 16, 20, 22, 24, 28, 30, 32, 34, 36, 40, 42, 44, 46, 48, and 50
After Week 4, subjects/caregivers who have met the training requirement, are given the option to 
self-administer majority of the study agent doses off-site that do not coincide with study visits. 
As detailed in Section 6.2
and the IFU, subjects/caregivers will receive training on 

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administration during the first 3 dosing visits, and at study visits preceding off-site
administration subjects will receive the appropriate study agent devices for dosing until the next 
dosing visit as well as supplies and instructions on handling and storage before and after usage. 
Subjects/caregivers will enter information including date and time of dosing, device used, 
anatomic site injected, and person administering dose into their eDiary. Subjects/caregivers will 
be asked to closely monitor the study agent injection site for at least 30 minutes and 
intermittently thereafter. During self-administration, subjects/caregivers are to contact the 
study-site team in the event of problems or complication including but not limited to signs of 
immediate or delayed local or systemic reaction (Section 9.9). These dose administrations should 
occur ± 3 day of target dosing day as detailed above.
For subjects/caregivers unwilling or unable to administer the injection, subjects/caregivers are to 
work with the site team to develop a visit schedule to meet the dosing criteria in Section 9.1.3
and per the Time and Events Schedule. These study agent dosing-only visits are to take place 
± 3 days of the target dosing day.
9.1.3.3.
Off-Therapy Follow-up Period – Weeks 52 to 104
The last dose of study agent is to be administered at the Week 52 study visit. Subjects will 
remain in the study until Week 104, continue recording data in their eDiary and followed for 
evaluations of safety, PK/anti-drug antibodies, and durability of response. Subjects will have 
assessments only at Week 78 and Week 104. All safety and efficacy assessments will be 
performed at these visits according to the Time and Events Schedule. The visit windows for 
these 2 visits are ± 10 days of the target visit day.
During the treatment and off-therapy follow-up periods subjects will continue to receive 
intensive management of their diabetes and maintain tight glycemic control according to the 
current ADA.67
9.1.4.
Optional Screening - Open-Label Extension
For the open-label extension period, the optional screening visit should take place no later than 
21 days after the subject has been offered the opportunity to enter open-label extension period
and in any event must occur within 14 days prior to Week 104.
9.1.5.
Open-Label Extension Period
Subjects meeting the inclusion criteria applicable for responders and who are willing to 
participate will restart active study treatment in the open-label extension period.
9.1.5.1.
Active Treatment Period: OL Weeks 0 To 52
Restart: OL Week 0
Restart will occur no later than 14 days after screening is initiated and will be designated as 
Week 0 and Day 1 of the study. In no event can a subject be restarted if they have completed the 
Week 104 visit. At this visit, inclusion and exclusion criteria, concomitant medications, and 
laboratory evaluations should be reviewed and documented to determine that a subject remains 

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eligible for participation in the study. All paper diary data collected since screening will be 
reviewed by clinic staff. Subjects should have at least 10 days of daily insulin use immediately 
preceding restart. Subjects will be restarted to receive golimumab as described in Section 3.1. 
Subject weight and height will be obtained to determine dose and device.
The dose of study agent (golimumab) will be administered at the study site. Subjects should be 
monitored for at least 30 minutes following injection and be observed for any adverse reactions, 
including injection site reactions (See Section 9.9). Subjects/caregivers who want to participate 
in study agent “self-administration” outside of some study visits begin training on using the 
sponsor-supplied single-use injection devices (See details Section 6.2). Additional training on the 
paper diary and glucometer will be given as needed.
Future target dosing and study visit days will be calculated based on the day of initial dosing 
(Week 0) and will not be redefined later during the study. Therefore, the study staff are 
encouraged to discuss the study visit days with subjects/caregivers and consider this schedule to 
determine what might be the anticipated (ie, day of the week) for future dosing and study visits. 
Specific study visits and study agent treatment windows and impact on study compliance is 
detailed in Section 7.
At this visit, subjects/caregivers will be supplied with a calendar with target dosing days and 
target study visit days that show dosing and visit windows (See Section 7.1.2.1).
Study Visits: OL Weeks 2 and 4
At these visits, subjects will have medical and paper diary review and other assessments per the 
Time and Events Schedule. Subjects will receive study agent by study staff and should be 
monitored for at least 30 minutes following injection and be observed for any adverse reactions, 
including injection site reaction (Section 9.9). In addition, for those who will be administering 
the injection outside of study visits (“self-administration”), subjects and/or caregivers should 
continue and complete administration training, including conducting a successful injection by the 
subject or caregiver using the device to be used for self-injection. If the training was considered
successful and the site staff considers that the subject or caregiver can successfully 
self-administer, the subject will be sent home with study agent injection devices at OL Week 4, 
with instructions for handling and storage of drug and used devices. The visit window for OL 
Week 2 and Week 4 visits is ±1 day and ±3 days, respectively from the target dosing day.
Study Visits Including Study Agent Dosing: OL Weeks 12, 20, 28, 36, 44, and 52
During Weeks 12 through 52, subjects will return to the site for their scheduled visit, have 
predose PK/immunogenicity sample drawn, have safety and/or efficacy assessments performed, 
and receive study agent dosing by site staff according to the Time and Events Schedule. All 
subject required data, including that recorded via paper diary data, will be reviewed. During 
these visits, subjects/caregivers who are administering injections are to return used devices and 
receive additional devices and supplies per the Time and Events Schedule since the last visit. At 
these visits, subjects/caregivers will also receive additional device training as needed. During OL 
Weeks 12, 28, and 44, subjects are to have their weight and height reassessed to determine if 

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dosing adjustments need to be made for the next interval as described in Section 6.1, with 
additional training as needed. The visit windows for these study visits are ± 3 days from the 
target dosing day.
Study Visits for PK Sampling and Clinical Review Only: OL Weeks 0, 4, 12, 28, and 52
A PK sample will be drawn at visits in OL Weeks 0, 4, 12, 28, and 52. Subjects/caregivers who 
are participating in administering injections are to return used devices and receive additional 
injection devices and supplies, if needed, at these visits. The visit windows for these study visits 
are ± 3 days from the target dosing (visit) day except for OL Week 0.
9.1.5.2.
Study Agent Self-Administration or Dosing-Only Visits: OL Weeks 0, 
2, 4, 12, 20, 28, 36, 44, and 50
After OL Week 4, subjects/caregivers who have met the training requirement, are given the 
option to self-administer majority of the study agent doses off-site that do not coincide with 
study visits. As detailed in Section 6.2 and the IFU, subjects/caregivers will receive training on 
administration during the first 3 dosing visits, and at study visits preceding off-site 
administration subjects will receive the appropriate study agent devices for dosing until the next 
dosing visit as well as supplies and instructions on handling and storage before and after usage. 
Subjects/caregivers will enter information including date and time of dosing, device used, 
anatomic site injected, and person administering dose into their paper diary. Subjects/caregivers 
will be asked to closely monitor the study agent injection site for at least 30 minutes and 
intermittently thereafter. During self-administration, subjects/caregivers are to contact the 
study-site team in the event of problems or complication including but not limited to signs of 
immediate or delayed local or systemic reaction (Section 9.9). These dose administrations should 
occur ± 3 day of target dosing day as detailed above.
For subjects/caregivers unwilling or unable to administer the injection, subjects/caregivers are to 
work with the site team to develop a visit schedule to meet the dosing criteria in Section 9.1.5
and per the Time and Events Schedule. These study agent dosing-only visits are to take place 
± 3 days of the target dosing day except for OL Weeks 0 and 2.
9.1.5.3.
Post-Treatment Visit
The last dose of study agent is to be administered at the Week 50. A post-treatment visit will be 
conducted for all subjects at OL Week 60 or 10 weeks after the last dose of study agent to collect 
SAEs and AEs of interest since the last visit unless the subject has died, has been lost to 
follow-up, or has withdrawn consent. If a study visit is not possible, follow-up information may 
be collected via email or other electronic means.
9.1.6.
All Study Visits - 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 the
Time and Events Schedule). The following series of questions is suggested for use during the 
evaluation and should be addressed at all study visits:

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
“Have you/Has your child had a new cough of >14 days’ duration or a change in a chronic 
cough?”

“Have you/Has your child had any of the following symptoms:

Persistent fever?

Unintentional weight loss?

Night sweats?”

“Have you/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, 
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 
should be referred for appropriate treatment.
Subjects who experience close contact with an individual with active TB during the conduct of 
the study must have a chest radiograph, a repeat QuantiFERON-TB Gold test 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. Study agent administration should be 
interrupted during the investigation. If the QuantiFERON-TB Gold test result is indeterminate, 
the test should be repeated as outlined in Section 9.1.2 and Section 9.1.2.1. Subjects should be 
encouraged to return for all subsequent scheduled study visits according to the protocol.
9.2.
Study Endpoints and Evaluations
9.2.1.
Efficacy Evaluations
The following efficacy evaluations will be assessed:

A 4-hour MMTT will be performed to assess C-peptide levels and the C-peptide AUC at 
screening and Weeks 12, 26, 38, 52, 78, and 104. For additional details, see the Time and 
Events Schedule.

Blood glucose levels between visits will be obtained by downloading home-glucometer 
readings.

Hemoglobin A1c (as % HbA1c) and insulin as U/kg body weight/day. An HbA1c 
measurement will be done at each study visit and subjects should record the type and 
amount of insulin they have used during the 7-day period immediately preceding each study 
visit.

Hypoglycemic events, defined as a BG level of ≤70 mg/dL or clinical sequelae consistent 
with hypoglycemia without a BG reading, will be documented throughout the study.

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
Records of glucose measurements, insulin use and hypoglycemic events and communication 
with the subject will be kept in source documentation, on the appropriate CRF, or in the 
patient diary.
9.2.1.1.
Efficacy Evaluations - Open-Label Extension Period

A 4-hour MMTT will be performed to assess C-peptide levels and the C-peptide AUC at OL 
screening (unless performed <3 months ago), OL Week 28, and OL Week 52. For 
C-responders who are lacking the necessary information to calculate IDAA1c score, an 
HbA1c will be performed and 10 days of insulin dose information will be required. For 
additional details, see the Time and Events Schedule.

During the open-label extension period, subjects may use either fingersticks or continuous 
glucose monitoring (CGM) at the discretion of the investigator and/or according to local 
practice. The subjects will not be required to download BG values from the eDiary.

Hemoglobin A1c (as % HbA1c) and insulin as U/kg body weight/day. An HbA1c 
measurement will be done at each study visit and subjects should record the type and 
amount of insulin they have used during the 10-day period.

Hypoglycemic events, defined as a BG level of ≤70 mg/dL or clinical sequelae consistent 
with hypoglycemia without a BG reading, will be documented throughout the study.

Records of glucose measurements, insulin use and hypoglycemic events and communication 
with the subject will be kept in source documentation, on the appropriate CRF, or in the 
patient diary. 
9.2.2.
Efficacy Endpoints
9.2.2.1.
Primary
The primary endpoint is the MMTT-stimulated 4-hour C-peptide AUC at Week 52.
9.2.2.2.
Major Secondary

Change from baseline in insulin use in units per kilogram body weight per day at Week 52.

Change from baseline in HbA1c at Week 52.

Hypoglycemic event rates (defined as BG levels of ≤70, 55, and 35 mg/dL or clinical 
sequelae consistent with severe hypoglycemia in the absence of a BG reading) through 
Week 52.
9.2.2.3.
Other Endpoints

Change from baseline in MMTT-stimulated 4-hour C-peptide AUC over time.

Change from baseline in comparative MMTT-stimulated 2-hour C-peptide AUC over time.

Change from baseline in MMTT-stimulated C-peptide over time.

Change from baseline in insulin use in units per kilogram body weight per day over time.

The proportions of subjects with hypoglycemia from baseline to Week 104, from baseline to 
Week 52 and from Week 52 to Week 104.

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
The event rates of hypoglycemia from baseline to Week 104 and from Week 52 through 
Week 104.

Change from baseline in HbA1c levels over time.

Proportion of subjects with peak MMTT-stimulated C-peptide ≥0.2 pmol/mL over time.

Time to peak MMTT-stimulated C-peptide <0.2 pmol/mL.
9.2.2.4.
Exploratory Efficacy Endpoints – Open-Label Extension Period
All the efficacy endpoints defined for the double-blind period will be exploratory for the open-
label extension period and will be summarized descriptively. Disease progression will be 
compared between the double-blind period and the extension period in subjects who attended the 
open-label extension period if deemed reasonable.
9.2.3.
Safety Endpoints

Proportion of subjects with treatment-emergent AEs and severe AEs through Weeks 52 and 
104.

Proportion of subjects with study agent injection site reactions through Week 52.

Proportion of subjects with severe infections through Weeks 52 and 104.
9.2.3.1.
Safety Endpoints – Open-Label Extension Period

Proportion of subjects with treatment-emergent AEs and severe AEs through OL Weeks 52
and 60.

Proportion of subjects with study agent injection site reactions through OL Week 52.

Proportion of subjects with severe infections through OL Weeks 52 and 60.
9.2.4.
Exploratory Endpoints
9.2.4.1.
Mechanistic


9.2.4.2.
Metabolic



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9.3.
Clinical Pharmacology
9.3.1.
Evaluations
Serum samples will be used to evaluate the PK, the immunogenicity of golimumab (antibodies to 
golimumab), and pharmacodynamics (PD; free/total TNFα). Sera collected may additionally be 
used to evaluate biomarkers for safety or efficacy aspects to address concerns that may arise 
during or after the study. Subject confidentiality will be maintained. Sera for the measurement of 
golimumab concentration, antibodies to golimumab, and free/total TNFα will be derived from 
the same blood draw.
Instructions for the collection, handling, and shipment of these samples are found in the 
Laboratory Reference Manual provided by the sponsor.
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.
Pharmacodynamics
Serum samples will be analyzed to determine concentrations of free and total TNFα (sample 
volume permitting) using a qualified method by or under the supervision of the sponsor.
9.3.3.
Pharmacokinetic Parameters
Serum golimumab concentrations will be evaluated and summarized over time for the specified 
visits as indicated in the Time and Events Schedule.
A population PK analysis with data through Week 52 may be performed to characterize the PK 
of golimumab as well as to identify and quantify important covariates of PK (eg, body weight, 
sex and immunogenicity) in subjects with T1D, if necessary. Apparent clearance (CL/F) and 
volume of distribution (Vd/F) will be estimated using a nonlinear mixed effects modeling 
(NONMEM) approach.
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. 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.

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Serum samples will be screened for antibodies binding to golimumab and the titer of confirmed 
positive samples will be reported. For subjects positive for antibodies to golimumab, the positive 
samples will be evaluated for neutralizing antibodies. Other analyses may be performed to more 
fully characterize the immunogenicity of golimumab in this population.
The incidence of antibodies to golimumab during the study will be determined.
9.3.5.
Clinical Pharmacology – Open-Label Extension Period
The same procedures explained in Sections 9.3.1, 9.3.2, 9.3.3, and 9.3.4 for evaluations, 
analytical procedures, pharmacokinetics parameters, and immunogenicity assessments, 
respectively will be applied for open-label extension period.
9.4.
Biomarkers
In addition to samples collected for efficacy and safety evaluation, samples will be collected to 
assist in the understanding of how golimumab may affect general and T1D-specific immune and 
metabolic responses. Specifically, serum and cell-based biomarkers will be evaluated for 
inflammation-associated proteins, changes in immune cell subsets, and will be used to better 
understand the biology of T1D, to provide a biological assessment of the response of subjects to 
treatment with golimumab, to analyze differences between responders and nonresponders, and to 
determine if the markers can be used to classify patients as potential responders prior to 
treatment. It is important to note that these evaluations will be exploratory in nature as there are 
no validated measures to interrogate these areas. These studies may help to explain 
inter-individual variability in clinical outcomes or may help to identify population subgroups in 
this study that respond preferentially to golimumab (see Section 9.2), and thus characteristics of 
those with T1D who might benefit the most from golimumab therapy in the future.
Immune assessments may include but are not limited to monitoring T-cell profiles (including 
changes in specific subtypes such as activated, effector, and regulatory T cells) and B cell 
profiles by flow cytometry.61 In addition, serum levels of circulating pro- and anti-inflammatory 
cytokines, non-specific markers of inflammation (ie, C-reactive protein), and changes in T1D 
autoantibody profiles may be assessed.
Metabolic assessments may include innovative assessments of β-cell stress and death, which are 
anticipated to include pro-insulin:C-peptide ratios
and serum levels of circulating 
methylated-insulin DNA, (see Section 9.5, Pharmacogenomic [DNA] Evaluations).1,63,66
Samples for serum and cellular biomarkers will be collected for all subjects as indicated in the 
Time and Events Schedule. To assist a number of these assessments, samples will be obtained 
and banked for later batch analysis.
9.4.1.
Biomarkers – Open-Label Extension Period
The same procedure as explained in Section 9.4 will be followed for the open-label extension 
period.

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9.5.
Pharmacogenomic (DNA) Evaluations
In addition to immune and metabolic factors that may be affected by golimumab and give insight 
to clinical responses, as discussed above it is recognized that genetic variation can be an 
important contributory factor to inter-individual differences in drug distribution and response and 
can also serve as a marker for disease susceptibility, prognosis, and response to therapy.
Required Pharmacogenomic (DNA) Assessments: An individual’s MHC haplotype gives insight 
to interactions of distinct types of lymphocytes that may cause T1D and may help to identify 
those who are at risk of developing T1D.6,8 Genetic assessments of MHC haplotypes, may help 
to explain inter-individual variability in clinical outcomes and may help to identify subgroups 
that respond preferentially to golimumab. Agreeing to participate in this assessment is required
for this study.
Optional Exploratory Pharmacogenomic (DNA) Assessments: Pharmacogenomic research may 
consist of the analysis of one or more genetic markers throughout the genome in relation to 
golimumab or T1D clinical endpoints. One goal of this study to use genetic markers, such as but 
not limited to the methylation status of insulin DNA, obtained from serum to assist in the 
identification of individuals with T1D who may preferentially respond to golimumab and better 
understand the magnitude and mechanism of this response. DNA samples will be used for 
research related to golimumab or T1D. They may also be used to develop tests/assays related to 
golimumab and or other immune modulators and improved understanding of T1D or other 
immune-mediated diseases. Subjects participating in this portion of the study must sign a 
separate pharmacogenetics informed consent/assent and opt-in for exploratory pharmacogenetics 
research. Further, a subject may withdraw such consent/assent at any time without affecting their 
participation in other aspects of the study, or their future participation in the study.
9.5.1.
Pharmacogenomic (DNA) Evaluations – Open-Label Extension Period
Pharmacogenomic assessment of molecular MHC haplotype and insulin DNA methylation will 
not be performed for the open-label extension period. The open-label extension period will 
include PBMC sample collection and serum biomarker sample collection.
9.6.
Safety Evaluations
There will be thorough monitoring and evaluation of subjects in this study focusing on study 
agent, device-related, and disease-related safety issues.
Study Agent Related:
Safety evaluation will include regular monitoring for clinically-related AEs, and in addition, 
monitoring of clinical laboratory changes (ie, hematological and serum chemistry panel), and
active monitoring of early detection of active tuberculosis Monitoring of CMV and EBV viral 
load will be done to detect if there is any study agent effect on primary immune response to these 
infections that often take place during childhood and adolescence or impact reactivation of these 
virus in those who have been infected previously.

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Device-related:
Device-related AEs, for the PFS-U and the VarioJect, will be collected. Device-related issues 
may include those that lead to a missed dose, overdose, underdose, application-site bruise, 
injection site pain, accidental exposure to product, or needle-stick injury issue, for example.
Disease-related: Hypoglycemia
As indicated elsewhere, subjects, and when applicable their caregivers, must agree to follow the 
current recommendations of tight glycemic control as defined by the ADA. In order to achieve 
these goals, this may require enhanced BG monitoring and greater amounts and frequency of 
insulin administration and may have the unintended side effects of hypoglycemia.
Hypoglycemia may have severe sequelae including loss of consciousness, coma or death. 
Subjects and their caregivers must work with local PIs and their primary care physicians to 
determine an approach that is best, and most safely, allows subjects to target their specific 
HbA1c goal.
Any BG levels ≤70 mg/dL from the glucometer captured in the eDiary will prompt 
subjects/caregivers document signs and symptoms consistent with hypoglycemia at the time of 
(possible) hypoglycemic episodes, interventions administered, and levels of assistance required 
by the subject. In addition, subjects/caregivers are to document any instances of suspected 
(clinical) hypoglycemia in the eDiary even in the absence of a confirmatory BG reading.
Serious adverse event reports will be provided to the DMC members on an ongoing basis. The 
DMC will have access to unblinded data and review tabulated safety summaries (if appropriate) 
and any additional data that the DMC may request during the conduct of the study. No formal 
statistical hypothesis testing is planned. In addition, during the study, the sponsor's Study 
Responsible Physician (or designee) will regularly review blinded safety data from the sites and 
notify the DMC and appropriate sponsor personnel of any issues. The remit of the DMC and the 
roles and responsibilities of the members will be described in a separate DMC charter.
Details regarding the Independent DMC are provided in Section 11.11.
Any clinically relevant changes in subjects occurring during the entirety of 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 
timepoints provided in the Time and Events Schedule:
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.

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Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory results, 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 a Central Laboratory:

Hematology Panel
-hemoglobin
-white blood cell (WBC) count with differential
-hematocrit
-platelet count

Serum Chemistry Panel
-sodium
-calcium
-potassium
-phosphate
-chloride
-albumin
-bicarbonate
-total protein
-blood urea nitrogen (BUN)
-total and direct bilirubin
-creatinine
-aspartate aminotransferase (AST)
-glucose
-alanine aminotransferase (ALT)
-alkaline phosphatase
Additional Laboratory Tests
-HbA1c
-Type 1 diabetes antibodies (anti-insulin, anti-GAD-65, ICA, anti-ZnT8, anti-IA2)
- C-peptide
-insulin
-pro-insulin
-C-reactive protein
-CD4 T-cell count
-CD8 T-cell count
-HIV antibody - only at screening
-hepatitis B antibody/antigen panel - only at screening
-hepatitis C virus antibody - only at screening
-CMV and EBV DNA PCR
-MHC haplotype – only at Week 0 (randomization)
-Lipids (cholesterol, HDL, LDL, Triglycerides) – Only done at fasting visits: screening,
Week 12, 26, 38, 52, 78 and 104.
-Coagulation panel (PT/PTT/INR) - only at screening
-Serum pregnancy testing - only at screening (for females of childbearing potential)
The following test will be performed at the study site:

Urine pregnancy testing (for females of childbearing potential)

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During the study, all abnormal laboratory values will require further explanation from the 
investigator. Clinically significant abnormal laboratory values should be repeated until they 
return to normal or are otherwise explained by the investigator.
Clinical Assessments:
Vital Signs (oral or tympanic temperature, pulse/heart rate, respiratory rate, blood 
pressure)
Blood pressure and pulse/heart rate measurements can be assessed with a completely automated 
device. Manual techniques will be used if an automated device is not available. Blood pressure 
and pulse/heart rate measurements should be preceded by at least 5 minutes of rest in a quiet 
setting without distractions (eg, television, cell phones).
Physical Examination
Physical examinations (PE; full or brief) sometimes including height and body weight will be 
conducted at times indicated in the Time and Events Schedule.
A full physical exam includes an evaluation of general appearance, head, eyes, ears, nose, and 
throat evaluation, neck palpation for thyroid, lymphadenopathy and tenderness, auscultation of 
the heart, lungs and abdomen, palpation of abdomen, external evaluation of genitalia with Tanner 
Staging, evaluation of extremities and skin, and gross neurologic evaluation of strength, 
sensation and balance.
A brief physical examination includes general appearance, head, eyes, and throat evaluation, 
neck palpation for thyroid, lymphadenopathy and tenderness, auscultation of the heart, lungs and 
abdomen, palpation of abdomen, evaluation of extremities and skin.
Any clinically relevant finding or change in physical exam occurring during the study must be 
recorded on the Adverse Event section of the CRF.
Weight will be measured using a calibrated scale at each weight measurement and subjects will 
be instructed to remove shoes and outdoor apparel and gear.
9.6.1.
Safety Evaluations – Open-Label Extension Period
There will be thorough monitoring and evaluation of subjects in this study focusing on study 
agent, device-related, and disease-related safety issues.
Study Agent Related (Open-Label Extension Period):
Safety evaluation will include regular monitoring for clinically-related AEs, and in addition, 
monitoring of clinical laboratory changes (ie, hematological and serum chemistry panel), and 
active monitoring of early detection of active tuberculosis Monitoring of CMV and EBV viral 
load will be done to detect if there is any study agent effect on primary immune response to these 
infections that often take place during childhood and adolescence or impact reactivation of these 
virus in those who have been infected previously.

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Device-related (Open-Label Extension Period):
Device-related AEs, for the PFS-U and the VarioJect, will be collected. Device-related issues 
may include those that lead to a missed dose, overdose, underdose, application-site bruise, 
injection site pain, accidental exposure to product, or needle-stick injury issue, for example.
Disease-related: Hypoglycemia (Open-Label Extension Period)
As indicated elsewhere, subjects, and when applicable their caregivers, must agree to follow the 
current recommendations of tight glycemic control as defined by the ADA. In order to achieve 
these goals, this may require enhanced BG monitoring and greater amounts and frequency of 
insulin administration and may have the unintended side effects of hypoglycemia.
Hypoglycemia may have severe sequelae including loss of consciousness, coma or death. 
Subjects and their caregivers must work with local PIs and their primary care physicians to 
determine an approach that is best, and most safely, allows subjects to target their specific 
HbA1c goal.
Any BG levels ≤70 mg/dL from the glucometer will prompt subjects/caregivers document signs 
and symptoms consistent with hypoglycemia at the time of (possible) hypoglycemic episodes, 
interventions administered, and levels of assistance required by the subject. In addition, 
subjects/caregivers are to document any instances of suspected (clinical) hypoglycemia in the 
paper diary even in the absence of a confirmatory BG reading.
Serious adverse event reports will be provided to the DMC members on an ongoing basis. The 
DMC will have access to unblinded data and review tabulated safety summaries (if appropriate) 
and any additional data that the DMC may request during the conduct of the study. No formal 
statistical hypothesis testing is planned. In addition, during the study, the sponsor's Study 
Responsible Physician (or designee) will regularly review blinded safety data from the sites and 
notify the DMC and appropriate sponsor personnel of any issues. The remit of the DMC and the 
roles and responsibilities of the members will be described in a separate DMC charter.
Details regarding the Independent DMC are provided in Section 11.11.
Any clinically relevant changes in subjects occurring during the entirety of 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 
timepoints provided in the Time and Events Schedule:
Adverse Events (Open-Label Extension Period)
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.

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Clinical Laboratory Tests (Open-Label Extension Period)
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory results, 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 a Central Laboratory:

Hematology Panel
-hemoglobin
-white blood cell (WBC) count with differential
-hematocrit
-platelet count

Serum Chemistry Panel
-sodium
-calcium
-potassium
-phosphate
-chloride
-albumin
-bicarbonate
-total protein
-blood urea nitrogen (BUN)
-total and direct bilirubin
-creatinine
-aspartate aminotransferase (AST)
-glucose
-alanine aminotransferase (ALT)
-alkaline phosphatase
Additional Laboratory Tests (Open-Label Extension Period)
-HbA1c
- C-peptide
-insulin
-pro-insulin
-C-reactive protein
-CD4 T-cell count
-CD8 T-cell count
-HIV antibody - only at screening
-hepatitis B antibody/antigen panel - only at screening
-hepatitis C virus antibody - only at screening
-CMV and EBV DNA PCR
-Lipids (cholesterol, HDL, LDL, Triglycerides) will not be measured during the open-label
extension period.
-Coagulation panel (PT/PTT/INR) - only at screening
-Serum pregnancy testing - only at screening (for females of childbearing potential)
The following test will be performed at the study site:

Urine pregnancy testing (for females of childbearing potential)
During the study, all abnormal laboratory values will require further explanation from the 
investigator. Clinically significant abnormal laboratory values should be repeated until they 
return to normal or are otherwise explained by the investigator.

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Clinical Assessments (Open-Label Extension Period):
Vital Signs (oral or tympanic temperature, pulse/heart rate, respiratory rate, blood 
pressure)
Blood pressure and pulse/heart rate measurements can be assessed with a completely automated 
device. Manual techniques will be used if an automated device is not available. Blood pressure 
and pulse/heart rate measurements should be preceded by at least 5 minutes of rest in a quiet 
setting without distractions (eg, television, cell phones).
Physical Examination (Open-Label Extension Period)
Physical examinations (PE; full or brief) sometimes including height and body weight will be 
conducted at times indicated in the Time and Events Schedule.
A full physical exam includes an evaluation of general appearance, head, eyes, ears, nose, and 
throat evaluation, neck palpation for thyroid, lymphadenopathy and tenderness, auscultation of 
the heart, lungs and abdomen, palpation of abdomen, external evaluation of genitalia with Tanner 
Staging, evaluation of extremities and skin, and gross neurologic evaluation of strength, 
sensation and balance.
A brief physical examination includes general appearance, head, eyes, and throat evaluation, 
neck palpation for thyroid, lymphadenopathy and tenderness, auscultation of the heart, lungs and 
abdomen, palpation of abdomen, evaluation of extremities and skin.
Any clinically relevant finding or change in physical exam occurring during the study must be 
recorded on the Adverse Event section of the CRF.
Weight will be measured using a calibrated scale at each weight measurement and subjects will 
be instructed to remove shoes and outdoor apparel and gear.
9.7.
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.
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.
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.

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9.8.
Data to be Collected by Subjects
For this study subjects/caregivers will obtain and record a number of pieces of data to aid in 
endpoint analysis and compliance. The data will be collected using an eDiary that will be 
supplied by the sponsor to the subject/caregiver during the screening visit. Training on devices 
and what data is to be collected will be conducted by study-site staff at that visit, and at 
subsequent visits as needed. All data recorded in the eDiaries will be reviewed by study staff 
during study visits. For the open-label extension period, paper diaries instead of eDiaries will be 
provided.

Exogenous insulin administration. Subjects/caregiver are to record the type and amount of 
insulin they have used during the 7-day period immediately preceding each study visit (see 
the Time and Events Schedule). This data will be used to calculate exogenous insulin use in 
units/kg/day. During the open-label extension period, subjects will be required to record 
10 days of insulin use prior to each visit.

Hypoglycemic events. Subjects/caregivers are to record information surrounding all BG
measure measurement that are ≤70 mg/mL or of suspected hypoglycemia due to clinical 
symptomatology. Data including BG level, clinical symptoms (including but not limited to 
change in mental status or loss of consciousness), length of the event, therapies used to treat 
the event, and if assistance or medical care (including clinic, emergency room or 
hospitalization) was required for the event.

Study agent dosing. For subjects/caregivers participating in self-administration they are to 
record study agent administration date, time, and anatomic location of the injection, person 
administering study agent, and if there are any complications associated with study agent 
administration.

Glucometer readings.

Screening –
Double-blind Week 104: Subjects/caregivers will be given a 
sponsor-supplied glucometer and supplies to self-monitor BG levels during the study. 
Subjects/caregivers may not use their own glucometers. Blood glucose readings should 
take place at least 4 times a day, ie, premeal and at bedtime, as needed and at any time 
of suspected hypoglycemia. Blood glucose readings from the provided glucometers will 
be electronically transmitted to the eDiaries provided or when BG levels ≤70 mg/mL 
during the double-blind period (Weeks 0 to 104).

Open-label Weeks 0 to 52: During this phase, subjects may use either fingersticks or 
continuous glucose monitoring (CGM) at the discretion of the investigator and/or 
according to local practice. The subjects will not be required to download BG values 
from the eDiary.
9.9.
Injection Site Reaction Monitoring
Injection reactions or allergic reactions have been observed with administration of monoclonal 
antibodies. Mild to serious local and systemic reactions (including anaphylaxis) may occur at any 
time during the administration of study agent.

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Study agent must not be administered to individuals with known or suspected intolerance or 
hypersensitivity to any biologic medication or known allergies or clinically significant reactions 
to human proteins, to monoclonal antibodies or antibody fragments, or to any components of 
golimumab or its excipients.
A physician must be immediately available at the site during the first 3 dose administrations of 
study agent for the double-blind period and open-label extension period. All subjects receiving 
study agent must be carefully observed for symptoms of an injection site reaction and a systemic 
reaction for at least 30 minutes after study agent administration.
Injection Site Reactions
An injection site reaction is any unfavorable or unintended sign that occurs at the study agent 
injection site. If an injection site reaction is observed, the subject should be treated at the 
investigator’s discretion. Any adverse reaction (eg, swelling, induration, redness/erythema, 
pain/tenderness, warmth, bruising or bleeding) should be recorded on the AE page of the CRF. 
The type of reaction should also be indicated.
Delayed Injection Site, Allergic, and Hypersensitivity Reactions
Reactions following study agent administration may occur 1 to 21 days after study agent
injection and presentation can be variable, and can, for example include myalgia and/or 
arthralgia with fever and/or rash. In some cases, these may be accompanied by other symptoms 
including pruritus, localized or systemic edema, dysphagia, urticaria, sore throat, and/or 
headache. Any and all such adverse reactions should be recorded on the AE page of the CRF. 
The type of reaction should also be indicated.
Self-Assessment
In addition to recording the details of the study agent dosing day, time, anatomic site and if there 
were any complications of the injection, subjects and/or caregivers should be instructed to
monitor the injection site for any reactions, including, but not limited to swelling, 
redness/erythema, pain, tenderness, warmth, bruising, or bleeding. For severe injection site 
reactions or changes at the injection site hours to days following injection, the subject/caregiver 
should contact the study site for consultation.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she has completed assessments 
at Week 104 of the off-therapy follow-up period or Week 60 of the open-label extension period 
of the study.
Subjects who prematurely terminate study participation for any reason before completion of the 
study will not be considered to have completed the study. Subjects are able to initiate the 
prohibited medicines and activities per the guidance provided in Section 4.3 and Section 8.3.

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10.2.
Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if they have to temporarily or 
permanently discontinue treatment before the end of the treatment regimen.
If a subject permanently discontinues study treatment for any reason before the end of the 
treatment phase (Week 52), they should be encouraged to continue with all scheduled visits to 
and including the final study visit (Week 104), but without receiving study agent administration. 
If unwilling or unable to participate in all visits, subjects should be encouraged to participate in 
as many of the planned study visits as possible for continued assessment, but without receiving 
study agent administration. If the subject is not able to participate in the next 2 sequential study 
visits that include an MMTT, they should be encouraged to return for the End of Study visits (per 
the Time and Events Tables) approximately 10 weeks after their last dose administration.
Similarly, if a subject withdraws following the treatment period (after Week 52) they should be 
encouraged to participate in the Week 78 and Week 104 visits, as applicable. If the subject is 
unwilling or unable to complete any of the remaining scheduled study visits, they should be 
encouraged to return for the End of Study visit (per Time and Events Schedule) approximately 
10 weeks after their last dose administration, as applicable.
Following randomization (ie, between Week 0 and Week 104), consecutive MMTTs should not 
be repeated if the time interval between them is less than 10 weeks. The MMTT can be repeated 
in less than 10 weeks only for repeat testing during the screening period or for rescreening.
SAEs will be requested to be submitted for subjects who withdraw early from the study for a 
year after their last study agent dose (Section 12.4.1).
Subjects who permanently discontinue active treatment during the open-label extension period 
will have their end-of-study visit followed by the post-treatment visit 10 weeks later.
Study treatment may be temporarily or permanently discontinued due to events described 
below.

Events That Result in Permanent Discontinuation of Study Treatment.

The investigator believes that for safety reasons or tolerability reasons it is in the best 
interest of the subject to discontinue study treatment.

The subject becomes pregnant.

The subject has a severe infection requiring inpatient hospitalization or repeated doses 
of parenteral antibiotics.

The subject has a severe hypersensitivity reaction, such as anaphylaxis or angioedema, 
to the study agent.

The subject has a clinically significant cardiovascular event.

The subject is deemed ineligible according to the following TB screening criteria:

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o
A diagnosis of active TB is made.
o
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.
o
A subject undergoing evaluation has a chest radiograph with evidence of current 
active TB and/or a positive QuantiFERON-TB Gold test result and/or an 
indeterminate QuantiFERON-TB Gold test result on repeat testing (see
Section 9.1.2 and Section 9.1.2.1).

The subject misses 3 consecutive study agent administrations.

A general lack of compliance with study visits and procedures per study team or 
sponsor.

One confirmed episode of ALT and/or AST >3x upper limit of normal (ULN) as 
defined in Attachment 5. If a subject has an ALT or AST value of >3x ULN, the next 
dose of study agent administration should be held pending repeat confirmatory testing 
which is to take place as soon as possible and preferably within 72 hours. If the value is 
still >3x ULN then the subject is to permanently discontinue study treatment. If the 
repeat value is <2x ULN then dosing may proceed. If the repeat value is ≥2x ULN) and 
≤3x ULN, follow guidelines in the next section.

The subject meets criteria for permanent study agent discontinuation based on 
AST/ALT elevations, AEs, or infections in the next subsection below (Events Resulting 
In Temporary and Potentially Permanent Discontinuation of Study Agent).

Events Resulting in Temporary and Potentially Permanent Discontinuation of Study 
Treatment.

An ALT and/or AST elevation ≥2 x the upper limit of normal (ULN) and ≤3x ULN (as
defined in exclusion criteria in Section 4.2.1 and Attachment 5).

Repeat AST and ALT as soon as possible but preferably within 72 hours of receipt of the 
confirmed results. If one or both are ≥2 x the ULN and ≤3x ULN then:

Suspend administration of study treatment and recheck the subject within 72 hours and at 
least weekly as needed thereafter.

If AST and ALT are <2x ULN on repeat testing, resume dosing at the next expected 
interval.

If AST and ALT are not <2x ULN by 4 weeks, permanently discontinue study treatment.
Note: Three independent temporary suspensions from study treatment due to transient 
elevations in ALT and/or AST ≥2x but ≤3x ULN is allowed during the entire treatment 
period. If a third elevation occurs that requires a dose to be held, permanently discontinue 
study treatment.

A Significant Infection.

Defined as:
1.
Any severe infection meeting SAE criteria as defined in Section 12, or

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2.
Any infection not meeting SAE criteria but otherwise clinically significant per 
investigator’s judgment, or
3.
Infection or reactivation of EBV or CMV as defined by clinical signs of infection; 
or if the EBV viral load is ≥10,000 copies per mL plasma or the CMV viral load is 
≥10,000 copies per mL plasma.

Suspend administration of study treatment and recheck any abnormal laboratory values as 
soon as possible and preferably within 72 hours.

Monitor the subject and abnormal labs at least weekly.

If the AE resolves or reduces to mild or less, dosing may resume at the next expected 
interval.

If the AE does not resolve in 4 weeks, permanently discontinue study treatment.

A Serious Adverse Event or Study Agent-related Severe Adverse Event.

Defined as:
1.
Any SAE (as defined in Section 12.1.1) or
2.
Any severe AE that is considered related (possibly, probably, or very likely related) 
to study agent (as defined in Section 12.1.2).

With the exception of:
When clinical and laboratory abnormalities are considered related to T1D disease activity 
(ie, hypoglycemia and hyperglycemia) and study treatment is not considered a 
contributing factor, administration may not need to be modified. The site investigator 
should consult with the sponsor if this is encountered.

Suspend administration of study treatment and recheck the subject at least weekly; if based 
on abnormal laboratory values, repeat abnormal laboratory values as soon as possible within 
72 hours.

If the AE resolves or reduces to a moderate AE (Section 12.1.2) or less, dosing may resume 
at the next expected interval.

If the AE does not resolve to a moderate AE or less (Section 12.1.2) in 4 weeks, discontinue 
study treatment permanently.
Note: If there are more than 2 suspensions from study treatment due to a specific SAE or related-
SAE as defined above, permanently discontinue study treatment.
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/assent.

Death.

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
The study investigator or sponsor, for any reason, decides the subject should be withdrawn 
from the study.
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 sponsor and the DMC chair is to be 
notified and the reason for withdrawal is to be documented in the CRF and in the source 
document. Study agent 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 study, all attempts should be made to obtain End of Study assessments.
In addition to the above withdrawal criteria, C+R and R responders will be withdrawn if on 2 
consecutive occasions 2 months apart, the remission score is >9. The C responders will be 
discontinued if their remission score is increasing on 2 consecutive occasions by more than 0.5
or if their remission score is 12, whichever comes first.
10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional
research samples:
The collected samples will be retained and used in accordance with the subject's original separate
informed consent/assent for optional research samples.
The subject may withdraw consent/assent for optional research samples, in which case the 
samples will be destroyed, and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the sponsor study-site contact of withdrawal of 
consent/assent for the optional research samples and to request sample destruction. The sponsor 
study-site contact will, in turn, contact the biomarker representative to execute sample 
destruction. If requested, the investigator will receive written confirmation from the sponsor that 
the samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining In The Main Study
The subject may withdraw consent/assent for optional research samples while remaining in the 
study. In such a case, the optional research samples will be destroyed. The sample destruction 
process will proceed as described above.
Withdrawal From The Use Of Samples In Future Research
The subject may withdraw consent/assent for use of samples for research (refer to Section 16.2.5, 
Long-Term Retention of Samples for Additional Future Research). In such a case, samples will 
be destroyed after they are no longer needed for the clinical study. Details of the sample 
retention for research are presented in the main ICF.

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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 (SAP).
Descriptive statistics (eg, mean, median, standard deviation [SD], minimum, and maximum) will 
be used to summarize continuous variables. Counts and percentages will be used to summarize 
categorical variables. Graphic data displays may also be used to summarize the data.
Efficacy analyses will be based on the modified intent-to-treat (mITT) population (ie, all 
randomized subjects who have received at least 1 dose of study agent). Subjects included in the 
efficacy analyses will be summarized according to their assigned treatment group regardless of 
whether or not they receive the assigned treatment.
Safety analyses will include all subjects who received at least 1 dose of study treatment.
Pharmacokinetics and immunogenicity analyses for golimumab will include all subjects who 
receive at least 1 dose of golimumab and have at least 1 post-dose sample collection.
The baseline measurement is defined as the closest measurement taken at or before the time of 
the Week 0 administration for the double-blind period. The baseline measurement for the open-
label extension period is the closest measurement taken at or before the time of the Week 0 
administration of the open-label extension period.
No hypotheses testing will be performed for open-label extension period, and data generated will 
be summarized descriptively.
11.1.
Subject Information
For all subjects who receive at least 1 dose of study agent, descriptive statistics will be provided.
Subject baseline data, demographic, and baseline clinical disease characteristics will be 
summarized for all mITT subjects.
11.2.
Sample Size Determination
The sample size calculation is based on the primary endpoint, an MMTT 4-hour C-peptide AUC 
at Week 52. Due to skewed C-peptide AUC data, normalizing transformation of log (AUC +1) is 
applied for sample size assessment. The method has been well accepted and used in numerous 
clinical studies25,26,42,57,60 Based on published data, a common SD of log (AUC+1) of 0.215 is 
assumed, and the back-transformed means for 4-hour C-peptide AUC are assumed to be 
0.385 and 0.635 for the placebo and golimumab groups respectively, ie the expected treatment 
difference (back-transformed) is 0.25. With 81 subjects (54 on golimumab and 27 on placebo) 
and an alpha of 0.05 (2-sided), there is 90% power to detect the treatment difference through a 
2-sample t-test.

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11.3.
Efficacy Analyses
All efficacy analyses will be performed on the mITT population unless otherwise specified. The 
mITT population includes all randomized subjects who have received at least 1 dose of study 
agent. The primary efficacy endpoint will be analyzed by using a mixed model for repeated 
measures (MMRM).
Primary Endpoints
The primary endpoint is the MMTT-stimulated 4-hour C-peptide AUC at Week 52. To address 
the primary objective of the study, the primary endpoint will be analyzed by using a MMRM 
based on restricted maximum likelihood. The model will be based on a normalizing 
transformation of log(AUC+1). The analysis will use post-baseline log(AUC+1) data as the 
response variable and will include the fixed, categorical effects of gender, treatment, time, and
treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and 
baseline-by-time interaction. An unstructured covariance will be used to model the within-patient 
errors. The treatment comparison at Week 52 in terms of the least square mean difference and 
the 2-sided 95% confidence interval will be estimated based on this model. Descriptive statistics 
and estimates from the above model will be presented on the back-transformed scale. 
Specifically, the back-transformed mean is the geometric-like mean derived through exp(y)-1, 
where y = log(AUC+1). For transparency and completeness, descriptive statistics on the raw 
scale will be presented as well. Additional details will be presented in the SAP.
To assess the robustness of the primary analysis result, some sensitivity analyses will be 
conducted. Such analyses include but are not limited to the following:
1.
Similar repeated measure analysis with some data imputed. If a subject’s last observed AUC 
value prior to Week 52 is 0, then all missing values through Week 52 will be imputed with 
zero. Repeated measure analysis will be conducted on the partially imputed data.
2.
An analysis of covariance (ANCOVA) model with log(AUC+1) at Week 52 as the response 
variable, baseline log(AUC+1) and age as covariates, and treatment and gender as fixed 
factors. Different missing data handling strategies such as completers’ analysis, and multiple 
imputation will be explored.
3.
Similar ANCOVA model by using different transformation functions.
4.
Comparing change from baseline in 4-hour C-peptide AUC directly by using non-parametric 
method such as rank analysis of covariance or ANCOVA model if the normality assumption 
holds.
Subgroup analysis of the primary endpoint by selected baseline characteristics will be presented. 
Details will be outlined in the SAP.
Secondary Endpoints
The major secondary endpoints listed below will be analyzed without multiplicity adjustment. 
Treatment effect in these endpoints will be estimated by the difference between the treatment 

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groups along with their associated 95% confidence intervals. The hypoglycemia event rate 
(number of hypoglycemia episodes per patient-year exposure) at Week 52 will be analyzed using 
a Poisson regression model. Change from baseline in insulin use and change from baseline in 
HbA1c will be analyzed by using an MMRM model. Additional details will be provided in the 
SAP.
1.
Change from baseline in insulin use in units per kilogram body weight per day at Week 52.
2.
Change from baseline in HbA1c at Week 52.
3.
Hypoglycemic event rates (defined as BG levels of ≤70, 55, and 35 mg/dL or clinical 
sequelae consistent with severe hypoglycemia in the absence of a BG reading) through 
Week 52.
11.3.1.
Exploratory Efficacy Analyses – Open-Label Extension Period
All the efficacy endpoints defined for the double-blind period will be exploratory for the 
open-label extension period and will be summarized descriptively. Disease progression will be 
compared between the double-blind period and the extension period in subjects who attended the 
open-label extension period if deemed reasonable.
11.4.
Pharmacokinetic Analyses
Data will be listed for all subjects with available serum concentrations per treatment. All 
concentrations below the lowest quantifiable concentration (LQC) in a sample or missing data 
will be labeled as such in the concentration data listings. Concentrations below the LQC in a 
sample will be treated as 0 in the summary statistics and for the calculation of PK parameters. 
All subjects and samples excluded from the analysis will be clearly documented in the study 
report.
For each dose group, descriptive statistics, including arithmetic mean, SD, coefficient of 
variation, median, minimum, and maximum will be calculated for the golimumab serum 
concentrations at each sampling time of golimumab.
Serum golimumab concentrations will be summarized over time. In addition, if necessary, a 
population PK analysis will be performed to characterize the PK of golimumab as well as to 
identify and quantify important covariates of PK in the T1D population. The apparent total 
systemic clearance (CL/F) and apparent volume of distribution (V/F) will be estimated using a 
NONMEM approach and will be presented in a separate technical report.
The same analyses will be performed for the open-label extension period.
11.5.
Immunogenicity Analyses (Antibodies to Golimumab)
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).

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The incidence of neutralizing antibodies (NAbs) to golimumab will be summarized for subjects 
who are positive for antibodies to golimumab and have samples evaluable for NAbs to 
golimumab.
Other immunogenicity analyses may be performed to further characterize the immune responses 
that are generated.
The same analyses will be performed for the open-label extension period.
11.6.
Biomarker Analyses
Results from exploratory analyses will be presented in a separate biomarker technical report.
The same analyses will be performed for the open-label extension period.
11.7.
Pharmacokinetic/Pharmacodynamic Analyses
If data permits, the relationships between serum golimumab concentration and efficacy may be 
analyzed graphically. If a visual trend is observed, a suitable PK/PD model may be developed to 
describe the exposure-response relationship and will be presented in a separate technical report.
The same analyses will be performed for the open-label extension period.
11.8.
Pharmacogenomic Analyses
For the double-blind period, results from exploratory and haplotype analyses will be presented in 
a separate biomarker technical report.
For the open-label extension period, results from the exploratory analyses will be presented in a 
separate biomarker technical report.
11.9.
Safety Endpoints and Analyses
Safety assessments will include the examination of the incidence rates of AEs, vital signs, 
laboratory parameters, and physical examinations. Safety analyses will be conducted on the 
safety analysis set, which is defined as all subjects who have received at least a 1 dose of study 
agent.
Adverse Events
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs are AEs 
with onset during the treatment period or that are a consequence of a pre-existing condition that 
has worsened since baseline. All reported treatment-emergent AEs will be included in the 
analysis. For each AE, the percentage of subjects who experience at least 1 occurrence of the 
given event will be summarized by system organ class and preferred term for treatment group. 
Treatment-emergent AEs will also be summarized by a maximum severity and relationship to 
study agent. Separate summaries will be provided for SAEs and AEs leading to study agent 
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In addition, summary tables will be presented by treatment group for each of the endpoints
within each specified period:
Double-Blind Period:
a.
Proportion of subjects with treatment-emergent AEs and severe AEs through Weeks 52 
and 104.
b.
Proportion of subjects with study agent injection site reactions through Week 52.
c.
Proportion of subjects with severe infections through Weeks 52 and 104.
d.
Open-Label Extension Period: 
1.
Continue to evaluate safety and exploratory efficacy endpoints as per the Time and 
Events Schedule (open-label extension period) and no new efficacy hypotheses will be 
tested compared to the double-blind period.
Listings, datasets, or subject narratives may be provided, as appropriate, for those subjects who 
die, who discontinue treatment due to an AE, or who experience a severe or an SAE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly 
abnormal results (specified in the SAP) will be used in the summary of laboratory data. 
Descriptive statistics will be calculated for each laboratory analyte at baseline and for observed 
values and changes from baseline at each scheduled timepoint. Frequency tabulations of the 
changes from baseline will be presented in pre- versus post-treatment 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 be 
provided.
Vital Signs
Descriptive statistics of temperature, pulse/heart rate, respiratory rate, and blood pressure 
(systolic and diastolic) values and changes from baseline will be summarized at each scheduled 
timepoint. The percentage of subjects with values beyond clinically important limits will be 
summarized and a corresponding listing will be provided.
Physical Examination
Proportion of subjects with abnormal physical examination findings will be summarized at each 
scheduled timepoint. Subjects with any post-treatment abnormalities will be listed.
Open-Label Extension Period
Clinical laboratory tests, vital signs, and physical examination for the open-label extension 
period will be assessed as similar to the double-blind period.

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11.10. Interim Analysis
An interim analysis using the 4-hour C-peptide AUC in response to a MMTT will be planned for 
the study. The primary goal of this analysis will be to obtain an early examination of the 
treatment effect to facilitate the planning of future studies. It is anticipated that the interim 
analysis will take place after at least 60% of subjects complete their Week 26 4-hour, MMTT 
assessment. All available 4-hour, C-peptide AUC data at interim analysis will be incorporated in 
this analysis. No formal DBL is planned for this interim analysis.
An IAC will be established to review the interim data and formulate recommendations in 
accordance with the objectives of the interim analysis. The IAC will consist of at least a clinician 
and a statistician (neither of whom are involved in the conduct of the study or compound 
development), one of whom will chair the committee, and other members as required based on 
the results of the interim analysis. Details will be provided in the IAC charter. The DMC serves 
the IAC function. The disclosure of unblinded results will be limited to specific sponsor 
personnel not involved in the study. Interim analyses results will not be disseminated to 
investigators or individuals associated with the conduct of the study. The interim analyses will 
not have any statistical impact on the analyses of any other endpoints.
11.11. Data Monitoring Committee
An Independent DMC consisting of external experts and internal experts not associated with this 
study will be established to monitor data on an ongoing basis to ensure the continuing safety of 
the subjects enrolled in this study. The committee will meet periodically to review interim data. 
After the review, the DMC will make recommendations regarding the continuation of the study. 
The details will be provided in a separate DMC charter.
The DMC will consist of at least one medical expert in the relevant therapeutic area and at least 
one statistician. The DMC responsibilities, authorities, and procedures will be documented in its 
charter.
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 
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 AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 

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relationship with the treatment. An AE 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 AEs starting with the signing of the ICF (refer to Section 12.4.1, All 
Adverse Events, for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and European 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.

Unlisted (Unexpected) Adverse Event/Reference Safety Information.

An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For golimumab, the expectedness of an AE will be 
determined by whether or not it is listed in the Investigator's Brochure. For exogenous 
insulin with a marketing authorization, the expectedness of an AE will be determined by 
whether or not it is listed in the package insert/summary of product characteristics.

Adverse Event Attribution Definitions.

The following provides guidance on how the study team is to assess and categorize the 
relationship of AEs in relation to study agent:

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Adverse Event Association With The Study Agent

Not Related: An AE that is not related to the use of the drug.

Doubtful: An AE 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 AE 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 AE 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 AE 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).
This study will utilize sponsor-supplied study agent dosing devices, the PFS-U and VarioJect as 
detailed in the SIPPM. The following provides guidance on how the study team is to assess and 
categorize the relationship of AEs in relation to these devices.
Adverse Event Association With The Study Device

Not related: There is another obvious cause of the AE other than the study device.

Unlikely: There is another more likely cause of the AE other than the study device.

Possibly: The AE could be due to the study device.

Probably: The AE is probably attributable to the study device.

Definitely: The AE is most likely or definitely attributable to the study device.
12.1.2.
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).

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12.2.
Hypoglycemia Definitions, Recording and Interpretation
This study will use the ADA suggested classification of hypoglycemia to guide the collection of 
episodes of asymptomatic and/or symptomatic hypoglycemia.65A hypoglycemic BG reading will 
be classified as any confirmed BG reading of ≤70 mg/dL.
In clinical practice, severe hypoglycemia is considered an event requiring assistance of another 
person for support which may include administration of carbohydrates or glucagon. Individuals 
with severe hypoglycemia may, experience events such as a seizure, altered/loss of 
consciousness, or coma. Such events do not need to have a documented BG reading to be 
classified clinically as a severe hypoglycemic event. This study will collect this "clinical 
practice" definition of severe hypoglycemia, whether or not the symptoms are associated with an 
abnormal/low BG reading. Data on all hypoglycemic events as described above will be collected 
as part of the efficacy analyses.
In terms of AE reporting in this study, the severity of a hypoglycemia AE should be classified as 
mild, moderate, or severe, or as an SAE according to the definitions in Section 12.1.1, Section 
12.1.2, and Section 12.4.1. Because there may be difference in terminology used in clinical 
practice and AE recording in clinical trials, a hypoglycemic episode that is considered “severe” 
using clinical definitions may not necessarily be classified as a “severe” (or serious) AE, and 
conversely an episode the does not meet the common clinical definition of severe hypoglycemia 
may be classified as a severe AE. Again, it is the investigator’s responsibility to categorize the 
severity of a hypoglycemic event in terms of AE reporting.
12.3.
Special Reporting Situations
Safety events of interest on a sponsor study agent that may require expedited reporting and/or 
safety evaluation include, but are not limited to:

Overdose of a sponsor study agent

Suspected abuse/misuse of a sponsor study agent

Accidental or occupational exposure to a sponsor study agent

Medication error involving a sponsor product (with or without subject/patient exposure to 
the sponsor study agent, eg, name confusion)

Special reporting situations should be recorded in the CRF. Any special reporting situation 
that meets the criteria of an SAE should be recorded on the SAE page of the CRF.
12.4.
Procedures
12.4.1.
All Adverse Events
All AEs 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 52 weeks after the last dose of study 
agent (which is the end of the study), must be reported using the Serious Adverse Event Form. In 

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addition, SAEs will be requested to be submitted for subjects who withdraw early from the study 
for a year after their last study agent dose. The sponsor will evaluate any safety information that 
is spontaneously reported by an investigator beyond the time frame specified in the protocol.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether 
they are protocol-specific assessments. Anticipated events will be recorded and reported as 
described in Attachment 6.
All AEs, regardless of seriousness, severity, or presumed relationship to study agent or device, 
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 AE to study therapy. All measures required for AE management must be 
recorded in the source document and reported according to sponsor instructions.
All devices associated with device-related AEs will be investigated including the return of the 
device to the sponsor for inspection.
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute 
where required) all suspected unexpected serious adverse reactions (SUSARs). The investigator 
(or sponsor where required) must report SUSARs to the appropriate Independent Ethics 
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise 
required and documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities 
unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR summary, 
unless otherwise specified.
For all studies with an outpatient period, 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
12.4.2.
Serious Adverse Events
All SAEs 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.

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Information regarding SAEs 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 an SAE should be made by 
facsimile (fax).
All SAEs 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 agent 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 an SAE. 
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 an SAE, except hospitalizations 
for the following:

Hospitalizations not intended to treat an acute illness or AE (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).
The cause of death of a subject in a study within 52 weeks of the last dose of study agent, 
whether or not the event is expected or associated with the study agent, is considered an SAE.
Disease progression should not be recorded as an AE or SAE term; instead, signs and symptoms 
of clinical sequelae resulting from disease progression/lack of efficacy will be reported if they 
fulfill the SAE
definition (refer to
Section 12.1.1, Adverse Event Definitions and 
Classifications).
12.4.3.
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects 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, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs 
and must be reported using the Serious Adverse Event Form. Any subject who becomes pregnant 
during the study must be promptly withdrawn from the study and discontinue further study 
treatment.

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Because the effect of the study agent on sperm is unknown, pregnancies in partners of male 
subjects included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.4.4.
Events of Special Interest
Any newly identified malignancy, opportunistic infections, or case of 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 9.1.6. 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 an SAE.
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 in 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, device, 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.
All VarioJect devices associated with device-related PQCs will be investigated including the 
return of the device to the sponsor for inspection. PFS-U should be retained for further 
investigation if requested by the sponsor.
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 an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (refer to Section 12.4.2, Serious Adverse 
Events). A sample of the suspected product should be maintained for further investigation if 
requested by the sponsor.

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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 in the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
Golimumab will be supplied as a sterile, clear to slightly opalescent, colorless to light yellow 
liquid for SC injection in single-use prefilled syringes. Each prefilled syringe contains 50 mg 
(0.5 mL of liquid) of golimumab, histidine, sorbitol and polysorbate 80 at pH 5.5. No 
preservatives are present. Details regarding the study agent composition are found in the SIPPM.
The placebo will employ the same product presentation without the presence of active drug.
14.2.
Packaging
Two dosage forms will be used in this study, PFS-U and VarioJect assembled with a PFS. Both 
dosage forms will be packaged in individual subject kits in tamper resistant packaging.
Ultrasafe Passive Delivery System With Prefilled Syringe (PFS-U)
The UltraSafe Passive Delivery System (UltraSafe) is a manually-operated, single-use, 
disposable needle guard system that is an accessory to a PFS. Each 50 mg-single dose prefilled 
glass syringe (27-gauge ½ inch needle) contains 50 mg of golimumab per 0.5 mL of solution.
VarioJect
A new adjustable dose presentation known as the VarioJect injection device has been developed 
by the sponsor as a platform device for multiple pediatric indications. This device allows for 
tiered-fixed dosing in pediatric subjects who are dosed by BSA. The VarioJect is a manual 
injector capable of delivering doses of 10 mg through 45 mg in 5 mg increments.
For the most comprehensive information regarding the VarioJect, refer to the current version of 
the VarioJect IB.
14.3.
Labeling
Study agent labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage
All study agents must be stored at controlled temperatures ranging from 36°F to 46°F (2°C to 
8°C). Study agent must be handled in strict accordance with the protocol and the container label 
and will be stored in a limited access area or in a locked cabinet under appropriate environmental 
conditions.
Refer to the pharmacy manual/study SIPPM for additional guidance on study agent preparation, 
handling, and storage.

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Subjects or caregivers who are able and who have been appropriately trained in the administration 
of golimumab may administer golimumab off-site in accordance with Section 6. Study personnel 
will instruct subjects on how to transport, store and administer medication for off-site use as 
indicated for this protocol. Details will be provided in the SIPPM.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study agent received at the site is inventoried 
and accounted for throughout the study according to the Time and Events Schedule. In instances 
where the study agent is administered to the subject, it must be documented on the drug 
accountability form. All study agent will be stored and disposed of according to the sponsor's 
instructions. Study-site personnel must not combine contents of the study agent containers.
The dispensing of study agent to the subject, and the return of study agent from the subject (if 
applicable), must be documented on the drug accountability form. Subjects, or their legally 
acceptable representatives where applicable, must be instructed to return all original containers, 
whether empty or containing study agent.
Study agent 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 agent, and study agent returned by the subject, 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 agent, or used returned study agent for destruction, will be 
documented on the drug return form. When the study site is an authorized destruction unit and 
study agent 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.
Study agent 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 agent will be supplied only 
to subjects participating in the study. Returned study agent must not be dispensed again, even to 
the same subject. Study agent may not be relabeled or reassigned for use by other subjects. The 
investigator agrees neither to dispense the study agent from, nor store it at, any site other than the 
study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following:

Investigator's Brochures

SIPPM Laboratory manual

Sponsor-approved Informed Consent/Assent Form

Dose assignment system manual

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
Investigator site file

Electronic data capture (eDC) Manual

IWRS Manual

Subject eDiaries and manuals

Subject glucometers and manuals

Study-specific Patient Participation Cards

Materials for off-site administration
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/assent 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 AEs of the study, and provide their consent/assent 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 legally acceptable representative(s), as required by local regulations, must give 
written consent/assent (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/assent (and assent as applicable) refers 
to the subjects and his or her parent(s) or the subject's legal guardian(s) or legally acceptable 
representative(s) who have provided consent/assent 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 from each subject, including during screening, the 
52-week treatment period and 52-week off-therapy follow-up period is approximately 436 mL
for subjects <35 kg and 505 mL in subjects 35 kg. During the open-label extension period,
approximately 210 mL for subjects <35 kg and 234 mL for subjects ≥35 kg will be drawn.

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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, unless required locally), the ICF, applicable 
recruiting materials, and 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.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
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:

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
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 AEs that are serious, unlisted/unexpected, and associated with the study agent.

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, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion.
16.2.3.
Informed Consent and Assent Form
Each subject or a legally acceptable representative must give written consent/assent 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 is/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/assent 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, 
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participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent/assent to participate at any time. They will be 
informed that choosing not to 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 and denotes that the subject agrees to allow 
his or her study physician to recontact the subject for the purpose of obtaining consent/assent for 
additional safety evaluations, and subsequent disease-related treatments, if needed.
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/assent 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/assent, a copy of the ICF must be given to the subject.
Subjects will be asked for consent/assent to provide optional samples for research. After 
informed consent/assent for the study is appropriately obtained, the subject or his or her legally 
acceptable representative will be asked to sign and personally date a separate ICF indicating 
agreement to participate in the optional research component. Refusal to participate in the 
optional research will not result in ineligibility for the study. A copy of this signed ICF will 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/assent 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 
copy of the assent form must be given to the subject and to the subject's parent or if applicable to 
the subject's legally acceptable representative. If subjects meet "responder" definition and are 
interested in participating in open-label extension phase of study, subjects and parents/legal 
guardians will have to sign new ICF/assent forms.
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.

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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/assent
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/assent 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 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand golimumab, to 
understand T1D autoimmunity and/or immune modulation, to understand differential drug 
responders, and to develop tests/assays related to golimumab. 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/assent for their samples to 
be stored for research (see Section 10.3, Withdrawal From the Use of Research Samples)
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 
IEC/IRB (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 listed in the Contact Information page(s), which will be provided as a separate

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document. 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 agent 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 
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).

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
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 randomized 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 documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
subject identification, eligibility, and study identification; study discussion and date of signed 
informed consent/assent; dates of visits; results of safety and efficacy parameters as required by 
the protocol; record of all AEs and follow-up of AEs; concomitant medication; drug 
receipt/dispensing/return records; study agent administration information; and date of study 
completion and reason for early discontinuation of study agent or withdrawal from the study, if 
applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.1.2, 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

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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.
An electronic source system may be utilized, which contains data traditionally maintained in a 
hospital or clinic record to document medical care (eg, electronic source documents) as well as 
the clinical study-specific data fields as determined by the protocol. This data is electronically 
extracted for use by the sponsor. If the electronic source system is utilized, references made to 
the CRF in the protocol include the electronic source system but information collected through 
the electronic source system may not be limited to that found in the CRF. Data in this system 
may be considered source documentation.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All data relating to the study must be recorded in CRF. All CRF entries, corrections, and 
alterations must be made by the investigator or authorized study-site personnel. The investigator 
must verify that all data entries in the CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
sponsor.
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 documents. Data must be entered into 
CRF in English. The CRF must be completed 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.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after 
the initial entry into the CRF, this can be done in either of the following ways:

Investigator and 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).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and
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 into the sponsor's data base. 
Written instructions will be provided for collection, handling, storage, and shipment of samples.

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Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study.
The sponsor will review CRF 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 CRF 
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). 
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 use a combination of monitoring techniques central, remote, or on-site 
monitoring to monitor this study.
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 CRF
with the source documents
(eg, hospital/clinic/physician’s office medical records). 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 

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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 documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review 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 documents 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.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The study is considered completed with the last visit 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 visit 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 agent development

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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. 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 
previously published, and any data, including pharmacogenomic and/or exploratory biomarker 
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 data from all study sites that participated in the study as per protocol. 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 pharmacogenomic and/or
exploratory biomarker 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 

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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 
review of the paper, and given final approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.

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18.
PROTOCOL AMENDMENTS HISTORY
Protocol Version 
Issue Date
Original Protocol
26 April 2016
Amendment 1
02 Jun 2016
Amendment 2
09 May 2017
Amendments below are listed beginning with the most recent amendment.
Amendment 2 (09 May 2017)
The overall reason for the amendment: The overall reason for the amendment is to update testing parameters, to 
address clarifications needed for severe hypoglycemia definition and to correct inconsistencies within the protocol.
Applicable Section(s)
Description of Change(s)
Rationale: To provide clarity and consistency, the units of laboratory tests for viral load measurements cited in the 
protocol are being updated to match the units actually used by the Central Laboratory.
4.2.
Exclusion Criteria; 
criterion 11 and criterion 12,
and
10.2.
Discontinuation of 
Study 
Treatment/Withdrawal from 
the Study
CMV and EBV viral load units updated to match the Covance laboratory units used by 
the Central Laboratory. Updated to: EBV viral load ≥10,000 copies per mL of plasma 
and CMV viral load ≥10,000 copies per mL of plasma. 
Rationale: Text describing events resulting in temporary and potentially permanent discontinuation of study agent 
was updated to provide clarity.
10.2.
Discontinuation of 
Study 
Treatment/Withdrawal from 
the Study; Discontinuation 
of study treatment;
Study treatment may be 
temporarily or permanently 
discontinued due to events 
described below 
Text was updated/rearranged. Instructions were updated to clarify that the subject 
should be rechecked within 72 hours of receipt of confirmed results. Clarification of 
resumed dosing updated to specify AST and ALT on repeat dosing.
Definitions and instructions updated.
Section rearranged with minor edits to provide clarity.
The following bullet was removed from the protocol:

The overall course of study treatment will not be extended and missed doses will 
not be administered.
10.2.
Discontinuation of 
Study 
Treatment/Withdrawal from 
the Study; Discontinuation 
of study treatment
Text added to clarify intervals between sequential Mixed-Meal Tolerance Tests 
(MMTT). 
Rationale: Definitions of terms and examples were updated or added to the protocol to provide clarity. 
12.2.
“Severe” 
Hypoglycemia
Section title updated to “Hypoglycemia Definitions, Recording and Interpretation”.
Hypoglycemia definitions clarified to assist identification, recording, and interpreting 
these events. Seaquist ER, Anderson J, Childs B, et al reference added. 
4.2.
Exclusion Criteria; 
criterion 4
Celiac disease was added to the list of examples.

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Applicable Section(s)
Description of Change(s)
Rationale: Removal of a full physical exam at Week 0 so that the Tanner Staging at Screening does not need to be 
repeated at Week 0. 
Time And Events Schedule
The full physical exam at Week 0 was changed to a brief physical exam at Week 0.
Rationale: Analysis of TNFα levels added to the protocol in response to Food and Drug Administration (FDA) 
Investigational New Drug (IND) request for pharmacokinetic (PK)/pharmacodynamics (PD) modeling
Time And Events Schedule
Free/total TNFα row added under the Clinical Pharmacology section.
Time And Events Schedule
Subheading row Pharmacokinetics/Immunogenicity changed to Clinical 
Pharmacology to encompass all procedures in this subcategory.
Time And Events Schedule, 
footnote n
Footnote updated to include further instructions on timing and bioanalysis of the 
samples.
SYNOPSIS, 
Pharmacokinetic and 
Immunogenicity 
Evaluations and
9.3.
Pharmacokinetics 
and Immunogenicity
The synopsis subsection title updated was updated to Clinical Pharmacology 
Evaluations.
Section title updated to 9.3.
Clinical Pharmacology. 
SYNOPSIS, 
Pharmacokinetic and 
Immunogenicity 
Evaluations and
9.3.
Pharmacokinetics 
and Immunogenicity
The synopsis subsection Clinical Pharmacology and the first paragraph of the protocol 
body section Pharmacokinetics and Immunogenicity was updated to include 
Total/Free TNFα. 
9.3.2. Analytical 
Procedures
Pharmacodynamic subsection added to include analysis of serum samples to 
determine concentrations of free and total TNFα.
Rationale: Text was updated to match sample names to what is reflected in the laboratory manual and to clarify that 
optional pharmacogenomics serum collection and optional DNA collections are to be collected prior to dosing.
Time And Events Schedule
Serum sample collection renamed serum biomarker sample.
Time And Events Schedule
Optional pharmacogenomics serum collection was renamed DNA Methylation 
(Optional).
9.5. Pharmacogenomic 
(DNA) Evaluations
Optional added to the Subsection title: Exploratory Pharmacogenomic (DNA) 
Assessments. Subsection now called: Optional Exploratory Pharmacogenomic (DNA) 
Assessments:
Time And Events Schedule
New footnote “s” added to state biomarker and pharmacogenomics sample must be 
collected prior to study agent administration. 
Rationale: Blood volumes were updated to align with the Central Laboratory blood volumes.
9. Study Evaluations;
9.1.
Study Procedures; 
9.1.1. Overview
and
16.1.
Study-Specific 
Design Considerations
Blood volumes were updated to reflect the Central Laboratory blood volume table.

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Applicable Section(s)
Description of Change(s)
Rationale: Additional text was added to provide clarity around rounding rules for body weight.
Attachment 2:
Dose And 
Device Charts For Study 
CNTO148DML2001 In 
Subjects With Type 1 
Diabetes; Attachment 2-A:
Dosing Chart for 
Induction Doses at Week 0 
and Week 2
Text added to provide additional information around rounding rules for body weight 
and an example was provided.
Rationale: Approximately was added to the length of the enrollment period to allow for flexibility. 
3.1.
Overview of Study 
Design
The enrollment period of 12 to 18 months was updated to approximately 12 to 
18 months. 
Rationale: Change in description of the packaging of the devices used to match the description in the device 
packaging.
14.2.
Packaging
The term child resistant was changed to tamper resistant.
Rationale: Correction of terminology used in the protocol
Attachment 3:
Procedures for 
Performing the Mixed-Meal 
Tolerance Test
The term Boost High Protein was changed to Boost original.
The term central operations manual was changed to Central Laboratory manual. 
Rationale: Text was added in order for local laboratory testing of Quantiferon-TB samples to be allowed in the study. 
Attachment 1:
Quantiferon-TB Gold 
Testing
Sentence added to allow for local laboratory to perform the QuantiFERON test in 
select circumstances approved by the sponsor. 
Rationale: Text describing type of data used for efficacy analyses was updated to provide clarity and the timepoint at 
Week 52 was removed.
11.3.
Efficacy Analyses; 
Primary Endpoints
The text was updated to include the fact that the analysis will use post-baseline 
log(AUC+1) data and the Week 52 timepoint was removed. 
Rationale: Text was updated to provide clarity on 2 MMTT-stimulated C-peptide endpoints.
9.2.2.3.
Other Endpoints
The description of peak was added to the MMTT-simulated C-peptide endpoint.
Rationale: The timepoints for the distribution of study agent injection devices was corrected in the Time and Events 
Schedule. 
Time And Events Schedule
Distribute study agent injection devices was updated to include Week 33 and Week 45
Footnote g was updated with detailed instructions around study agent administration 
and PK sampling for clarity.

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Applicable Section(s)
Description of Change(s)
Rationale: Minor errors were noted
Throughout the protocol
Minor grammatical, formatting, or spelling changes were made.
References
VarioJect Injection Pen Investigator’s Brochure and Seaquist ER, Anderson J, Childs 
B, et al references were added to the list of references.
10.2.
Discontinuation of 
Study 
Treatment/Withdrawal from 
the Study
Encouraged to participate in the Week 104 and Week 52 visits was changed to 
encouraged to participate in the Week 52 and Week 104 visits.
Amendment 1 (02 June 2016)
The overall reason for the amendment: The overall reason for the amendment is to incorporate feedback from 
health authorities into the protocol.
Applicable Section(s)
Description of Change(s)
Rationale: An additional inclusion criterion was needed to confirm current or future immunization status.
4.1. Inclusion Criteria; 
inclusion criterion 11
New criterion added to confirm current or future immunization status.
Rationale: Clarification of the definition and timing for immunizations that can be received was needed in the 
protocol. 
8.2. Permitted 
Medications
Details were added around vaccines permitted in the study and their schedule. 
Rationale: The handling of laboratory samples from the Mixed-Meal Tolerance Test (MMTT) needed clarification 
for storage and shipping instructions in the protocol.
Attachment 3: 
Procedures for 
Performing the Mixed-
Meal Tolerance Test
Instructions were added for processing, storage, and shipping of laboratory samples from 
the MMTT.
Rationale: Recognition that those with clinically stable autoimmune thyroiditis may be able to participate in this 
study needed to be added to the protocol.
4.2. Exclusion Criteria; 
criterion 4
Criterion updated to provide an exception for subjects with clinically stable autoimmune 
thyroiditis. 
Rationale: Clarity needed around the number of injections in Table 1. 
6.1. Dosage; Table 1
Number of injections updated to number of injections/dose in Table 1. 

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Applicable Section(s)
Description of Change(s)
Rationale: Consistency needed in the protocol in relation to neutralizing antibodies.
9.3.4. Immunogenicity 
Assessments 
(Antibodies to 
golimumab)
Text added describing evaluation of positive samples for neutralizing antibodies.
Rationale: The title of the study was decided after issuing of the protocol.
Title page
The study title was added to the cover page of the protocol.
Rationale: Where to record self-administration done at the study site needed clarification. 
TIME AND EVENTS 
SCHEDULE; 
Screening through Off-
therapy Follow-up; 
Footnote b
Footnote updated to include instructions for recording self-administration done at the 
study site.
7.1.1. Dosing 
Recording
Text added to clarify self-administration done at the study site should not be recorded 
into an eDiary.
Rationale: Clarification was needed on subject/caregiver data collection using the sponsor-supplied eDiary and 
glucometer. 
9.1.1. Overview
Collection of hypoglycemic events was added to list of data that subject/caregivers are to 
collect using the sponsor-supplied eDiary and glucometer.
Rationale: Clarification was needed around length of time subject/caregivers need to record data in their eDiary.
9.1.3.3. Off-Therapy 
Follow-up Period –
Weeks 52 to 104
Text was added instructing subject/caregivers to record data in their eDiary until 
Week 104.
Rationale: Members of the Independent DMC needed to be defined in the protocol.
11.11. Data Monitoring 
Committee
Text was added to define associations of individuals who can be members of the 
Independent DMC for this study. 
Rationale: The IAC may consist of individuals external to the sponsor.
11.10. Interim Analysis
Removed “internal” in reference to the IAC.
Rationale: Clarification regarding timing of administration of study agent needed in the dosing charts.
Attachment 2-A;
Attachment 2-A
Title of the tables were updated with range of weeks for study agent administration. 

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Applicable Section(s)
Description of Change(s)
Rationale: Minor errors were noted.
1. INTRODUCTION; 
Type 1 Diabetes
Shots changed to injections.
4.2. Exclusion Criteria; 
criterion 14
Current of prior corrected to: current or prior.
ABBREVIATIONS
Abbreviations for CDC and HPV were added to the list of abbreviations.

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Argiles JM, Lopez-Soriano J, Lopez-Soriano FJ. Cytokines and diabetes: the final step? Involvement of TNF-
alpha in both type I and II diabetes mellitus. Horm Metab Res. Oct 1994;26(10):447-449.
3.
Arif S, Cox P, Afzali B, et al. Anti-TNFalpha therapy--killing two birds with one stone? Lancet. 
2010;375(9733):2278.
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Asvold BO, Sand T, Hestad K, Bjorgaas MR. Cognitive function in type 1 diabetic adults with early exposure 
to severe hypoglycemia: a 16-year follow-up study. Diabetes Care. 2010;33:1945-1947.
5.
Atkinson MA, Bluestone JA, Eisenbarth GS, et al. How does type 1 diabetes develop?: the notion of homicide 
or beta-cell suicide revisited. Diabetes. 2011;60(5):1370-1379.
6.
Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383:69-82.
7.
Bjorgaas MR. Cerebral effects of severe hypoglycemia in young people with type 1 diabetes. Pediatr Diabetes. 
2012;13:100-107.
8.
Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. 
Nature. 2010;464(7293):1293-1300.
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Approved, Date: 23 August 2019
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Clinical Protocol CNTO148DML2001 Amendment 3
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Approved, Date: 23 August 2019
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Attachment 1: Quantiferon-TB Gold Testing
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).

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Performing the QuantiFERON-TB Gold In-Tube 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.
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 3000g. 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. Subjects who have an indeterminate result should have the test repeated.
In select circumstances as approved by the sponsor, a local laboratory may be used to perform 
the QuantiFERON®-TB Gold test.
Adherence to Local Guidelines
Local country guidelines for immunocompromised patients should be consulted for acceptable 
antituberculous treatment regimens for latent TB. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
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;361:1168-1173.

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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.
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: Dose and Device Charts for Study CNTO148DML2001 in Subjects With Type 1 
Diabetes
DOSE AND DEVICE CHARTS FOR STUDY CNTO148DML2001 IN SUBJECTS WITH 
TYPE 1 DIABETES
Attachment 2-A:
Dosing Chart for Induction Doses at Week 0 and Week 2
Volume (mL) from VarioJect (shaded white) and/or 50 mg PFS-U (shaded light gray)

Body weight rounded to the nearest 5 kg and height rounded to the nearest 10 cm using 
standard rounding rules, round body weight up or down to the nearest 5 kg and height up or 
down to the nearest 10 cm. (Example: weight of 27.6 kg and height of 114.9 cm round 
weight up to 30 kg, and height down to 110 cm, resulting in an induction dose volume of 
0.55 mL).

See device selection table (Attachment 2-C) for additional administration instructions.
Induction Dosing Chart - VarioJect or PFS-U Volume to be Dispensed (mL) for Week 0 and 
Week 2 Only*
Height (cm)
Weight (kg)
10
15
20
25
30
35
40
45
80
0.30
0.35
0.40
0.45
90
0.30
0.35
0.40
0.45
0.50
0.55
100
0.30
0.40
0.45
0.50
0.55
0.60
0.65
1.00 with 2 
PFS-U
110
0.35
0.40
0.45
0.50
0.55
0.60
0.65
1.00 with 2 
PFS-U
120
0.35
0.40
0.50
0.55
0.60
0.65
0.70
1.00 with 2 
PFS-U
130
0.45
0.50
0.55
0.60
0.65
0.70
1.00 with 2 
PFS-U
140
0.45
0.55
0.60
0.65
0.70
0.75
1.00 with 2 
PFS-U
150
0.55
0.60
0.65
0.70
0.75
1.00 with 2 
PFS-U
160
0.55
0.65
0.70
0.75
0.80
1.00 with 2 
PFS-U
170
0.65
0.70
0.75
0.80
1.00 with 2 
PFS-U
180
0.75
0.80
0.85
1.00 with 2 
PFS-U
* See Attachment 2-C:Device Selection Chart for device(s) and settings to achieve the total dose indicated above

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Attachment 2-B:
Dosing Chart for Maintenance Dosing Regimens at Week 4 through Week 52
Volume (mL) from VarioJect (shaded white) or 50 mg PFS-U (shaded light gray)

Body weight rounded to the nearest 5 kg and height rounded to the nearest 10 cm.

See device selection table (Attachment 2-C) for additional administration instructions.
Maintenance Dosing Chart - VarioJect (White) or PFS-U (Light Gray) Volume to be Dispensed 
(mL) for Week 4 Through Week 52*
Height (cm)
Weight (kg)
10
15
20
25
30
35
40
45
80
0.15
0.15
0.20
0.20
90
0.15
0.20
0.20
0.25
0.25
0.30
100
0.15
0.20
0.20
0.25
0.25
0.30
0.30
0.50 with 
PFS-U
110
0.15
0.20
0.25
0.25
0.30
0.30
0.35
0.50 with 
PFS-U
120
0.15
0.20
0.25
0.25
0.30
0.30
0.35
0.50 with 
PFS-U
130
0.20
0.25
0.30
0.30
0.35
0.35
0.50 with 
PFS-U
140
0.25
0.25
0.30
0.30
0.35
0.35
0.50 with 
PFS-U
150
0.25
0.30
0.35
0.35
0.40
0.50 with 
PFS-U
160
0.30
0.30
0.35
0.35
0.40
0.50 with 
PFS-U
170
0.35
0.35
0.40
0.40
0.50 with 
PFS-U
180
0.35
0.40
0.40
0.50 with 
PFS-U
* See Attachment 2-C: Device Selection Chart for device and settings to achieve the dose indicated above

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Attachment 2-C:
Device Selection Chart
Volume (mL) from VarioJect or PFS-U
Device Selection Chart**
Volume 
(mL)
Induction Dose
Maintenance Dose
Number of Devices
Volume
Number of Devices
Volume
0.15
1 VarioJect
1 VarioJect: 0.15 mL
0.20
1 VarioJect
1 VarioJect: 0.20 mL
0.25
1 VarioJect
1 VarioJect: 0.25 mL
0.30
1 VarioJect
1 VarioJect: 0.30 mL
1 VarioJect
1 VarioJect: 0.30 mL
0.35
1 VarioJect
1 VarioJect: 0.35 mL
1 VarioJect
1 VarioJect: 0.35 mL
0.40
1 VarioJect
1 VarioJect: 0.40 mL
1 VarioJect
1 VarioJect: 0.40 mL
0.45
1 VarioJect
1 VarioJect: 0.45 mL
N/A
N/A
0.50
2 VarioJects
1st VarioJect: 0.25 mL;
2nd VarioJect : 0.25 mL
1 PFS-U 50 mg
PFS-U: whole volume
0.55
2 VarioJects
1st VarioJect: 0.25 mL;
2nd VarioJect : 0.30 mL
0.60
2 VarioJects
1st VarioJect: 0.30 mL;
2nd VarioJect : 0.30 mL
0.65
2 VarioJects
1st VarioJect: 0.30 mL;
2nd VarioJect: 0.35 mL
0.70
2 VarioJects
1st VarioJect: 0.35 mL;
2nd VarioJect: 0.35 mL
0.75
2 VarioJects
1st VarioJect: 0.35 mL;
2nd VarioJect: 0.40 mL
0.80
2 VarioJects
1st VarioJect: 0.40 mL;
2nd VarioJect: 0.40 mL
0.85
2 VarioJects
1st VarioJect: 0.40 mL;
2nd VarioJect: 0.45 mL
0.90
N/A
N/A
0.95
N/A
N/A
1.00
2 PFS-U 50 mg
1st PFS-U: whole 
volume; 2nd PFS-U: 
whole volume
** Due to a rare chance of excess study agent administration with the 0.10 ml setting on the VarioJect, this dose 
increment is not to be used.
NA = Not applicable

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Attachment 3: Procedures for Performing the Mixed-Meal Tolerance Test
NOTE: These procedures for performing the mixed-meal tolerance test instructions are a 
summary of the how subjects should prepare for the MMTT and how the test should be 
performed by the study team. Further detail will be provided in the Central Laboratory manual. 
Minor adjustments of this procedure may occur by the sponsor including, but not limited, to 
modifications or refinements of sample preparation and processing that will not necessitate a 
protocol amendment.
Procedures for Performing the Mixed-Meal Tolerance Test:
The MMTT is performed in the morning (between 7:00 a.m. and 10:00 a.m.), which means that 
administration must begin within this time. It is recommended that the tests be scheduled early in 
the morning (7:00–7:30 am) because BG will be more likely to be within the target range at that 
time.
The mixed-meal used in this protocol will be the Boost original Nutritional Energy Drink®
(Mead-Johnson). If a subject has a known food allergy to one or more components of Boost, an 
equivalent substitution may be used contingent upon agreement with the study team. The 4-hour 
MMTT should take 250 minutes to perform.
Dietary Guidelines and Pretest Instructions:
Carbohydrates (CHO) should not be restricted from the diet before the test. A general guideline 
is that preadolescent subjects should consume at least 25 kcal (6.25 g) CHO/kg/day and 
adolescent and adult subjects should consume at least 15 kcal (3.75 g) CHO/kg/day for 3 days 
before the test. These are minimum amounts of CHO; most diets will include greater amounts of 
CHO. There is no need to alter the subject’s diet unless he or she has been on a CHO-restricted 
diet.
In preparation for the visit, each subject should:

Fast for at least 10 hours (but not more than 16 hours) before the test. Fasting should start 
the night before the test and should continue up until the start of the test. Subjects should not 
eat or drink anything except water. This means no coffee, tea, soda, cigarettes, alcohol, or 
chewing gum during the fasting period.

Refrain from vigorous exercise during the fasting period.

Refrain from working the night before the morning of the test.

Discontinue taking any prescription medications that must be taken daily.
Glucose and Insulin Before the Test:

Short-acting insulin analogues (such as lispro or l-aspart) may be administered up to 2 hours 
before the test.

Regular insulin may be administered up to 6 hours before the test.

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
Intermediate-acting insulin (such as Neutral Protamine Hagedorn [NPH]) may be 
administered on the evening before the MMTT, but not on the morning of the test. Subjects 
managed with intermediate-acting insulin (NPH or Lente) should administer their usual dose 
on the evening before the MMTT, but not on the morning of the test.

Long-acting basal (such as glargine) insulin or continuous subcutaneous insulin infusion 
may be administered before, during and after the test as usual. Subjects on glargine may take 
their usual injection at the appropriate time, and those on continuous subcutaneous insulin 
infusion may continue with their usual basal settings.
Target Glucose Level at the Start of Test:
The target glucose level at the start of the test is between 70 and 200 mg/dL. Regular insulin or 
short-acting insulin analogues may be used up to 6 and 2 hours before the test, respectively, to 
achieve the desired glucose level. The principal investigator and the study subject should discuss 
the individual situation for insulin administration to attain the goal of meter capillary glucose 
values within the range of 70–200 mg/dL at the start of the test. For example, as a practical 
matter, subjects may be instructed to check their BG by meter before coming to the study site 
2 hours before the start of the test, so that marked hyperglycemia can be treated with a 
short-acting insulin analogue. Alternatively, subjects who arrive at the research unit with 
elevated BG can receive additional short-acting insulin analogues at the time of their arrival, if 
the test itself does not start until at least 2 hours after insulin administration and occurs before 
10 a.m.
If a subject’s BG is below the limit (70 mg/dL) prior to performing the MMTT, the subject 
should be treated according to local practice, and the MMTT should be rescheduled.
IV Placement During the Test:
The IV should be in place for the duration of the test and must be flushed after each draw with 
saline solution or heparin flush.
The subject should remain sitting or resting in bed quietly throughout the test and until the test is 
completed. However, he or she may engage in quiet, non-strenuous activities, such as reading, 
playing cards, or watching TV. The subject may walk to the bathroom between blood draws if 
necessary.
Testing Instructions:
Timepoint −10 minutes
The first sample should be taken at least 10 minutes after establishing the line(s) and when the 
subject is calm and relaxed (if possible, depending on age) ― this is the “−10 minute” sample.
Draw one 2-mL sample into the purple-top tube. After each vacutainer is collected the tube must 
be inverted gently at least 8 to 10 times. Chill sample in a bucket of crushed ice or in a 
refrigerator set at 4˚C for 20 to 30 minutes. At the laboratory, spin the tube in a tabletop 

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centrifuge (1000–1300 g, ~3000 RPM) for 10 minutes. Tubes must be spun within 30 to 
60 minutes from blood draw. Freeze, store, and ship spun samples according to the Central 
Laboratory manual instructions.
Timepoint 0 minutes
The second sample should be taken just before the subject drinks the Boost; this is the 
“0-minute” sample.
Then the MMTT dose should be given with 6 kcal/kg @ 1 kcal/mL of mixed-meal to a 
maximum of 360 mL. The subject should consume the MMTT dose in no more than 5 minutes.
Timepoints 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes
Draw one 2-mL sample into the purple-top tube.
Invert all tubes gently 8 to 10 times after collection. If it is not possible to centrifuge the sample 
immediately post collection, chill sample in a bucket of crushed ice or in a refrigerator set at 4˚C 
for 20 to 30 minutes. Refrigerate the sample no longer than one hour prior to centrifugation. 
Freeze, store and ship the spun samples according to the Central Laboratory manual instructions.
Please check and record BG by meter at each timepoint.
At the conclusion of the test, please check BG by glucometer, and administer insulin as per 
subject’s standard insulin plan.
Tube-Processing Instructions:
Spin the purple---top tubes, then transfer the plasma into 2 individual vials. Please make sure that 
each vial is properly identified with a label that indicates the timepoint.
Freeze, store and ship the spun samples according to the Central Laboratory manual instructions.
A clogged line, missed sample, or other deviation from the protocol must be noted on the 
Comments section of the MMTT specimen transmittal form.
Sample:
Time (minutes)
Sample Collection*
–10
x
0
x
Subjects drinks Boost
15
x
30
x
60
x
90
x
120
x

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Time (minutes)
Sample Collection*
150
x
180
x
210
x
240
x
*assessments to include C-peptide, insulin, glucose, and/or pro-insulin per the Central 
Laboratory manual

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Attachment 4: Hepatitis B Virus (HBV) Screening
Hepatitis B Virus (HBV) Screening
Subjects must undergo screening for hepatitis B virus (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 5: Study Defined AST and ALT Normal Ranges, 2x ULN, and 3x ULN
AST and ALT normal ranges, 2x ULN, and 3x ULN*
Test
Sex
Age Range
(Yrs)
Normal Range
(U/L)
2x ULN (U/L)
3x ULN (U/L)
AST
Female
Through 6
10-48
96
144
7 through 17
10-40
80
120
18 and above
9-34
68
102
Males
Through 6
10-59
118
177
7 through 17
10-40
80
120
18 and above
11-36
72
108
ALT
Female
6 and above
6-34
68
102
Male
6 through 9
6-34
68
102
10 and above
6-43
86
129
* From Covance Laboratories

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Attachment 6: Anticipated Events
An anticipated event is an AE (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:
1.
Severe hypoglycemia. This is defined as a BG reading of <70 mg/dL and/or clinical signs 
and symptoms consistent with hypoglycemia even in the absence of a BG reading.
2.
Diabetic Ketoacidosis (DKA). This is a condition of ketosis and metabolic acidosis that can 
occur in individuals with T1D.
Both severe hypoglycemia and DKA may present along a spectrum of severity. The site principal 
investigator will be responsible for the AE classification according to the definitions in Section 
12.
Reporting of Anticipated Events
These events will be captured on the CRF and in the database and will be reported to the sponsor 
as described in Section 12.4.1, All Adverse Events. Any event that meets SAE criteria will be 
reported to the sponsor within the appropriate timeline as described in Section 12.4.2, 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 agent, the sponsor will report these events in an 
expedited manner.
Anticipated Event Review Committee (ARC)
An Anticipated Event Review Committee (ARC) will be established to perform reviews of pre-
specified anticipated 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 agent. As this is a blinded study, an unblinded 
physician within the sponsor’s organization not involved with the study but with subject matter 
expertise will be available to assist the ARC in the assessment and categorization of AEs if 
needed.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and 
threshold to trigger an aggregate analysis of anticipated events will be described in a separate 
Anticipated Events Safety Monitoring Plan (ASMP).

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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this 
study. I will conduct the study as outlined herein and will complete the study within the time 
designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that 
they are fully informed regarding the study drug, the conduct of the study, and the obligations of 
confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Donald Raible, MD
Institution:
Janssen Research & Development
Signature:
[electronic signature appended at the end of the protocol]
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the 
study, written notification will be provided by the investigator to the sponsor, and a protocol 
amendment will not be required.

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 24 April 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
T1GER
Protocol CNTO148DML2001; Phase 2a
SIMPONI®  (golimumab)
*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 Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; 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.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Status:
Approved
Date:
24 April 2020
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-37356, 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
CNTO148DML2001 
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT02846545

COVID-19 Appendix
SIMPONI® (golimumab)
Clinical Protocol CNTO148DML2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 24 April 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for 
study -related participant management in the event of disruption to the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of participants and site staff. If 
at any time a participant’s safety is considered to be at unacceptable risk, study intervention will 
be discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted after consultation between the participant and investigator, and with the agreement of 
the sponsor (see below). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
medical officer or designee to discuss plans for study intervention and follow-up. 
ADDITIONAL ELEMENTS, WHERE APPLICABLE:

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of participant care and study integrity. 
Certain measures, such as those listed below, may be necessary and should be instituted in 
accordance with applicable (including local) laws, regulations, guidelines, and procedures:
o
remote (e.g. by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures e.g. those related 
to safety monitoring / efficacy evaluation / study intervention storage and 
administration (including training where pertinent)

COVID-19 Appendix
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Status: Approved,  Date: 24 April 2020
o
procurement of study intervention by participants (or designee) or shipment of study 
intervention from the study site directly to participants for at home administration 
(including the potential for self-administration of study intervention)
o
laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed
o
other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations.  Discontinuations of study interventions and withdrawal from the 
study should be documented with the prefix “COVID-19-related” in the case report form 
(CRF).  
o
other relevant study data elements impacted by the pandemic should also be 
documented / labeled as “COVID-19-related” in CRFs and / or other study systems, 
as directed by detailed sponsor guidance. These may include missed / delayed / 
modified study visits / assessments / dosing, and instances where temporary 
measures such as those above are implemented.  

The sponsor will evaluate the totality of impact of COVID-19 on collection of key study 
data and additional data analyses will be outlined in study SAP(s). 

Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol:
o
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 
(clinical features without documented test results), OR (c) close contact with a 
person with known or suspected SARS-CoV-2 infection 

Exception: may be included with a documented negative result for a 
validated SARS-CoV-2 test
(i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from 
resolution of key clinical features if present, e.g. fever, cough, dyspnea)
AND
(ii) with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit 

COVID-19 Appendix
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Status: Approved,  Date: 24 April 2020

NOTES on COVID-related exclusion:
1. If a participant is excluded due to recent COVID-19-related features, the reason for 
screen failure should be documented in the case report form under the exclusion 
criterion of having a condition for which participation would not be in the participant’s 
interest or could confound study assessments. 
2. The field of COVID-related testing (for presence of, and immunity to, the SARS-CoV-
2 virus) is rapidly evolving. Additional testing may be performed as part of screening 
and/or during the study if deemed necessary by the investigator and in accordance with 
current regulations / guidance from authorities / standards of care. 

Precaution: for those who may carry a higher risk for severe COVID-19 illness (e.g. those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks of enrolling in the study, and during participation in the study. 

COVID-19 Appendix
SIMPONI® (golimumab)
Clinical Protocol CNTO148DML2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 24 April 2020
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study intervention, the conduct of the study, and the obligations 
of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Frank Vercruysse MD
Institution:
Janssen Research & Development 
Signature:
electronic signature appended at the end of the protocol
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.