A Phase-IV, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of Golimumab (MK-8259 [SCH 900259]) After Treatment Withdrawal, Compared With Continued Treatment (Either Full- or Reduced-Treatment Regimen), In Subjects With Non-Radiographic Axial Spondyloarthritis
Phase: PHASE4
Conditions: Spondyloarthritis
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title: 
NCT number: 
NCT03253796 
Document Date: 
21-Mar-2017
A Phase-IV, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Trial to Evaluate the Efficacy and Safety of Golimumab 
(MK-8259 [SCH 900259]) After Treatment Withdrawal, Compared With 
Continued Treatment (Either Full- or Reduced-Treatment Regimen), In 
Subjects With Non-Radiographic Axial Spondyloarthritis

Product:  MK-8259 (SCH 900259)
1
Protocol/Amendment No.: 038-01 
MK-8259-038-01 Final Protocol
21-Mar-2017
Confidential
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC., 
WHITEHOUSE STATION, NJ, U.S.A.
SPONSOR:
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 
(hereafter referred to as the Sponsor or Merck)
One Merck Drive
P.O. Box 100
Whitehouse Station, NJ 08889-0100, U.S.A.
Protocol-specific Sponsor Contact information can be found in the Investigator Trial File
Binder (or equivalent).
TITLE:
A Phase-IV, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to 
Evaluate the Efficacy and Safety of Golimumab (MK-8259 [SCH 900259]) After Treatment 
Withdrawal, Compared With Continued Treatment (Either Full- or Reduced-Treatment 
Regimen), In Subjects With Non-Radiographic Axial Spondyloarthritis
IND NUMBER:  12729
EudraCT NUMBER:  2015-004020-65
 
 
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TABLE OF CONTENTS
SUMMARY OF CHANGES................................................................................................ 10
1.0
TRIAL SUMMARY.................................................................................................. 16
2.0
TRIAL DESIGN........................................................................................................ 16
Trial Design ........................................................................................................... 16
2.1
Trial Diagram........................................................................................................ 19
2.2
3.0
OBJECTIVE(S) & HYPOTHESIS(ES).................................................................. 19
Primary Objective(s) & Hypothesis(es) .............................................................. 19
3.1
Secondary Objective(s) & Hypothesis(es)........................................................... 20
3.2
Exploratory Objectives......................................................................................... 20
3.3
4.0
BACKGROUND & RATIONALE.......................................................................... 20
Background ........................................................................................................... 20
4.1
Pharmaceutical and Therapeutic Background .................................................... 21
4.1.1
Rationale................................................................................................................ 21
4.2
Rationale for the Trial and Selected Subject Population .................................... 21
4.2.1
Rationale for Dose Selection/Regimen............................................................... 22
4.2.2
Rationale for Endpoints ...................................................................................... 22
4.2.3
4.2.3.1
Efficacy Endpoints....................................................................................... 22
4.2.3.2
Safety Endpoints .......................................................................................... 23
4.2.3.3
Planned Exploratory Biomarker Research................................................... 23
4.2.3.4
Future Biomedical Research........................................................................ 23
Benefit/Risk ........................................................................................................... 24
4.3
5.0
METHODOLOGY ................................................................................................... 24
Entry Criteria........................................................................................................ 24
5.1
Diagnosis/Condition for Entry into the Trial ...................................................... 24
5.1.1
Subject Inclusion Criteria.................................................................................... 25
5.1.2
Subject Exclusion Criteria .................................................................................. 30
5.1.3
Trial Treatment(s) ................................................................................................ 33
5.2
Dose Selection .................................................................................................... 34
5.2.1
5.2.1.1
Dose Selection (Preparation) ....................................................................... 34
5.2.1.2
Dose Modification (Escalation) ................................................................... 34
 
 
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Timing of Dose Administration .......................................................................... 35
5.2.2
Trial Blinding/Masking....................................................................................... 35
5.2.3
Randomization or Treatment Allocation............................................................ 35
5.3
Stratification.......................................................................................................... 35
5.4
Concomitant Medications/Vaccinations (Allowed & Prohibited).................... 35
5.5
Rescue Medications & Supportive Care............................................................. 36
5.6
Diet/Activity/Other Considerations..................................................................... 36
5.7
Subject Withdrawal/Discontinuation Criteria................................................... 37
5.8
Subject Replacement Strategy............................................................................. 38
5.9
Beginning and End of the Trial ........................................................................... 38
5.10
Clinical Criteria for Early Trial Termination ................................................... 38
5.11
6.0
TRIAL FLOW CHART ........................................................................................... 39
Period 1: Open-Label Run-in .............................................................................. 39
6.1
Period 2: Double-blind Withdrawal.................................................................... 42
6.2
7.0
TRIAL PROCEDURES ........................................................................................... 44
Trial Procedures ................................................................................................... 44
7.1
Administrative Procedures.................................................................................. 44
7.1.1
7.1.1.1
Informed Consent......................................................................................... 44
7.1.1.1.1
General Informed Consent.................................................................... 44
7.1.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research................................................................................................ 45
7.1.1.2
Inclusion/Exclusion Criteria ........................................................................ 45
7.1.1.3
Subject Identification Card .......................................................................... 45
7.1.1.4
Medical History ........................................................................................... 45
7.1.1.5
Prior and Concomitant Medications Review ............................................... 46
7.1.1.5.1
Prior Medications.................................................................................. 46
7.1.1.5.2
Concomitant Medications..................................................................... 46
7.1.1.6
Assignment of Screening Number............................................................... 46
7.1.1.7
Assignment of Randomization Number....................................................... 46
7.1.1.8
Trial Compliance (Medication).................................................................... 46
7.1.1.9
Trial Medication Injection Administration .................................................. 47
7.1.1.10 Trial Medication Injection Log.................................................................... 48
 
 
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7.1.1.11 Issue and Review Comments Card .............................................................. 48
Clinical Procedures/Assessments........................................................................ 48
7.1.2
7.1.2.1
Physical Examination................................................................................... 48
7.1.2.2
Vital Signs.................................................................................................... 48
7.1.2.3
Chest X-ray (CXR) ...................................................................................... 49
7.1.2.4
X-Rays of Sacroiliac Joints.......................................................................... 49
7.1.2.5
Magnetic Resonance Imaging of Sacroiliac Joints ...................................... 49
7.1.2.6
Bath Ankylosing Spondylitis Disease Activity Index (Patient Reported 
Outcome) ..................................................................................................... 50
7.1.2.7
Bath Ankylosing Spondylitis Functional Index (Patient Reported 
Outcome) ..................................................................................................... 50
7.1.2.8
Patient Global Disease Assessment (Patient Reported Outcome) ............... 50
7.1.2.9
Total Back Pain (Patient Reported Outcome).............................................. 50
7.1.2.10 Global Assessment of Disease by Investigator ............................................ 51
7.1.2.11 Record Adverse Events................................................................................ 51
7.1.2.12 Monitoring Malignancies............................................................................. 51
Laboratory Procedures/Assessments .................................................................. 51
7.1.3
7.1.3.1
Laboratory Safety Evaluations (Hematology, Chemistry and Other 
Tests)............................................................................................................ 51
7.1.3.2
Serum/Urine Pregnancy Testing and Follow-up of Pregnancy ................... 52
7.1.3.3
Tuberculosis (TB) Screening ....................................................................... 53
7.1.3.4
HLA-B27 Gene Status ................................................................................. 53
7.1.3.5
Screening for Hepatitis B Virus (HBV)....................................................... 54
7.1.3.6
Pharmacokinetic (PK) and Immunogenicity Evaluations............................ 54
7.1.3.6.1
Blood Collection for Plasma MK-8259................................................ 54
7.1.3.6.2
Blood Collection for Antibodies to Golimumab (MK-8259) ............... 54
7.1.3.7
Future Biomedical Research........................................................................ 55
7.1.3.8
Planned Genetic Analysis Sample Collection.............................................. 55
Other Procedures................................................................................................. 55
7.1.4
7.1.4.1
Withdrawal/Discontinuation........................................................................ 55
7.1.4.1.1
Withdrawal From Future Biomedical Research ................................... 55
7.1.4.2
Blinding/Unblinding .................................................................................... 56
7.1.4.3
Calibration of Critical Equipment................................................................ 56
 
 
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Visit Requirements.............................................................................................. 56
7.1.5
7.1.5.1
Screening and Baseline Eligibility (Visit 1 and Visit 2).............................. 56
7.1.5.2
Month-4 Clinic Visit (Visit 10).................................................................... 57
7.1.5.3
Month-7 Clinic Visit (Visit 16).................................................................... 57
7.1.5.4
Month-10 Clinic Visit (Visit 23) ................................................................. 58
7.1.5.5
Unscheduled Visit(s) to Confirm a “Flare” during Period 2........................ 58
7.1.5.6
Safety Follow-Up Telephone call ................................................................ 59
Assessing and Recording Adverse Experiences ................................................. 60
7.2
Definition of an Overdose for This Protocol and Reporting of Overdose to 
7.2.1
the Sponsor.......................................................................................................... 61
Reporting of Pregnancy and Lactation to the Sponsor ....................................... 61
7.2.2
Immediate Reporting of Adverse Events to the Sponsor.................................... 62
7.2.3
7.2.3.1
Serious Adverse Events ............................................................................... 62
7.2.3.2
Events of Clinical Interest............................................................................ 62
Evaluating Adverse Events ................................................................................. 63
7.2.4
Sponsor Responsibility for Reporting Adverse Events ...................................... 66
7.2.5
TRIAL GOVERNANCE AND OVERSIGHT ................................................... 66
7.3
Scientific Advisory Committee........................................................................... 66
7.3.1
8.0
STATISTICAL ANALYSIS PLAN ........................................................................ 66
Statistical Analysis Plan Summary ..................................................................... 66
8.1
Responsibility for Analyses / In-House Blinding ............................................... 67
8.2
Hypotheses / Estimation ....................................................................................... 67
8.3
Analysis Endpoints ............................................................................................... 67
8.4
Efficacy Endpoints.............................................................................................. 68
8.4.1
8.4.1.1
Primary Efficacy Endpoint .......................................................................... 68
8.4.1.2
Secondary Efficacy Endpoints..................................................................... 68
8.4.1.3
Exploratory Endpoints ................................................................................. 68
Safety Endpoints ................................................................................................. 69
8.4.2
8.4.2.1
Events of Clinical Interest............................................................................ 69
8.4.2.2
Other Safety Endpoints:............................................................................... 69
8.4.2.3
PK and Immunogenicity Endpoints ............................................................. 69
Derivations of Efficacy Endpoints...................................................................... 69
8.4.3
 
 
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8.4.3.1
Bath Ankylosing Spondylitis Disease Activity Index ................................. 69
8.4.3.2
Ankylosing Spondylitis Disease Activity Score.......................................... 70
8.4.3.3
Assessment 
in 
SpondyloArthritis 
international 
Society-related 
Endpoints ..................................................................................................... 70
8.4.3.4
Bath Ankylosing Spondylitis Functional Index ........................................... 71
8.4.3.5
Morning Stiffness......................................................................................... 71
8.4.3.6
Patient’s Global Disease Assessment .......................................................... 71
8.4.3.7
Total Back Pain............................................................................................ 71
Derivations of Safety Endpoints ......................................................................... 71
8.4.4
Analysis Populations............................................................................................. 72
8.5
Efficacy Analysis Populations ............................................................................ 72
8.5.1
Safety Analysis Populations ............................................................................... 73
8.5.2
Statistical Methods................................................................................................ 73
8.6
Statistical Methods for Efficacy Analyses .......................................................... 73
8.6.1
Statistical Methods for Safety Analyses ............................................................. 75
8.6.2
Summaries of Baseline Characteristics, Demographics, and Other Analyses .... 77
8.6.3
8.6.3.1
Demographic and Baseline Characteristics ................................................. 77
8.6.3.2
Antibodies to Golimumab............................................................................ 77
8.6.3.3
Pharmacokinetic Data .................................................................................. 77
Interim Analyses ................................................................................................... 77
8.7
Multiplicity ............................................................................................................ 78
8.8
Sample Size and Power Calculations .................................................................. 78
8.9
Subgroup Analyses and Effect of Baseline Factors ........................................... 79
8.10
Compliance (Medication Adherence).................................................................. 80
8.11
Extent of Exposure................................................................................................ 80
8.12
9.0
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ................................................................................................................. 80
Investigational Product ........................................................................................ 80
9.1
Packaging and Labeling Information ................................................................. 81
9.2
Clinical Supplies Disclosure................................................................................. 81
9.3
Storage and Handling Requirements.................................................................. 81
9.4
Discard/Destruction/Returns and Reconciliation .............................................. 82
9.5
Standard Policies................................................................................................... 82
9.6
 
 
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10.0
ADMINISTRATIVE AND REGULATORY DETAILS....................................... 82
Confidentiality....................................................................................................... 82
10.1
Confidentiality of Data ....................................................................................... 82
10.1.1
Confidentiality of Subject Records ..................................................................... 82
10.1.2
Confidentiality of Investigator Information........................................................ 83
10.1.3
Confidentiality of IRB/IEC Information............................................................. 83
10.1.4
Compliance with Financial Disclosure Requirements....................................... 83
10.2
Compliance with Law, Audit and Debarment ................................................... 84
10.3
Compliance with Trial Registration and Results Posting Requirements ........ 86
10.4
Quality Management System............................................................................... 86
10.5
Data Management................................................................................................. 86
10.6
Publications ........................................................................................................... 86
10.7
11.0
LIST OF REFERENCES......................................................................................... 88
12.0
APPENDICES........................................................................................................... 89
Merck Code of Conduct for Clinical Trials........................................................ 89
12.1
Collection and Management of Specimens for Future Biomedical 
12.2
Research................................................................................................................. 91
Pharmacogenetics 
Informational 
Brochure 
for 
IRBs/IECs 
& 
12.3
Investigational Site Staff ...................................................................................... 95
Approximate Blood Volumes Drawn/Collected............................................... 104
12.4
List of Abbreviations .......................................................................................... 105
12.5
Bath Ankylosing Spondylitis Disease Activity Index....................................... 107
12.6
Bath Ankylosing Spondylitis Functional Index................................................ 108
12.7
Patient Global Disease Assessment ................................................................... 110
12.8
Total Back Pain................................................................................................... 111
12.9
Global Assessment of Disease by Investigator ................................................. 112
12.10
13.0
SIGNATURES......................................................................................................... 113
Sponsor's Representative ................................................................................... 113
13.1
Investigator.......................................................................................................... 113
13.2
 
 
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LIST OF TABLES
Table 1  Trial Treatment ......................................................................................................... 33
Table 2  Laboratory Tests ....................................................................................................... 52
Table 3  Evaluating Adverse Events....................................................................................... 64
Table 4  Markedly Abnormal Criteria for Laboratory Parameters ......................................... 72
Table 5  Analysis Strategy for Efficacy Variables.................................................................. 75
Table 6  Analysis Strategy for Safety Parameters .................................................................. 75
Table 7  Power for the Primary Endpoint, Comparing Two Treatment Arms ....................... 79
Table 8  Product Descriptions................................................................................................. 81
 
 
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LIST OF FIGURES
          
Figure 1  Trial Schematic........................................................................................................ 19
 
 
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SUMMARY OF CHANGES
PRIMARY REASON(S) FOR THIS AMENDMENT:
Section 
Number(s)
Section Title(s)
Description of Change (s)
Rationale
5.1.1
Inclusion Criteria
The Inclusion criterion #3 was updated to include male 
contraception language:
Current: If a female subject of child-bearing potential, agree to
abstain from heterosexual activity or use a medically accepted
method of contraception prior to enrollment, while receiving
protocol-specified medication and for 6 months after stopping the 
medication.
Medically accepted methods of contraception include condoms
(male or female) with or without a spermicidal agent, diaphragm or
cervical cap with spermicide, medically prescribed intrauterine
device (IUD), inert or copper-containing IUD, hormone- releasing  
IUD,  
systemic  
hormonal  
contraceptive, and surgical 
sterilization (eg, hysterectomy or tubal ligation). Other methods may
be used as required by local legislation.
Postmenopausal women are not required to use contraception.
Postmenopausal is defined as at least 12 consecutive months without
a spontaneous menstrual period.
Revised: Meet one of the following categories:
a) The subject is a male who is not of reproductive potential, 
defined as a male who has azoospermia (whether due to having 
had a vasectomy or due to an underlying medical condition).  
b)  The subject is a female who is not of reproductive potential, 
defined as a female who either:  (1) Postmenopausal is defined as 
at least 12 consecutive months without a spontaneous menstrual 
period; 
(2) 
has 
had 
a 
hysterectomy 
and/or 
bilateral 
Male contraception language 
is needed in the protocol.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change (s)
Rationale
oophorectomy, bilateral salpingectomy, or bilateral tubal 
ligation/occlusion at least 6 weeks prior to screening; OR (3) has 
a congenital or acquired condition that prevents childbearing.
c)  The subject is a female or a male who is of reproductive potential 
and agrees to avoid becoming pregnant or impregnating a partner 
while receiving trial medication or within 6 months after the last 
dose of trial medication by complying with one of the following:  
(1) practice abstinence† from heterosexual activity OR (2) use 
(or have their partner use) acceptable contraception during 
heterosexual activity.
Acceptable methods of contraception are‡:

intrauterine device (IUD)

vasectomy of a female subject’s male partner 

contraceptive rod implanted into the skin

barrier method (includes diaphragm, cervical cap, and male 
or female condom) combined with spermicidal gel or foam

hormonal 
contraceptive: 
oral 
contraceptive 
pill 
(estrogen/progestin pill or progestin-only pill), contraceptive 
skin patch, vaginal contraceptive ring, or subcutaneous 
contraceptive injection
†Abstinence (relative to heterosexual activity) can be used as the 
sole method of contraception if it is consistently employed as the 
subject’s preferred and usual lifestyle and if considered acceptable 
by local regulatory agencies and ERCs/IRBs.  Periodic abstinence 
(e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, 
etc.) and withdrawal are not acceptable methods of contraception. 
 
 
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Section 
Number(s)
Section Title(s)
Description of Change (s)
Rationale
‡If a contraceptive method listed above is restricted by local 
regulations/guidelines, then it does not qualify as an acceptable 
method of contraception for subjects participating at sites in this 
country/region.
5.1.3
Exclusion Criteria
The following new exclusion criterion (No. 3) was added.
Intends to donate eggs (female subjects) or sperm (male subjects) 
while receiving trial medication or within 6 months after the last 
dose of trial medication.
Language regarding the egg 
and sperm donation is needed 
in the protocol.
7.1.3
Laboratory 
Procedures/Assess
ments
The title of the Section 7.1.3.2 was revised as follow:
Current: Serum/Urine Pregnancy Test
Revised:
Serum/Urine Pregnancy Testing and Follow-up of 
Pregnancy
The section was revised to include that male subjects must use a 
medically accepted method of contraception during the trial or 
within 6 months after the last dose of trial medication. 
The following language was also added for male subjects.
Male subjects who may have fathered a child during the trial or 
within 6 months after stopping the trial medication must notify the 
site immediately. 
Language 
regarding 
male 
contraception language and 
follow-up of pregnancy is 
needed in the protocol.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change (s)
Rationale
7.2.2
Reporting 
of 
Pregnancy 
and 
Lactation 
to 
Sponsor
The Section was updated as follow to collect pregnancy/lactation 
information from the partner of a male subject.
Although pregnancy and lactation are not considered adverse events, 
it is the responsibility of investigators or their designees to report 
any pregnancy or lactation in a subject (spontaneously reported to 
them), including the pregnancy of a male subject's female partner 
that occurs during the trial. 
Pregnancies and lactations of subjects and female partners of male 
subjects from the time the consent form is signed but before 
treatment allocation/ randomization must be reported by the 
investigator if they cause the subject to be excluded from the trial, or 
are the result of a protocol-specified intervention, including but not 
limited to washout or discontinuation of usual therapy, diet, placebo 
treatment or a procedure. Pregnancies and lactations of subjects and 
female partners of male subjects that occur from the time of 
treatment allocation/ randomization through 6 months following 
cessation of Sponsor’s product must be reported. All reported 
pregnancies must be followed to the completion/ termination of the 
pregnancy. Pregnancy outcomes of spontaneous abortion, missed 
abortion, benign hydatidiform mole, blighted ovum, fetal death, 
intrauterine death, miscarriage and stillbirth must be reported as 
serious events (Important Medical Events). If the pregnancy 
continues to term, the outcome (health of infant) must also be 
reported. 
Such events must be reported within 24 hours to the Sponsor either 
by electronic media or paper. Electronic reporting procedures can be 
found in the EDC data entry guidelines. Paper reporting procedures 
can be found in the Investigator Trial File Binder (or equivalent).
Language regarding follow-
up of pregnancy to include 
female 
partners 
of 
male 
subjects is needed in the 
protocol.
 
 
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ADDITIONAL CHANGE(S) FOR THIS AMENDMENT:
Section 
Number (s)
Section Title (s)
Description of Change (s)
Rationale
6.1
Study Flow Chart: 
Period 1: Open-
Label Run-in
Scheduled Month for Safety F/U telephone call was updated 
from 13 to 12.
Typographical error
6.1
Study Flow Chart: 
Period 1: Open-
Label Run-in
Two footnotes were updated to describe scheduling Visits 17 
and 24 following assessments for disease activity at Month 7 
(Visit 16) and at Month 10 (Visit 23):
d.  At Month 7 (Visit 16), subjects are assessed for Inactive 
Disease status (defined as ASDAS <1.3). Subjects who do not 
attain Inactive Disease status are discontinued; these subjects are 
to be scheduled for the DC visit to perform procedures (vital 
signs, Physician Global Disease Assessment, routine laboratory 
blood draw, and pregnancy test if required) that were not done at 
the Month 7 visit (Visit 16) but are required per DC visit. 
Subjects who attain inactive disease status (i.e., ASDAS <1.3) at 
Visit 16 will be scheduled for Visit 17 (within 2-7 days) to 
continue 
to 
receive 
open-label 
golimumab 
for 
self-
administration at home in Period 1.
e.  At Month 10 (Visit 23), subjects complete Period 1 and are 
assessed for Period 2. Subjects who attain Inactive Disease 
(defined as ASDAS <1.3) status enter Period 2. Subjects who do 
not attain Inactive Disease status are discontinued, and all 
procedures outlined for the DC visit are to be performed. 
Subjects who attain inactive disease status (i.e., ASDAS <1.3) at 
Visit 23 will be scheduled for Visit 24 (within 2-7 days) to enter 
Period 2 and receive double-blind treatment.
Adds clarity for scheduling the 
clinic visits 
 
 
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Section 
Number (s)
Section Title (s)
Description of Change (s)
Rationale
6.2
Study Flow Chart: 
Period 2: Double-
blind Withdrawal
The following footnote was added to the Flow Chart.
c. If the subject discontinued from the trial during Period 2, trial
medication will not be administered at the DC clinic visit.
All procedures to be performed 
at Visit 48 and discontinuation 
visits are the same, except for 
administration 
of 
trial
medication. Trial
medication 
will be administered at the last 
clinic visit (Visit 48) but will 
not be administered if subjects 
discontinued from Period 2 for 
any reason.
7.1.5.5
Unscheduled 
Visit(s) to confirm 
a “Flare” during 
Period 2
The timing between visits needed to confirm the “flare” was 
updated.
Current: If this ASDAS shows absolute score ≥2.1 and/or post-
withdrawal increase of ≥1.1, then the subject will be asked to 
come to the clinic, for an unscheduled visit, for an additional 
assessment for confirmation of a “flare”. This additional 
assessment should occur within ideally < 10 days (but no more 
than 3 weeks); or this assessment can occur at a previously 
scheduled clinic visit, if the timing fits within ideally <10 days 
(but no more than 3 weeks) from the first assessment.
Revised: If this ASDAS shows absolute score ≥2.1 and/or post-
withdrawal increase of ≥1.1, then the subject will be asked to 
come to the clinic, for an unscheduled visit, for an additional 
assessment for confirmation of a “flare”. This additional 
assessment should occur within ideally 2 to 10 days (but no 
more than 3 weeks); or this assessment can occur at a previously 
scheduled clinic visit, if the timing fits within ideally 2 to 10 
days (but no more than 3 weeks) from the first assessment.
To clarify the timing between 
visits needed to confirm a flare
 
 
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1.0 TRIAL SUMMARY
Abbreviated Title
Golimumab (MK-8259 / SCH 900259) in nr-axSpA: Withdrawal trial 
(GO-BACK)
Trial Phase
IV
Clinical Indication
Treatment of non-radiographic axial spondyloarthritis (nr-axSpA)
Trial Type
Interventional
Type of control
Placebo
Route of administration
Subcutaneous
Trial Blinding
Double-blind
Treatment Groups

Treatment withdrawal: Placebo every month (QM)

Golimumab every month (QM)

Golimumab every 2 months (Q2M)
Number of trial subjects
Approximately 300 subjects will be enrolled.
Estimated duration of trial
The sponsor estimates that the trial will require approximately 3.6 
years from the time the first subject signs the informed consent until 
the last subject’s last visit.
Duration of Participation
Each subject participates in the trial for up to approximately 
27 months from the time the subject signs the Informed Consent Form
(ICF) through the final contact. After a screening phase of no more 
than 2 months, each subject enters an approximately 10-month open-
label run-in period, followed by an approximately 12-month double-
blind withdrawal or continued treatment period. After the last dose of 
trial medication, each subject is followed for an additional 3 months.
Randomization Ratio
1:1:1
A list of abbreviations used in this document can be found in Section 12.5.
2.0 TRIAL DESIGN
Trial Design
2.1
This is a randomized, double-blind, parallel-group, withdrawal trial of golimumab 
(MK-8259) in subjects with nonradiographic axial spondyloarthritis (nr-axSpA) to be 
conducted in conformance with Good Clinical Practices (GCPs). In brief, subjects with active 
nr-axSpA are treated with open-label golimumab. Those subjects who attain inactive disease 
status when assessed after both 7 and 10 months on open-label therapy are then randomized 
to be either withdrawn from golimumab or continued on golimumab using either a full (every 
month [QM]) or a reduced (every 2 months [Q2M]) regimen. Randomized subjects are 
followed for approximately 12 months to characterize the incidence of a “flare” in disease 
activity. Those subjects who have a disease “flare” following randomization are then re-
treated with open-label golimumab to characterize the clinical response to re-treatment after a 
“flare”.
 
 
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To be eligible for the run-in period (i.e., to receive open-label golimumab), subjects must 
have objective signs of inflammation, defined as elevated serum C-reactive protein (CRP)
measured at the Screening visit (Visit 1), or evidence of active inflammation in the sacroiliac 
(SI) joints on magnetic resonance imaging (MRI) available at the Baseline visit (Visit 2). SI-
joint MRIs and plain conventional x-rays must undergo central reading to determine study 
eligibility. A maximum of 40% of subjects may have a normal CRP level at the initial (i.e., 
Screening) visit. 
Period 1:  Open-label Run-in (approximately 10 months duration)
After a screening period (up to 2 months [60 days]), eligible subjects enter the run-in period
to receive open-label golimumab 50 mg subcutaneous (SC) monthly, starting at Month 0.
Subjects are assessed by the investigator at study visits scheduled at Months 0, 1, 4, 7, and 
10. Additionally, during this open-label period, subjects must complete the Bath Ankylosing 
Spondylitis Disease Activity Index (BASDAI) questionnaire twice monthly. Subjects who 
achieve a clinical response by Month 4 (or earlier) continue to receive golimumab monthly 
through Period 1 (i.e., for an additional 6 months). A clinical response is defined as an
improvement in BASDAI score of ≥2 (on a numerical rating scale [NRS] from 0 to 10) or
≥50% improvement in BASDAI score when determined relative to the score at Month 0.
Subjects who have not attained a clinical response by Month 4 of treatment with open-label
golimumab are discontinued from the study at Month 4 (and will have a safety follow-up 
telephone call 3 months after their last dose of trial medication; see Section 7.1.5.2 for more 
details). At Month 7, evaluations will be performed to calculate Ankylosing Spondylitis 
Disease Activity Score (ASDAS). Subjects who attain inactive disease status (defined as 
ASDAS <1.3) continue to receive golimumab monthly through Period 1. Subjects who do 
not have inactive disease by Month 7 are discontinued from the study (and will have a safety 
follow-up telephone call 3 months after their last dose of trial medication; see Section 7.1.5.3 
for more details).
Period 2:  Double-blind Withdrawal Versus Continued Therapy (approximately 12 
months duration)
At Month 10 (Visit 23; see also Trial Flow Chart – Section 6.1), evaluations are performed to 
calculate ASDAS. Subjects who have attained inactive disease status (defined as ASDAS 
<1.3) at both Months 7 and 10 of open-label treatment are eligible to enter the double-blind 
withdrawal period (see Section 7.1.5.4 for more details); only these subjects are to be 
scheduled for the next clinic visit (Visit 24), which begins Period 2. Eligible subjects undergo 
stratified randomization in a 1:1:1 ratio to one of the following 3 treatment arms:
1) treatment-withdrawal (i.e., monthly injections of matching-placebo for golimumab),
2) golimumab QM (i.e., a full-treatment regimen, per approved labeling), or 3) golimumab
Q2M (i.e., a reduced-treatment regimen, via monthly injections that alternate between 
golimumab and matching-placebo for golimumab). Strata are defined by the presence or 
absence of elevated CRP (>6.0 mg/L vs. ≤6.0 mg/L) at the Screening visit. Eligible subjects 
receive their initial dose of blinded trial medication during Visit 24. Subjects who do not 
have inactive disease at Visit 23 do not enter Period 2; these subjects are discontinued from 
the study (and will have a safety follow-up telephone call 3 months after their last dose of 
trial medication).
 
 
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Over the course of 12 months during Period 2, subjects return to the trial site for evaluation, 
including laboratory testing, approximately every 2 months (starting from the initial dose of 
double-blind trial medication). Subjects also continue to complete the BASDAI questionnaire
twice monthly in order to rate disease activity. If there is an increase of ≥2 (on the 0 to 10 
NRS) in BASDAI score compared to Month 10 (Visit 23), the trial site calls the subject to 
initiate a full evaluation of whether a “flare” (indicative of increased disease activity) is 
occurring; assessments include information obtained over the phone and/or at an unscheduled 
visit. A “flare” is defined by ASDAS collected at 2 consecutive assessments that both show 
absolute score ≥2.1 and/or post-withdrawal increase (i.e., change from Visit 23) of ≥1.1 (see 
Section 7.1.5.5 for details on confirming a “flare”). 
If a “flare” occurs during Period 2, then subjects discontinue blinded therapy (placebo, 
golimumab QM, or golimumab Q2M) and begin re-treatment with open-label golimumab
QM. There should be an interval of at least 10 days between the last dose of Period-2 double-
blind therapy and the first dose of open-label golimumab after a “flare” is confirmed. 
Thereafter, it is expected that re-treatment with open-label golimumab continues monthly
through the end of Period 2. A clinical response to re-treatment is defined as a BASDAI 
score improvement of ≥2 or ≥50% improvement (measured relative to the mean of the 2 
BASDAI scores that were collected at the 2 consecutive assessments that defined the “flare”) 
that occurs within 3 months of restarting open-label treatment. If a subject shows insufficient 
improvement after 3 months of restarting open-label treatment for a “flare”, the investigator 
may consider discontinuing this subject from the study (based on clinical judgment) and will 
ensure a safety follow-up telephone call 3 months after the last dose of trial medication. If the 
subject is determined to have experienced a first “flare” between Months 19 and 22, the
subject then completes a course of re-treatment (i.e., 3 monthly open-label golimumab 
injections) and will have a safety follow-up telephone call 3 months after the last dose of 
open-label golimumab. Subjects who do not experience a “flare” during Period 2 are to
complete the study at Month 22 and will have a safety follow-up telephone call 3 months 
after their last dose of blinded trial medication.
Approximately 300 subjects are expected to enter Period 1. Based on the response to 
golimumab observed in the recently completed GO-AHEAD trial (P07642)
[1], 
approximately 114 subjects are expected to continue into Period 2, based on attaining 
inactive disease status (ASDAS <1.3) at both Months 7 and 10 of open-label golimumab. If 
the number of subjects who attain inactive disease is fewer than expected, additional subjects 
may need to enter Period 1 in order to randomize approximately 114 subjects with inactive 
disease status in Period 2. 
It is anticipated that most of the subjects who enter Period 2 will participate in the trial for up 
to approximately 27 months from the time the subject signs the ICF through the final contact. 
For subjects determined to have experienced a “flare” for the first time between Months 19 
and 22, the duration of participation in the trial may exceed 27 months (i.e., up to 30 months)
to allow completion of a 3-month course of re-treatment after the “flare”.
Specific procedures to be performed during the trial, as well as their prescribed times and 
associated visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each 
procedure are provided in Section 7.0 – Trial Procedures.
 
 
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Trial Diagram
2.2
The trial design is depicted in Figure 1. 
Figure 1  Trial Schematic
3.0 OBJECTIVE(S) & HYPOTHESIS(ES)
Primary Objective(s) & Hypothesis(es)
3.1
In adults with active nr-axSpA who attain inactive disease after receiving open–label 
golimumab during a 10-month run-in (Period 1):
Primary Objective: To evaluate the effect of treatment withdrawal vs continued treatment 
with golimumab (either QM or Q2M) on the incidence of a “flare” during up to 12 months of 
Period 2. 
Hypothesis: Continued treatment with golimumab is superior to treatment withdrawal, based 
on the proportion of subjects without a “flare” during up to 12 months of Period 2.
 
 
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Secondary Objective(s) & Hypothesis(es)
3.2
In subjects who withdraw from or continue treatment with golimumab during Period 2: 
(1)
Objective: To characterize the proportion of subjects with a “flare” in the treatment-
withdrawal group or the reduced-treatment group who then show a clinical response 
after retreatment with open-label golimumab.
(2)
Objective: To evaluate the time to first “flare” after withdrawal of golimumab vs
continuous treatment with golimumab (either QM or Q2M).
(3)
Objective: To evaluate the symptoms and signs of nr-axSpA (e.g., Assessment of 
SpondyloArthritis international Society [ASAS]20, ASAS40, BASDAI50, ASAS 
partial remission and ASDAS <1.3) after withdrawal of golimumab vs continuous 
treatment with golimumab (either QM or Q2M) and after re-treatment with open-
label golimumab if needed for a “flare”.
(4)
Objective: To characterize the safety and tolerability of golimumab treatment.
Exploratory Objectives
3.3
For subjects who withdraw from or continue treatment with golimumab during Period 2: 
(1)
Objective: To explore baseline demographic and disease characteristics as predictors 
of a “flare”.
(2)
Objective: To characterize the clinical response after re-treatment for a “flare”.
(3)
Objective: To characterize the clinical response as measured by patient-reported 
symptoms, C-reactive protein, and based on a global assessment of disease by the 
investigator.
(4)
Objective: To explore the relationship between genetic variation and response to the 
treatment(s) administered. Variation across the human genome may be analyzed for 
association with clinical data collected in this study.
4.0 BACKGROUND & RATIONALE
Background
4.1
Refer to the Investigator’s Brochure (IB) and approved product labeling for detailed 
background information on golimumab MK-8259.
 
 
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Pharmaceutical and Therapeutic Background
4.1.1
Golimumab is a human monoclonal antibody (mAb) that is directed against tumor necrosis 
factor alpha (TNFα) and is referred to as a TNF inhibitor. Golimumab, administered SC, is 
registered for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), ulcerative 
colitis, and nr-axSpA indications.  
The ASAS has recommended use of TNF inhibitors, following failure of 2 nonsteroidal anti-
inflammatory drugs (NSAIDs) or intolerance to such agents [2]. TNF inhibitors such as 
adalimumab, certolizumab, etanercept, and golimumab have proven to be highly effective in 
the treatment of nr-axSpA when NSAIDs have failed to provide adequate efficacy.
A recent trial has assessed golimumab as treatment for nr-axSpA. Results in the GO-AHEAD 
(P07642) trial demonstrated that golimumab is efficacious in subjects with nr-axSpA. In Part
1 of this trial, which was through 16 weeks of double-blind treatment, golimumab was shown 
to be superior to placebo, as measured by the proportions of subjects achieving ASAS20, 
ASAS40, BASDAI50, ASAS Partial Remission and by the change from baseline in SI-joint
inflammation on MRI using the SPARCC score [1]. Furthermore, golimumab provided 
substantial benefits to subjects with nr-axSpA by improving multiple aspects of range of 
motion, physical function, and health-related quality of life. In Part 2 of the GO-AHEAD 
trial, which was an open-label long-term extension through 52 weeks of treatment, 
improvements in disease activity were retained, both in the subjects who received golimumab 
in Part 1 and Part 2 and in the subjects who switched from placebo in Part 1 to golimumab in 
Part 2. The incidence of serious adverse events (SAEs) and other significant adverse events 
(AEs) was comparable between the subjects treated with golimumab and those treated with 
placebo during Part 1. No new safety signals were identified with golimumab treatment for
nr-axSpA during Part 1 or Part 2 of the trial. These results demonstrate a favorable 
benefit:risk profile for golimumab treatment in subjects with nr-axSpA.
Rationale
4.2
Rationale for the Trial and Selected Subject Population
4.2.1
The current paradigm for treatment of nr-axSpA with TNF inhibitors is to maintain treatment 
on a chronic basis. Data regarding alternate treatment paradigms with TNF inhibitors for the 
long-term management of nr-axSpA are not available. An example of an alternate treatment 
paradigm is to adjust the dosing regimen, guided by clinical symptoms and signs. The 
purpose of this trial is to evaluate the effects of golimumab treatment withdrawal, compared 
with continued golimumab treatment (either QM or Q2M), during approximately up to 12 
months. Efficacy and safety results of this trial will provide investigators and clinicians with 
important information regarding dose optimization of golimumab for treatment of nr-axSpA, 
especially for subjects who show a good response to golimumab within 4 months and then 
have inactive disease status after both 7 and 10 months of open-label treatment in Period 1.
The subject population in this trial is aligned with the population for which golimumab is 
approved for use in the European Union (EU). Namely, subjects to be enrolled must have 
active nr-axSpA with objective signs of inflammation who are either intolerant of, or have 
 
 
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demonstrated a lack of response to, NSAIDs. Subjects are adults (i.e., age ≥18 years) who are 
≤45 years of age; excluding older adults is consistent with guidance from ASAS 
classification criteria for axial spondyloarthritis (SpA).
Rationale for Dose Selection/Regimen
4.2.2
The dose and regimen of golimumab selected for open-label treatment in this study is 
consistent with its approved use:  

Golimumab 50 mg is given SC monthly. 

For subjects with a body weight more than 100 kg who do not achieve an adequate 
clinical response after up to 3 doses, increasing the dose of golimumab to 100 mg SC 
monthly may be considered (as described in Section 5.2.1.2).
Rationale for Endpoints
4.2.3
4.2.3.1
Efficacy Endpoints
Inactive disease status and a disease “flare” in this trial are defined using the ASDAS. The 
ASDAS was developed by ASAS as an index for disease activity measurement in axial SpA
that includes subjective measures (rated by the subject) and objective measure (CRP) to 
create a well-balanced index [3]. This score combines 5 disease activity variables that have 
only partial overlap, resulting in one single score with better validity, enhanced 
discriminative capacity, and improved sensitivity to change as compared with single-item 
variables. Cutoffs to identify “disease activity states” and “response criteria” using the 
ASDAS were first identified in 2011 [4]. This trial will use the cutoffs defined by ASAS: 

Level of ASDAS to identify subjects with inactive disease: ASDAS <1.3;

Level of ASDAS to identify subjects with a “flare”: ASDAS ≥2.1 (which defines high 
disease activity) and/or a change in ASDAS by ≥1.1 (which is considered a clinically 
important change).
The BASDAI score, which combines 6 questions that are self-assessed by subjects, is used to 
define a clinical response in this trial, both to open-label treatment with golimumab and to re-
treatment with open-label golimumab after a “flare”. Clinical response is defined as a 
BASDAI score improvement by ≥2 (on a 0 to 10 scale) and/or score improvement by ≥50%.
This definition of a “responder” is from the ASAS recommendations for use of TNF 
inhibitors in subjects with Axial SpA [2]. To assess the response to open-label golimumab, 
the response is compared with the BASDAI score at Month 0; to assess the response to re-
treatment, the response is compared with the mean of the 2 BASDAI scores obtained when 
the “flare” was diagnosed.
To characterize the symptoms and signs of nr-axSpA in subjects treated with golimumab or 
withdrawn from golimumab, other secondary endpoints will be assessed in this trial. These 
include ASAS20, ASAS40, BASDAI50, and ASAS Partial Remission. All of these endpoints 
have been studied in many previous studies of axial SpA. Of note, in the GO-AHEAD 
 
 
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(P07642) trial in subjects with nr-axSpA, golimumab was shown to be superior to placebo 
for each of these endpoints [1].
4.2.3.2
Safety Endpoints
The analysis of safety results will follow a tiered approach; the tiers differ with respect to the 
analyses that will be performed (as described in Section 8.6.2). Adverse events (AEs) refer to 
both clinical and laboratory AEs. The safety tiers are defined as follows:
Tier 1: Serious Infections, serious opportunistic infections, active tuberculosis, malignancies, 
and serious systemic hypersensitivity (including anaphylactic reaction) are 
prespecified as “Tier-1” events (for analysis of differences between treatments) in 
double-blind Period 2; and as “Select safety endpoints of interest” (for display as 
listings) in open-label Period 1. 
Any AEs (specific terms, as well as system organ class terms) that are not pre-specified as 
Tier-1 endpoints will be classified as belonging to "Tier 2" or "Tier 3", based on the numbers 
of events observed.
Tier 2: Treatment-emergent AEs that occur with at least 4 events in at least one treatment 
group)
Tier 3: Treatment-emergent AEs that occur with inadequate frequency to qualify as Tier-2 
AEs, predefined limits of change for laboratory test results, routine safety measures 
including vital signs. 
4.2.3.3
Planned Exploratory Biomarker Research
Understanding genetic determinants of drug response is an important endeavor during 
medical research. This research will evaluate whether genetic variation within a clinical trial 
population correlates with response to the treatment(s) under evaluation. If genetic variation 
is found to predict efficacy or AEs, the data might inform optimal use of therapies in the 
patient population. This research contributes to understanding genetic determinants of 
efficacy and safety associated with treatments in this study.
4.2.3.4
Future Biomedical Research
The Sponsor will conduct Future Biomedical Research on DNA specimens collected for 
future biomedical research during this clinical trial.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol (as part of the main trial) and will only be conducted on specimens from 
appropriately consented subjects. The objective of collecting specimens for Future 
Biomedical Research is to explore and identify biomarkers that inform the scientific 
understanding of diseases and/or their therapeutic treatments. The overarching goal is to use 
such information to develop safer, more effective drugs/vaccines, and/or to ensure that 
subjects receive the correct dose of the correct drug/vaccine at the correct time. The details of 
this Future Biomedical Research sub-trial are presented in Section 12.2 - Collection and 
Management of Specimens for Future Biomedical Research. Additional informational 
 
 
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material for institutional review boards/ethics committees (IRBs/ERCs) and investigational 
site staff is provided in Section 12.3.
Benefit/Risk
4.3
Golimumab has been shown to be effective and generally safe and well-tolerated in subjects 
for the treatment of nr-axSpA, and it is currently approved for use in this disease. The risks 
of golimumab include
serious infections (including opportunistic infections and 
tuberculosis), congestive heart failure, lymphoma (and other malignancies), infusion-related 
reactions, and other risks as detailed in the current product labeling.
In this trial, subjects who have insufficient benefit from the approved regimen of golimumab, 
after approximately 4 months of open-label treatment, are to be discontinued from the study, 
so they can seek alternative therapy. Subjects are also discontinued from the study if they 
have not attained inactive disease status after either 7 or 10 months of open-label treatment. 
Subjects who attain inactive disease after both 7 and 10 months of open-label golimumab can 
then be randomly withdrawn from treatment or continued on treatment using a full regimen 
(golimumab QM) or a reduced regimen (golimumab Q2M). All randomized subjects are 
monitored for the risk of a worsening in their disease: subjects are closely followed (using 
self-ratings of their disease, collected twice monthly) and closely observed (at clinic visits 
every 2 months). The risk of this investigational treatment paradigm is that subjects may 
experience worsening of their symptoms upon withdrawal of golimumab and may not 
respond as effectively to golimumab when it is reinitiated to treat a “flare”.
The benefits of this investigational treatment paradigm are that subjects will receive 
golimumab at the approved dose and regimen for the first 10 months of the trial and can 
reasonably expect to experience adequate control of their disease. The trial may demonstrate 
that control of symptoms is adequate following withdrawal of golimumab for a period of 
time and that continuous use (whether using a full regimen or a reduced regimen) is not 
necessary in all subjects. The benefit of this paradigm will be less exposure to golimumab 
and potentially the reduction in established risks associated with use of a TNF-inhibitor, such 
as serious infections and malignancies. 
Additional details regarding specific benefits and risks for subjects participating in this 
clinical trial may be found in the accompanying Investigators Brochure (IB) and ICF
documents.
5.0 METHODOLOGY
Entry Criteria
5.1
Diagnosis/Condition for Entry into the Trial
5.1.1
Adult subjects with active nr-AxSpA, who have objective signs of inflammation and 
intolerance or inadequate response to NSAIDs, will be enrolled in this trial.
 
 
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Subject Inclusion Criteria
5.1.2
In order to be eligible for participation in this trial, the subject must:
1. Be male or female and must be 18 to 45 years of age.
2. Be able to provide written informed consent for the trial and may also provide 
consent for Future Biomedical Research. However, the subject may participate in the 
trial without participating in Future Biomedical Research.
3. Meet one of the following categories:
a) The subject is a male who is not of reproductive potential, defined as a male who 
has azoospermia (whether due to having had a vasectomy or due to an underlying 
medical condition).  
b) The subject is a female who is not of reproductive potential, defined as a female 
who either: (1)Postmenopausal is defined as at least 12 consecutive months 
without a spontaneous menstrual period; (2) has had a hysterectomy and/or 
bilateral 
oophorectomy, 
bilateral 
salpingectomy, 
or 
bilateral 
tubal 
ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or 
acquired condition that prevents childbearing.
c) The subject is a female or a male who is of reproductive potential and agrees to 
avoid becoming pregnant or impregnating a partner while receiving trial
medication or within 6 months after the last dose of trial medication by complying 
with one of the following:  (1) practice abstinence† from heterosexual activity OR 
(2) use (or have their partner use) acceptable contraception during heterosexual 
activity.
Acceptable methods of contraception are‡:
•
intrauterine device (IUD)
•
vasectomy of a female subject’s male partner 
•
contraceptive rod implanted into the skin
•
barrier method (includes diaphragm, cervical cap, and male or female 
condom) with spermicidal gel or foam
•
hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or 
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or 
subcutaneous contraceptive injection
†Abstinence (relative to heterosexual activity) can be used as the sole method of 
contraception if it is consistently employed as the subject’s preferred and usual 
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.  
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation 
methods, etc.) and withdrawal are not acceptable methods of contraception. 
 
 
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‡If a contraceptive method listed above is restricted by local regulations/guidelines, 
then it does not qualify as an acceptable method of contraception for subjects 
participating at sites in this country/region.
4. Have chronic back pain of ≥3 months duration by history.
5. Have a physician’s diagnosis of active nr-axSpA with disease duration ≤5 years.
Note: Disease duration is defined as the length of time since onset of symptoms
6. Meet either criterion “a” or “b” as adopted from ASAS classification criteria:
a. Active inflammation on MRI highly suggestive of sacroiliitis associated with 
spondyloarthropathy and
1 or more of the following spondyloarthritis 
characteristics:

Inflammatory back pain, defined as having at least 4 out of the 5 following 
parameters:
o
age at onset <40 years;
o
insidious onset;
o
improvement with exercise;
o
no improvement with rest;
o
pain at night (with improvement upon getting up);

Arthritis diagnosed by a physician;

Enthesitis (heel) diagnosed by a physician: Spontaneous pain or tenderness at 
examination of the site of the insertion of the Achilles tendon or plantar fascia 
at the calcaneus;

Dactylitis diagnosed by a physician;

Psoriasis diagnosed by a physician;

History of inflammatory bowel disease (IBD) diagnosed by a physician;

History of uveitis confirmed by an ophthalmologist;

Good response to NSAIDs: (Good response is defined as “24-48h after a full 
dose of NSAID the back pain is not present anymore or is much better”);

Family history for SpA: Presence in first-degree (mother, father, sisters, 
brothers, children) or second-degree (maternal and paternal grandparents, 
aunts, uncles, nieces and nephews) relatives of any of the following: (1) AS; 
(2) psoriasis; (3) acute uveitis; (4) reactive arthritis; (5) IBD;

Elevated CRP (based on values obtained through a central laboratory);

Human leukocyte antigen B27 (HLA-B27)+ gene
 
 
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OR
b. HLA-B27+ gene and 2 or more of the following spondyloarthritis characteristics:

Inflammatory back pain, defined as having at least 4 out of the 5 following 
parameters:
o
age at onset <40 years;
o
insidious onset;
o
improvement with exercise;
o
no improvement with rest;
o
pain at night (with improvement upon getting up);

Arthritis diagnosed by a physician;

Enthesitis (heel) diagnosed by a physician:
Spontaneous pain or tenderness at examination of the site of the insertion of 
the Achilles tendon or plantar fascia at the calcaneus;

Dactylitis;

Psoriasis diagnosed by a physician;

History of inflammatory bowel disease (IBD) diagnosed by a physician

History of uveitis confirmed by an ophthalmologist;

Good response to NSAIDs;
Note: Good response is defined as “24-48h after a full dose of NSAID the 
back pain is not present anymore or is much better”

Family history for SpA:
Presence in first-degree (mother, father, sisters, brothers, children) or second-
degree (maternal and paternal grandparents, aunts, uncles, nieces and 
nephews) relatives of any of the following: (1) AS; (2) psoriasis; (3) acute 
uveitis; (4) reactive arthritis; (5) IBD;

Elevated CRP (based on values obtained through a central laboratory).
7. Have elevated CRP at the Screening visit or evidence of active inflammation in the SI 
joints on MRI.
Note: Elevated CRP is defined as a value that is >6.0 mg/L; a maximum of 40% of 
enrolled subjects may have normal CRP at the Screening visit. All MRIs must 
undergo central reading to determine study eligibility.
8. Have ASDAS ≥2.1 at the Screening visit.
9. Show high disease activity at Screening and Baseline of both a Total Back Pain score
of ≥4 and a BASDAI score of ≥4 (each on a NRS of 0 to 10).
 
 
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10. Have an acceptable history of use of NSAIDs: either an inadequate response, as 
assessed by the investigator, with maximal recommended daily doses of at least 2
NSAIDs; or must be unable to receive maximal NSAID therapy because of 
intolerance, toxicity, or contraindications to NSAIDs. (Note: It is possible that a 
subject had a good response initially to NSAIDs but subsequently had inadequate 
response or developed intolerance to NSAIDs therapy).
11. Have acceptable current use of NSAIDs at Screening:

If currently using an NSAID, must be on a stable daily dose for at least 14 days 
prior to Screening
Note: Such use of NSAIDs is allowed and will be monitored during the study.

If not currently using an NSAID, short-term use is allowed (up to 1 week) during 
Period 1 and is allowed as needed during Period 2.
Note: Such use of NSAIDs will be monitored during the study.
12. Tuberculosis Assessment (see also Section 7.1.3.3):
a.
Have no history of untreated latent or active tuberculosis (TB) prior to screening.  
An exception is made for subjects who have a history of latent TB and are 
currently receiving treatment for latent TB, will initiate treatment for latent TB 
prior to first administration of study agent, or have documentation of having 
completed appropriate treatment for latent TB within 5 years prior to the first dose 
of administration of study agent. It is the responsibility of the investigator to 
verify the adequacy of previous anti-tuberculous treatment and provide 
appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination.
c.
Have had no recent close contact with a person with active TB or, if there has 
been such contact, will be referred to a physician specializing in TB to undergo 
additional evaluations and receive appropriate treatment for latent TB prior to the 
first administration of study agent.
 
 
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d. Within 6 weeks prior to the first administration of study agent, have a negative 
QuantiFERON®-TB Gold test result, or have a newly identified positive 
QuantiFERON®-TB Gold test result in which active TB has been ruled out and 
for which appropriate treatment for latent TB has been initiated prior to the first 
administration of study agent. Within 6 weeks prior to the first administration of 
study agent, a negative tuberculin skin test, or a newly identified positive 
tuberculin skin test in which active TB has been ruled out and for which 
appropriate treatment for latent TB has been initiated prior to the first 
administration of study agent, is additionally required if the QuantiFERON®-TB 
Gold test is not approved/registered in that country or the tuberculin skin test is 
mandated by local health authorities.

If, based on the investigator’s judgment of a subject’s high risk of latent TB 
infection, the QuantiFERON®-TB Gold test and the tuberculin skin test are 
both performed, and if either is positive, and if active TB has been ruled out, 
then appropriate treatment for latent TB must be initiated prior to the first 
administration of study agent.

Subjects with persistently indeterminate QuantiFERON®-TB Gold test 
results may be enrolled without treatment for latent TB, if active TB is ruled 
out, their chest radiograph shows no abnormality suggestive of TB (active or 
old, inactive TB), and the subject has no additional risk factors for TB as 
determined by the investigator. This determination must be promptly 
reported to the sponsor’s medical monitor and recorded in the subject's 
source documents and initialed by the investigator.

The QuantiFERON®-TB Gold test and the tuberculin skin test are not
required at screening for subjects with a history of latent TB and ongoing 
treatment for latent TB or documentation of having completed adequate
treatment as described above; subjects with documentation of having 
completed adequate treatment as described above are not required to initiate 
additional treatment for latent TB.
e.
Have a chest radiograph (both posterior-anterior and lateral views) within 
3 months prior to the first administration of study agent and read by a qualified 
radiologist, with no evidence of current, active TB or old, inactive TB.
13. Be judged to be medically stable, other than nr-axSpA, based on medical history, 
physical examination, and routine laboratory tests.
 
 
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14. Undergo screening for hepatitis B virus (HBV), which at a minimum includes testing 
for HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), and HBV core 
antibody (anti-HBc total), and demonstrate to be eligible based on the following 
results:
Action
Hepatitis B Surface 
Antigen(HBsAg)
Hepatitis B Surface 
Antibody(anti-HBs)
Hepatitis B Core 
Antibody(anti-HBc Total)
Exclude
+
–  or +
– or +
Include
–
+
+
Include
–
+
–
Include
–
–
–
Require Hepatitis B viral 
DNA (HBV DNA) 
testing*
–
–
+
*
If HBV DNA is detectable or there is evidence of chronic liver disease, exclude from clinical trial. 
If the HBV DNA test is negative, the subject is eligible for this trial.  In the event the HBV DNA 
test cannot be performed, the subject is not eligible for this trial.
Subject Exclusion Criteria
5.1.3
The subject must be excluded from participating in the trial if the subject:
1. Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on 
conventional x-rays (to exclude subjects who meet modified New York criteria for AS).
Note: SI-joint x-rays must undergo central reading to determine study eligibility.  
Subjects who have a SI joint x-ray performed within 6 months prior to Screening do not 
need to have a SI joint x-ray repeated at Screening.
2. If female, is nursing, pregnant, or intending to become pregnant within 6 months after 
receiving the last administration of trial medication.
3. Intends to donate eggs (female subjects) or sperm (male subjects) while receiving trial
medication or within 6 months after the last dose of trial medication.
4. Has any clinically significant condition or situation, other than those listed as exclusion 
criteria that, in the opinion of the investigator, would interfere with the trial evaluations 
or participation in the trial.
5. Has ever received any cytotoxic drugs, including but not limited to chlorambucil, 
cyclophosphamide, nitrogen mustard, or other alkylating agents.
 
 
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6. Has received any treatment listed in the table below more recently than the indicated off-
drug period prior to Screening.
Medications, Supplements, and Other Substances that are Prohibited for Trial Entry
Prohibited Medications, Supplements, and Other Substances
Off-Drug Period 
Prior to Screening
Disease modifying anti-rheumatic drugs such as but not limited to:
Methotrexate
Sulfasalazine
Leflunomide
Hydroxychloroquine
Steroids (oral, parenteral, intra-articular)
Cyclosporine (Note:  ophthalmic use is allowed)
Mycophenolate mofetil
Azathioprine.
30 days
(8 weeks for leflunomide 
unless subject undergoes 
standard cholestyramine or 
activated charcoal washout)
Live vaccinations
3 months
Investigational medications
30 days or 5 half lives
(whichever is longer)
Bacille Calmette-Guerin (BCG) vaccination
12 months
7. Has ever received TNF-α targeted therapy or any other biological agents intended to treat 
immune-mediated diseases, including but not limited to infliximab, etanercept, 
adalimumab, certolizumab, golimumab, alefacept, efalizumab, rituximab, natalizumab, 
secukinumab, ixekizumab, ustekinumab, or vedolizumab.
8. Has an allergy/sensitivity to golimumab or its excipients.
9. Has any systemic inflammatory condition from Screening up to Baseline with signs and 
symptoms including, but not limited to:
a.
psoriatic arthritis,
b. active Lyme disease,
c.
systemic lupus erythematosus,
d. infectious arthritis,
e.
vasculitis,
f.
parvovirus infection,
g. rheumatoid arthritis,
h. active uveitis,
i.
active IBD.
10. Has a history of latent or active granulomatous infection, including histoplasmosis, or 
coccidioidomycosis, prior to Screening.
11. Had a nontuberculous mycobacterial infection or opportunistic infection (e.g., 
cytomegalovirus, Pneumocystis jirovecii [carinii], aspergillus) within 6 months prior to 
Screening.
12. Has a history of an infected joint prosthesis, or has received antibiotics for a suspected 
infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
 
 
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13. Had a serious infection (including but not limited to, hepatitis, pneumonia, sepsis, or 
pyelonephritis), or has been hospitalized for an infection, or has been treated with IV 
antibiotics for an infection within 2 months prior to Baseline. Less serious infections (eg, 
acute upper respiratory tract infection, simple urinary tract infection) need not be 
considered exclusionary at the discretion of the investigator.
14. Had a history of, or ongoing, chronic or recurrent infectious disease, including but not 
limited to, chronic renal infection, chronic chest infection (e.g., bronchiectasis), sinusitis, 
recurrent urinary tract infection (e.g., recurrent pyelonephritis, chronic nonremitting 
cystitis), an open, draining, or infected skin wound, or an ulcer.
15. Is known to be infected with human immunodeficiency virus (HIV) or seropositive for 
hepatitis C virus (HCV).
Note: Subject infected with HCV is eligible if there are 2 negative HCV RNA test results 
6 months apart prior to Screening and there is a third negative HCV RNA test result at 
Screening.
16. Has a chest x-ray within 2 months prior to Screening that shows an abnormality 
suggestive of a current active infection or malignancy.
17. Has a history of lymphoproliferative disease, including lymphoma, or signs suggestive of 
possible lymphoproliferative disease such as lymphadenopathy of unusual size or 
location and/or clinically significant splenomegaly, or monoclonal gammopathy of 
undetermined significance.
18. Has had a malignancy within 5 years before screening (exceptions are squamous and 
basal cell carcinomas of the skin that have been treated, with no evidence of recurrence 
for at least 3 months prior to Baseline; and carcinoma in situ of cervix that has been 
surgically cured).
19. Has a history of known demyelinating diseases such as multiple sclerosis or optic 
neuritis.
20. Has a history of or concurrent congestive heart failure ([CHF] of any grade [I-IV]), 
including medically controlled, asymptomatic CHF.
21. Has a transplanted organ (with the exception of a corneal transplant performed ≥3 months 
prior to baseline).
22. Has current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, 
cardiovascular, metabolic, ophthalmological, respiratory, hematologic, gastrointestinal, 
endocrine, pulmonary, neurologic, psychiatric, cerebral, or other significant medical 
illness or disorder that, in the judgment of the investigator, could interfere with the trial, 
or require treatment that might interfere with the trial. Other conditions that are well 
controlled and stable will not prohibit participation if deemed appropriate per the 
investigator's judgment. The Sponsor's medical monitor should be consulted if there are 
any questions regarding a specific medical condition.
23. Is a user of recreational or illicit drugs or has or had a substance abuse (drug or alcohol) 
problem within the previous 2 years.
 
 
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24. Has participated in any other interventional clinical trial within 30 days, inclusive, of 
signing the informed consent form of the current trial.
25. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or 
child) who is investigational site or sponsor staff directly involved with this trial.
Trial Treatment(s)
5.2
The treatments to be used in this trial are outlined below in Table 1.
Table 1  Trial Treatment
Biologic
Dose/Potency
Dose 
Frequency
Route of 
Administration
Regimen
(Treatment Period)
Use
Golimumab
Per 
approved 
label: 50 mg 
(or 100 mg)†
Every 
month
(QM)
Subcutaneous
(SC)
Open-label 
from 
Month 0 to Month 9
(Period 1); switch to 
open-label golimumab 
upon “flare” (Period 
2)
Standard 
of 
Care
Golimumab
(full-treatment 
regimen)
Per 
approved 
label:
50 mg
(or 100 mg)†
Every 
month
(QM)
Subcutaneous
(SC)
Double-blind monthly 
injections of active 
golimumab 
for 
12 
months
(or 
until
“flare”)
Experimental
Golimumab
(reduced-
treatment 
regimen)
50 
mg 
(or 100 mg)†
Every 
2 
months 
(Q2M)
Subcutaneous
(SC)
Double-blind monthly 
injections of active 
golimumab, 
alternating 
with 
placebo 
for 
golimumab,
for 
12 
months 
(or 
until 
“flare”)
Experimental
Matching 
placebo 
for 
golimumab 
Every 
month 
(QM)
Subcutaneous
(SC)
Double-blind monthly 
injections of placebo 
for golimumab for 12 
months 
(or 
until 
“flare”)
Experimental
† For subjects with body weight more than 100 kg, increasing the dose of golimumab to 100 mg may be 
considered during the Open-label Period 1 (and would continue during Period 2, depending on the 
randomization schedule).
The frequency of SC injections is monthly during the entire trial. After an initial dose has 
been given, administration then continues preferably on the same day of every month 
(consistent with approved labeling) with an allowed window of ±5 days. As the trial 
progresses, the day of the month that is targeted for dosing can be re-set, if needed (see 
Section 7.1.1.10). Depending on the period of the trial (open-label Period 1 or double-blind 
Period 2) and on the randomization schedule for treatment withdrawal or continued treatment 
(during Period 2), an individual injection may contain active golimumab or a matching 
placebo. 
 
 
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The first dose of golimumab 50 mg SC is administered at the study center by site personnel
on the day of enrollment at Visit 2 (considered “Month 0”). If allowed by local guidelines 
and after proper training in injection technique, subjects may self-inject if determined by 
their physician that it is appropriate and with medical follow-up as necessary. For subjects 
with a body weight of more than 100 kg, increasing the dose of golimumab to 100 mg SC 
may be considered; see Section 5.2.1.2.
Open-label golimumab is administered monthly during Period 1. After 10 months on 
open-label therapy, eligible subjects will be randomized, in a double-blind manner, to 1 of 3 
treatment arms to
receive
either
matching-placebo for golimumab (i.e., treatment 
withdrawal), continued treatment with golimumab every month (as a full-treatment regimen), 
or continued treatment with golimumab every 2 months (as a reduced-treatment regimen), 
via monthly injections that alternate between golimumab and matching placebo. If a “flare”
is confirmed, subjects are treated with open-label golimumab monthly until Month 22 (end of 
Period 2). There should be an interval of at least 10 days between the last dose of Period-2 
assigned double-blind therapy and starting open-label golimumab.
All supplies indicated in Table 1 above will be provided centrally by the Sponsor or locally 
by the trial site, subsidiary or designee, depending on local country operational or regulatory 
requirements.
For any commercially available product that is provided by the trial site, subsidiary or 
designee every attempt will be made to source these supplies from a single lot/batch number. 
The trial site will be responsible for recording the lot number, manufacturer and expiry date 
of any locally purchased product.
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of trial 
treatments in accordance with the protocol and any applicable laws and regulations.
Dose Selection
5.2.1
5.2.1.1
Dose Selection (Preparation)
The rationale for selection of doses to be used in this trial is provided in Section 4.0 –
Background & Rationale.  There are no specific calculations or evaluations required to be 
performed in order to administer the proper dose to each subject.
5.2.1.2
Dose Modification (Escalation)
For subjects with body weight more than 100 kg who, based on the investigator’s clinical 
judgment, do not achieve an adequate clinical response after up to 3 doses, increasing the 
dose of golimumab to 100 mg SC may be considered. This may require an unscheduled visit 
at Month 2 or Month 3, to enable a clinical evaluation by the investigator at that time for the 
decision to increase the dose to 100 mg SC. No other dose modifications for escalation are 
permitted during the trial. If a decision is made to increase to 100 mg (which requires 2 
injections of 50 mg) for a given subject in Period 1, then administration of 2 injections at the 
time of each dose administration is also expected to continue for this subject through Period 
2. 
 
 
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Timing of Dose Administration
5.2.2
There are no specific instructions for the time of day for dosing. General considerations 
regarding the monthly schedule for dosing are described in Section 5.2.  
Trial Blinding/Masking
5.2.3
A double-blind/masking technique will be used during Period 2. Golimumab (MK-8259) and 
placebo will be packaged identically so that blind/masking is maintained. The subject, the 
investigator, and Sponsor personnel or delegate(s) who are involved in the treatment or clinical 
evaluation of the subjects are unaware of the group assignments.
During Period 2, subjects assigned to receive golimumab Q2M will receive monthly injections 
that alternate between golimumab and matching placebo.
Randomization or Treatment Allocation
5.3
Period 1: Subjects in Period 1 are assigned an allocation number using an interactive voice 
response system / integrated web response system (IVRS/IWRS) and will receive 
open-label golimumab by non-random assignment.
Period 2: Random assignment of eligible subjects to double-blind treatment occurs centrally 
using an IVRS/IWRS. Only subjects who qualify for Period 2 are to be randomly 
assigned to 1 of the 3 treatment arms in 1:1:1 ratio: treatment withdrawal (i.e., 
placebo QM), golimumab QM, or golimumab Q2M.
The allocation number assigned for Period 1 is maintained during Period 2.
Stratification
5.4
The following entry criterion is used as the stratification factor for randomization in Period 2:

CRP category at Screening (>6.0 mg/L or ≤6.0 mg/L, as reported by the central 
laboratory).
Concomitant Medications/Vaccinations (Allowed & Prohibited)
5.5
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing trial.  If there is a clinical indication for any medication or vaccination
specifically prohibited during the trial, discontinuation from trial therapy or vaccination may 
be required.  The investigator should discuss any questions regarding this with the Sponsor
Clinical Director.  The final decision on any supportive therapy or vaccination rests with the 
investigator and/or the subject's primary physician.  However, the decision to continue the 
subject on trial therapy or vaccination schedule requires the mutual agreement of the 
investigator, the Sponsor and the subject.
 
 
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Prohibited Medications
The following therapies are prohibited during the course of the trial:

Disease modifying anti-rheumatic drugs such as but not limited to:
o
Methotrexate 
o
Sulfasalazine
o
Leflunomide
o
Hydroxychloroquine 
o
Steroids (oral, parenteral)
o
Cyclosporine (Note:  ophthalmic use is allowed)
o
Mycophenolate mofetil
o
Azathioprine

Live vaccinations

Investigational medications

Drugs of abuse/recreational use of drug

Bacille Calmette-Guerin (BCG) vaccination

TNF-α targeted therapy or any biological agents used for treatment of immune-
mediated diseases, including but not limited to infliximab, etanercept, adalimumab, 
certolizumab, alefacept or efalizumab, rituximab,
natalizumab,
secukinumab, 
ixekizumab, ustekinumab, or vedolizumab.
Allowed Medications
The following are specific instructions regarding concomitant NSAID use during the course 
of the trial:

If the subject is a NSAID user at the time of screening, the use of NSAIDs is allowed 
to continue during the study (Period 1 and Period 2).

If the subject is not a NSAID user at the time of screening, short-term use (up to a 
week) is allowed during Period 1, then NSAID use is allowed as needed during 
Period 2.
All use of NSAIDs will be monitored, and the data will be collected in the database.
Rescue Medications & Supportive Care
5.6
No rescue or supportive medications are specified to be used in this trial.
Diet/Activity/Other Considerations
5.7
There are no diet restrictions. Subjects should maintain a normal diet and activity level.
The subject will receive a paper comment card to assist in capturing information regarding 
AEs and use of concomitant medication between visits.
 
 
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Subject Withdrawal/Discontinuation Criteria
5.8
Subjects may withdraw consent at any time for any reason or be dropped from the trial at the 
discretion of the investigator should any untoward effect occur.  In addition, a subject may be 
withdrawn by the investigator or the Sponsor if enrollment into the trial is inappropriate, the 
trial plan is violated, or for administrative and/or other safety reasons.  Specific details 
regarding discontinuation or withdrawal procedures; including specific details regarding 
withdrawal from Future Biomedical Research, are provided in Section 7.1.4 – Other 
Procedures.
Discontinuation from treatment is “permanent”.  Once a subject is discontinued, he/she shall 
not be allowed to restart treatment.
A subject must be discontinued from the trial for any of the following reasons:
●
The subject or legal representative (such as a parent or legal guardian) withdraws 
consent.
A subject must be discontinued from treatment and followed for approximately 3 months
after the last dose of trial medication for any of the following reasons:

Subject initiates medications prohibited during this trial that will alter evaluation of 
safety or efficacy.  The Sponsor's trial physician should be consulted if there are any 
questions regarding a specific medication.

Investigator or Sponsor’s trial physician deems treatment discontinuation is in the 
subject’s best interest.

Subject does not attain clinical response (based on BASDAI) by end of Month 4.

Subject does not attain inactive disease status (ASDAS <1.3) by end of Month 7 or by 
end of Month 10.
A subject must be discontinued from treatment (but may continue to be monitored in the 
trial) for any of the following reasons:

Subject becomes pregnant. 

Subject develops reaction resulting in bronchospasm with wheezing and/or dyspnea 
requiring ventilatory support, or symptomatic hypotension with a ≥40mm Hg 
decrease in systolic blood pressure that occurs following a trial medication injection.

Subject develops reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of trial 
medication. These may be accompanied by other events including pruritus; facial, 
hand, or lip edema; dysphagia; urticaria; sore throat; and/or headache.

Subject develops severe opportunistic infection.

Subject develops malignancy, excluding nonmelanoma skin cancer.

Subject develops congestive heart failure.

Subject develops demyelinating disease.
 
 
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
Subject develops active TB.
Subject Replacement Strategy
5.9
A subject who discontinues from the trial will not be replaced.
Beginning and End of the Trial
5.10
The overall trial begins when the first subject signs the informed consent form.  The overall 
trial ends when the last subject completes the last study-related phone-call or visit,
discontinues from the trial or is lost to follow-up (i.e. the subject is unable to be contacted by 
the investigator).
Clinical Criteria for Early Trial Termination
5.11
There are no pre-specified criteria for terminating the trial early.
 
 
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6.0 TRIAL FLOW CHART
Period 1: Open-Label Run-in
6.1
Trial Period:
Screening
Period 1: Open-Label Run-in
Visit Number/ Title:
1/
Scree
ning
2/
Enroll
ment
3/
RCa
4
5-9/
RCa
10
11-15/ 
RCa
16
17
18-22/ 
RCa
23 or 
DC
Safety 
F/Ub TC
Scheduled Month:
-2
0
0.5
1
1.5; 2; 
2.5; 3; 
3.5
4c
4.5; 5; 
5.5; 6; 
6.5
7d
7
7.5; 8; 
8.5; 9; 
9.5
10e
12
Scheduling Window Days:
± 7 days for clinic visit; ± 3 days for remote completion of BASDAI
Screening/Administrative
Informed Consent
X
Informed Consent For Future Biomedical 
Research
X
Demographic
X
Inclusion/Exclusion Criteria
X
X
Medical History
X
Prior and Concomitant Therapy Review
X
X
X
X
X
X
X
Subject Identification Cardf
X
Contact IVRS/IWRSg
X
X
X
X
X
X
Trial Medication Accountability
X
X
X
X
X
Dispense Trial Medication for Monthly
Self-administration at Homeh
X
X
X
Issue/Review Trial Medication Injection Log
X
X
X
X
Issue/Review Comments Card
X
X
X
X
X
X
Clinical Procedures/ Assessments
Physical Examinationi
X
X
X
X
X
X
Vital Signs (BP, Temp, HR)j
X
X
X
Chest x-rayk
X
X-rays of SI Jointsl
X
MRI of SI Jointsm
X
 
 
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Protocol/Amendment No.: 038-01 
MK-8259-038-01 Final Protocol
21-Mar-2017
Confidential
Trial Period:
Screening
Period 1: Open-Label Run-in
Visit Number/ Title:
1/
Scree
ning
2/
Enroll
ment
3/
RCa
4
5-9/
RCa
10
11-15/ 
RCa
16
17
18-22/ 
RCa
23 or 
DC
Safety 
F/Ub TC
Scheduled Month:
-2
0
0.5
1
1.5; 2; 
2.5; 3; 
3.5
4c
4.5; 5; 
5.5; 6; 
6.5
7d
7
7.5; 8; 
8.5; 9; 
9.5
10e
12
Scheduling Window Days:
± 7 days for clinic visit; ± 3 days for remote completion of BASDAI
BASDAIn
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
Patient Global Disease Assessment (PGDN)
X
X
X
X
X
X
Total Back Painn (TBP)
X
X
X
X
X
X
Global Assessment of Disease by Investigator 
(GADI)
X
X
Assess Eligibility to Continue in Period 1c,d
X
X
Assess Eligibility for Period 2e
X
Adverse Events
X
X
X
X
X
X
Administer Trial Medication in Clinic
X
X
Clinical Laboratory Assessments
Routine Laboratory (Hematology, Chemistry)
X
X
X
C-reactive Protein (CRP)
X
X
X
X
Serum Pregnancy Testo
X
X
Urine Pregnancy Test
X
X
X
X
QuantiFERON®-TB Gold test 
(tuberculin skin test also, only if needed)p
X
HLA-B27 Gene Statusq
X
HBV/HCV Screening
X
Sample for PKr
X
X
X
X
X
Serum Sample for Analysis of Antibodies to 
GLM, and Neutralizing Antibodyr,s
X
X
X
X
X
Blood for Genetic Analysist
X
 
 
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Protocol/Amendment No.: 038-01 
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21-Mar-2017
Confidential
AE=adverse event; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BP=Blood Pressure; 
CRP=C-reactive protein; DC=discontinuation; DNA= Deoxyribonucleic Acid; FBR=future biomedical research; F/U=Follow Up; GLM=golimumab; HBV=hepatitis-B virus; 
HLA-B27=Human Leukocyte Antigen B27; HR=Heart Rate; IVRS=interactive voice response system; IWRS=interactive web response system; MRI=magnetic resonance 
imaging; PK=Pharmacokinetic; RC=remote completion; SI joint=sacroiliac joint; TB=Tuberculosis; TC=telephone call. 
a. Remote completion (e.g., at home) of the BASDAI questionnaire by subjects, twice monthly, using an electronic device.
b. The telephone call for safety follow-up is made approximately 3 months after the last dose of trial medication.
c. At Month 4 (Visit 10), subjects are assessed for Clinical Response (BASDAI improvement ≥2 or ≥50% since start of re-treatment). Subjects who do not attain Clinical 
Response are to be discontinued from the study. All procedures outlined for the DC visit are to be performed.
d. At Month 7 (Visit 16), subjects are assessed for Inactive Disease status (defined as ASDAS <1.3). Subjects who do not attain Inactive Disease status are discontinued; these 
subjects are to be scheduled for the DC visit to perform procedures (vital signs, Physician Global Disease Assessment, routine laboratory blood draw, and pregnancy test if 
required) that were not done at the Month 7 visit (Visit 16) but are required per DC visit. Subjects who attain inactive disease status (i.e., ASDAS <1.3) at Visit 16 will be 
scheduled for Visit 17 (within 2-7 days) to continue to receive open-label golimumab for self-administration at home in Period 1.
e. At Month 10 (Visit 23), subjects complete Period 1 and are assessed for Period 2. Subjects who attain Inactive Disease (defined as ASDAS <1.3) status enter Period 2.
Subjects who do not attain Inactive Disease status are discontinued, and all procedures outlined for the DC visit are to be performed. Subjects who attain inactive disease 
status (i.e., ASDAS <1.3) at Visit 23 will be scheduled for Visit 24 (within 2-7 days) to enter in Period 2 and to receive double-blind treatment.
f. Also contains contact information for the emergency unblinding call center so that a health care provider can obtain information about trial medication in emergency 
situations when the investigator is not available.
g. Sites to call IVRS to register the subject at V1; to assign allocation number at V2; to assign trial medications from V2 to V23; to update subject disposition at DC visit.
h. After proper training, subjects may self-inject trial medication monthly ± 5 days, if their physician determines it is appropriate and with medical follow-up as necessary.
i. The first physical exam (PE) (performed at Screening) will be a complete PE, including a full skin examination and excluding genital and urinary.  Subsequent PEs would 
include a full skin assessment and would be directed to evaluate signs and symptoms of potential AEs.
j. Height (with the shoes removed) and weight (in street clothing with jacket/coat and shoes removed) should be collected at the screening visit only. 
k. Subjects who have chest x-ray performed within 3 months prior to Screening with no clinically significant findings do not need to have chest x-ray repeated at Screening
l. For subjects who have a SI joint x-ray performed within 6 months prior to Screening, the site can send the x-ray for central reading. If these x-rays are evaluable by central 
reading, then these subjects do not need to have a SI joint x-ray repeated at Screening
m. Screening MRI should be performed for subjects only if the CRP value is normal and subject is otherwise deemed to be eligible for the study. For subjects who have MRI 
performed within 6 months prior to Screening, the site can send MRI films for central reading. If these films are evaluable by central reading, then these subjects with clinical 
evidence of inflammation do not need to have a MRI repeated at Screening.
n. Each subject must show high disease activity at Screening and Baseline as measured by Total Back Pain score ≥4 and a BASDAI score ≥4 on 0 to 10 NRS.
o. If local law requires more frequent pregnancy testing, the site will perform the assessments as per local requirement.
p. The tuberculin skin test is additionally required if the QuantiFERON®-TB Gold test is not approved/registered in the country participating in the trial or the tuberculin skin 
test is mandated by local health authorities. If, based on the investigator’s judgment, the subject is at high risk of latent TB infection, the QuantiFERON®-TB Gold test and 
the tuberculin skin test may both be performed.
q. HLA-B27 status only has to be assessed at Screening, and if previously documented, it is not necessary to assess again for this trial.
r. At all visits, samples MUST be collected BEFORE the administration of trial medication. 
s. The same sample will be used for detection of antibodies to golimumab and neutralizing antibody analysis.
t. This sample should be drawn for planned analysis of the association between genetic variants in DNA and drug response. If there is either a documented law or regulation 
prohibiting collection, or if the IRB/IEC does not approve the collection of the sample for these purposes, then this sample will not be collected. If the sample is collected, 
leftover extracted DNA will be stored for future biomedical research if the subject signs the FBR consent. If the planned genetic analysis is not approved, but the FBR is 
approved and consent is given, this sample will be collected for the purpose of FBR.
 
 
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21-Mar-2017
Confidential
Period 2: Double-blind Withdrawal
6.2
Trial Period:
Period 2: Double-blind Withdrawal
Visit Number/ Title:
24a
25-
27/
RCb
28
29-
31/
RCb
32
33-
35/
RCb
36
37-
39/
RCb
40
41-
43/
RCb
44
45-
47/
RCb
48/ 
DCc
Uns
TCd
Unse,f
Safety 
F/Ug
TC
Scheduled Month:
10
10.5; 
11; 
11.5
12
12.5; 
13; 
13.5
14
14.5; 
15; 
15.5
16
16.5; 
17; 
17.5
18
18.5; 
19; 
19.5
20
20.5; 
21; 
21.5
22
25
Scheduling Window Days:
± 7 days for clinic visit; ±  3 days for remote completion of BASDAI
Administrative
Concomitant Therapy
X
X
X
X
X
X
X
Contact IVRS/IWRSh
X
X
X
X
X
X
X
X
Trial Medication Accountability
X
X
X
X
X
X
Dispense Trial Medication 
for Self-administration at Homei
X
X
X
X
X
X
Issue/Review Comments Card
X
X
X
X
X
X
X
Issue/Review Trial Medication Log
X
X
X
X
X
X
X
Clinical Procedures/Assessments
Physical Examinationj
X
X
X
X
X
X
Vital Signs (BP, Temp, HR)
X
BASDAI
X
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
Patient Global Disease Assessment 
(PGDN)
X
X
X
X
X
X
X
X
Total Back Pain (TBP)
X
X
X
X
X
X
X
Global Assessment of Disease by 
Investigator (GADI)
X
X
Adverse Events
X
X
X
X
X
X
X
Administer Trial Medication in Clinic
X
X
X
X
X
X
X
X
Clinical Laboratory Assessments
Serum Pregnancy Testk
X
Urine Pregnancy Test
X
X
X
X
X
Routine Laboratory (Hematology, 
Chemistry) Testing
X
X
C-reactive Protein (CRP)
X
X
X
X
X
X
X
Sample for PKl
X
X
X
X
X
X
Serum Sample for Analysis of 
Antibodies to GLM, and Neutralizing 
Antibodyl,,m
X
X
X
 
 
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Product:  MK-8259 (SCH 900259)
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Protocol/Amendment No.: 038-01 
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21-Mar-2017
Confidential
AE = adverse event; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index; BP = Blood pressure; CRP = C-
reactive protein; DC=discontinuation; F/U=Follow up; GLM = golimumab; HR = Heart Rate; IVRS = interactive voice-response system; IWRS = interactive web-response 
system; PK = Pharmacokinetic; RC=remote completion; TC= Telephone call; Uns= Unscheduled. 
a. Subjects who attain Inactive Disease Status (i.e., ASDAS <1.3) at Visit 23 will be scheduled for Visit 24 so that they can be randomized in Period 2 and receive the first dose of 
Period 2 double-blind trial medication.
b. Remote completion of the BASDAI questionnaire by subjects, twice monthly, using an electronic device.
c. If the subject discontinued from the trial during Period 2, trial medication will not be administered at the DC clinic visit.
d. If subjects report an increase of ≥2 BASDAI score compared with Month 10 (Visit 23), site is to call subject to obtain Patient Global Disease Assessment, and then use the CRP 
value from the previous clinic visit to calculate ASDAS. See Section 7.1.5.4 for more details.
e. If “flare” (defined as ASDAS absolute score ≥2.1 and/or post-withdrawal increase (i.e., change from Visit 23) of ≥1.1 at 2 consecutive visits) is confirmed during a “flare 
confirmation” visit (based on the BASDAI and PGDN obtained at that visit), subject will begin re-treatment with open-label golimumab for the confirmed “flare” at that visit. 
Clinic visits are then to be scheduled every 2 months from the date of the initial re-treatment with open-label golimumab
f. If “flare” is confirmed after a “flare confirmation” visit (based on the CRP result as eventually received from that visit), then the subject is asked to return to the clinic to begin 
re-treatment with open-label golimumab for the “flare”. Clinic visits are then to be scheduled every 2 months from the initial re-treatment with open-label golimumab.
g. The safety follow-up phone call is made approximately 3 months after the last dose of trial medication.
h. When it is confirmed at Visit 23 that a subject is eligible for Period 2, site to call IVRS/IWRS to randomize the subject into Period 2 (Double-blind) prior to administering the 
trial medication; assign trial medication at all clinic visits; update the subject status at V48/DC visit.
i. During Period 2, site personnel will administer the trial medication (± 5 days) during clinic visits. If subjects are self-injecting, the monthly dose to be administered (± 5 days) 
between clinic visits will be dispensed for subjects to self-inject at home.
j. PEs would include a full skin assessment and would be directed to evaluate signs and symptoms of potential AEs assessment.
k. If local law requires more frequent pregnancy testing, the site will perform the assessments as per local requirement
l. At all visits, samples MUST be collected BEFORE the administration of trial medication.
m. The same sample will be used for detection of antibodies to golimumab and neutralizing antibody analysis. 
 
 
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21-Mar-2017
Confidential
7.0 TRIAL PROCEDURES
Trial Procedures
7.1
The Trial Flow Chart - Section 6.0 summarizes the trial procedures to be performed at each 
visit.  Individual trial procedures are described in detail below.  It may be necessary to 
perform these procedures at unscheduled time points if deemed clinically necessary by the 
investigator.
Furthermore, additional evaluations/testing may be deemed necessary by the investigator and 
or the Sponsor for reasons related to subject safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (e.g., HIV, Hepatitis C, etc.), and thus local regulations 
may require that additional informed consent be obtained from the subject.  In these cases, 
such evaluations/testing will be performed in accordance with those regulations.
Administrative Procedures
7.1.1
7.1.1.1
Informed Consent
The investigator or qualified designee must obtain documented consent from each potential 
subject or each subject’s legally acceptable representative prior to participating in a clinical 
trial or Future Biomedical Research.
7.1.1.1.1 General Informed Consent
Consent must be documented by the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature on a consent form along with the dated signature 
of the person conducting the consent discussion. 
A copy of the signed and dated consent form should be given to the subject before 
participation in the trial.
The initial informed consent form, any subsequent revised written informed consent form 
and any written information provided to the subject must receive the IRB/ERC’s 
approval/favorable opinion in advance of use.  The subject or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes available 
that may be relevant to the subject’s willingness to continue participation in the trial.  The 
communication of this information will be provided and documented via a revised consent 
form or addendum to the original consent form that captures the subject’s dated signature or 
by the subject’s legally acceptable representative’s dated signature.
Specifics about a trial and the trial population will be added to the consent form template at 
the protocol level.  
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations 
and Sponsor requirements.
 
 
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7.1.1.1.2 Consent and Collection of Specimens for Future Biomedical Research
The investigator or qualified designee will explain the Future Biomedical Research consent 
to the subject, answer all of his/her questions, and obtain written informed consent before 
performing any procedure related to the Future Biomedical Research sub-trial.  A copy of the 
informed consent will be given to the subject.
7.1.1.2
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria specified in Section 5.1 will be reviewed by the 
investigator or qualified designee to ensure that the subject qualifies for the trial.  All 
appropriate medications and washout periods will be discussed with the subject, including 
those that will be prohibited and allowed throughout the duration of the trial.
7.1.1.3
Subject Identification Card
All subjects will be given a Subject Identification Card identifying them as participants in a 
research trial.  The card will contain trial site contact information (including direct telephone 
numbers) to be utilized in the event of an emergency.  The investigator or qualified designee 
will provide the subject with a Subject Identification Card immediately after the subject 
provides written informed consent.
The subject identification card also contains contact information for the emergency 
unblinding call center so that a health care provider can obtain information about trial 
medication/vaccination in emergency situations where the investigator is not available.
7.1.1.4
Medical History
A medical history should be obtained by the investigator or qualified designee. Subject 
history should include information on clinically significant personal history including 
identification of major cardiovascular risk factors, current and past smoking history, current 
alcohol use, past history of infections (including hepatitis, serious infection requiring 
hospitalization or IV antibiotics, tuberculosis), malignancies, and major cardiovascular 
conditions (including myocardial infarction, cardiac revascularization, angina [stable or 
unstable], stroke [ischemic or hemorrhagic] or transient ischemic stroke [TIA], congestive 
heart failure, arrhythmias, hypertension, diabetes, hyperlipidemia, and peripheral vascular 
disease [venous or arterial]). Any clinically relevant changes found at any time during the 
study will be recorded as adverse events. On the medical history form, nr-axSpA will be 
recorded as the primary condition.
 
 
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Confidential
7.1.1.5
Prior and Concomitant Medications Review
7.1.1.5.1 Prior Medications
At the Screening visit, the investigator or qualified designee should review all appropriate 
prior and prohibited medications and the necessary medication off-drug times with the 
subject. A record of prior medications taken by the subject within 3 months before screening 
is to be obtained. In addition, the use of BCG vaccine should be captured within 12 months 
before screening.  All medications used for the treatment of nr-axSpA at any time prior to 
Screening should be recorded on the electronic case report form (eCRF).
7.1.1.5.2 Concomitant Medications
The investigator or qualified designee should record medication, if any, taken by the subject 
at all visits after the subject consent is obtained until the conclusion of the protocol-specified 
follow-up period.
7.1.1.6
Assignment of Screening Number
All consented subjects will be given a unique screening number that will be used to identify 
the subject for all procedures that occur prior to randomization or allocation.  Each subject 
will be assigned only one screening number.  Screening numbers must not be re-used for 
different subjects.
Any subject who is screened multiple times will retain the original screening number 
assigned at the initial screening visit.
Specific details on the screening visit requirements (screening/rescreening) are provided in
Section 7.1.5.1.  
7.1.1.7
Assignment of Randomization Number
All eligible subjects will be randomly allocated and will receive a randomization number.  
The randomization number identifies the subject for all procedures occurring after 
randomization.  Once a randomization number is assigned to a subject, it can never be re-
assigned to another subject.
A single subject cannot be assigned more than 1 randomization number.
Subjects will be randomized to 1 of the 3 treatment arms in the double-blind Period 2. 
The randomization for Period 2 treatments will be based on a randomization schedule; 
however, each subject will retain his/her original allocation number.
7.1.1.8
Trial Compliance (Medication)
At all protocol-specified visits, the investigator or qualified designee must record whether 
treatment had been taken per protocol in the preceding interval. If not, the date(s) and reason 
for each dosing noncompliance must be recorded. 
 
 
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Protocol/Amendment No.: 038-01 
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21-Mar-2017
Confidential
During Periods 1 and 2, the investigator staff will contact each subject during each dosing 
window to remind the subject to administer trial medication. 
7.1.1.9
Trial Medication Injection Administration
After an initial injection has been given, administration is generally expected to continue 
preferably on the same day of every month, with an allowed window of ±5 days. As the trial 
progresses, the day of the month that is targeted for dosing can be re-set, if needed. If a dose 
is administered outside the ±5-day window (and assuming there is no other reason the subject 
must discontinue trial medication in the trial), then the day of that month when the dose was 
administered becomes the new target day for subsequent administration, again with a ±5-day 
window. For example, if a subject receives the initial dose on March 10, the next target day 
of administration will be April 10. If this second dose is instead administered on April 15 
(which is delayed, but still within the allowed time window), then the next target day is 
May 10. If the second dose is administered on April 18 (which is outside the ±5-day window 
[e.g., rescheduling due to an AE or other concerns]), then the new target day is May 18.
During Period 1, the first injection of open-label golimumab SC will be administered in the 
clinic by the appropriate site personnel at the Month-0 visit (Visit 2). After proper training in 
injection technique, subjects may self-inject the next dose in the clinic in the presence of site 
personnel at the Month-1 visit. If allowed by the local guidelines, subjects may self-inject the 
subsequent doses of trial medication at home between clinic visits, or subjects may opt to 
continue receiving trial medication at the study center after the Month 1 visit. Each injection 
of golimumab should be given at a different location of the body than the previous injection. 
Injections should be done in the abdomen, thigh or upper arm. Injections in the upper arm 
should be done by someone other than the subject. If subjects will be self-injecting at home, 
then enough trial medication to last until the next visit will be provided to the subjects to take 
home. The final dose of open-label golimumab during Period 1 will be administered at 
Month 9; response will be assessed at Month 10 (Visit 23) after approximately 10 months of 
open-label therapy to determine if the subject has attained inactive disease status. 
During Period 2, eligible subjects will be randomly allocated to receive either a full regimen 
of golimumab (50 mg QM), a reduced regimen of golimumab (50 mg Q2M), or treatment 
withdrawal (placebo QM) in a double-blind manner. The blinded trial medication will be 
administered by the site personnel during the clinic visits, which are scheduled to occur every 
2 months. If subjects are self-injecting at home, the monthly dose to be administered between 
the clinic visits will be dispensed. 
Verbal and written instructions for proper storage, handling and administration of the trial 
medication will be given to subjects and will include instructions to contact the study site 
immediately if they experience problems with the trial medication administration.
Interruptions from the protocol specified treatment for ≥60 days require consultation between 
the investigator and the Sponsor and written documentation of the collaborative decision on 
subject management.
 
 
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7.1.1.10 Trial Medication Injection Log 
If subjects opt to self-administer injections at home, each subject will be provided with a 
Trial Medication Injection Log at the Month-1 visit to collect the date and time of each dose 
of self-administered trial medication. This information will be recorded on the log by the 
subject for all trial medication doses administered away from the clinic, or by site personnel 
when trial medication is administered at the site. The subject must bring his/her injection log 
to all trial visits. At each visit, the site will review the log, record the new information in the 
eCRF, and return the log to the subject. Subjects will be instructed to return the completed 
injection log at their final visit.
7.1.1.11 Issue and Review Comments Card
The subject will receive a separate paper comment card to assist in capturing information 
regarding AEs and use of concomitant medication between visits. The comment card should 
be returned at each visit, and the information should be discussed with the investigator and/or 
qualified designee. If the data from the card reflect a change in concomitant medication, 
occurrence of AEs, explanation of non-compliance, or other relevant information pertaining 
to a subject's involvement in this trial, it should be captured in the appropriate section of the 
eCRF. Card comments that are not considered to be relevant to the investigator should be 
indicated as such, during the site’s review of the card, in the space provided. All comments 
cards should be initialed and dated by the reviewer at the time of collection from the subject. 
The comment card will be collected from each subject at his/her final clinic visit and will 
remain at the site as a source.
Clinical Procedures/Assessments
7.1.2
7.1.2.1
Physical Examination
The first physical exam (PE) (performed at Screening) will be a complete PE, excluding 
genitourinary system. This complete PE should also include a full skin examination. 
Subsequent PEs will be symptom-directed as determined by the investigator. These directed 
PEs should also include a full skin assessment as clinically indicated based upon symptoms
and signs. If the subject is discontinued for any reason during Period 1 or 2, every attempt 
should be made to perform a final PE, which will also be a PE that is symptom-directed.
7.1.2.2
Vital Signs
Systolic and diastolic blood pressure (mmHg); oral, axillary or tympanic temperature (C or 
F); and pulse (beats per minute) will be recorded while the subject is seated. 
Note:  Vital signs should be evaluated and recorded at any other time before, during, or after 
the trial medication injection if required by local regulations and/or local clinical practice, or 
when medically indicated.
 
 
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Any clinically significant abnormalities in vital signs noted after the subject signs the ICF 
will be recorded as an AE in the eCRF.
Height and weight should be collected at the Screening visit only.
Height should be taken without shoes.
Weight should be taken in street clothing with jacket/coat and shoes removed.
7.1.2.3
Chest X-ray (CXR)
For this protocol, a chest x-ray is mandatory to assess the tuberculosis (TB) screening 
eligibility criterion. Subjects should have a chest x-ray within 3 months prior to the screening 
visit with no evidence of current active TB or old inactive TB. If a negative chest x-ray is not 
available, then the subject must have a chest x-ray performed during screening showing no 
evidence of active or inactive TB.
7.1.2.4
X-Rays of Sacroiliac Joints
Subjects will undergo x-rays of SI joints at screening. The x-rays will be read by the central 
vendor for determination of subject eligibility according to exclusion criterion #1 (See 
Section 5.1.3). The central vendor eligibility report regarding the SI-joint x-rays must be 
received before a subject may undergo the Magnetic Resonance imaging (MRI) for screening 
purposes (in the scenario that the C-reactive protein [CRP] test is normal at the Screening 
visit).
Note: For subjects who have a SI joint x-ray performed within 6 months prior to screening, 
the site can send the x-ray for central reading. If these x-rays are evaluable by central 
reading, then these subjects do not need to have a SI joint x-ray repeated at the Screening
visit.
7.1.2.5
Magnetic Resonance Imaging of Sacroiliac Joints
An MRI of the SI joints should be performed at Screening only if the CRP value is normal 
and the subject is otherwise deemed to be eligible for the trial. In this situation, the central 
vendor’s MRI report must be received prior to a subject being allowed to receive open-label 
golimumab in Period 1.
For subjects who have had an MRI performed within 6 months prior to the Screening visit,
the site can send these MRI films for central reading. If these MRI films are evaluable by 
central reading, the central reader will report the presence or absence of active inflammation 
of SI joints, highly suggestive of sacroiliitis. These subjects with clinical evidence of 
inflammation do not need to have an MRI repeated at Screening.
Separately, historical MRI results can also be used to help document the medical diagnosis of 
nr-axSpA. If subjects have had historical MRI films taken within 3 years prior to the 
Screening visit, the site will send them to central reader. If these MRI films are evaluable by 
central reading, the presence or absence of SI-joint inflammation will be reported. 
 
 
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Note: The evaluation of MRI results obtained >6 months prior to the Screening visit will be 
used only as historical information to help document the diagnosis of the disease; MRI 
results obtained >6 months before the Screening visit will not be used to assess the presence 
or absence of active inflammation of SI joints at the Baseline (i.e., not to determine eligibility 
to receive open-label golimumab in Period 1, in the scenario that the CRP test is normal at 
the Screening visit).
7.1.2.6
Bath Ankylosing Spondylitis Disease Activity Index (Patient Reported 
Outcome)
Subjects will complete the BASDAI by answering 6 questions at all clinic visits, as well as 
twice monthly between clinic visits, using the 0 to 10 NRS. Subjects will be instructed by site 
personnel on how to use an electronic device to record their ratings for each question; 
subjects will also be able to use an electronic device remotely (i.e., at home) to record their 
ratings between clinic visits.
Q1. Fatigue/tiredness
Over past week:  0 to 10 = None to Very severe
Q2. Neck, back, or hip (spinal) pain 
Over past week:  0 to 10 = None to Very severe
Q3. Pain/swelling in joints other than neck, back, or hip
Over past week:  0 to 10 = None to Very severe
Q4. Tenderness 
Over past week: 0 to 10 = None to Very severe
Q5. Level of morning stiffness  
Since awakening: 0 to 10 = None to Very severe
Q6. Duration of morning stiffness 
Since awakening: 0 to 10 = Zero to 2-or-more hours
Calculation of the BASDAI score is described in Section 8.4.3. Three of the questions on the 
BASDAI are also components of the ASDAS, as described in Section 8.4.3. Details on scales 
and questions are provided in Appendix 12.6 [9].
7.1.2.7
Bath Ankylosing Spondylitis Functional Index (Patient Reported Outcome)
Subjects will complete the BASFI by answering 10 questions using the 0 to 10 NRS at all 
clinic visits. Eight of the questions relate to the functional capacity of the subject and 2 relate 
to the subject’s ability to cope with everyday life. An increase along the scale indicates a 
worsening condition, ranging from “Easy” to “Impossible.” Details on scales and questions 
are provided in Appendix 12.7 [9].
7.1.2.8
Patient Global Disease Assessment (Patient Reported Outcome)
Subjects will be asked to make an overall global assessment of their disease activity over the 
past week using the 0 to 10 NRS, with 0 being not active to 10 being extremely active. The 
Patient’s Global Disease assessment (on Numeric scale) (PGDN) is one of the domains of the 
ASDAS (see Section 8.4.3). Details are provided in Appendix 12.8 [9].
7.1.2.9
Total Back Pain (Patient Reported Outcome)
Subjects will be asked to assess their average total back pain (TBP) over the past week using 
the 0 to 10 NRS, with 0 being no pain to 10 being extreme pain.  Total Back Pain is one of 
the domains of the ASAS. Details are provided in Appendix 12.9 [9].
 
 
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7.1.2.10 Global Assessment of Disease by Investigator 
A Global assessment of disease by investigator (GADI) will be recorded using a Likert scale
(Very Well, Well, Fair, Poor, Very Poor). Details are provided in Appendix 12.10.
7.1.2.11 Record Adverse Events
At all visits after the subject consent is obtained until the conclusion of the protocol-specified 
follow-up period, the investigator or designee will solicit from the subject information 
concerning AEs. All AEs experienced since the previous visit or contact will be recorded on 
the eCRF. Flares of uveitis, psoriasis, IBD should be recorded. For instructions regarding 
AEs, see Section 7.2 Assessment and Reporting of Adverse Events.
7.1.2.12 Monitoring Malignancies
There will be follow-up communications between the Sponsor and the investigator regarding 
all malignancies that occur in subjects ages 30 years or younger. Twice a year, the Sponsor 
will review the AE database for possible premalignant conditions occurring in subjects ages 
30 years or younger. If any are reported, the Sponsor will contact the investigator with a 
dedicated follow-up request that needs to be completed. This will be done via a dedicated 
Malignancy Follow-up Questionnaire. Within 2 weeks of receiving the questionnaire from 
the Sponsor, the investigator(s) must complete the questionnaire and submit it to the Sponsor 
via a designated fax number. In case a pre-malignant condition has progressed to a 
malignancy, the investigator will also need to complete the Malignancy Follow-Up 
Questionnaire. To obtain the information necessary to complete the Malignancy Follow-up 
Questionnaire, the investigator must make at least 2 attempts to contact the subject or 
guardian. If the attempts are not successful, the reason for each unsuccessful attempt must be
documented (e.g., subject lost-to-follow-up, subject refuses to supply the additional 
information, etc.).
Laboratory Procedures/Assessments
7.1.3
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below. The total amount of blood/tissue to be drawn/collected over the course of 
the trial (from pre-trial to post-trial visits), including approximate blood/tissue volumes 
drawn/collected by visit and by sample type per subject can be found in Section 12.4.
7.1.3.1
Laboratory Safety Evaluations (Hematology, Chemistry and Other Tests)
Laboratory tests for hematology, chemistry and additional tests are specified in Table 2.
 
 
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Table 2  Laboratory Tests
Hematology
Chemistry
Additional Tests
Basophils
Albumin
CRP
Eosinophils
Alkaline phosphatase
Serum Pregnancy
Hematocrit
ALT 
QuantiFERON®-TB Gold Test
Hemoglobin
AST 
HCV
Lymphocytes
Bilirubin
HLA-B27
Monocytes
Blood urea nitrogen
HBV surface antigen (HBsAg),
Neutrophils
Calcium
HBV surface antibody(anti-HBs)
Platelets
Chloride
HBV core antibody(anti-HBc total)
Red blood cell count
GGT
HBV DNA testing*
White blood cell count
Potassium
Serum Creatinine
Sodium
Total protein
*HBV DNA test will be performed only if HBs Ag and anti-HBs are negative and anti-HBc total is positive. 
Note:  Routine laboratory examinations should be performed, evaluated, and recorded at any 
other time if required by local regulations and/or local clinical practice, or when medically 
indicated.
Nonclinically significant laboratory data will be kept in the subject’s source document but 
any clinically significant abnormalities in laboratory data noted after the subject signs the 
ICF will be recorded as AEs in the eCRF.
7.1.3.2
Serum/Urine Pregnancy Testing and Follow-up of Pregnancy
Female subjects of childbearing potential will have serum and urine pregnancy tests
performed at visits specified in Trial Flow Charts - Section 6.0. If local law requires more 
frequent pregnancy testing, the site will perform the assessments.
In order to be eligible for the trial, female subjects of childbearing potential and male 
subjects must agree to use a medically accepted method of contraception prior to enrollment, 
while receiving trial medication or within 6 months after stopping the medication 
(Section 5.1.2). Female subjects who become pregnant during the trial must discontinue 
treatment (Section 5.8). Male subjects who may have fathered a child during the trial or 
within 6 months after stopping the trial medication must notify the site immediately. The site 
will report pregnancies to the Sponsor’s designee via appropriate eCRF within 24 hours as 
described in Section 7.2.2.
 
 
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7.1.3.3
Tuberculosis (TB) Screening
For this protocol, a chest x-ray AND a QuantiFERON-TB Gold test are mandatory, 
regardless of local guideline preferences. In addition, all subjects must undergo all additional 
applicable tests for TB (such as tuberculin skin test) and latent TB screening in accordance 
with local guidelines and protocol requirements. 
Subjects who have negative diagnostic TB test results are considered eligible for the trial. A 
subject with a positive result for active TB should not be included in the current trial. The TB 
testing should be completed during the Screening visit and the results must be reviewed to 
assess subject eligibility prior to the Baseline visit. Tests include, but are not limited to 
posterior-anterior and lateral chest x-rays (unless a chest x-ray has been performed within 3 
months prior to first treatment administration) and QuantiFERON-TB Gold test (unless 
performed within 6 weeks prior to the first treatment administration), and tuberculin skin test. 
Within 6 weeks prior to first administration of trial medication, subjects should have:

negative diagnostic TB test results (defined as a negative QuantiFERON-TB Gold test
[and a negative tuberculin skin test, but only if tuberculin skin test is needed]), OR 

a newly identified positive TB test result (defined as positive QuantiFERON-TB Gold 
test [and/or a positive tuberculin skin test, but only if tuberculin skin test is needed])
during Screening for which active TB has been ruled out and for which appropriate 
treatment for latent TB has been initiated prior to the first administration of trial 
medication. The duration of the treatment before the first administration should be in 
accord with local guidelines, if any.
Investigators have the option to use both the QuantiFERON-TB Gold test and the tuberculin 
skin test to screen for latent TB if they believe, based on their judgment, that the use of both 
tests is clinically indicated in order to evaluate a subject who has high risk of having latent 
TB. Local guidelines specifically directed to high risk and/or immunocompromised subjects 
should be used for screening and interpreting positive test results for TB.
QuantiFERON-TB Gold testing (and tuberculin skin testing also, but only if needed) must be 
performed and read by experienced, trained, and licensed personnel according to published 
local guidelines, either at the participating trial site, a local public health clinic, or a primary 
care physician’s office. If this testing was performed at any site other than the investigator’s 
facility, the results must be made available in written form as source documentation. 
7.1.3.4
HLA-B27 Gene Status
HLA-B27 gene testing will be done at Screening to document a subject’s HLA-B27 status. If 
previously documented, it is not necessary to perform this assessment for this trial; however, 
actual results need to be captured in the subject’s medical records.
 
 
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7.1.3.5
Screening for Hepatitis B Virus (HBV)
Each subject must undergo a screening for hepatitis B virus (HBV), which at a minimum 
includes testing for HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), and 
HBV core antibody total (anti-HBc total), and demonstrate to be eligible based on the 
following results: 
a.
Subjects who test positive for surface antigen (HBsAg+) are not eligible for this trial, 
regardless of the results of other hepatitis B tests.
b. 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 trial.
c.
Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this 
trial.
d. Subjects who test positive only for core antibody (anti-HBc+) must undergo further 
testing for hepatitis B deoxyribonucleic acid (HBV DNA test). If the HBV DNA test is 
positive, the subject is not eligible for this trial. If the HBV DNA test is negative, the 
subject is eligible for this trial. In the event the HBV DNA test cannot be performed, the 
subject is not eligible for this trial.
Action
Hepatitis B Surface 
Antigen(HBsAg)
Hepatitis B Surface 
Antibody(anti-HBs)
Hepatitis B Core 
Antibody(anti-HBc Total)
Exclude
+
–  or +
–  or +
Include
–
+
+
Include
–
+
–
Include
–
–
–
Require Hepatitis B viral 
DNA (HBV DNA) testing*
–
–
+
* If HBV DNA is detectable or there is evidence of chronic liver disease, exclude from clinical trial. If 
the HBV DNA test is negative, the subject is eligible for this trial. In the event the HBV DNA test 
cannot be performed, the subject is not eligible for this trial.
7.1.3.6
Pharmacokinetic (PK) and Immunogenicity Evaluations
7.1.3.6.1 Blood Collection for Plasma MK-8259
Analyses for MK-8259 (golimumab) concentration will be performed using a validated 
method. It is important to accurately record the date/time of administration of the trial
medication as well as the date/time that each sample was collected for PK analysis. Sample 
collection, storage and shipment instructions for plasma samples will be provided in the 
central operations/laboratory manual. 
7.1.3.6.2 Blood Collection for Antibodies to Golimumab (MK-8259)
Serum samples will be used to evaluate the antibodies to golimumab. Instructions for the 
collection, handling, and shipping of blood samples are provided in the Laboratory manual. 
 
 
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7.1.3.7
Future Biomedical Research
The following specimens are to be obtained as part of Future Biomedical Research:

DNA for future research
7.1.3.8
Planned Genetic Analysis Sample Collection
Sample collection, storage and shipment instructions for planned genetic analysis samples 
will be provided in the central operations/laboratory manual.
Other Procedures
7.1.4
7.1.4.1
Withdrawal/Discontinuation
Subjects who discontinue/withdraw from treatment prior to completion of the treatment
should be encouraged to continue to be followed for all remaining study visits.
When a subject discontinues/withdraws from participation in the trial, all applicable activities 
scheduled for the discontinuation visit should be performed at the time of discontinuation.  
Any adverse events which are present at the time of discontinuation/withdrawal should be 
followed in accordance with the safety requirements outlined in Section 7.2 - Assessing and 
Recording Adverse Events and subjects will have a safety follow-up telephone call 3 months 
after their last dose of trial medication.
7.1.4.1.1 Withdrawal From Future Biomedical Research
Subjects may withdraw their consent for Future Biomedical Research and have their 
specimens and all derivatives destroyed.   Subjects may withdraw consent at any time by 
contacting the principal investigator for the main trial.  If medical records for the main trial 
are still available, the investigator will contact the Sponsor using the designated mailbox 
(clinical.specimen.management@merck.com), and a form will be provided by the Sponsor to 
obtain appropriate information to complete specimen withdrawal.  Subsequently, the 
subject's specimens will be removed from the biorepository and be destroyed.  A letter will 
be sent from the Sponsor to the investigator confirming the destruction. It is the 
responsibility of the investigator to inform the subject of completion of destruction.  Any 
analyses in progress at the time of request for destruction or already performed prior to the 
request being received by the Sponsor will continue to be used as part of the overall research 
trial data and results.   No new analyses would be generated after the request is received.
In the event that the medical records for the main trial are no longer available (e.g., if the 
investigator is no longer required by regulatory authorities to retain the main trial records) or 
the specimens have been completely anonymized, there will no longer be a link between the 
subject’s personal information and their specimens.  In this situation, the request for 
specimen destruction cannot be processed.
 
 
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7.1.4.2
Blinding/Unblinding
When the investigator or sub-investigator needs to identify the drug used by a subject and the 
dosage administered in case of emergency e.g., the occurrence of serious adverse 
experiences, he/she will contact the emergency unblinding call center by telephone and make 
a request for emergency unblinding.  As requested by the investigator or sub-investigator the 
emergency unblinding call center will provide the information to him/her promptly and 
report unblinding to the sponsor.  The emergency unblinding call center will make a record 
promptly however, the investigator or sub-investigator must enter the intensity of the adverse 
experiences observed,   their relation to study drug, the reason thereof, etc., in the medical 
chart etc., before unblinding is performed.  
Additionally, the investigator must go into the IVRS system and perform the unblind in the 
IVRS system to update drug disposition.  In the event that the emergency unblinding call 
center is not available for a given site in this trial, IVRS/IWRS should be used for emergency 
unblinding in the event that this is required for subject safety.
In the event that unblinding has occurred, the circumstances around the unblinding (e.g., date 
and reason) must be documented promptly, and the Sponsor Clinical Director notified as 
soon as possible.  Only the principal investigator or delegate and the respective subject’s 
code should be unblinded.  Trial site personnel and Sponsor personnel directly associated 
with the conduct of the trial should not be unblinded.
7.1.4.3
Calibration of Critical Equipment
The investigator or qualified designee has the responsibility to ensure that any critical device
or instrument used for a clinical evaluation/test during a clinical trial that provides important 
information about inclusion/exclusion criteria and/or safety or efficacy parameters shall be 
suitably calibrated and maintained to ensure that the data obtained is reliable and/or 
reproducible.  Documentation of equipment calibration must be retained as source 
documentation at the trial site.
Critical Equipment for this trial includes:

Weight scale

Centrifuge
Visit Requirements
7.1.5
Visit requirements are outlined in Section 6.0 - Trial Flow Chart.   Specific procedure-related 
details are provided above in Section 7.1 - Trial Procedures.
7.1.5.1
Screening and Baseline Eligibility (Visit 1 and Visit 2)
All screening procedures (including MRI) required to assess subjects’ eligibility for the trial 
should be completed within the 2 months (60 days) prior to administration of the first dose of 
open-label golimumab at Visit 2. IVRS/IWRS should be used beginning with the Screening 
visit and ending with completion/discontinuation visit. 
 
 
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Subjects in this study may be rescreened once prior to receiving open-label golimumab, with 
prior approval by the Sponsor trial physician. If a subject is rescreened, the same screening 
number must be used.
When it is confirmed at Baseline (Visit 2 or “Month 0”) that a subject is eligible to enter 
Period 1 (to receive open-label golimumab), the subject should be assigned an allocation
number using the IVRS/IWRS. Refer to the IVRS/IWRS user manual for additional details. 
7.1.5.2
Month-4 Clinic Visit (Visit 10)
At Month 4 (Visit 10), all subjects will be assessed for clinical response based on BASDAI 
score. Subjects who attain a clinical response by Month 4 (or earlier) will continue to receive 
golimumab monthly during Period 1. A clinical response is defined as a BASDAI score 
improvement of ≥2 (on a NRS from 0 to 10) or ≥50% improvement, when determined 
relative to the score at Month 0. Subjects who have not attained a clinical response by Visit 
10 will be discontinued from the study and will have a safety follow-up telephone call 3
months after their last dose of trial medication.
7.1.5.3
Month-7 Clinic Visit (Visit 16)
At Month 7 (Visit 16), all assessments listed in Trial Flow Chart - Section 6.0 will be 
performed including those required to calculate ASDAS: BASDAI, PGDN and CRP testing.
Trial medication will not be administered at Visit 16. Once the Visit-16 CRP test result is 
available (from the central laboratory), the site will determine the ASDAS in order to assess 
for inactive disease status (defined as ASDAS <1.3).

Subjects who show ASDAS <1.3 at Visit 16 are to continue in the trial and complete 
Period 1. Sites will schedule only these eligible subjects for the next clinic visit (Visit 17, 
which should occur about 2 to 7 days after Visit 16) to dispense open-label golimumab to 
complete Period 1. 

Subjects who show ASDAS ≥1.3 at Visit 16 will be discontinued from the trial. Sites will
call these subjects for an unscheduled visit to perform procedures that are required at the 
Discontinuation (DC) visit but were not performed at Visit 16. These procedures include 
obtaining vital signs, GADI, routine laboratory blood testing, and pregnancy test (if 
required). These subjects will have a safety follow-up telephone call 3 months after their 
final dose of trial medication. 
 
 
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7.1.5.4
Month-10 Clinic Visit (Visit 23)
After approximately 10 months of open-label therapy (with the final dose of open-label 
golimumab during Period 1 administered at Month 9), assessments at Visit 23 will be 
performed, including those required to calculate the ASDAS: BASDAI, PGDN and CRP 
testing. Trial medication will not be administered at Visit 23. Once the Visit-23 CRP test 
result is available (from the central laboratory), the site will determine the ASDAS in order to 
assess for inactive disease status (defined as ASDAS <1.3).

Subjects who show ASDAS <1.3 at Visit 23 are eligible to enter Period 2 and receive 
double-blind treatment. Sites will schedule only these eligible subjects for the next clinic 
visit (Visit 24, which should occur about 2 to 7 days after Visit 23). At Visit 24, subjects 
will receive their initial dose of blinded trial medication and thereafter will continue 
monthly administration during Period 2. The next clinic visit (Visit 28) should be 
scheduled about 2 months after Visit 24.

Subjects who show ASDAS ≥1.3 at Visit 23 will be discontinued from the trial. These 
subjects will have a safety follow-up telephone call 3 months after their final dose of trial 
medication.
7.1.5.5
Unscheduled Visit(s) to Confirm a “Flare” during Period 2
Evaluations by Telephone Contact(s) during Period 2
As obtained (via electronic device) during Period 2, if the BASDAI score is increased by ≥2
(on the 0 to 10 NRS) compared to Month 10 (Visit 23), then sites will call subjects to also 
obtain a Patient Global Disease assessment (on Numeric scale) (PGDN) score. (Subjects may 
also contact the clinic if they believe a “flare” is occurring, regardless of their BASDAI 
score. In this situation, sites will call the subject to obtain both the BASDAI and the PGDN.
Similarly, if the BASDAI increase by ≥2 is observed at a regularly scheduled clinic visit, 
then this situation can initiate the additional assessments to confirm a “flare”.) Using these 
values obtained for BASDAI and PGDN, sites will also use the last available CRP value (i.e., 
the CRP result from the previous clinic visit) to determine the ASDAS. Based on this
ASDAS, there are 2 possible decisions:
(1) If this ASDAS shows absolute score <2.1 and post-withdrawal increase (i.e., change from 
Visit 23) of <1.1, then this assessment is not consistent with a “flare”. The subject is
expected to continue the double-blind trial-medication administration and the scheduled 
clinic visits without change.
(2) If this ASDAS shows absolute score ≥2.1 and/or post-withdrawal increase of ≥1.1, then 
the subject will be asked to come to the clinic, for an unscheduled visit, for an additional 
assessment for confirmation of a “flare”. This additional assessment should occur within 
ideally 2 to 10 days (but no more than 3 weeks); or this assessment can occur at a 
previously scheduled clinic visit, if the timing fits within ideally 2 to 10 days (but no 
more than 3 weeks) from the first assessment.
 
 
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Evaluations during a Clinic Visit needed to Confirm a “Flare”
During a “flare-confirmation” visit, evaluations required to calculate ASDAS (BASDAI, 
PGDN, CRP testing) will be performed. Using the BASDAI and PGDN obtained during this 
“flare-confirmation” visit (and understanding that the result of the CRP test collected during
this visit is not yet available), the investigator will determine the ASDAS using the BASDAI 
and PGDN scores and assuming the minimum value of CRP that is defined for use in 
calculating ASDAS, which is CRP = 2 mg/L [8]. This ASDAS determines the decision
among the following: 
(1) If the ASDAS shows absolute score ≥2.1 and/or post-withdrawal increase (i.e., change 
from Visit 23) of ≥1.1, then this will confirm that a “flare” is occurring. The subject will 
begin re-treatment with open-label golimumab, which is then to be continued monthly 
through the end of Period 2. The next clinic visit should be scheduled about 2 months 
after the first dose of re-treatment with open-label golimumab.
(2) If the ASDAS shows absolute score <2.1 and post-withdrawal increase of <1.1, the 
subject will not be treated with the open-label golimumab at this unscheduled visit. 
However, when the CRP value becomes available from the sample collected at this
“flare-confirmation” visit, the investigator must then re-calculate the ASDAS.  
(2a) If the re-calculation of ASDAS (now using the new CRP value) shows absolute 
score ≥2.1 and/or post-withdrawal increase of ≥1.1, then this will confirm that a 
“flare” is occurring. Once it is confirmed that a “flare” is occurring, the subject will 
be asked to return for a second unscheduled visit in order to begin re-treatment with 
open-label golimumab, which should then continue monthly through the end of 
Period 2. The next clinic visit should be scheduled about 2 months after the first 
dose of re-treatment with open-label golimumab.
(2b) If the re-calculation of ASDAS (now using the new CRP value) shows absolute 
score <2.1 and post-withdrawal increase of <1.1, then this second assessment does 
not confirm a “flare”. The subject is expected to continue the double-blind trial-
medication administration and the scheduled clinic visits without change.
Note:  In a scenario in which the BASDAI increase by ≥2 is observed at a regularly 
scheduled clinic visit and the “flare-confirmation” visit is then scheduled within ideally 2 to 
10 days (but no more than 3 weeks), the CRP obtained at the regularly scheduled clinic visit
can be used in the confirmatory determination of the ASDAS during the “flare-confirmation” 
visit. In this scenario, decisions (1) or (2b) above will pertain.
7.1.5.6
Safety Follow-Up Telephone call
All subjects who have either completed the trial or discontinued from the trial will have a 
safety follow-up phone call approximately 3 months after the last dose of trial medication.
 
 
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Assessing and Recording Adverse Experiences
7.2
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An adverse event can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product or protocol-
specified procedure, whether or not considered related to the medicinal product or protocol-
specified procedure.  Any worsening (i.e., any clinically significant adverse change in 
frequency and/or intensity) of a preexisting condition that is temporally associated with the 
use of the Sponsor’s product, is also an adverse event.
Changes resulting from normal growth and development that do not vary significantly in 
frequency or severity from expected levels are not to be considered adverse events.  
Examples of this may include, but are not limited to, teething, typical crying in infants and 
children and onset of menses or menopause occurring at a physiologically appropriate time.
Sponsor's product includes any pharmaceutical product, biological product, device, 
diagnostic agent or protocol-specified procedure, whether investigational (including placebo 
or active comparator medication) or marketed, manufactured by, licensed by, provided by or 
distributed by the Sponsor for human use.
Adverse events may occur during clinical trials, or as prescribed in clinical practice, from 
overdose (whether accidental or intentional), from abuse and from withdrawal.
All adverse events that occur after the consent form is signed but before treatment 
allocation/randomization must be reported by the investigator if they cause the subject to be 
excluded from the trial, or are the result of a protocol-specified intervention, including but 
not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a 
procedure. From the time of treatment allocation/randomization through 90 days following 
cessation of treatment, all adverse events must be reported by the investigator. Such events 
will be recorded at each examination on the Adverse Event case report forms/worksheets.  
The reporting timeframe for adverse events meeting any serious criteria is described in 
section 7.2.3.1. The investigator will make every attempt to follow all subjects with non-
serious adverse events for outcome.
Electronic reporting procedures can be found in the Electronic Data Capture (EDC) data 
entry guidelines. Paper reporting procedures can be found in the Investigator Trial File 
Binder (or equivalent).
 
 
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Definition of an Overdose for This Protocol and Reporting of Overdose to the 
7.2.1
Sponsor
In this trial, an overdose is any dose higher than the dose specified in Section 5.2 of this 
protocol.
If an adverse event(s) is associated with (“results from”) the overdose of Sponsor's product or 
vaccine, the adverse event(s) is reported as a non-serious adverse event, unless other serious 
criteria are met.
If a dose of Sponsor's product or vaccine meeting the protocol definition of overdose is taken 
without any associated clinical symptoms or abnormal laboratory results, the overdose is 
reported as a non-serious adverse event using the terminology “accidental or intentional 
overdose without adverse effect.”
All reports of overdose with and without an adverse event must be reported by the 
investigator within 24 hours to the Sponsor either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent).
Reporting of Pregnancy and Lactation to the Sponsor
7.2.2
Although pregnancy and lactation are not considered adverse events, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject 
(spontaneously reported to them), including the pregnancy of a male subject's female partner 
that occurs during the trial. 
Pregnancies and lactations of subjects and female partners of male subjects from the time the 
consent form is signed but before treatment allocation/randomization must be reported by the 
investigator if they cause the subject to be excluded from the trial, or are the result of a 
protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment or a procedure. Pregnancies and lactations of subjects
and female partners of male subjects that occur from the time of treatment 
allocation/randomization through 6 months following cessation of Sponsor’s product must be 
reported. All reported pregnancies must be followed to the completion/termination of the 
pregnancy. Pregnancy outcomes of spontaneous abortion, missed abortion, benign 
hydatidiform mole, blighted ovum, fetal death, intrauterine death, miscarriage and stillbirth 
must be reported as serious events (Important Medical Events). If the pregnancy continues to 
term, the outcome (health of infant) must also be reported. 
Such events must be reported within 24 hours to the Sponsor either by electronic media or 
paper. Electronic reporting procedures can be found in the EDC data entry guidelines. Paper 
reporting procedures can be found in the Investigator Trial File Binder (or equivalent).
 
 
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Immediate Reporting of Adverse Events to the Sponsor
7.2.3
7.2.3.1
Serious Adverse Events
A serious adverse event is any adverse event occurring at any dose or during any use of 
Sponsor's product that:
●
Results in death;
●
Is life threatening;
●
Results in persistent or significant disability/incapacity;
●
Results in or prolongs an existing inpatient hospitalization;
●
Is a congenital anomaly/birth defect;
●
Is an other important medical event. 
Note: In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Sponsor in the same timeframe 
as SAEs to meet certain local requirements. 
●
Is a cancer;
●
Is associated with an overdose.
Refer to Table 3 for additional details regarding each of the above criteria.
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause, that occurs to any subject must be reported within 24 hours 
to the Sponsor if it causes the subject to be excluded from the trial, or is the result of a 
protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 90 days 
following cessation of treatment, any serious adverse event, or follow up to a serious adverse 
event, including death due to any cause, whether or not related to the Sponsor's product, must 
be reported within 24 hours to the Sponsor either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent).
Additionally, any serious adverse event, considered by an investigator who is a qualified 
physician to be related to the Sponsor's product that is brought to the attention of the 
investigator at any time outside of the time period specified in the previous paragraph also 
must be reported immediately to the Sponsor. 
All subjects with serious adverse events must be followed up for outcome.
7.2.3.2
Events of Clinical Interest
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported to the Sponsor.
 
 
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For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any subject must be 
reported within 24 hours to the Sponsor if it causes the subject to be excluded from the trial, 
or is the result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 90 days 
following cessation of treatment, any ECI, or follow up to an ECI, whether or not related to 
the Sponsor’s product, must be reported within 24 hours to the Sponsor, either by electronic 
media or paper.  Electronic reporting procedures can be found in the EDC data entry 
guidelines.  Paper reporting procedures can be found in the Investigator Trial File Binder (or 
equivalent).
Events of clinical interest for this trial include:
1.
an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of
normal and an elevated total bilirubin lab value that is greater than or equal to 2X the 
upper limit of normal and, at the same time, an alkaline phosphatase lab value that is 
less than 2X the upper limit of normal, as determined by way of protocol-specified 
laboratory testing or unscheduled laboratory testing.*
*Note:  These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may 
require an additional evaluation for an underlying etiology. The trial site guidance for 
assessment and follow up of these criteria can be found in the Investigator Trial File 
Binder (or equivalent).
2.
Clinically significant opportunistic infections and TB.
3.
Clinically significant hypersensitivity reactions.
Evaluating Adverse Events
7.2.4
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 3. The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 3 for instructions in evaluating adverse events.
 
 
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Table 3  Evaluating Adverse Events
Maximum
Mild
awareness of sign or symptom, but easily tolerated  (for pediatric trials, awareness of symptom, but easily tolerated)
Intensity
Moderate
discomfort enough to cause interference with usual activity (for pediatric trials, definitely acting like something is wrong)
Severe
incapacitating with inability to work or do usual activity (for pediatric trials, extremely distressed or unable to do usual activities)
Seriousness
A serious adverse event (AE) is any adverse event occurring at any dose or during any use of Sponsor's product that:
†Results in death; or
†Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred [Note: This does not include an adverse 
event  that, had it occurred in a more severe form, might have caused death.]; or
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even if the 
hospitalization is a precautionary measure for continued observation.   (Note: Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not a serious adverse event.  A pre-existing condition is a clinical condition that is diagnosed prior to the use of a Merck product and is documented in the 
patient’s medical history.); or
†Is a congenital anomaly/birth defect  (in offspring of subject taking the product regardless of time to diagnosis); or
Is a cancer (although not serious per ICH definition, is reportable to the Sponsor within 24 hours to meet certain local requirements); or
Overdose, although not serious per ICH definition, whether accidental or intentional, with or without an accompanying adverse event/serious adverse event, is
reportable to the Sponsor within 24 hours to meet certain local requirements.
Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
previously (designated above by a †).
Duration
Record the start and stop dates of the adverse event.  If less than 1 day, indicate the appropriate length of time and units
Action taken 
Did the adverse event cause the Sponsor's product to be discontinued?
Relationship to 
Sponsor's 
Product
Did the Sponsor's product cause the adverse event?   The determination of the likelihood that the Sponsor's product caused the adverse event will be provided by an 
investigator who is a qualified physician.  The investigator’s signed/dated initials on the source document or worksheet that supports the causality noted on the AE form, 
ensures that a medically qualified assessment of causality was done.  This initialed document must be retained for the required regulatory time frame.  The criteria below 
are intended as reference guidelines to assist the investigator in assessing the likelihood of a relationship between the test drug and the adverse event based upon the 
available information
The following components are to be used to assess the relationship between the Sponsor's product and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the Sponsor's product caused the adverse event:
Exposure
Is there evidence that the subject was actually exposed to the Sponsor's product such as:  reliable history, acceptable compliance assessment (pill 
count, diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily specimen?
Time Course
Did 
the 
AE 
follow 
in 
a 
reasonable 
temporal 
sequence 
from 
administration 
of 
the 
Sponsor's 
product? 
Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational medicinal product)?
Likely Cause
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or environmental factors
Relationship
The following components are to be used to assess the relationship between the Sponsor's product and the AE:  (continued)
to Sponsor's 
Product
(continued) 
Dechallenge
Was the Sponsor's product discontinued or dose/exposure/frequency reduced?
      If yes, did the AE resolve or improve?
           If yes, this is a positive dechallenge.    If no, this is a negative dechallenge.
(Note:  This criterion is not applicable if:  (1) the AE resulted in death or permanent disability; (2) the AE resolved/improved despite continuation of 
the Sponsor's product; (3) the trial is a single-dose drug trial); or (4) Sponsor's product(s) is/are only used one time.)
 
 
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Rechallenge
Was the subject re-exposed to the Sponsor's product in this trial?
      If yes, did the AE recur or worsen?
          If yes, this is a positive rechallenge.    If no, this is a negative rechallenge.
(Note:  This criterion is not applicable if:  (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-dose drug trial); or (3) 
Sponsor's product(s) is/are used only one time.)
NOTE:  IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY HAVE BEEN 
CAUSED BY THE SPONSOR'S PRODUCT, OR IF RE-EXPOSURE TO THE SPONSOR'S PRODUCT POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE SUBJECT THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR 
CLINICAL DIRECTOR AND THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE.
Consistency 
with Trial 
Treatment 
Profile
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding the Sponsor's product or drug class pharmacology 
or toxicology?
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical judgment, including 
consideration of the above elements.
Record one of the following:
Use the following scale of criteria as guidance (not all criteria must be present to be indicative of a Sponsor's product relationship).
Yes, there is a reasonable 
possibility of Sponsor's product 
relationship.
There is evidence of exposure to the Sponsor's product.  The temporal sequence of the AE onset relative to the administration of the Sponsor's 
product is reasonable.  The AE is more likely explained by the Sponsor's product than by another cause. 
No, there is not a reasonable 
possibility of Sponsor's product 
relationship
Subject did not receive the Sponsor's product OR temporal sequence of the AE onset relative to administration of the Sponsor's product is not 
reasonable OR the AE is more likely explained by another cause than the Sponsor’s product.  (Also entered for a subject with overdose without an 
associated AE.)
 
 
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Sponsor Responsibility for Reporting Adverse Events
7.2.5
All Adverse Events will be reported to regulatory authorities, IRB/IECs and investigators in 
accordance with all applicable global laws and regulations, i.e., per ICH Topic E6 (R1) 
Guidelines for Good Clinical Practice.
TRIAL GOVERNANCE AND OVERSIGHT
7.3
Scientific Advisory Committee
7.3.1
This trial was developed in collaboration with a Scientific Advisory Committee (SAC).  The 
SAC comprises both Sponsor and non-Sponsor scientific experts who provide input with 
respect to trial design, interpretation of trial results and subsequent peer-reviewed scientific 
publications.
8.0 STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study. Changes to
analyses made after the protocol has been finalized, but prior to unblinding, will be 
documented in a supplemental SAP (sSAP) and referenced in the Clinical Study Report 
(CSR) for the study. Post hoc exploratory analyses will be clearly identified in the CSR.
Statistical Analysis Plan Summary
8.1
Key elements of the statistical analysis plan are summarized below; the comprehensive plan 
is provided in Sections 8.2-8.12.
Study Design Overview
Phase IV, randomized, double-blind withdrawal study to evaluate the 
efficacy and safety of golimumab (MK-8259, GLM) after treatment 
withdrawal, compared with continuous treatment (either full- or reduced-
treatment regimen), in subjects with nr-axSpA
Treatment Assignment
In Period 1, all subjects receive open-label GLM. In Period 2, subjects who 
attained inactive disease status (at both Month 7 and Month 10 of open-
label golimumab treatment) in Period 1 undergo stratified randomization, in 
a 1:1:1 ratio (Placebo QM : GLM QM : GLM Q2M). 
Analysis Populations
Efficacy: The primary efficacy population is: subjects who are randomized 
in Period 2 and take at least one dose of trial medication in Period 2.  
Safety: All Subjects as Treated (ASaT).  
Primary Endpoint(s)
Proportion of subjects without a “flare” during up to 12 months in Period 2. 
Key Secondary Endpoints
None
Statistical Methods for Key 
Efficacy Analyses
The primary hypothesis will be evaluated by comparing treatment 
withdrawal (PBO) versus continued treatment with either GLM QM or 
GLM Q2M in the proportion of subjects without a “flare”, using a stratified 
Miettenen and Nurminen (M&N) test. 
Statistical Methods for 
Safety Analyses
Percentages of subjects with AEs in Period 2 will be summarized, using 
95% CIs based on the M&N method, for broad AE categories (subjects 
with: Any AE, a Drug-related AE, a Serious AE, an AE that is both Drug-
related and Serious, and Discontinuation due to AE). 
Interim Analyses
No interim analysis is planned.
 
 
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Multiplicity
The Type-I error rate over the multiple treatment comparisons will be 
controlled by a sequential (step down) testing procedure.  
Sample Size and Power 
Approximately 300 subjects will be enrolled to yield approximately 114 
subjects eligible for randomization in Period 2 of the study, assuming the 
proportion of subjects with inactive disease in Period 1 at both Months 7 
and 10 is about 38% in GLM-treated subjects (based on study P07642).
Using a randomization ratio of 1:1:1 into the PBO, GLM QM, and GLM 
Q2M arms, there will be 38 subjects in each treatment arm. Based on the 
results of prior studies, the proportion without “flare” during the 12 months 
following randomization is expected to be approximately 80% in subjects 
on continued monthly GLM and 30% in subjects in the treatment 
withdrawal (PBO) arm. Under these assumptions, the power to detect a 
difference between treatment withdrawal (PBO) and continued GLM
treatment (QM or Q2M) in the proportions of subjects without a “flare”
exceeds 99%, given α=0.05 (2-sided). As the “flare” rates may differ from 
those observed in prior studies, the targeted sample sizes of 38 subjects per 
arm will provide 88% power to detect differences of 75% vs. 40% in the 
continued GLM (QM or Q2M) vs. PBO treatment arms.
Responsibility for Analyses / In-House Blinding
8.2
The statistical analysis of the data obtained from this study will be the responsibility of the 
designee/ Clinical Biostatistics department of the Sponsor.
Period 1 is conducted using an open-label design, i.e., subjects, investigators, and Sponsor
personnel will be aware of subject treatment assignments after each subject is enrolled and 
treatment is assigned.  Period 2 is conducted using a double-blind design under in-house 
blinding procedures. The official, final database for Period 2 will not be unblinded until 
medical/scientific review has been performed, protocol deviations have been identified, and 
data have been declared final and complete.
Results of both periods will be presented in the CSR.
The interactive voice response system (IVRS) will generate and implement the randomized 
allocation schedule(s) for study treatment assignment.  
Hypotheses / Estimation
8.3
The hypothesis and objectives of the study are stated in Section 3.0. 
Analysis Endpoints
8.4
Efficacy and safety endpoints to be evaluated are listed below, followed by the descriptions 
of the derivations of selected endpoints. Additional exploratory endpoints to characterize the 
clinical response after re-treatment for a “flare” during Period 2 (such as time to response and 
extent of response), as well as disease control during Period 2, will be fully described in the 
supplemental SAP.
The baseline value will be defined as the latest measurement collected prior to the first dose 
of golimumab in Period 1 (Visit 2).
 
 
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Efficacy Endpoints
8.4.1
8.4.1.1
Primary Efficacy Endpoint
The primary efficacy endpoint for this trial is the proportion of subjects without a disease 
activity “flare” during up to 12 months in Period 2 (in subjects who attained inactive disease 
status after receiving open-label golimumab in Period 1).
A “flare” is defined as ASDAS at two consecutive visits that both show either absolute score 
≥2.1 or post-withdrawal increase (i.e., change from Visit 23) of ≥1.1.
8.4.1.2
Secondary Efficacy Endpoints
During Period 2: 

Proportion of subjects with a “flare” in the treatment-withdrawal group or the reduced-
treatment group who then show a clinical response after re-treatment with open-label 
golimumab;

Time to a first “flare”;

Proportion of subjects achieving ASAS20 response;

Proportion of subjects achieving ASAS40 response; 

Proportion of subjects achieving BASDAI50 response;

Proportion of subjects achieving ASAS partial remission;

Proportion of subjects achieving inactive disease status: ASDAS <1.3 score.
8.4.1.3
Exploratory Endpoints 

Predictors of “flare” after withdrawal of GLM.

Time to clinical response after re-treatment with golimumab for a “flare”;

Extent of clinical response after re-treatment with golimumab for a “flare” (including at 
12 weeks after re-treatment)

Proportion of subjects with disease control (subjects without “flare” or who attain clinical 
response after re-treatment for a “flare”);

Change from Baseline in components of the (composite) secondary endpoints:  

BASDAI (0 to10 NRS);

Total Back Pain (0 to10 NRS);

Morning Stiffness (0 to10 NRS);

BASFI (0 to10 NRS);

Patient's Global Disease Assessment (0 to10 NRS);

ASDAS;

CRP (mg/L).

Global Assessment of Disease by Investigator
 
 
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Safety Endpoints
8.4.2
An initial description of safety measures is provided in Section 4.2.3.2.
Serious infections, serious opportunistic infections, active tuberculosis, malignancies, and 
serious systemic hypersensitivity (including anaphylactic reaction) are prespecified as 
“Tier-1” events (for analysis of differences between treatments) in double-blind Period 2.
8.4.2.1
Events of Clinical Interest
The following serious and non-serious AEs are considered events of clinical interest (ECI)
and monitored for this trial:

Elevated AST or ALT lab value that is ≥3 x the upper limit of normal (ULN) and an 
elevated total bilirubin lab value that is ≥2 x ULN and, at the same time, an alkaline 
phosphatase lab value that <2 x ULN, as determined by way of protocol-specified 
laboratory testing or unscheduled laboratory testing.

Clinically significant opportunistic infections and TB

Clinically significant hypersensitivity reactions
8.4.2.2
Other Safety Endpoints:

Change from baseline for laboratory safety parameters and vital signs; 

Proportion of subjects with clinical AEs, laboratory AEs, and anti-GLM antibodies; 

Markedly abnormal (MA) laboratory values 
8.4.2.3
PK and Immunogenicity Endpoints

GLM concentrations (PK endpoints/analyses are described in a supplemental SAP)

Antibody status (positive/negative) for antibodies to GLM
Derivations of Efficacy Endpoints
8.4.3
8.4.3.1
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI is defined as follows:
Subject self-assessment of 6 questions, on a NRS from 0 to 10:
Q1. Fatigue/tiredness
Q2. Neck, back, or hip (spinal) pain
Q3. Pain/swelling in joints other than neck, back, or hip
Q4. Tenderness
Q5. Level of morning stiffness
Q6. Duration of morning stiffness
BASDAI score = 0.2 (Q1+Q2+Q3+Q4 + 0.5 [Q5+Q6])

BASDAI50 is defined as at least 50% improvement from baseline in the BASDAI score.
 
 
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8.4.3.2
Ankylosing Spondylitis Disease Activity Score
The ASDAS is a composite index to assess disease activity in axial spondyloarthropathies. 
The ASDAS is defined by calculating the following formula: 
0.12 x Back Pain      + 
0.06 x Duration of Morning Stiffness    + 
0.11 x Patient Global   + 
0.07 x Peripheral Pain/Swelling     + 0.58 x Ln(CRP+1)
1. Back pain – BASDAI question 2: "How would you describe the overall level of neck, back or hip 
pain you have had?"
2. Duration of Morning Stiffness – BASDAI question 6: "How long does your morning stiffness last 
from the time you wake up?"
3. Patient Global – Patient global disease assessment (PGDN) "How active was your spondylitis on 
average during the last week?"
4. Peripheral Pain/Swelling – BASDAI question 3: "How would you describe the overall level of 
pain/swelling in joints other than neck, back or hips you have had?"
5. Ln(CRP+1): natural logarithm of the C-reactive protein (mg/L) + 1
Back pain, duration of morning stiffness, patient global, and peripheral pain/swelling are all 
assessed on a NRS from 0 to 10 to calculate the ASDAS. When the CRP level is below the 
limit of detection (or when the CRP level is <2 mg/L), a value of 2 mg/L is used to calculate 
the ASDAS [8]. 
8.4.3.3
Assessment in SpondyloArthritis international Society-related Endpoints

ASAS20: A 20% improvement in response on the Assessment in SpondyloArthritis 
international Society (ASAS) scale is defined as meeting both criteria:
1. An improvement of 20% from Baseline and an absolute improvement from 
Baseline of 1 score (0 to10 NRS) in at least 3 of the following 4 domains:
a) Pain:  Total Back Pain score 
b) Morning Stiffness (average of questions 5 & 6 of the BASDAI concerning 
morning stiffness)
c) Function: Bath Ankylosing Spondylitis Functional Index (BASFI)
d) Patient Global Disease assessment (on Numeric scale) (PGDN)
2. Absence of deterioration from Baseline (20% and an absolute change of 1
score (0 to 10 NRS) in the potential remaining domain.

ASAS40: An ASAS40 response is defined as meeting 40% improvement (with absolute 
improvement of 2 score (0 to10 NRS) in at least 3 of the 4 domains and no worsening at 
all in the potential remaining domain.

ASAS Partial Remission: ASAS partial remission is defined as reaching 2 score (0 to 10 
NRS) in all 4 ASAS domains.
 
 
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8.4.3.4
Bath Ankylosing Spondylitis Functional Index
The BASFI is calculated as the mean of 10 NRSs (0 to 10 score). Eight of the scales relate to 
functional capacity of subjects, while the other 2 relate to a subject’s ability to cope with 
everyday life. An increase along the scale indicates a worsening condition.
8.4.3.5
Morning Stiffness
Morning stiffness is defined as the mean of questions 5 and 6 of the BASDAI concerning 
morning stiffness.
8.4.3.6
Patient’s Global Disease Assessment
The PGDN is completed as follows:
Subjects make an overall assessment of disease activity over the past week on NRS from 0 to 
10, with 0 being not active to 10 being extremely active.  
8.4.3.7
Total Back Pain
The TBP is completed as follows:
Subjects assess their average total back pain over the past week on a NRS from 0 to 10, with 
0 being no pain to 10 being extreme pain. 
Derivations of Safety Endpoints
8.4.4
Levels of laboratory values that are considered to be markedly abnormal have been defined 
for each laboratory parameter in Table 4.
 
 
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Table 4  Markedly Abnormal Criteria for Laboratory Parameters
Hematology laboratory parameters
Test
Criteria Value
Hemoglobin (g/dL) 
Decrease > 2.0 and Value < 8.0 
Hematocrit (%) 
Value < 27 
Total WBC (x103/μL) 
Value < 2.0 or Value > 20.0 
Eosinophils, absolute (x103/μL) 
Percent increase ≥ 100 and Value > 0.8 
Lymphocytes, absolute (x103/μL) 
Percent decrease ≥ 33 and Value < 1.0 
Neutrophils, absolute (x103/μL) 
Percent decrease ≥ 33 and Value < 1.5 
Platelets (x103/μL) 
Percent decrease ≥ 50 and Value < 75 
Clinical chemistry laboratory parameters
Test
Criteria Value
Albumin (g/dL) 
Decrease ≥ 1.0 and Value < 2.5 
Alkaline phosphatase (IU/L) 
Percent increase ≥ 100 and Value > 250 
ALT (IU/L) 
Percent increase ≥ 100 and Value > 150 
AST (IU/L) 
Percent increase ≥ 100 and Value > 150 
BUN (mg/dL) 
Percent increase ≥ 66 and Value > 40 
Calcium (mg/dL) 
(Increase ≥ 2.0 and Value > 11.5) or
(Decrease ≥ 1.5 and Value < 7.5) 
Chloride (mEq/L) 
Value < 85 or Value > 120 
Creatinine (mg/dL) 
Percent increase ≥ 66 and Value > 2.5 
Potassium (mEq/L) 
(Increase ≥ 0.8 and Value > 5.5) or
(Decrease ≥ 0.8 and Value < 3.0) 
Sodium (mEq/L) 
(Increase ≥ 10 and Value > 150) or 
(Decrease ≥ 5 and Value < 125) 
Total Bilirubin (mg/dL) 
Percent increase ≥ 100 and Value > 1.5 
Total protein (g/dL) 
Value < 4.5 or Value > 10.0 
Analysis Populations
8.5
Efficacy Analysis Populations
8.5.1
Period 2: The Full Analyses Set (FAS) population consists of all randomized subjects who 
received at least one dose of post-randomization study treatment. The “flare” Full Analyses 
Set (“flare” FAS) population is defined as all FAS subjects in the Treatment Withdrawal 
(PBO) arm or in the GLM Q2Mdose interval arm who “flare” during Period 2. 
Subjects will be included in the treatment group to which they are randomized for the 
analysis of efficacy data using the FAS population. Details on the approach to handling 
missing data are provided in Section 8.6 Statistical Methods.
 
 
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Safety Analysis Populations
8.5.2
Period 1 safety data will be analyzed separately from Period-2 safety data. 
Period 2: The ASaT population consists of all Period 2 randomized subjects who receive at 
least one dose of post-randomization study treatment.
At least one laboratory or vital sign measurement obtained subsequent to at least one dose of 
study treatment is required for inclusion in the analysis of each specific parameter. To assess 
change from baseline, a baseline measurement is also required.
Subjects will be included in the treatment group corresponding to the study treatment they 
actually received for the analysis of safety data using the ASaT population. For most subjects 
this will be the treatment group to which they are randomized. Subjects who take incorrect 
study treatment for the entire treatment period will be included in the treatment group 
corresponding to the study treatment actually received. 
Details on the approach to handling missing data for safety analyses are provided in 
Section 8.6 Statistical Methods.
Statistical Methods
8.6
Statistical approaches for efficacy analyses are described in Section 8.6.1. Statistical 
approaches for safety analyses are described in 8.6.2. Ninety-five percent confidence 
intervals will be generated for response rates of various endpoints as detailed below. Efficacy 
results that will be deemed to be statistically significant after consideration of the Type I 
error control strategy are described in Section 8.8, Multiplicity. Unless otherwise stated, all 
statistical tests will be conducted at the α=0.05 (2-sided) level.
Statistical Methods for Efficacy Analyses
8.6.1
This section describes the statistical methods that address the primary and secondary 
objectives. Methods related to exploratory objectives and related to analyses of data during 
Period 1 will be described in the supplemental SAP.
Efficacy data for continuous and categorical endpoints from Period 1 and Period 2 will be 
summarized separately. In Period 2, efficacy data will be summarized for each treatment 
comparison (GLM QM vs. withdrawal [PBO] and GLM Q2M vs. withdrawal [PBO]). In case 
of re-treatment following a “flare”, efficacy data will also be summarized for the time before 
re-treatment vs. the time after re-treatment. 
The primary efficacy endpoint, the proportion of subjects without a “flare” (comparing 
between the PBO and GLM QM arms and between the PBO and GLM Q2M arms) will be 
analyzed using the stratified Miettinen and Nurminen (M&N) method [5], with stratification 
based on CRP level (>6.0 mg/L or ≤6.0 mg/L) and weighting scheme based on sample-size
weights.
 
 
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In addition, a comparison of GLM QM vs. GLM Q2M will be conducted as an exploratory 
analysis. 
The exact binomial method of Clopper and Pearson [6] will be used to calculate a 95% CI on 
the proportion of subjects re-treated with golimumab after a “flare” who show a clinical 
response.
Missing data for the primary endpoint will be handled as follows:

Discontinuations: Subjects who enroll in Period 2 but discontinue prior to a “flare” will 
be counted as having a “flare”.

Missing components: If partial data are missing for the components of ASDAS (BASDAI 
questions 2, 3, 6, PGDN, and CRP), then a multiple imputation (MI) procedure will be 
used to calculate the ASDAS. Details of the MI procedure will be provided in the sSAP.
Missing data for the secondary endpoint of proportion of subjects with a clinical response to 
re-treatment with GLM for a “flare” will be handled as follows:

Discontinuations:  Subjects who “flare” in Period-2 but do not undergo re-treatment or 
discontinue prior to re-attainment of inactive disease will be counted in the group having
“flare” without clinical response to re-treatment.

Missing components data will be handled similarly as for the primary endpoint.
Time to first “flare” and time to clinical response after a “flare” will be summarized using a 
Kaplan-Meier (K-M) analysis and a stratified log rank test. The time to first “flare” analysis
will be conducted in the FAS. Day 1 for the K-M analysis will be the start date of Period 2. 
Subjects who do not “flare” will be censored at the time of study discontinuation; subjects 
who are lost-to-follow-up will be censored at the time of last data available. For the time to 
first “flare” analysis, missing component data will be imputed as specified for the primary 
endpoint. Summaries may include the pooled dose-reduction arms (Treatment Withdrawal 
[PBO] arm plus GLM Q2M arm) vs. GLM QM arm, as well as the 3 treatment arms 
separately.
The proportion of subjects with a clinical response to re-treatment with GLM for a “flare”
and the time to clinical response after re-treatment with GLM for a “flare” analysis will be 
conducted in the “flare” FAS.  
Other binary-response endpoints will be summarized by time point with 95% confidence 
intervals calculated using the exact binomial method of Clopper and Pearson (Period 1) and 
stratified M&N (Period 2). These summaries will be based on observed data; no missing data 
will be imputed.
Continuous endpoints will be summarized by time point using descriptive statistics. These 
summaries will be based on observed data; no missing data will be imputed.
Table 5 summarizes the key efficacy analyses.
 
 
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Table 5  Analysis Strategy for Efficacy Variables
Endpoint/Variable
(Description, Time Point)
Primary vs. 
Supportive 
Approach
Statistical Method
Analysis 
Population
Missing Data Approach
Primary Objective
Proportion of subjects without a 
disease activity “flare”, in 
subjects who attained inactive 
disease status in Period 2
Primary
Stratified M&N‡
FAS
Non-responder imputation for 
early discontinuations, 
MI§ for missing components
Secondary Objectives
Proportion of subjects with a 
clinical response to re-
treatment  with golimumab 
after a “flare” in Period 2
Primary
Clopper and 
Pearson
Flare FAS
Non-clinical response  
imputation for early 
discontinuations or “flare”
without re-treatment, 
MI§ for missing components
Time to first “flare” in Period 2
Primary
Kaplan-Meier
FAS
MI§ for missing components
 ‡
Miettenen and Nurminen.
  §
MI=Multiple Imputation of ASDAS individual components used to determine Inactive Disease status.
Statistical Methods for Safety Analyses
8.6.2
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
adverse experiences (AEs), laboratory tests and vital signs measurements.
The analysis of safety results will follow a tiered approach (Table 6). The tiers differ with 
respect to the analyses that will be performed. 
Table 6  Analysis Strategy for Safety Parameters
Safety 
Tier
Safety Endpoint†
p-Value
95% CI
Descriptive 
Statistics
Tier 1 ‡
Serious infections, serious opportunistic infections, 
active tuberculosis, malignancies, and serious systemic 
hypersensitivity (including anaphylactic reaction)
X
X
X
Tier 2
Any AE
X
X
Any Serious AE
X
X
Any Drug-Related AE
X
X
Any Serious and Drug-Related AE
X
X
Discontinuation due to AE
X
X
Specific AEs, SOCs or MA lab values
(incidence ≥4 subjects in one of the treatment groups)
X
X
Tier 3
Specific AEs, SOCs or MA lab values
(incidence <4 subjects in all of the treatment groups)
X
Change from Baseline Results (Labs, Vital Signs)
X
†
Adverse Experience references refer to both Clinical and Laboratory AEs.
‡     Applies to Period 2 only.
Note: SOC=System Organ Class; MA=Markedly Abnormal; X = results will be provided.
 
 
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Tier 1 analysis will be performed in Period 2 only if there are at least 4 events in one of the 
treatment arms, using the Miettinen and Nurminen method for between-treatment differences 
in the percentage of subjects with events. In the case of less than 4 events in each treatment 
arms, the Tier 1 events will be listed by subject, treatment and period. Other safety 
parameters will be considered Tier 2 or Tier 3. Tier 2 parameters will be assessed via point 
estimates with 95% confidence intervals provided; only point estimates are provided for 
Tier 3 safety parameters. Adverse experiences (specific terms as well as system organ class 
terms) that are not pre-specified as Tier-1 endpoints will be classified as belonging to 
"Tier 2" or "Tier 3", based on the number of events observed. Membership in Tier 2 requires 
that at least 4 subjects in any treatment group exhibit the event; all other adverse experiences 
and predefined limits of change will belong to Tier 3. For this protocol, broad clinical and 
laboratory AE categories (consisting of the percentage of subjects with: Any AE, a Drug-
related AE, a Serious AE, an AE that is both Drug-related and Serious, and Discontinued due 
to an AE) will be considered Tier 2 endpoints. Using the exact binomial method of Clopper 
and Pearson (Period 1) and Miettenen and Nurminen (Period 2), 95% confidence intervals 
will be provided for the percentages of subjects with events. 
The threshold of at least 4 events was chosen because the 95% confidence interval for the 
between-group difference in percent incidence will always include zero when treatment 
groups of equal size each have less than 4 events and thus would add little to the 
interpretation of potentially meaningful differences. Because many 95% confidence intervals 
may be provided without adjustment for multiplicity, the confidence intervals should be 
regarded as a helpful descriptive measure to be used in review, not a formal method for 
assessing the statistical significance of the between-group differences in adverse experiences 
and predefined limits of change. 
Safety data from Period 1 and Period 2 will be summarized separately. Period-2 safety data 
will be summarized for each treatment group (GLM QM, GLM Q2M, and PBO); in the case 
of re-treatment, safety data will also be summarized for the time before re-treatment vs. the 
time after re-treatment.
Continuous measures, such as changes from baseline in laboratory and vital signs parameters,
will be considered Tier 3 safety parameters. Summary statistics for baseline, on-treatment, 
and change from baseline values will be provided by treatment group in table format.  
Events of clinical interest will be listed by subject. Other selected safety endpoints of interest 
will be listed by subject, treatment and period; these endpoints include:  serious infections, 
serious opportunistic infections, active tuberculosis, malignancies, and serious systemic 
hypersensitivity (including anaphylactic reaction).
 
 
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Summaries of Baseline Characteristics, Demographics, and Other Analyses
8.6.3
8.6.3.1
Demographic and Baseline Characteristics
The comparability of the treatment groups for each relevant characteristic will be assessed by 
the use of tables and/or graphs. No statistical hypothesis tests will be performed on these 
characteristics. The number and percentage of subjects screened, enrolled in Period 1, 
enrolled in Period 2, the primary reasons for screening failure, and the primary reason for 
discontinuation will be displayed. Demographic variables (e.g., age, gender, race), baseline 
characteristics, primary and secondary diagnoses, and prior and concomitant therapies will be 
summarized either by descriptive statistics or categorical tables.
8.6.3.2
Antibodies to Golimumab
Blood samples will be collected to examine the formation of antibodies to GLM at the visits 
specified in the flow chart. Antibody data will be summarized as follows:

Antibody status (positive/negative) of subjects will be summarized by treatment group. 
Further details about defining the treatment groups and approach to summarizing the data 
are described in a supplemental SAP.
o
GLM QM (both before and after Re-treatment, if needed);
o
GLM Q2M (both before and after Re-treatment, if needed); 
o
PBO (both before and after Re-treatment, if needed).
In general, incidences of broad category AEs and injection-site reactions will be summarized 
by antibody status and treatment group.

The proportion of subjects who show clinical response following re-treatment with GLM
for a “flare” will be summarized by antibody status. The proportion of subjects who do 
not “flare” after withdrawal of GLM, or after reduction to GLM Q2M dosing, will also be 
summarized by antibody status. Efficacy endpoints (for example, ASDAS, ASAS20
response, ASAS40 response, and BASDAI50 response), occurrence of “flare”, clinical 
response after re-treatment for a “flare”, and antibody status will be listed by time point 
for subjects with positive antibody status.
8.6.3.3
Pharmacokinetic Data
The approach to summarizing the PK data is described in a supplemental SAP.
Interim Analyses
8.7
No interim analyses are planned for this study.
 
 
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Multiplicity
8.8
The Type-I error rate over the multiple treatment comparisons will be controlled by a 
sequential (step down) testing procedure. Testing of the primary hypotheses will begin with 
comparison of the GLM QM versus PBO. The GLM Q2M versus PBO comparison will be 
performed only if the primary efficacy GLM QM versus PBO analysis is statistically
significant at two-sided α = 0.05.
All other efficacy analyses will be considered supportive and/or exploratory. 
Sample Size and Power Calculations
8.9
A total of approximately 300 subjects will be enrolled. Assuming the proportion of subjects 
who attain inactive disease in Period 1 at both Months 7 and 10 is about 38% (based on the 
GO-AHEAD study, P07642 [1]), 300 enrolled subjects would result in approximately 114
subjects eligible for Period 2 of the study. With 114 subjects randomized in a ratio of 1:1:1
into the PBO, GLM QM, and GLM Q2M arms, 38 subjects are expected in each treatment
arm. 
Based on an expected proportion who do not “flare” of 80% in the GLM QM arm (based on 
study P07642) and 30% in the PBO arm (based on studies of subjects with early axial 
spondyloarthritis [7]), the power to detect a difference between treatment withdrawal (PBO) 
vs. continued treatment with GLM QM in the proportion of subjects who do not “flare”
exceeds 99%, given α=0.05 (2-sided).  (See the bold text in Table 6 below.) If the primary 
hypothesis is rejected for the GLM QM vs. PBO (treatment withdrawal) comparison, then 
tests of GLM Q2M vs. PBO will be conducted.  It is not known if the proportion who do not 
“flare” for the GLM Q2M arm will be similar to that for the GLM QM arm; but with a 
sample size of 38 per arm, the study will have 88% power to detect differences of 75% vs. 
40% in the proportions of subjects who do not “flare”, should the estimates of absence of 
“flare” differ from what has been observed in prior studies [7]. (See the bold italic text in 
Table 7 provides estimates of power for several response scenarios.
 
 
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Table 7  Power for the Primary Endpoint, Comparing Two Treatment Arms 
Treatment withdrawal: 
Placebo arm
Continued golimumab: 
QM or Q2M arm
Proportion who 
Do not “flare”
(N=38)
Proportion who 
Do not “flare”
(N=38)
Power†
20%
80%
99%
75%
99%
70%
99%
65%
98%
60%
96%
30%
80%
99%
75%
98%
70%
95%
65%
87%
60%
75%
40%
80%
96%
75%
88%
70%
75%
65%
59%
60%
41%
†Assumes α=0.05 and 2-sided test
QM=every month; Q2M=every 2 months
Subgroup Analyses and Effect of Baseline Factors
8.10
To explore whether the treatment effect is consistent across various subgroups, the estimate 
of the treatment effect (with a nominal 95% CI) for the primary endpoint, the proportion of 
subjects without a “flare” during up to 12 months, will be estimated and plotted within each 
category of each subgroup.  The following are examples of classification variables: 

CRP category (>6.0 mg/L or ≤6.0 mg/L)

MRI category for SI joint sacroiliitis (positive or negative)

Gender (male or female)

Age (≤30 years or >30 years)
In addition, a Forest plot will be produced, which provides the point estimates and 
confidence intervals for the treatment effect across the categories of subgroups listed above.
The consistency of the treatment effect will be assessed descriptively via summary statistics 
by category for the classification variables listed above.
 
 
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Compliance (Medication Adherence)
8.11
Drug accountability data for GLM will be collected during the study. Compliance (also 
termed “medication adherence”) rates will be summarized (N, mean, median, standard 
deviation, range [min and max]) by period and by treatment group and overall in Period 2.
The compliance rate for a subject will be defined as the total number of doses taken divided 
by the total number of doses the subject was supposed to take during the treatment period. 
The number of injections (administrations) will be summarized similarly as described above 
for the compliance rates. In addition, descriptive statistics (counts and percentages) will be 
provided for the number of injections administrated by period and by treatment group and 
overall in Period 2.
Extent of Exposure
8.12
The Extent of Exposure to study treatment will be evaluated by summary statistics (N, mean, 
median, and standard deviation) for the “Number of Days on Therapy” by Period and 
treatment group.  A summary of total GLM exposure across Periods 1 and 2 will also be 
provided.
Period-2 duration of exposure will be calculated as follows:

GLM QM group = the number of days from the first dose of GLM at Month 10 to the last 
dose + 30 days; 

GLM Q2M group = the number of days from the first dose of GLM at Month 10 to the 
last dose of GLM + 30 days; 

Placebo (withdrawal) group = number of days from Month 10 to the first dose of GLM
given as re-treatment for a “flare” or to study discontinuation for subjects who don’t 
undergo re-treatment with GLM. 
Due to the long half-life of GLM, the above subject-time computations will ignore the 
missing doses. The total subject-time of exposure for a group will be the sum of the subject-
time of exposure of all subjects in the group.
9.0 LABELING, PACKAGING,
STORAGE AND RETURN OF CLINICAL 
SUPPLIES
Investigational Product
9.1
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of 
investigational product in accordance with the protocol and any applicable laws and 
regulations.
Clinical Supplies will be provided by the Sponsor as summarized in Table 8.
 
 
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Table 8  Product Descriptions
Product Name & Potency
Dosage Form
golimumab 50mg/0.5mL
Injection
placebo for golimumab 50mg/0.5mL
Injection
All placebos were created by the Sponsor to match the active product.
Packaging and Labeling Information
9.2
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.
During Period 1 Open-label Run-in phase, subjects will receive open-label, kitted golimumab 
50mg/0.5mL. Each kit will contain a single pre-filled syringe and each subject will receive 
1 kit at the first dispensing visit followed by 3 kits at all subsequent dispensing visits. During
Period 2 Double-blind, subjects will receive blinded, kitted golimumab 50mg/0.5mL or 
placebo. Each subject will be dispensed 2 kits every 2 months and each kit will contain 1 pre-
filled syringe.
Clinical Supplies Disclosure
9.3
The emergency unblinding call center will use the randomization schedule for the trial to 
unblind subjects and to unmask treatment identity for the double-blind Period 2 of this trial.
In the event that the emergency unblinding call center is not available for a given site in this 
trial, the central electronic randomization system (IVRS/IWRS) should be used in order to 
unblind subjects and to unmask treatment/vaccine identity.
The Sponsor will not provide 
random code/disclosure envelopes or lists with the clinical supplies.
Treatment identification information is to be unmasked ONLY if necessary for the welfare of 
the subject.  Every effort should be made not to unblind the subject unless necessary. 
In the event that unblinding has occurred, the circumstances around the unblinding (e.g., date 
and reason) must be documented promptly, and the Sponsor Clinical Director notified as 
soon as possible.  Only the principal investigator or delegate and the respective subject’s 
code should be unblinded.  Trial site personnel and Sponsor personnel directly associated 
with the conduct of the trial should not be unblinded.
Storage and Handling Requirements
9.4
Clinical supplies must be stored in a secure, limited-access location under the storage 
conditions specified on the label.  
Receipt and dispensing of trial medication must be recorded by an authorized person at the 
trial site.
Clinical supplies may not be used for any purpose other than that stated in the protocol.
 
 
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Discard/Destruction/Returns and Reconciliation
9.5
The investigator is responsible for keeping accurate records of the clinical supplies received 
from the Sponsor or designee, the amount dispensed to and returned, and the amount 
remaining at the conclusion of the trial. For all trial sites, the local country Sponsor personnel 
or designee will provide appropriate documentation that must be completed for drug 
accountability and return, or local discard and destruction if appropriate. Where local discard 
and destruction is appropriate, the investigator is responsible for ensuring that a local 
discard/destruction procedure is documented.
Standard Policies
9.6
Trial site personnel will have access to a central electronic randomization system 
(IVRS/IWRS system) to allocate subjects, to assign treatment to subjects and to manage the 
distribution of clinical supplies. Each person accessing the IVRS system must be assigned an 
individual unique PIN.  They must use only their assigned PIN to access the system, and they 
must not share their assigned PIN with anyone.
10.0 ADMINISTRATIVE AND REGULATORY DETAILS
Confidentiality
10.1
Confidentiality of Data
10.1.1
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the institutional review board, ethics review committee (IRB/ERC) or similar 
or expert committee; affiliated institution and employees, only under an appropriate 
understanding of confidentiality with such board or committee, affiliated institution and 
employees.  Data generated by this trial will be considered confidential by the investigator, 
except to the extent that it is included in a publication as provided in the Publications section 
of this protocol.
Confidentiality of Subject Records
10.1.2
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/ERC, or regulatory authority representatives may consult and/or copy trial documents in 
order to verify worksheet/case report form data.  By signing the consent form, the subject 
agrees to this process.  If trial documents will be photocopied during the process of verifying 
worksheet/case report form information, the subject will be identified by unique code only; 
full names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all subject data used and disclosed in 
connection with this trial in accordance with all applicable privacy laws, rules and 
regulations.
 
 
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Confidentiality of Investigator Information
10.1.3
By signing this protocol, the investigator recognizes that certain personal identifying 
information with respect to the investigator, and all subinvestigators and trial site personnel, 
may be used and disclosed for trial management purposes, as part of a regulatory 
submissions, and as required by law.  This information may include:
1.
name, address, telephone number and e-mail address;
2.
hospital or clinic address and telephone number;
3.
curriculum vitae or other summary of qualifications and credentials; and
4.
other professional documentation.
Consistent with the purposes described above, this information may be transmitted to the 
Sponsor, and subsidiaries, affiliates and agents of the Sponsor, in your country and other 
countries, including countries that do not have laws protecting such information.  
Additionally, the investigator’s name and business contact information may be included 
when reporting certain serious adverse events to regulatory authorities or to other 
investigators.  By signing this protocol, the investigator expressly consents to these uses and 
disclosures.
If this is a multicenter trial, in order to facilitate contact between investigators, the Sponsor 
may share an investigator’s name and contact information with other participating 
investigators upon request.
Confidentiality of IRB/IEC Information
10.1.4
The Sponsor is required to record the name and address of each IRB/IEC member that 
reviews and approves this trial.  The Sponsor is also required to document that each IRB/IEC 
meets regulatory and ICH GCP requirements by requesting and maintaining records of the 
names and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
Compliance with Financial Disclosure Requirements
10.2
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54).  It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required.  It is the investigator's/subinvestigator's 
responsibility to comply with any such request.  
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements.  
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor or through a secure password-protected electronic portal provided by the 
 
 
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Sponsor.  The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes.  This may involve the 
transmission of information to countries that do not have laws protecting personal data.
Compliance with Law, Audit and Debarment
10.3
By signing this protocol, the investigator agrees to conduct the trial in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of Good 
Clinical Practice (e.g., International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice: 
Consolidated Guideline and other generally accepted standards of good clinical practice); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical trial.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by Merck, is provided in Section 12.1 -
Merck Code of Conduct for Clinical Trials.
The investigator also agrees to allow monitoring, audits, IRB/ERC review and regulatory 
authority inspection of trial-related documents and procedures and provide for direct access 
to all trial-related source data and documents.
The investigator agrees not to seek reimbursement from subjects, their insurance providers or 
from government programs for procedures included as part of the trial reimbursed to the 
investigator by the Sponsor.
The investigator shall prepare and maintain complete and accurate trial documentation in 
compliance with Good Clinical Practice standards and applicable federal, state and local 
laws, rules and regulations; and, for each subject participating in the trial, provide all data, 
and, upon completion or termination of the clinical trial, submit any other reports to the 
Sponsor as required by this protocol or as otherwise required pursuant to any agreement with 
the Sponsor.
Trial documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the trial site upon request for inspection, 
copying, review and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities.  The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor as a result of an audit to cure deficiencies in the trial documentation 
and worksheets/case report forms.
The investigator must maintain copies of all documentation and records relating to the 
conduct of the trial in compliance with all applicable legal and regulatory requirements.  This 
documentation includes, but is not limited to, the protocol, worksheets/case report forms, 
advertising for subject participation, adverse event reports, subject source data, 
correspondence with regulatory authorities and IRBs/ERCs, consent forms, investigator’s 
curricula vitae, monitor visit logs, laboratory reference ranges, laboratory certification or 
quality control procedures and laboratory director curriculum vitae.  By signing this protocol, 
 
 
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the investigator agrees that documentation shall be retained until at least 2 years after the last 
approval of a marketing application in an ICH region or 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.  
Because the clinical development and marketing application process is variable, it is 
anticipated that the retention period can be up to 15 years or longer after protocol database 
lock. The Sponsor will determine the minimum retention period and notify the investigator 
when documents may be destroyed.  The Sponsor will determine the minimum retention 
period and upon request, will provide guidance to the investigator when documents no longer 
need to be retained.  The sponsor also recognizes that documents may need to be retained for 
a longer period if required by local regulatory requirements. All trial documents shall be 
made available if required by relevant regulatory authorities. The investigator must consult 
with and obtain written approval by the Sponsor prior to destroying trial and/or subject files.  
ICH Good Clinical Practice guidelines recommend that the investigator inform the subject’s 
primary physician about the subject’s participation in the trial if the subject has a primary 
physician and if the subject agrees to the primary physician being informed.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this trial.
Persons debarred from conducting or working on clinical trials by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s trials.  The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the trial is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
In the event the Sponsor prematurely terminates a particular trial site, the Sponsor will
promptly notify that trial site’s IRB/IEC.
According to European legislation, a Sponsor must designate an overall coordinating 
investigator for a multi-center trial (including multinational).  When more than one trial site 
is open in an EU country, Merck, as the Sponsor, will designate, per country, a national 
principal coordinator (Protocol CI), responsible for coordinating the work of the principal 
investigators at the different trial sites in that Member State, according to national 
regulations.  For a single-center trial, the Protocol CI is the principal investigator.  In 
addition, the Sponsor must designate a principal or coordinating investigator to review the 
trial report that summarizes the trial results and confirm that, to the best of his/her 
knowledge, the report accurately describes the conduct and results of the trial [Clinical Study 
Report (CSR) CI].  The Sponsor may consider one or more factors in the selection of the 
individual to serve as the Protocol CI and or CSR CI (e.g., availability of the CI during the 
anticipated review process, thorough understanding of clinical trial methods, appropriate 
enrollment of subject cohort, timely achievement of trial milestones).  The Protocol CI must 
be a participating trial investigator.
 
 
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Compliance with Trial Registration and Results Posting Requirements
10.4
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the Sponsor of the trial is solely 
responsible for determining whether the trial and its results are subject to the requirements 
for submission to the Clinical Trials Data Bank, http://www.clinicaltrials.gov.  Merck, as 
Sponsor of this trial, will review this protocol and submit the information necessary to fulfill 
these requirements.  Merck entries are not limited to FDAMA/FDAAA mandated trials. 
Information posted will allow subjects to identify potentially appropriate trials for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate trial locations and trial site contact information.    
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAMA/FDAAA are that of the Sponsor and agrees not to submit any information about this 
trial or its results to the Clinical Trials Data Bank.
Quality Management System
10.5
By signing this protocol, the Sponsor agrees to be responsible for implementing and 
maintaining a quality management system with written development procedures and 
functional area standard operating procedures (SOPs) to ensure that trials are conducted and 
data are generated, documented, and reported in compliance with the protocol, accepted 
standards of Good Clinical Practice, and all applicable federal, state, and local laws, rules and 
regulations relating to the conduct of the clinical trial.
Data Management
10.6
The investigator or qualified designee is responsible for recording and verifying the accuracy 
of subject data.  By signing this protocol, the investigator acknowledges that his/her 
electronic signature is the legally binding equivalent of a written signature.  By entering 
his/her electronic signature, the investigator confirms that all recorded data have been 
verified as accurate.
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
Publications
10.7
This trial is intended for publication, even if terminated prematurely. Publication may include 
any or all of the following: posting of a synopsis online, abstract and/or presentation at a 
scientific conference, or publication of a full manuscript.  The Sponsor will work with the 
authors to submit a manuscript describing trial results within 12 months after the last data 
become available, which may take up to several months after the last subject visit in some 
cases such as vaccine trials.  However, manuscript submission timelines may be extended on 
OTC trials.  For trials intended for pediatric-related regulatory filings, the investigator agrees 
to delay publication of the trial results until the Sponsor notifies the investigator that all 
relevant regulatory authority decisions on the trial drug have been made with regard to 
 
 
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pediatric-related regulatory filings. Merck will post a synopsis of trial results for approved 
products on www.clinicaltrials.gov by 12 months after the last subject's last visit for the
primary outcome, 12 months after the decision to discontinue development, or product 
marketing (dispensed, administered, delivered or promoted), whichever is later.
These timelines may be extended for products that are not yet marketed, if additional time is 
needed for analysis, to protect intellectual property, or to comply with confidentiality 
agreements with other parties.  Authors of the primary results manuscript will be provided 
the complete results from the Clinical Study Report, subject to the confidentiality agreement. 
When a manuscript is submitted to a biomedical journal, the Sponsor's policy is to also 
include the protocol and statistical analysis plan to facilitate the peer and editorial review of 
the manuscript.  If the manuscript is subsequently accepted for publication, the Sponsor will 
allow the journal, if it so desires, to post on its website the key sections of the protocol that 
are relevant to evaluating the trial, specifically those sections describing the trial objectives 
and hypotheses, the subject inclusion and exclusion criteria, the trial design and procedures, 
the efficacy and safety measures, the statistical analysis plan, and any amendments relating to 
those sections.  The Sponsor reserves the right to redact proprietary information.
For multicenter trials, subsequent to the multicenter publication (or after public disclosure of 
the results online at www.clinicaltrials.gov if a multicenter manuscript is not planned), an 
investigator and his/her colleagues may publish their data independently.  In most cases, 
publication of individual trial site data does not add value to complete multicenter results, 
due to statistical concerns.  In rare cases, publication of single trial site data prior to the main 
paper may be of value.  Limitations of single trial site observations in a multicenter trial 
should always be described in such a manuscript.
Authorship credit should be based on 1) substantial contributions to conception and design, 
or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising 
it critically for important intellectual content; and 3) final approval of the version to be 
published. Authors must meet conditions 1, 2 and 3.  Significant contributions to trial 
execution may also be taken into account to determine authorship, provided that 
contributions have also been made to all three of the preceding authorship criteria.  Although 
publication planning may begin before conducting the trial, final decisions on authorship and 
the order of authors’ names will be made based on participation and actual contributions to 
the trial and writing, as discussed above. The first author is responsible for defending the 
integrity of the data, method(s) of data analysis and the scientific content of the manuscript.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or 
presentations regarding this trial 45 days prior to submission for publication/presentation. 
Any information identified by the Sponsor as confidential must be deleted prior to 
submission; this confidentiality does not include efficacy and safety results. Sponsor review 
can be expedited to meet publication timelines.
 
 
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11.0 LIST OF REFERENCES
1. Sieper J, van der Heijde D, Dougados D, Maksymowych WP, Scott BB, Boice JA, 
Berd Y, Bergman G, Curtis S, Tzontcheva A, Huyck S, Weng HH. A randomized, 
double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in 
patients with active non-radiographic axial spondyloarthritis. Arthritis Rheumatol 
2015; 67(10); 2702-2712.
2. Van der Heijde D, Sieper J, Maksymowych WP, et al. 2010 Update of the 
international ASAS recommendations for the use of anti-TNF agents in patients with 
axial spondyloarthritis. Ann Rheum Dis 2011; 70: 905–908.
3. Machado PMMC, Landewé RBM, van der Heijde DM. Endorsement of definitions of 
disease activity states and improvement scores for the Ankylosing Spondylitis 
Disease Activity Score: Results from OMERACT 10. J Rheumatol 2011; 38: 1502–
1506. 
4. Machado P, Landewé R, Lie E, Kvien TK, Braun J, Baker D, van der Heijde DM for 
the Assessment of SpondyloArthritis international Society. Ankylosing Spondylitis 
Disease Activity Score (ASDAS): Defining cut-off values for disease activity states 
and improvement scores. Ann Rheum Dis 2011;70: 47–53.
5. Miettenen O, Nurminen M. Comparative analysis of two rates. Statistics in medicine 
1985; Vol.4: 213-226.
6. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the 
case of binomial. Biometrika 1934; 26: 404-413. 
7. Song IH, Haibel H, Poddubnyy D, Braun J, Sieper J. Withdrawal of biologic therapy 
in axial spondyloarthritis: the experience in early disease. Clin Exp Rheumatol 2013; 
31 (Suppl.78):S37-S42.
8. Machado P, Navarro-Compán V, Landewé R, van Gaalen FA, Roux C, van der 
Heijde D. Calculating the Ankylosing Spondylitis Disease Activity Score if the 
conventional C-Reactive Protein level is below the limit of detection or if high-
sensitivity C-Reactive Protein is used: An analysis in the DESIR Cohort. Arthritis 
Rheumatol 2015; 67: 408-413.
9. Sieper J, Rudwaleit, M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, Dougados 
D, Hermann K-G, Landewé R, Maksymowych WP, van der Heijde D. The 
Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to 
assess spondyloarthritis. Ann Rheum Dis 2009;68 (Suppl II): ii1–ii44.
 
 
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12.0 APPENDICES
Merck Code of Conduct for Clinical Trials
12.1
Merck*
Code of Conduct for Clinical Trials
I.
Introduction
A. Purpose
Merck, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing and reporting these trials in 
compliance with the highest ethical and scientific standards. Protection of subject safety is the overriding concern in 
the design of clinical trials. In all cases, Merck clinical trials will be conducted in compliance with local and/or 
national regulations and in accordance with the ethical principles that have their origin in the Declaration of Helsinki. 
B. Scope
Such standards shall be endorsed for all clinical interventional investigations sponsored by Merck irrespective of the 
party (parties) employed for their execution (e.g., contract research organizations, collaborative research efforts). This 
Code is not intended to apply to trials which are observational in nature, or which are retrospective. Further, this Code 
does not apply to investigator-initiated trials which are not under the control of Merck.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of Merck or comparator products.  Alternatively, Merck may 
conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to determine 
subject preferences, etc.  
The design (i.e., subject population, duration, statistical power) must be adequate to address the specific purpose 
of the trial.  Research subjects must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
Merck selects investigative sites based on medical expertise, access to appropriate subjects, adequacy of facilities 
and staff, previous performance in Merck trials, as well as budgetary considerations.  Prior to trial initiation, sites 
are evaluated by Merck personnel to assess the ability to successfully conduct the trial.
3. Site Monitoring/Scientific Integrity
Trial sites are monitored to assess compliance with the trial protocol and general principles of Good Clinical 
Practice.  Merck reviews clinical data for accuracy, completeness and consistency. Data are verified versus source 
documentation according to standard operating procedures.  Per Merck policies and procedures, if fraud, 
misconduct or serious GCP-non-Compliance are suspected, the issues are promptly investigated. When necessary, 
the clinical site will be closed, the responsible regulatory authorities and ethics review committees notified and 
data disclosed accordingly. 
B. Publication and Authorship
To the extent scientifically appropriate, Merck seeks to publish the results of trials it conducts.  Some early phase or 
pilot trials are intended to be hypothesis-generating rather than hypothesis testing.  In such cases, publication of 
results may not be appropriate since the trial may be underpowered and the analyses complicated by statistical issues 
of multiplicity.
Merck’s policy on authorship is consistent with the requirements outlined in the ICH-Good Clinical Practice 
guidelines. In summary, authorship should reflect significant contribution to the design and conduct of the trial, 
performance or interpretation of the analysis, and/or writing of the manuscript.  All named authors must be able to 
defend the trial results and conclusions.  Merck funding of a trial will be acknowledged in publications. 
 
 
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III. Subject Protection
A. IRB/ERC review
All clinical trials will be reviewed and approved by an independent IRB/ERC before being initiated at each site.  
Significant changes or revisions to the protocol will be approved by the IRB/ERC prior to implementation, except that 
changes required urgently to protect subject safety and well-being may be enacted in anticipation of IRB/ERC 
approval. For each site, the IRB/ERC and Merck will approve the subject informed consent form. 
B. Safety
The guiding principle in decision-making in clinical trials is that subject welfare is of primary importance.  Potential 
subjects will be informed of the risks and benefits of, as well as alternatives to, trial participation. At a minimum, trial
designs will take into account the local standard of care.  Subjects are never denied access to appropriate medical care 
based on participation in a Merck clinical trial. 
All participation in Merck clinical trials is voluntary.  Subjects are enrolled only after providing informed consent for 
participation.  Subjects may withdraw from a Merck trial at any time, without any influence on their access to, or 
receipt of, medical care that may otherwise be available to them.
C. Confidentiality
Merck is committed to safeguarding subject confidentiality, to the greatest extent possible.  Unless required by law, 
only the investigator, sponsor (or representative) and/or regulatory authorities will have access to confidential medical 
records that might identify the research subject by name.  
D. Genomic Research
Genomic Research will only be conducted in accordance with informed consent and/or as specifically authorized by 
an Ethics Committee.
IV. Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive.  It is Merck’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of Merck trials.   Merck does not pay incentives to 
enroll subjects in its trials.  However, when enrollment is particularly challenging, additional payments may be made 
to compensate for the time spent in extra recruiting efforts.
Merck does not pay for subject referrals.  However, Merck may compensate referring physicians for time spent on 
chart review to identify potentially eligible subjects.
B. Clinical Research Funding 
Informed consent forms will disclose that the trial is sponsored by Merck, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial.  However, the local IRB/ERC may wish to alter 
the wording of the disclosure statement to be consistent with financial practices at that institution.  As noted above, 
publications resulting from Merck trials will indicate Merck as a source of funding.
C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices including, in the U.S., those established by the American Medical 
Association (AMA). 
V. Investigator Commitment
Investigators will be expected to review Merck’s Code of Conduct as an appendix to the trial protocol, and in signing 
the protocol, agree to support these ethical and scientific standards.
* In this document, "Merck" refers to Merck Sharp & Dohme Corp. and Schering Corporation, each of which is a 
subsidiary of Merck & Co., Inc.  Merck is known as MSD outside of the United States and Canada.  As warranted by 
context, Merck also includes affiliates and subsidiaries of Merck & Co., Inc."
 
 
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Collection and Management of Specimens for Future Biomedical Research
12.2
1. Definitions
a.
Biomarker:  A biological molecule found in blood, other body fluids, or tissues that is a 
sign of a normal or abnormal process or of a condition or disease.  A biomarker may be 
used to see how well the body responds to a treatment for a disease or condition.1
b. Pharmacogenomics:  The investigation of variations of DNA and RNA characteristics as 
related to drug/vaccine response.2
c.
Pharmacogenetics:  A subset of pharmacogenomics, pharmacogenetics is the influence of 
variations in DNA sequence on drug/vaccine response.2
d. DNA:  Deoxyribonucleic acid.
e.
RNA:  Ribonucleic acid.
2. Scope of Future Biomedical Research
The specimens collected in this trial as outlined in Section 7.1.3.7 – Future Biomedical 
Research Sample Collection will be used to study various causes for how subjects may 
respond to a drug/vaccine.  Future biomedical research specimen(s) will be stored to 
provide a resource for future trials conducted by the Sponsor focused on the study of 
biomarkers responsible for how a drug/vaccine enters and is removed by the body, how a 
drug/vaccine works, other pathways a drug/vaccine may interact with, or other aspects of 
disease. The specimen(s) may be used for future assay development and/or drug/vaccine 
development.
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations 
with the greatest need.  All specimens will be used by the Sponsor or those working for 
or with the Sponsor.
3. Summary of Procedures for Future Biomedical Research
a.
Subjects for Enrollment
All subjects enrolled in the clinical trial will be considered for enrollment in the 
Future Biomedical Research sub-trial.
b. Informed Consent
Informed consent for specimens (i.e., DNA, RNA, protein, etc.) will be obtained 
during screening for protocol enrollment from all subjects or legal guardians, at a trial 
visit by the investigator or his or her designate.  Informed consent for Future 
Biomedical Research should be presented to the subjects on Visit 1.  If delayed, 
present consent at next possible Subject Visit. Informed consent must be obtained 
prior to collection of all Future Biomedical Research specimens.  Consent forms 
signed by the subject will be kept at the clinical trial site under secure storage for 
regulatory reasons.  
 
 
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A template of each trial site’s approved informed consent will be stored in the 
Sponsor’s clinical document repository. Each consent will be assessed for appropriate 
specimen permissions.  
c.
eCRF Documentation for Future Biomedical Research Specimens
Documentation of subject consent for Future Biomedical Research will be captured in 
the electronic Case Report Forms (eCRFs). Any specimens for which such an 
informed consent cannot be verified will be destroyed.
d. Future Biomedical Research Specimen Collections
Collection of specimens for Future Biomedical Research will be performed as 
outlined in the trial flow chart. In general, if additional blood specimens are being 
collected for Future Biomedical Research, these will usually be obtained at a time 
when the subject is having blood drawn for other trial purposes.
4. Confidential Subject Information for Future Biomedical Research 
In order to optimize the research that can be conducted with Future Biomedical Research 
specimens, it is critical to link subject' clinical information with future test results. In fact 
little or no research can be conducted without connecting the clinical trial data to the 
specimen. The clinical data allow specific analyses to be conducted. Knowing subject 
characteristics like gender, age, medical history and treatment outcomes are critical to 
understanding clinical context of analytical results.
To maintain privacy of information collected from specimens obtained for Future 
Biomedical Research, the Sponsor has developed secure policies and procedures. All 
specimens will be single-coded per ICH E15 guidelines as described below. 
At the clinical trial site, unique codes will be placed on the Future Biomedical Research 
specimens for transfer to the storage facility.  This first code is a random number which 
does not contain any personally identifying information embedded within it. The link (or 
key) between subject identifiers and this first unique code will be held at the trial site.  No 
personal identifiers will appear on the specimen tube.  
5. Biorepository Specimen Usage
Specimens obtained for the Merck Biorepository will be used for analyses using good 
scientific practices.  Analyses utilizing the Future Biomedical Research specimens may 
be performed by the Sponsor, or an additional third party (e.g., a university investigator) 
designated by the Sponsor. The investigator conducting the analysis will follow the 
Sponsor’s privacy and confidentiality requirements. Any contracted third party analyses 
will conform to the specific scope of analysis outlined in this sub-trial. Future Biomedical 
Research specimens remaining with the third party after specific analysis is performed 
will be reported to the Sponsor.
6. Withdrawal From Future Biomedical Research 
Subjects may withdraw their consent for Future Biomedical Research and have their 
specimens and all derivatives destroyed.   Subjects may withdraw consent at any time by 
contacting the principal investigator for the main trial. If medical records for the main 
trial are still available, the investigator will contact the Sponsor using the designated 
 
 
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mailbox (clinical.specimen.management@merck.com) and a form will be provided to 
obtain appropriate information to complete specimen withdrawal. Subsequently, the 
subject's specimens will be removed from the biorepository and be destroyed. 
Documentation will be sent to the investigator confirming the destruction. It is the 
responsibility of the investigator to inform the subject of completion of destruction.  Any 
analyses in progress at the time of request for destruction or already performed prior to 
the request being received by the Sponsor will continue to be used as part of the overall 
research trial data and results. No new analyses would be generated after the request is 
received.
In the event that the medical records for the main trial are no longer available (e.g., if the 
investigator is no longer required by regulatory authorities to retain the main trial 
records) or the specimens have been completely anonymized, there will no longer be a 
link between the subject’s personal information and their specimens. In this situation, the 
request for specimen destruction can not be processed. 
7. Retention of Specimens 
Future Biomedical Research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from the end of the main study. Specimens may be stored for 
longer if a regulatory or governmental authority has active questions that are being 
answered. In this special circumstance, specimens will be stored until these questions 
have been adequately addressed.
Specimens from the trial site will be shipped to a central laboratory and then shipped to 
the Sponsor-designated biorepository. If a central laboratory is not utilized in a particular 
trial, the trial site will ship directly to the Sponsor-designated biorepository. The 
specimens will be stored under strict supervision in a limited access facility which 
operates to assure the integrity of the specimens.  Specimens will be destroyed according 
to Sponsor policies and procedures and this destruction will be documented in the 
biorepository database.
8. Data Security
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated trial administrator research 
personnel and/or collaborators. Database user authentication is highly secure, and is 
accomplished using network security policies and practices based on international 
standards (e.g., ISO17799) to protect against unauthorized access.
9. Reporting of Future Biomedical Research Data to Subjects
No information obtained from exploratory laboratory studies will be reported to the 
subject, family, or physicians. Principle reasons not to inform or return results to the 
subject include: Lack of relevance to subject health, limitations of predictive capability, 
and concerns regarding misinterpretation.
If any exploratory results are definitively associated with clinical significance for subjects 
while the clinical trial is still ongoing, investigators will be contacted with information. 
After the clinical trial has completed, if any exploratory results are definitively associated 
with clinical significance, the Sponsor will endeavor to make such results available 
 
 
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through appropriate mechanisms (e.g., scientific publications and/or presentations). 
Subjects will not be identified by name in any published reports about this study or in any 
other scientific publication or presentation.
10. Future Biomedical Research Study Population
Every effort will be made to recruit all subjects diagnosed and treated on Sponsor clinical 
trials for Future Biomedical Research.
11. Risks Versus Benefits of Future Biomedical Research 
For future biomedical research, risks to the subject have been minimized.  No additional
risks to the subject have been identified as no additional specimens are being collected 
for Future Biomedical Research (i.e., only leftover samples are being retained.
The Sponsor has developed strict security, policies and procedures to address subject data 
privacy concerns.  Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality.  In this highly unlikely situation there is risk that the 
information, like all medical information, may be misused.
12. Questions
Any questions related to the future biomedical research should be e-mailed directly to 
clinical.specimen.management@merck.com.
13. References
1. National Cancer Institute: http://www.cancer.gov/dictionary/?searchTxt=biomarker
2.
International Conference on Harmonization: DEFINITIONS FOR GENOMIC 
BIOMARKERS, PHARMACOGENOMICS, PHARMACOGENETICS, GENOMIC 
DATA 
AND 
SAMPLE 
CODING 
CATEGORIES 
-
E15; 
http://www.ich.org/LOB/media/MEDIA3383.pdf
 
 
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Pharmacogenetics Informational Brochure for IRBs/IECs & Investigational Site Staff
12.3 
 
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Approximate Blood Volumes Drawn/Collected 
12.4
Blood Volumes in milliliters (mL) by Trial Visit and by Sample Types
Screening
Visit
Visit 2
Visits 4, 
10, 16
Visit 23
Visits 28, 
32, 40, 44
Visits 36, 
48, Uns.
Blood Parameter 
Approximate Blood Volume (mL)
Hematology
5
5
5
5x2=10
Serum Chemistry
5
5
5
5x2=10
CRP
5
5
5
(V16 only)
5
5x4=20
5x3=10
(V36, 
V48, and 
Uns.)
Serum β-Human 
Chorionic Gonadotropin 
(β-hCG)
5
5
5
(V48 only)
Hepatitis B Virus 
Screen (Per site SOPs)/
Tuberculosis Test/HLA 
B-27
15
Blood for Genetic 
Analysis
8.5
Pharmacokinetic (PK)
5
5 x 3 visits 
=15
5
5x4=20
5x2=10
Anti-drug (MK-8259) 
antibody
5
5 x 3 visits 
=15
5
5x1=5
(V28 only)
5x2=10
Expected Total (mL)
35 mL
33.5 mL
Visits 4 
and 10 = 
10 mL; 
Visit 
16=15 mL
30 mL
V28=15 
mL
V32, V40, 
and 
V44=10 
mL
V36=25 
mL; V48
=30 mL; 
Uns.=5 
mL
 
 
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List of Abbreviations
12.5
Term
Definition
AE
Adverse Event
ALT
ALanine aminoTransferase (also known as SGPT)
AS
Ankylosing Spondylitis
ASAS
Assessment of the SpondyloArthritis international Society
ASaT
All Subjects as Treated
ASDAS
Ankylosing Spondylitis Disease Activity Score
AST
ASpartate aminoTransferase (also known as SGOT)
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BCG
Bacille Calmette-Guerin vaccination
CFR
Code of Federal Regulations
CHF
Congestive Heart Failure
CRF
Case Report Form
CRP
C-reactive protein
CSR
Clinical Study Report
DC
Discontinuation
DMARDs
Disease Modifying Anti-Rheumatic Drugs
DNA
DeoxyriboNucleic Acid
ECI
Event of Clinical Interest
eCRF
electronic Case Report Form
EU
European Union
FAS
Full Analysis Set
FBR
Future Biomedical Research
FDA
Food and Drug Administration, USA
GADI
Global Assessment of Disease by Investigator
GCP
Good Clinical Practice
GGT
Gamma-Glutamyl Transferase
GLM
Golimumab
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
HLA-B27
Human Leukocyte Antigen B27
IB
Investigator’s Brochure
 
 
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Term
Definition
IBD
Inflammatory Bowel Disease
IEC
Independent Ethics Committee
ICF
Informed Consent form
ICH
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human 
Use
IND
Investigational New Drug Application; legal instrument in the 
USA that allows trial of unapproved, investigational new drugs 
in human subjects
IRB
Institutional Review Board
IUD
Intrauterine Device
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
K-M
Kaplan-Meier
MAR
Missing At Random
MedDRA
Medical Dictionary for Regulatory Activities
MRI
Magnetic Resonance Imaging
NA, N/A
Not applicable
nr-axSpA
Non-radiographic axial SpondyloArthritis
NRS
Numerical Rating Scale
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
PE
Physical Exam
PGDN
Patient Global Disease assessment (on Numeric scale)
QM
Every Month
Q2M
Every 2 Months
SAE
Serious Adverse Event
SC
Subcutaneous 
SD
Standard Deviation
SE
Standard Error
SI joints
SacroIliac joints
SOP
Standard Operating Procedure
SpA
SpondyloArthritis
SPARCC
SPondyloArthritis Research Consortium of Canada
TB
TuBerculosis
TNFα
Tumor Necrosis Factor alpha
 
 
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Bath Ankylosing Spondylitis Disease Activity Index
12.6
 
 
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Bath Ankylosing Spondylitis Functional Index
12.7
 
 
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Patient Global Disease Assessment
12.8
 
 
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Total Back Pain
12.9
 
 
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Global Assessment of Disease by Investigator
12.10
 
 
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13.0 SIGNATURES
Sponsor's Representative
13.1
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
Investigator
13.2
I agree to conduct this clinical trial in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol (including other manuals and documents 
referenced from this protocol).  I agree to conduct the trial in accordance with generally 
accepted standards of Good Clinical Practice.  I also agree to report all information or data in 
accordance with the protocol and, in particular, I agree to report any serious adverse events 
as defined in Section 7.0 – Assessing and Recording Adverse Events.  I also agree to handle 
all clinical supplies provided by the Sponsor and collect and handle all clinical specimens in 
accordance with the protocol.  I understand that information that identifies me will be used 
and disclosed as described in the protocol, and that such information may be transferred to 
countries that do not have laws protecting such information.  Since the information in this 
protocol and the referenced Investigator’s Brochure is confidential, I understand that its 
disclosure to any third parties, other than those involved in approval, supervision, or conduct 
of the trial is prohibited.  I will ensure that the necessary precautions are taken to protect such 
information from loss, inadvertent disclosure or access by third parties.
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
 
 
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