A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis
Phase: PHASE2
Conditions: Rheumatoid Arthritis (RA)
Sponsor: AbbVie

NCT03823391

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
8
3
STUDY OBJECTIVES AND ENDPOINTS
9
3.1
OBJECTIVES
9
3.2
PRIMARY ENDPOINT
10
3.3
SECONDARY AND ADDITIONAL ENDPOINTS
10
3.4
SAFETY ENDPOINTS
10
3.5
PHARMACOKINETIC AND IMMUNOGENICITY ENDPOINTS
11
3.6
BIOMARKER ENDPOINTS
11
4
INVESTIGATIONAL PLAN
11
4.1
OVERALL STUDY DESIGN AND PLAN
11
4.2
DISCUSSION OF STUDY DESIGN
13
5
STUDY ACTIVITIES
14
5.1
ELIGIBILITY CRITERIA
14
5.2
CONTRACEPTION RECOMMENDATIONS
17
5.3
PROHIBITED MEDICATIONS AND THERAPY
18
5.4
PRIOR AND CONCOMITANT THERAPY
18
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
19
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
20
5.7
STUDY DRUG
21
5.8
RANDOMIZATION/DRUG ASSIGNMENT
22
5.9
PROTOCOL DEVIATIONS
23
6
SAFETY CONSIDERATIONS
23
6.1
COMPLAINTS AND ADVERSE EVENTS
23
6.2
TOXICITY MANAGEMENT
27

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
30
7.1
STATISTICAL AND ANALYTICAL PLANS
30
7.2
DEFINITION FOR ANALYSIS POPULATIONS
30
7.3
STATISTICAL ANALYSES FOR EFFICACY
31
7.4
STATISTICAL ANALYSES FOR SAFETY
33
7.5
STATISTICAL ANALYSIS OF PHARMACOKINETIC AND IMMUNOGENITICY DATA
33
7.6
STATISTICAL ANALYSIS OF BIOMARKER DATA
33
7.7
INTERIM ANALYSIS
33
8
ETHICS
34
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
34
8.2
ETHICAL CONDUCT OF THE STUDY
34
8.3
SUBJECT CONFIDENTIALITY
34
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
34
10 DATA QUALITY ASSURANCE
34
11 COMPLETION OF THE STUDY
35
12 REFERENCES
35
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCT
22
TABLE 2.
SPECIFIC TOXICITY MANAGEMENT GUIDELINES FOR ABNORMAL LABORATORY VALUES
28
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC
12
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
36
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
39

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
40
APPENDIX D.
ADDITIONAL ENDPOINT/ASSESSMENT DEFINITIONS
41
APPENDIX E.
JOINT EVALUATION WORKSHEET EXAMPLE
43
APPENDIX F.
REPORTED OUTCOMES VAS
44
APPENDIX G.
HEALTH ASSESSMENT QUESTIONNAIRE DISABILITY INDEX
45
APPENDIX H.
36-ITEM SHORT FORM HEALTH SURVEY SAMPLE
46
APPENDIX I.
RHEUMATOLOGY COMMON TOXICITY CRITERIA V.2.0
47
APPENDIX J.
ACTIVITY SCHEDULE
61
APPENDIX K.
SUMMARY OF CHANGES
65
APPENDIX L.
OPERATIONS MANUAL
68

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
Tumor necrosis factor (TNF)α antagonists reduce the signs and symptoms of disease by reducing 
inflammation and limiting the progression of tissue destruction and are considered effective therapies 
with established safety profiles in patients with immune-mediated inflammatory diseases, including 
rheumatoid arthritis (RA).  Nevertheless, TNFα antagonists as well as other biologics and targeted 
synthetic disease-modifying antirheumatic drugs (DMARDs) provide 50% improvement in arthritis scores 
(American College of Rheumatology 50% improvement criteria [ACR50]) for fewer than half of RA 
subjects, even in combination with methotrexate (MTX), indicating that there remains an unmet clinical 
need for improved therapies.
Glucocorticoid receptor modulators (GRMs) are potent drugs for treating many inflammatory diseases.  
In RA, GRMs such as prednisone are highly effective at reducing inflammation and fatigue as well as 
relieving pain.  However, the administration of GRMs is limited due to their side effect profile including 
(but not limited to) hypothalamic-pituitary-adrenal (HPA) axis suppression, increased rates of bone 
fracture due to osteoporosis, hyperglycemia, glaucoma, skin thinning and weight gain.1  Thus, the full 
efficacy of GRM therapy is not achieved with existing agents due to systemic side effects.
ABBV-3373 is an antibody-drug conjugate (ADC) composed of adalimumab (the active component of 
Humira®) conjugated to A-1677770, a proprietary, highly potent GRM (also referred to as the payload) 
being developed for the treatment of immune-mediated inflammatory diseases including RA.  This 
adalimumab/GRM ADC has the potential to deliver a highly potent anti-inflammatory payload selectively 
to the activated immune cells that express transmembrane TNF, and meanwhile to minimize systemic 
exposure to the free payload GRM.  Therefore, the adalimumab/GRM ADC is promising as a novel 
therapeutic agent which can achieve transformational efficacy relative to adalimumab while reducing 
side effects caused by free GRM systemic exposure.
Clinical Hypothesis
ABBV-3373 is safe and well-tolerated and provides superior efficacy in subjects with moderately to 
severely active RA on background MTX compared to adalimumab.
2.2 Benefits and Risks to Subjects
The clinical efficacy of TNF inhibitors and GRMs in the treatment of RA is well established.  Based on the 
preclinical data discussed in the ABBV-3373 Investigator's Brochure,2 ABBV-3373 is expected to 
demonstrate therapeutic benefit in treatment of RA and other immune-mediated inflammatory diseases 
with a favorable safety profile.  Preclinical toxicology of ABBV-3373 suggests that the potential risks to 
human subjects receiving ABBV-3373 treatment are consistent with known effects of adalimumab and 
glucocorticoids (GCs).  ABBV-3373 was tested in a Phase 1 single ascending dose (SAD) study in healthy 
volunteers in which 6 cohorts of subcutaneous (SC) (30, 100, 300 mg) and intravenous (IV) (30, 300, 
900 mg) successfully completed dosing.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Medical review of the available safety data from the Phase 1 study did not identify any unexpected risk 
or trend to the healthy volunteer population.  All single doses tested to date have been well tolerated.  
For further details, please see the ABBV-3373 Investigator's Brochure.2
In clinical settings, TNF antagonists and GCs have been associated with an increased risk of serious 
infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic 
pathogens.  Opportunistic infections have included tuberculosis (TB) and histoplasmosis.  Patients will 
be closely monitored during the clinical study for any signs of infection.
Tumor necrosis factor antagonists have also been associated with an increased risk for malignancy 
(including lymphoma), hepatitis B virus (HBV) reactivation, worsening or new onset heart failure, and 
rarely central nervous system demyelinating disease, pancytopenia including aplastic anemia, and lupus-
like syndrome.
The risk of hypersensitivity reaction or other post-dose systemic reaction for humans who receive 
multiple doses of ABBV-3373 is considered a potential risk.  During Study M16-560, 1 case of 
anaphylactic shock was observed following repeated eow IV (over 3 minute bolus injection) 
administration of ABBV-3373.  The event was assessed by the investigator and AbbVie to be reasonably 
related to study drug.  The administration of biologics may lead to such reactions; therefore, patients 
will be closely monitored during and post drug administrations.
Hypertension is one of the most commonly reported events for GCs in patients, especially with high 
doses of GCs.  Therefore, blood pressure and other vital signs will be monitored during the trial.
Based on the above considerations, the risk to RA patients receiving multiple doses of ABBV-3373 is 
considered manageable and acceptable.  In addition, based on the population and disease being studied 
and the anticipation that COVID-19 related risks are not expected to differ substantially between study 
subjects and the broader population of subjects receiving treatment for RA, no change to the 
benefit/risk balance for subjects in this study is expected.
3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
Primary
1.
To assess the safety, tolerability, and efficacy of ABBV-3373 administered every other week 
(eow) intravenously (IV) in subjects with moderately to severely active RA on background MTX.
2.
To compare clinical efficacy of ABBV-3373 with adalimumab and to test the concept that an 
anti-TNF antibody-drug-conjugate has the potential to provide superior efficacy than the 
traditional anti-TNF antibody in RA.
Secondary
3.
To compare adalimumab with synthetic placebo control to establish assay sensitivity.
4.
To assess the pharmacokinetics (PK), pharmacodynamics, and immunogenicity of ABBV-3373.
5.
To assess the duration of the treatment effect of ABBV-3373 after discontinuation.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3.2 Primary Endpoint
The primary endpoint is the change in disease activity score (DAS)28 (C-reactive protein [CRP]) from 
Baseline (BL) at Week 12.
3.3 Secondary and Additional Endpoints
Secondary Endpoints
1.
Change in clinical disease activity index (CDAI) from BL at Week 12 
2.
Change in simplified disease activity index (SDAI) from BL at Week 12 
3.
Change in disease activity score (28 joints) (DAS28) erythrocyte sedimentation rate (ESR) from 
BL at Week 12 
4.
Achievement of low disease activity (LDA) (DAS28 [CRP] ≤3.2) at Week 12 
5.
Achievement of American College of Rheumatology (ACR) 50 at Week 12 
Additional Endpoints
1.
Change from BL in DAS28 (CRP) and DAS28 (ESR) at all visits
2.
Change from BL in CDAI at all visits
3.
Change from BL in SDAI at all visits
4.
ACR20/50/70 response rates at all visits
5.
Change from BL in individual components of ACR response at all visits
6.
Achievement of LDA at all visits.  Low disease activity is defined as DAS28 (CRP) ≤3.2, 
DAS28(ESR) ≤ 3.2, CDAI ≤ 10, SDAI ≤ 11
7.
Achievement of clinical remission at all visits.  Clinical remission is defined as DAS28 (CRP) < 2.6, 
DAS28(ESR) < 2.6, CDAI ≤ 2.8, SDAI ≤ 3.3
8.
Change in Short Form-36 (SF-36) from BL at Week 12
9.
Achievement of minimal clinically important difference (MCID) in change from BL in Health 
Assessment Questionnaire Disability Index (HAQ-DI) (defined as change from BL in Health 
Assessment Questionnaire ≤ –0.22) at all visits among subjects who have HAQ ≥ 0.22 at BL
10. Achievement of response (such as LDA) based on DAS28 (CRP), CDAI, or SDAI over time from 
Week 12 to Week 24 among subjects who have achieved DAS28 (CRP), CDAI, or SDAI response 
at Week 12
Additional endpoint definitions are provided in Appendix D.
3.4 Safety Endpoints
The following safety evaluations will be performed during the study:

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1.
Treatment-emergent adverse events, serious adverse events (SAEs), adverse events (AEs) 
leading to discontinuation, AEs of special interest
2.
Percent of subjects meeting potentially clinically significant criteria for vital signs, laboratory 
variables, physical examination findings and electrocardiogram (ECG) interval variables
3.5 Pharmacokinetic and Immunogenicity Endpoints
Serum or plasma concentrations of the conjugated ADC (ABBV-3373), total antibody, free payload 
A-1677770, and adalimumab (in the comparator arm) will be determined during the treatment period 
and drug washout period.  If sufficient data are available from the optional intensive PK sampling group, 
terminal elimination half-life may be calculated and reported.
Anti-drug antibody (ADA) to either ABBV-3373 or adalimumab will be evaluated and if confirmed 
positive, titers will be measured.  If required, samples will be analyzed for neutralizing antibodies (nAb).
3.6 Biomarker Endpoints
Biospecimens (e.g., blood, serum, and plasma) will be collected at specified time points (Appendix J) 
throughout the study to evaluate known and/or novel disease-related or drug-related biomarkers.
The analyses of biomarker samples will include but are not limited to proteins and genetic markers that 
will help to understand the subject's disease and response to study treatments.  Changes in cortisol level 
under ABBV-3373 treatment and adalimumab will be assessed.  Genes of interest will include those 
associated with PK, genes within the target pathway, or other genes believed to be related to RA and 
other inflammatory diseases.  Samples for ribonucleic acid (RNA) and proteomics will be used to 
research if any genetic variants result in changes to gene expression or protein concentrations.  
Biomarker samples will be collected and analyzed from all subjects, unless precluded by local regulations 
or restrictions.  For any samples collected in Germany, the research will be restricted to study drug and 
RA.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a randomized, double-blind, double-dummy, adalimumab active-controlled (12-week) Phase 2a
study to assess the safety, tolerability, PK, pharmacodynamics, immunogenicity and efficacy following 
multiple IV administrations of ABBV-3373 or multiple SC injections of adalimumab in subjects with RA on 
background MTX.  In the actively controlled period of the first 12 weeks of treatment, 45 subjects will 
receive either ABBV-3373 100 mg IV and the matching placebo for adalimumab SC eow or in the control 
arm the matching placebo for ABBV-3373 IV and adalimumab 80 mg SC eow (double-dummy) according 
to a 2:1 ratio.  Thereafter all subjects enter a 12-week double-blind extension period.  At Week 12, the 
administration of ABBV-3373 will stop (i.e., the last dose of ABBV-3373 will be given at Week 10) to 
assess the durability of the observed clinical effects up to 24 weeks.  To keep blinding of the study 
beyond Week 12, the subjects randomized to ABBV-3373 will receive placebo injections, whereas 

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
subjects randomized into the adalimumab arm will continue their 80 mg dosing until Week 22.  At 
Week 12 and within the blinded extension period subjects who have not achieved at least a 20% 
improvement in both their swollen joint count (SJC) and tender joint count (TJC) based on 28 joint 
assessment compared with BL may be discontinued from the study at the discretion of the Investigator.  
Subsequently, standard of care may be administered at the discretion of the investigator.
After all endpoints are assessed at Week 24, a telephone contact is planned to follow up on safety 
70 days after the last dose.
After all ongoing subjects complete the Week 12 study visit, the primary analysis for the ABBV-3373 
cohort will be conducted to assess the primary/secondary endpoints and safety of this actively 
controlled period.  A final analysis will be conducted after all subjects have completed Week 24 plus 
their safety follow-up.  To maintain integrity of the trial, the study sites and subjects will remain blinded 
until the final analysis is completed.
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in Appendix K.
Figure 1.
Study Schematic
∆DAS28(CRP) = change in disease activity score (DAS)28(C-reactive protein [CRP]); EOW = every other week; IV = intravenous; 
SC = subcutaneous

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
See Section 5.1 for information regarding eligibility criteria.  See Section 5.8 for stratification factors for 
each cohort.
Pharmacokinetic Sampling
For ABBV-3373, blood samples for PK assessments will be collected according to the assessment 
schedule in Appendix J.  Data from the first 12 subjects treated for at least 4 doses will be used in the PK 
interim analyses.
In addition, optional PK samples will be collected from subjects who consent to participate in the more 
intensive sampling group to provide data for PK characterization following repeated administrations.  
For these subjects, in addition to the standard sampling schedule, blood samples at the following time 
points will also be collected:  Day 72, Day 73, Week 11, and Week 14.
4.2 Discussion of Study Design
Choice of Control Group
ABBV-3373 is an ADC, composed of adalimumab (the active component of Humira®) conjugated to
A-1677770, a proprietary, highly potent GRM.  In order to assess how the conjugation of adalimumab 
with the GRM impacts safety, tolerability and in particular whether it will provide additional efficacy 
versus (vs.) adalimumab, a direct comparison between the ADC and adalimumab is needed.  The chosen 
study design with adalimumab as the positive control group allows such direct comparison.  In addition, 
to compare clinical efficacy of the ADC with placebo control, and to address assay sensitivity, a synthetic 
placebo arm will be created with the propensity score matching approach using historical placebo 
subjects from similar trials with subject-level data.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy 
measurements in this study are standard for assessing disease activity in subjects with RA.  All clinical 
and laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
The specific population chosen was based on the unmet medical need of subjects as defined in 
Section 5.1.
Selection of Doses in the Study
Based on the clinical hypothesis, the ADC ABBV-3373 targets the activated immune cells that express 
transmembrane TNF to deliver the highly potent GRM selectively, therefore it has the potential to 
provide superior efficacy compared to a traditional anti-TNF antibody such as adalimumab.  The dose of 
100 mg IV eow for ABBV-3373 is selected to provide a similar systemic exposure to 80 mg adalimumab 
SC eow, which is a dose previously tested in RA subjects and twice as high as the recommended clinical 
regimen of 40 mg adalimumab SC eow.  The rationale for selecting this higher dose is to increase tissue 
penetration of ABBV-3373 to successfully engage its intended target of transmembrane TNF on 
activated immune cells.  Furthermore, the doses selected for ABBV-3373 and adalimumab are expected 
to generate similar systemic exposure to ensure a fair comparison between the two.  Finally, 100 mg IV 

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
ABBV-3373 is well within the range of doses that have been safely tested and well tolerated in the 
first-in-human SAD study.  Historical data with adalimumab 80 mg eow or even higher in Phase 1 and 2 
studies with adalimumab in the presence of MTX3,4 or 40 mg weekly as monotherapy in Phase 2 and 3 
studies5,6 have not shown any safety concerns.
Study Duration
For the patient population selected and the type of study drug tested, a 12-week primary endpoint to 
analyze the improvement of signs and symptoms and to assess the safety and tolerability of ABBV-3373 
is appropriate.  Preclinical data from a mouse collagen induced arthritis model2 have shown a long 
lasting effect of the ADC in comparison to adequate control groups.  Therefore, to assess the durability 
of the achieved clinical response at Week 12 in ABBV-3373-treated RA subjects, the subjects will be 
followed closely up to Week 24. While the maintenance of responses of ABBV-3373 will be monitored 
(under continuous placebo injections), subjects in the comparator arm will continue their adalimumab 
dosing to keep the blinding of the study.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.
Consent
1. Subjects or their legally authorized representative must voluntarily sign and date an informed 
consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), 
prior to the initiation of any screening or study-specific procedures.
Demographic and Laboratory Assessments
2. Adult male or female, between 18 and 75 years of age inclusive at Screening.
3. Body mass index (BMI) is ≥ 18.0 to ≤ 39.9 kg/m2 after rounding to the nearest tenth.  Body 
mass index is calculated as weight in kg divided by the square of height measured in meters.
4. Laboratory values meeting the following criteria within the screening period prior to the first 
dose of study drug:
!
Serum values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
< 2.5 × upper limit of normal (ULN);
!
Absolute neutrophil count (ANC) > 1,500/μL;
!
Creatinine < 1.5 × ULN.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5. Subject must have a negative test result for hepatitis A virus immunoglobulin M (HAV-IgM), 
hepatitis B surface antigen (HBsAg), HBc Ab (subjects who have been vaccinated against 
hepatitis B [HB] and are HBs Ab positive may be enrolled), hepatitis C virus (HCV) antibody (if 
Hepatitis C RNA level is undetectable at Screening, the subject can participate in this trial), and 
human immunodeficiency virus (HIV) Ab at Screening.
6. Subject is willing and able to comply with procedures required in this protocol.
Diagnosis and Disease Activity
7. Subject has the clinical diagnosis of RA for > 3 months based on the 1987 ACR classification 
criteria or 2010 ACR/European League against Rheumatism (EULAR) criteria.
8. Subject meets the following disease activity criteria:  ≥ 4 swollen joints (based on 28 joint 
count) and ≥ 4 tender joints (based on 28 joint count) at Screening and BL Visits; and 
DAS28(CRP) ≥ 3.2 at Screening.
9. Incomplete response to MTX.  Subjects must have been on oral or parenteral MTX therapy 
≥3 months and on a stable prescription of 15 to 25 mg/week (or ≥ 10 mg/week in subjects 
intolerant of MTX at doses ≥ 15 mg/week) for ≥ 4 weeks prior to the first dose of study drug.  
Subject must be expected to be able to continue on stable dose of MTX for the duration of study 
participation.
Subject History
10. Subject must not have been previously exposed to adalimumab or other anti-TNF biologics.
11. Subject must not have been previously exposed to non-anti-TNF biologics or targeted 
synthetic DMARDs for RA, with exception of subjects exposed for less than 3 months and 
terminated not due to lack of efficacy or intolerability.
12. No history of persistent chronic or active infection(s) requiring hospitalization or treatment 
with parenteral anti-infectives within 30 days, or oral anti-infectives within 14 days prior to the 
first dose of study drug administration.
13. No history of demyelinating disease (including myelitis) or neurologic symptoms suggestive 
of demyelinating disease.
14. No history of moderate to severe congestive heart failure (CHF) (New York Heart Association 
Class III or IV).
15. No history or evidence of active TB disease or evidence of risk factors for latent TB infection 
OR a history of positive TB skin test or QuantiFERON-TB Gold In-Tube (GIT assay) within 90 days 
prior to study drug administration.
16. No history of pre-existing hyperglycemia (HbA1c > 6.5%), no history of osteoporotic 
fractures, and no high fracture risk (severe osteoporosis).
17. No history of pre-existing glaucoma, severe acne, osteonecrosis, uncontrolled hypertension, 
or peripheral edema.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
18. No history of any malignancy except for successfully treated non-melanoma skin cancer 
(NMSC) or localized carcinoma in situ of the cervix.
19. No history of clinically significant (per investigator's judgment) drug or alcohol abuse within 
the last 6 months.
20. No history of clinically significant medical conditions or any other reason that the 
investigator determines would interfere with the subject's participation in this study or would 
make the subject an unsuitable candidate to receive study drug.
21. No history of an allergic reaction or significant sensitivity to any constituents of the study 
drug, or an anaphylactic reaction to any agent (e.g., food products and bee sting), or a major 
reaction to any immunoglobulin G-containing product.
22. Is not currently enrolled in another clinical study, and has not been previously enrolled in 
this study.
Contraception
23. For all females of child-bearing potential; a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at BL prior to the first dose of study drug.
24. Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 1 through at least 70 days after the last dose of 
study drug.  Female subjects of non-childbearing potential do not need to use birth control.
25. Female who is not pregnant, breastfeeding, or considering becoming pregnant during the 
study or for approximately 70 days after the last dose of study drug.
Concomitant Medications
26. Subject must have discontinued all conventional synthetic disease-modifying antirheumatic 
drugs (csDMARDs), except for MTX.  The washout periods for csDMARDs prior to the first dose 
of study are specified in Section 5.4.
27. Subject must not be on systemic GCs except for stable doses of GC (≤ 7.5 mg/d prednisone 
equivalent) in preceding 3 weeks prior to BL.
28. Subject must not have been treated with any investigational drug within 30 days or 5 half-
lives of the drug (whichever is longer) prior to the first dose of study drug.
29. Subject must not have been treated with any intra-articular, intramuscular, IV, trigger point 
or tender point, intra-bursa, or intra-tendon sheet corticosteroids in the preceding 8 weeks prior 
to the first dose of the study drug.
30. Subject must not have received any live vaccine within 4 weeks prior to the first dose of 
study drug, or expected need of live vaccination during study participation including at least 
12 weeks after the last dose of study drug.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:
!
Females, Non-Childbearing Potential
Females do not need to use birth control during or following study drug treatment if considered 
of non-childbearing potential due to meeting any of the following criteria:
!
Postmenopausal, age > 55 years with no menses for 12 or more months without an 
alternative medical cause.
!
Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND an FSH level > 40 IU/L.
!
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).
!
Females, of Childbearing Potential
!
Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 70 days after the last dose of study drug.
!
Females must commit to one of the following methods of birth control:
!
Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at 
least 30 days prior to study BL Day 1.
!
Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study BL Day 1.
!
Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).
!
Intrauterine device (IUD).
!
Intrauterine hormone-releasing system (IUS).
!
Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).
!
Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or 
sponge with spermicide should be used in addition to one of the highly effective birth control methods 
listed above (excluding true abstinence).

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Male subjects who are sexually active with a female partner of childbearing potential, must agree to use 
condoms, even if the male subject has undergone a successful vasectomy, from Study Day 1 through at 
least 70 days after the last dose of study drug.
Contraception recommendations related to use of concomitant therapies prescribed (e.g., MTX) should 
be based on the local label.
5.3 Prohibited Medications and Therapy
The following medications are prohibited throughout the duration of the study:
!
Systemic GCs except stable doses of GC (≤ 7.5 mg/d prednisone equivalent) at BL, which have to 
be tapered off completely by end of Week 4.
!
All csDMARDs, except MTX
!
All targeted synthetic DMARDs:  Examples include but are not limited to the following:  Xeljanz® 
(tofacitinib), Olumiant® (baricitinib), Rinvoq® (upadacitinib)
!
All biologic therapies.  Examples include but are not limited to the following:  Humira® 
(adalimumab), Enbrel® (etanercept), Remicade® (infliximab), Kineret® (anakinra), Rituxan® 
(rituximab), Cimzia® (certolizumab pegol), Simponi® (golimumab), Actemra® (tocilizumab), 
Raptiva® (efalizumab), Tysabri® (natalizumab), Stelara® (ustekinumab), Benlysta® (belimumab), 
Orencia® (abatacept), Prolia® (denosumab)
!
Any intra-articular, intramuscular, parenteral, trigger point or tender point, intra-bursa, or intra-
tendon sheet corticosteroids
!
Any investigational drugs
!
Any live vaccination
5.4 Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject is receiving at the time of enrollment or receives during the study 
must be recorded along with reasons for use; dates of administration, including start and end dates; and 
dosage information including dose, route, and frequency on the appropriate electronic case report form 
(eCRF) through the post-treatment contact (70 day follow-up call).
Non-Steroidal Anti-Inflammatory Drugs (NSAID) and low potency analgesics (i.e., tramadol, codeine, 
hydrocodeine, or propoxyphene) should continue to be used for the same reason and same dose each 
time but should not be taken within 24 hours prior to any study visit to avoid bias in outcome 
measurements.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with ABBV-3373 can be located in the 
ABBV-3373 Investigator's Brochure.2

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
progression, lack of response to treatment, an AE, safety concerns, or failure to comply with the 
protocol.  See Section 6.2 for toxicity management criteria.
Subjects will have study drug discontinued immediately if any of the following occur:
!
Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the Investigator or the AbbVie Therapeutic Area Medical Director (TA 
MD).
!
Serious infections (e.g., sepsis) that cannot be adequately controlled within 2 weeks by anti-
infective treatment or would put the subject at risk for continued participation in the trial as 
determined by the Investigator.
!
The Investigator believes it is in the best interest of the subject.
!
The subject requests withdrawal from the study.
!
Eligibility criteria violation was noted after the subject started study drug, when continuation of 
the study drug would place the subject at risk as determined by the AbbVie TA MD.
!
Introduction of prohibited medications or dosages when continuation of the study drug would 
place the subject at risk, as determined by the AbbVie TA MD.
!
Subject is non-compliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.
!
The subject becomes pregnant while on study drug.
!
Malignancy, except for localized NMSC or carcinoma in-situ of the cervix.
!
Subject is significantly non-compliant with study procedures which would put the subject at risk 
for continued participation in the trial as determined by the Investigator or the AbbVie TA MD.
!
The subject develops anaphylactic reactions or anaphylactic shock.
In order to minimize missing data for efficacy and safety assessments, subjects who prematurely 
discontinue study participation should complete a Premature Discontinuation (PD) visit.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
5.6 Follow-Up for Subject Withdrawal from Study
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug treatment should continue to be followed for all regularly scheduled visits, unless subjects 
have decided to discontinue the study participation entirely (withdrawal of informed consent).  Subjects 

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
should be advised on the continued scientific importance of their data even if they discontinue 
treatment with study drug early.
If a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the PD visit should be completed as soon as possible, preferably within 2 weeks.  
In addition, if subject is willing, a 70-day follow-up phone call after the last dose of study drug will be
completed to ensure all treatment-emergent AEs/SAEs have been resolved.
All attempts must be made to determine the date of the last study drug dose and the primary reason for 
discontinuation of study drug or study participation.  The information will be recorded on the 
appropriate eCRF page.  However, these procedures should not interfere with the initiation of any new 
treatments or therapeutic modalities that the Investigator feels are necessary to treat the subject's 
condition.  Following discontinuation of study drug, the subject should be treated in accordance with 
the Investigator's best clinical judgment irrespective of whether the subject decides to continue 
participation in the study.
Biomarker Research
In the event a subject withdraws consent from the clinical study, biomarker research will continue 
unless the subject explicitly requests analysis to be stopped.  When AbbVie is informed that samples are 
withdrawn from research, samples will not be analyzed, no new biomarker analysis data will be 
collected for the withdrawn subject or added to the existing data or database(s).  Data generated from 
clinical study and/or biomarker research, before subject withdrawal of consent, will remain part of the 
study results.
5.7 Study Drug
ABBV-3373 or matching placebo manufactured by AbbVie will be administered intravenously beginning 
on Day 1 (BL).  Adalimumab or matching placebo manufactured by AbbVie will be administered 
subcutaneously beginning on Day 1 (BL).  The administration of ABBV-3373 and matching placebo by 
venipuncture has to be given slowly over 15 – 30 minutes (via infusion line or infusion pump; the study 
drug can be diluted in 50 – 100 mL isotonic saline solution for this administration).  Subjects have to be 
observed for at least 30 minutes thereafter.
AbbVie will provide study drug for ABBV-3373 or matching placebo and adalimumab or matching 
placebo.  AbbVie-provided study drug should not be substituted or alternately sourced unless otherwise 
directed by AbbVie.
ABBV-3373 and matching placebo and adalimumab or matching placebo will be packaged in cartons 
with quantities sufficient to accommodate study design.  Each kit will be labeled per local requirements 
and this label must remain affixed to the kit.  Upon receipt, study drug should be stored as specified on 
the label and kept in a secure location.  Each kit will contain a unique kit number.  This kit number is 
assigned to a subject via interactive response technology (IRT) and encodes the appropriate study drug 
to be dispensed at the subject's corresponding study visit.  Site staff will complete all blank spaces on 
the label before dispensing to subjects.  Study drug will only be used for the conduct of this study.
AbbVie will provide instructions for drug preparation (Table 1).

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 1.
Identity of Investigational Product
Study Drug
Dosage Form
Strength
Route of 
Administration
Manufacturer
ABBV-3373
Lyophilized powder 
for solution for 
infusion in vials
50 mg/mL when 
reconstituted with 
1.2 mL of sterile water 
for injection; 
1 mL extractable 
volume per vial; further 
dilution into saline for 
IV infusion
IV
AbbVie
Placebo for ABBV-3373
Lyophilized powder 
for solution for 
infusion in vials
N/A
IV
AbbVie
Adalimumab
Pre-filled syringe
80 mg/0.8 mL
SC
AbbVie
Placebo for 
Adalimumab
Pre-filled syringe
N/A
SC
AbbVie
IV = intravenous; N/A = not applicable; SC = subcutaneous
5.8 Randomization/Drug Assignment
All subjects will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial screening visit should be 
used.  The IRT will assign a randomization number that will encode the subject's treatment group 
assignment according to the randomization schedule generated by the statistics department at AbbVie.
Randomization will be stratified by factors listed in Section 4.1.
Forty-five subjects will be randomized to either the ABBV-3373 or adalimumab control arm according to 
a 2:1 ratio.  Randomization will be stratified by the following factors:
!
Stratification by current use of systemic GC (≤7.5 mg/d prednisone equivalent) for treatment of 
RA at BL (yes/no).
!
Stratification by prior exposure to non-anti-TNF biologics or targeted synthetic DMARDs 
(< 3 months and terminated not due to lack of efficacy or intolerance) (yes/no).
All AbbVie personnel with direct oversight of the conduct and management of the trial (with the 
exception of AbbVie Drug Supply Management Team), the investigator, study site personnel, and the 
subject will remain blinded to each subject's treatment throughout the study.  To maintain the blind, the 
ABBV-3373 vials and matching placebo vials, as well as adalimumab PFS and matching placebo PFS, will 
be provided for the study.  The IRT will provide access to unblinded subject treatment information in the 
case of a medical emergency.  The procedure for breaking the blind is referenced in the IRT Training 
Slides provided to each study site.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
AbbVie must be notified before the blind is broken unless identification of the study drug is required for 
medical emergency, i.e., situation in which the knowledge of the specific blinded treatment will affect 
the immediate management of the subject/patient's conditions (e.g., antidote is available).  AbbVie 
must then be notified within 24 hours of the blind being broken.  See Appendix K for contact 
information, including 24/7 AbbVie emergency contact coverage.
5.9 Protocol Deviations
The investigator is responsible for complying with all protocol requirements, written instructions, and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified), the investigator is responsible for notifying IEC/independent review board (IRB), regulatory 
authorities (as applicable), and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Additionally, 
any elective or spontaneous abortion or stillbirth is considered an 
important medical event.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.
All adverse events reported from the time of study drug administration until 70 days after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, serious adverse events and protocol-related nonserious adverse 
events will be collected from the time the subject signs the study-specific informed consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local requirements.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Serious Adverse Event Reporting
AbbVie is committed to continue to collect safety information including those events that may occur in 
this trial in order to confirm this established safety profile and to identify any unknown potential 
adverse reactions, rare events, and those events with a long latency.  AbbVie is participating in a Food 
and Drug Administration-requested, TNF inhibitor class wide exploration of the rare appearance of 
malignancy in subjects/patients who are 30 years of age or younger at the time of diagnosis.  The risk of 
malignancy in this age group has not been established and is difficult to study due to its rarity.  AbbVie 
appreciates your attention to the additional reporting requirements needed in this unlikely event.  In the 
event of an SAE, and additionally, any nonserious event of malignancy in subjects 30 years of age and 
younger, whether related to SC study drug or not, the physician will notify Clinical Pharmacovigilance 
within 24 hours of the physician becoming aware of the event by entering the SAE or nonserious event 
of malignancy in subjects 30 years of age and younger data into the electronic data capture (EDC) 
system.  Serious adverse events and nonserious events of malignancy in subjects 30 years of age and 
younger, that occur prior to the site having access to the RAVE® EDC system or if RAVE® is not operable, 
should be documented on the SAE non-case report form forms and emailed (preferred route) or faxed 
to the Clinical Pharmacovigilance within 24 hours of being made aware of the SAE.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Adverse Events of Special Interest
The following adverse events of special interest will be monitored during the study:
!
Serious infections, opportunistic infections, herpes zoster, and TB;
!
Malignancy (all types);
!
Cardiovascular events (e.g., major adverse cardiovascular event [MACE]);
!
Hematologic disorders (i.e., anemia, neutropenia, lymphopenia);
!
Hepatic disorders;
!
Hypersensitivity reactions, including all serious allergic reactions;
!
Demyelinating disease;
!
Systemic GC side effects (i.e., infections, skin atrophy, weight gain, cataract, hypertension, 
indigestion, hyperglycemia).
Adverse Event Severity and Relationship to Study Drug
The investigator will classify AEs according to the Rheumatology Common Toxicity Criteria v.2.0 
(Appendix I).
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 1 working day after 
the site becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject or in the partner of a study subject, 
information regarding the pregnancy and the outcome will be collected.
In the event of pregnancy occurring in a subject's partner during the study, written informed consent 
from the partner must be obtained prior to collection of any such information.  AbbVie will provide a 
separate consent form for this purpose.  Pregnancy in a subject's partners will be collected from the 
date of the first dose through 70 days following the last dose of study drug.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.2 Toxicity Management
The management of specific AEs and laboratory parameters is described in Table 2 and in the 
Operations Manual (Appendix K).
The toxicity management of the AEs including AEs of special interest consists of safety monitoring 
(review of AEs on an ongoing basis, and periodical/ad hoc review of safety issues by a safety data 
monitoring committee), interruption of study drug dosing with appropriate clinical management if 
applicable, and discontinuation of the subjects from the study drug. The management of specific AEs 
and laboratory parameters is described below.
For subjects who discontinued study drug but continued study participation and are on standard of care 
therapies, these toxicity management requirements do not apply (including alerts from the central lab) 
and any intolerability to standard of care therapies should be managed by the prescribing physician.
Management of Hypersensitivity and Serious Allergic Reactions
Subjects should be closely monitored and assessed for the development of signs and symptoms of 
hypersensitivity reactions, including anaphylaxis.  Drug administration (ABBV-3373) should be done 
slowly over 15 – 30 minutes (via infusion line or infusion pump; the study drug can be diluted in 
50 – 100 mL isotonic saline solution for this administration), and subjects should be observed for at least 
30 minutes thereafter.  Study drug should be discontinued and appropriate therapy be instituted if a 
subject develops clinically significant hypersensitivity reactions.
Hypersensitivity Testing
In the event of a suspected systemic post-dose hypersensitivity reaction, if the clinical situation allows, 
every effort should be made to obtain a serum sample within 2 hours but no later than 6 hours from 
symptom onset for additional blood tests (e.g, tryptase, ADA, nAb, total IgE, total hemolytic 
complement, etc.).  Additional details regarding hypersensitivity testing can be found in the Operations 
Manual, Section 3.12 (Appendix K).
Management of Serious Infections
Subjects should be closely monitored for the development of signs and symptoms of infection during 
and after treatment with study drug.  Study drug should be interrupted if a subject develops a serious 
infection or a serious opportunistic infection.  A subject who develops a new infection during treatment 
with study drug should undergo prompt diagnostic testing appropriate for an immunocompromised 
subject.  As appropriate, antimicrobial therapy should be initiated, and the subject should be closely 
monitored.  Study drug may be restarted once the infection has been successfully treated.  Subjects who 
develop active TB must be permanently discontinued from study drug.
Management of Malignancy
Subjects who develop malignancy other than NMSC or carcinoma in-situ of the cervix must be 
discontinued from the study drug.  Information including histopathological results should be queried for 
the confirmation of the diagnosis.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Management of Demyelinating Disease
Subjects must be discontinued from study drug with new onset or exacerbation of clinical symptoms 
and/or radiographic evidence of central nervous system demyelinating disease (including multiple 
sclerosis), optic neuritis, and peripheral demyelinating disease (including Guillain Barré syndrome).
Management of Hypertension
Subjects should be closely monitored for the development of hypertension before and 30 minutes after 
treatment with study drug.  Study drug should be interrupted if a subject develops serious hypertension 
in which case they should be monitored under standard of care.
Management of Hyperglycemia
Subjects should be closely monitored for the development of hyperglycemia during and after treatment 
with study drug.  Study drug should be interrupted if a subject develops a serious hyperglycemia in 
which case they should be monitored under standard of care.
Management of GC-Induced Adrenal Insufficiency
High dose or long term use of corticosteroids can produce reversible HPA axis suppression with the 
potential for GC insufficiency after withdrawal of treatment.  Drug-induced secondary adrenocortical 
insufficiency may be minimized by gradual reduction of dosage.  This type of relative insufficiency may 
persist for months after discontinuation of therapy; therefore, hormone therapy should be reinstituted 
in any situation of stress occurring during that period.
Management of Select Laboratory Abnormalities
For any given laboratory abnormality, the investigator should assess the subject, apply the standard of 
care for medical evaluation and treatment following any local guidelines.  Specific toxicity management 
guidelines for selected abnormal laboratory values are described in Table 2, and may require a 
supplemental eCRF to be completed (Section 6.1 [Complaints and AEs]).  All abnormal laboratory tests 
that are considered clinically significant by the investigator will be followed to a satisfactory resolution.  
If a repeat test is required per Table 2, the repeat testing must occur as soon as possible.
Table 2.
Specific Toxicity Management Guidelines for Abnormal Laboratory Values
Laboratory 
Parameter
Toxicity Management Guideline
Hemoglobin
!
If hemoglobin < 8 g/dL interrupt study drug dosing and confirm by repeat testing 
with new sample
!
If hemoglobin decreases ≥ 3.0 g/dL from BL, without an alternative etiology, 
interrupt study drug dosing and confirm by repeat testing with new sample.
!
If hemoglobin decreases ≥ 3.0 g/dL from BL and an alternative etiology is known, the 
subject may remain on study drug at the investigator's discretion.
!
If confirmed, continue to withhold study drug until hemoglobin value returns to 
normal reference range or its BL value.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Laboratory 
Parameter
Toxicity Management Guideline
Absolute neutrophil 
count (ANC)
!
If confirmed < 1000/μL by repeat testing with new sample, interrupt study drug 
dosing until ANC value returns to normal reference range or its BL value.
!
Discontinue study drug if confirmed < 500/μL by repeat testing with new sample.
Absolute 
lymphocyte counts 
(ALC)
!
If confirmed < 500/μL by repeat testing with new sample, interrupt study drug 
dosing until ALC returns to normal reference range or its BL value.
Total white blood 
cell count
!
If confirmed < 2000/μL by repeat testing with new sample, interrupt study drug 
dosing until white blood cell count returns to normal reference range or its BL value.
Platelet count
!
If confirmed < 50,000/μL by repeat testing with new sample, interrupt study drug 
dosing until platelet count returns to normal reference range or its BL value.
AST or ALT
!
Interrupt study drug if confirmed ALT or AST > 3 × ULN by repeat testing with new 
sample and either a total bilirubin > 2 × ULN or an international normalized ratio 
(INR) > 1.5.
!
A separate blood sample for INR testing will be needed to measure INR at the 
time of repeat testing for ALT or AST.  A repeat test of INR is not needed for 
determination if above toxicity management criteria are met.
!
Interrupt study drug if confirmed ALT or AST > 3 × ULN by repeat testing with new 
sample along with appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (> 5%).
!
Interrupt study drug if confirmed ALT or AST > 5 × ULN by repeat testing with new 
sample for more than 2 weeks.
!
Interrupt study drug if confirmed ALT or AST > 8 × ULN by repeat testing with new 
sample.
Subjects who meet any of the above criteria should be evaluated for an alternative 
etiology of the ALT or AST elevation and managed as medically appropriate.  The 
investigator should contact the AbbVie TA MD to discuss the management of a subject 
when an alternative etiology has been determined.  The alternative etiology should be 
documented appropriately in the eCRF; study drug should be discontinued if no 
alternative etiology can be found and ALT or AST elevations persist.
For any confirmed ALT or AST elevations > 3 ULN, complete the appropriate 
supplemental hepatic eCRF(s).
!
Subjects with HBc Ab+ (irrespective of HBs Ab status) and negative HBV DNA PCR 
testing at Screening who develop the following should have HBV DNA PCR testing 
performed within one week:
!
ALT > 5 × ULN OR
!
ALT or AST > 3 × ULN and either a total bilirubin > 2 × ULN or INR > 1.5 OR
!
ALT or AST > 3 × ULN along with clinical signs of possible hepatitis.
A positive result for HBV DNA PCR testing will require immediate interruption of study 
drug (unless not acceptable by local practices) and a hepatologist consultation should 
occur within 1 week for recommendation regarding subsequent treatment.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Laboratory 
Parameter
Toxicity Management Guideline
Serum Creatinine
!
If serum creatinine is > 1.5 × the BL value and > ULN, repeat the test for serum 
creatinine (with subject in an euvolemic state) to confirm the results.  If the results 
of the repeat testing still meet this criterion, then interrupt study drug and re-start 
study drug once serum creatinine returns to ≤ 1.5 × BL value and ≤ ULN.
For the above serum creatinine elevation scenario, complete the appropriate 
supplemental renal eCRF(s).
Creatine 
Phosphokinase 
(CPK)
!
If confirmed CPK value ≥ 4 × ULN and there are no symptoms suggestive of myositis 
or rhabdomyolysis, the subjects may continue study drug at the investigator's 
discretion.
!
If CPK ≥ 4 × ULN accompanied by symptoms suggestive of myositis or 
rhabdomyolysis, interrupt study drug and contact AbbVie TA MD.
For the above CPK elevation scenarios, complete supplemental increased CPK eCRF.
Ab = antibody; ALC = Absolute lymphocyte counts; ALT = alanine aminotransferase; ANC = absolute neutrophil count; 
AST = aspartate aminotransferase; BL = baseline; CPK = creatine phosphokinase; DNA = deoxyribonucleic acid; eCRF = electronic 
case report form; HB = hepatitis B; HBV = hepatitis B virus; INR = international normalized ratio; PCR = polymerase chain 
reaction; TA MD = Therapeutic Area Medical Director; ULN = upper limit of normal
Management of ECG Abnormality
Subjects should be discontinued for an ECG change considered clinically significant OR a confirmed 
absolute QT interval corrected for heart rate using Fridericia's correction formula (QTcF) value 
> 500 msec.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on primary and secondary analyses.  
Complete and specific details of the statistical analysis will be described in the Statistical Analysis Plan 
(SAP).  All statistical analyses will be performed using SAS (SAS Institute Inc., Cary, North Carolina, USA).
7.2 Definition for Analysis Populations
The Full Analysis Set (FAS) includes all randomized subjects who received at least 1 dose of the study 
drugs.  The FAS will be used for all efficacy analyses. Subjects will be grouped according to treatment as 
randomized.  The Per-Protocol Analysis Set represents a subset of the FAS and consists of all FAS 
subjects without any major violations.  Additional analysis may be conducted on the Per-Protocol 
Analysis Set as deemed appropriate, in order to evaluate the impact of major protocol violations on the 
primary endpoint.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The Safety Analysis Set consists of all subjects who received at least 1 dose of the study drugs.  For the 
Safety Analysis Set, subjects are grouped based on the treatment actually received, regardless of the 
treatment randomized.
7.3 Statistical Analyses for Efficacy
Primary Endpoint Analysis
Analysis of the primary endpoint will be conducted on the FAS based on treatment as randomized.
The primary endpoint is the change from BL in DAS28(CRP) at Week 12.  The historical mean and 
standard deviation of the change from BL in DAS28(CRP) at Week 12 in adalimumab 80 mg eow are 
estimated to be –2.13 and 1.35 respectively based on a meta-analysis of 3 historical adalimumab studies 
(Studies DE007, DE009, and DE011).
The first comparison in order to achieve the first primary objective of assessing the efficacy of 
ABBV-3373 is to compare change from BL in DAS28(CRP) at Week 12 in the ABBV-3373 group with 
–2.13, the adalimumab 80 mg eow historical mean change from BL at Week 12 based on the meta-
analysis.  The treatment mean change from BL and 90% confidence interval of ABBV-3373 will be 
estimated from Mixed Effect Model Repeated Measurements (MMRM) method including up to Week 12 
data with treatment group, visits, treatment-by-visit interaction, BL values of the primary endpoint, and 
stratification factors with observed case (OC) data.  The study will be declared positive if the comparison 
is significant and favoring ABBV-3373.
In order to achieve the second primary objective of comparing clinical efficacy of ABBV-3373 with 
adalimumab and to test the concept that an anti-TNF ADC has the potential to provide superior efficacy 
than the traditional anti-TNF antibody in RA, the second comparison is to compare ABBV-3373 with 
adalimumab for the primary efficacy endpoint with a Bayesian historical data borrowing approach.  The 
same MMRM model as described in the first comparison will be used to estimate in-study mean and 
standard deviation.  Informative normal prior for adalimumab will be determined based on historical 
adalimumab data and a non-informative prior will be used for ABBV-3373.  The prior distributions and 
estimates from MMRM model will be combined to construct the posterior distributions which will be 
used for comparison between ABBV-3373 and adalimumab.
If the adalimumab group mean is not comparable with historical adalimumab data, for example, the 
confidence intervals of the mean based on historical and in-trial data don't overlap, the Bayesian 
approach based on historical data will not be performed, and the mean difference in change from BL in 
DAS28(CRP) at Week 12 between the ABBV-3373 group and adalimumab will be estimated only based 
on in-study data with the MMRM model described above.
Historical data borrowing will only apply to the primary endpoint.
To address the secondary objectives of assay sensitivity, a synthetic placebo arm will be created with the 
propensity score matching approach using historical placebo subjects from similar trials with subject-
level data. Details will be provided in the SAP.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Secondary Endpoints and Additional Endpoints Analyses for BL to Week 12
For the first 12 weeks of treatment period, continuous efficacy variables will be analyzed using an 
MMRM method.  Categorical efficacy variables will be analyzed using the Cochran-Mantel-Haenszel 
(CMH) test controlling for stratification variables.  Non-responder imputation (NRI) will be used for 
primary inference purpose.  Observed Case data will be summarized descriptively as a sensitivity 
analysis.
Additional Endpoints Analyses up to Week 24
Statistical inference of additional continuous endpoints at each visit up to Week 24 will be conducted 
using analysis of covariance (ANCOVA) with treatment and stratification factors as the fixed factors and 
the corresponding BL value as the covariate. Additional categorical efficacy variables up to Week 24 will 
be analyzed using the same CMH test as for the binary secondary endpoint analysis.
Details on the analyses of the primary and other efficacy endpoints will be provided in the SAP.
Sample Size Estimation
The primary endpoint is the mean change of DAS28(CRP) from BL at Week 12.  Two comparisons are 
considered.  The first one is to compare mean change in DAS28(CRP) of the ABBV-3373 group to that of 
historical adalimumab 80 mg eow, which is –2.13.  Assuming a mean DAS28(CRP) change from BL of
–2.769 to –2.982 for ABBV-3373 (corresponding to 30% to 40% more reduction than historical 
adalimumab) and a standard deviation of 1.35, 30 subjects on ABBV-3373 will provide an approximate 
81% to 96% power with a one-sample t-test and one-sided alpha = 0.05 significance level.
The second comparison is between ABBV-3373 arm and adalimumab arm with borrowed historical 
adalimumab data using a Bayesian approach.  When considering borrowing historical data, the planned 
sample size is 45 subjects (30 in ABBV-3373 and 15 in adalimumab).  The study will be considered 
successful if the posterior probability of mean difference < 0 is larger than 95%, i.e.,:
(μ	
 −μ < 0|) > 0.95.
Based on the historical mean and standard deviation from adalimumab meta-analysis, a prior 
distribution for adalimumab is N (–2.13, 0.2462) corresponding to the 30 historical subjects borrowed.  A 
noninformative prior for ABBV-3373 treatment group will be set.  Given the mean change from BL in 
DAS28 (CRP) is –2.13 for adalimumab, the probability to claim the study success is approximately 66% to 
88% if the mean change from BL in DAS28 (CRP) is –2.769 to –2.982 for ABBV-3373 (i.e., 30% to 40% 
more reduction than historical adalimumab), with at least 45 subjects for adalimumab (15 in-trial and at 
least 30 borrowed) and 30 subjects for ABBV-3373.  If both ABBV-3373 and adalimumab groups have the 
same mean change from BL of –2.13, the probability to claim study success (equivalent to type I error 
rate) is approximately 0.03 with the same sample sizes.  In the event that adalimumab variability 
precludes historic data borrowing, using only the in-study 15 adalimumab subjects and 30 ABBV-3373 
subjects will provide 43% to 63% power when ABBV-3373 in 30% to 40% more reduction than 
adalimumab respectively.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7.4 Statistical Analyses for Safety
Safety analyses will be carried out using the Safety Analysis Set.  There will be 2 sets of planned safety 
analyses:  safety analysis by Week 12 and long-term safety analysis.  Safety will be assessed by AEs, 
laboratory assessments, and vital signs.  Frequency tables of subjects with treatment emergent AEs by 
preferred term (PT), by system organ class (SOC) and PT as in the Medical Dictionary for Regulatory 
Activities, by severity, and by relationship to the study drug as assessed by the Investigator will be 
provided.
Summaries of SAEs, deaths, AEs leading to discontinuation, and Areas of Safety Interest will be provided 
as well.  The changes from BL in clinical laboratory and vital sign values by visit will be analyzed in a 
descriptive manner.  Shift of selected laboratory values from BL to defined time points will be tabulated.  
The number and percentage of subjects meeting the criteria for potentially clinically significant 
laboratory/vital sign/ physical examination/ECG values will be summarized.
No external data borrowing will be applied for safety analyses.
7.5 Statistical Analysis of Pharmacokinetic and Immunogeniticy Data
Concentrations of conjugated ADC (ABBV-3373), total antibody, free payload A-1677770, and 
adalimumab (in the comparator arm), along with all applicable PK parameters will be summarized at 
each time point for each group using descriptive statistics.
Population PK analyses combining the data from this study and other studies may be performed and 
reported outside of the clinical study report.
Anti-drug antibody and nAb incidence and ADA titer values will be summarized for each group using 
descriptive statistics.
7.6 Statistical Analysis of Biomarker Data
Analysis will be conducted on biomarker data for the purpose of identification of prognostic, predictive, 
surrogate, and pharmacodynamic biomarkers associated with efficacy or safety.  The association of 
biomarkers to the efficacy or safety endpoints will be explored for each biomarker one at a time, and 
also for combinations of biomarkers via some multivariate predictive modeling approaches.
7.7 Interim Analysis
An interim PK analysis after 12 subjects are treated for at least 4 doses will be performed to assess 
whether the observed total antibody systemic exposure following ABBV-3373 administration is in the 
approximate range of 80 mg adalimumab exposure based on trough concentration (Ctrough) levels and if 
there is a need for dose adjustment for ABBV-3373 and replacement of already-treated subjects.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the investigator are specified in Appendix B.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
11
COMPLETION OF THE STUDY
The end-of-study is defined as last subject last visit (70 day follow-up call).
12
REFERENCES
1.
Schäcke H, Döcke WD, Asadullah K.  Mechanisms involved in the side effects of glucocorticoids.  
Pharmacol Ther.  2002;96(1):23-43.
2.
AbbVie.  ABBV-3373 Investigator's Brochure Edition 3.  September 2019.  Addendum 1, 
Edition 3.  November 2019.
3.
Keystone E, Weinblatt M, Furst D, et al.  Adalimumab, a fully human anti-TNF monoclonal 
antibody α monoclonal antibody, for treatment of rheumatoid arthritis in patients taking 
concomitant methotrexate:  The ARMADA trial.  Arthritis Rheum.  2003;48(1):35-45.
4.
Weisman M, Keystone E, Paulus H, et al.  A dose escalation study designed to demonstrate the 
safety, tolerability and efficacy of the fully human anti-TNF antibody, D2E7, given in combination 
with methotrexate (MTX) in patients with active RA (abstract 1948).  Arthritis Rheum.  
2000;43(9):S391.
5.
van de Putte LBA, Rau R, Breedveld F, et al.  Efficacy and safety of the fully human anti-tumour 
necrosis factor α monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with 
rheumatoid arthritis:  a 12 week, phase II study.  Ann Rheum Dis.  2003;62(12):1168-77.
6.
van de Putte LB, Atkins C, Malaise M, et al.  Efficacy and safety of adalimumab as monotherapy 
in patients with rheumatoid arthritis for whom previous disease modifying anti-rheumatic drug 
treatment has failed.  Ann Rheum Dis.  2004;63(5):508-16.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
ACR
American College of Rheumatology
ACR20
American College of Rheumatology 20% improvement criteria
ACR50
American College of Rheumatology 50% improvement criteria
ADA
anti-drug antibody
ADC
antibody-drug conjugate
ADL
activities of daily living
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BL
baseline
BMI
body mass index
CDAI
clinical disease activity index
CHF
congestive heart failure
CMH
Cochran-Mantel-Haenszel
CR
clinical remission
CRF
case report form
CRP
C-reactive protein
csDMARD
conventional synthetic disease-modifying antirheumatic drug
Ctrough
trough concentration measured at the end of a dosing interval at steady state
DAS
disease activity score
DAS28
disease activity score (28 joints)
DMARD
disease-modifying antirheumatic drug
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
eow
every other week
ESR
erythrocyte sedimentation rate
EULAR
European League Against Rheumatism

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
FAS
full analysis set
FSH
follicle-stimulating hormone
GC
glucocorticoid
GCP
good clinical practice
GRMs
glucocorticoid receptor modulators
HAQ-DI
Health Assessment Questionnaire Disability Index
HAV
hepatitis A virus
HAV-IgM
hepatitis A virus immunoglobulin M
HB
hepatitis B
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HPA
hypothalamic-pituitary-adrenal
hs-CRP
high-sensitivity C-reactive protein
ICH
International Council for Harmonisation
IEC
Independent ethics committee
IL
interleukin
IMP
Investigational Medicinal Product
IRB
institutional review board
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous
LDA
low disease activity
MACE
major adverse cardiac event
MCID
minimal clinically important difference
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed Effect Model Repeated Measurements
MTX
Methotrexate
nAb
neutralizing antibody
NMSC
non-melanoma skin cancer
NRI
non-responder imputation
NSAID
nonsteroidal anti-inflammatory drug

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
OC
observed case
QTcF
QT interval corrected for heart rate using Fridericia's correction formula
PD
premature discontinuation
PK
pharmacokinetic(s)
PT
preferred term
RA
rheumatoid arthritis
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SDAI
simplified disease activity index
SF-36
36-Item Short Form Health Survey
SJC
swollen joint count
SOC
system organ class
SUSAR
suspected unexpected serious adverse reactions
TA MD
Therapeutic Area Medical Director
TB
tuberculosis
TJC
tender joint count
TNF
tumor necrosis factor
ULN
upper limit of normal
VAS
visual analogue scale
vs.
versus

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M16-560:  A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate 
the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects with Moderate to 
Severe Rheumatoid Arthritis
Protocol Date:  04 September 2020
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation 
(ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the study at the site 
location.  In signing the Investigator Agreement, the investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), except when necessary to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Clinical Program Development
Clinical Program Development
Medical Writing
Immunology Development
Data and Statistical Sciences
Data and Statistical Sciences
Clinical Pharmacology

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX D. ADDITIONAL ENDPOINT/ASSESSMENT 
DEFINITIONS
Physician's Global Assessment of Disease Activity
Physician's Global Assessment of Disease Activity (visual analogue scale [VAS]) allows physicians to score 
on a 100 mm horizontal scale (0 being very low and 100 being very high) to assess the patient's current 
disease activity.
DAS28
The DAS is a combined index used to measure the disease activity in patients with RA.  The DAS provides 
a score (between 0 and 10) indicating how active the disease is at the time of measurement.  The 
calculation of the DAS28 score used either ESR or CRP.
The calculation of the DAS28 score will use ESR based on the following formula:
DAS28 (ESR) = 0.56 × √TJC28 + 0.28 × √SJC28 + 0.70 × ln(ESR) + 0.014 × PtGA
The calculation of the DAS28 score will use CRP based on the following formula:
DAS28 (CRP) = 0.56 × √TJC28 + 0.28 × √SJC28 + 0.36 × ln(CRP + 1) + 0.014 × PtGA + 0.96
PtGA represents patient's global assessment of disease activity; ESR is measured in mm/h, CRP is 
measured in mg/L, TJC28 and SJC28 represent total TJC and total SJC, respectively, based on the 
28 joints (including the left and right side of the body).
American College of Rheumatology 20/50/70 Response (ACR20/50/70)
ACR20/50/70 is defined as
!
At least 20%/50%/70% improvement in SJC compared to BL AND
!
At least 20%/50%/70% improvement in TJC compared to BL AND
!
At least 20%/50%/70% improvement in at least 3 out of the following 5 variables
1.
Patient's Assessment of RA Pain Intensity VAS
2.
Patient's Global Assessment of Disease VAS
3.
Physician's Global Assessment of Disease Activity VAS
4.
Patient's Assessment of Disability on HAQ-DI
5.
Serum high-sensitivity C-reactive protein (hs-CRP).
Clinical Disease Activity Index (CDAI)
The CDAI is a composite index for assessing disease activity based on the summation of the count of 
swollen/tender joint count of 28 joints along with patient and physician global assessment on visual 
analogue scale (VAS) (0 – 10 cm) for estimating disease activity.  It has range from 0 to 76.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Simplified Disease Activity Index (SDAI)
The SDAI is the numerical sum of five outcome parameters:  tender and swollen joint count (based on a 
28-joint assessment), patient and physician global assessment of disease activity (VAS 0 - 10 cm) and 
level of CRP (mg/dl, normal < 1 mg/dl).  It has a range from 0 to 86.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. JOINT EVALUATION WORKSHEET EXAMPLE
JOINT
(Tick Correct Answer)
Subject Right
Subject Left
0 = Absent
1 = Present
9 = Replaced 
NA = No 
Assessment
0 = Absent
1 = Present
9 = Replaced 
NA = No 
Assessment
Pain/ 
Tenderness
Swelling
Joint
Pain/ 
Tenderness
Swelling
Joint
1.  Shoulder
0
1
0
1
9
NA
0
1
0
1
9
NA
2.  Elbow
0
1
0
1
9
NA
0
1
0
1
9
NA
3.  Wrist
0
1
0
1
9
NA
0
1
0
1
9
NA
4.  Metacarpophalangeal I
0
1
0
1
9
NA
0
1
0
1
9
NA
5.  Metacarpophalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
6.  Metacarpophalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
7.  Metacarpophalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
8.  Metacarpophalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
9.  Thumb Interphalangeal
0
1
0
1
9
NA
0
1
0
1
9
NA
10.  Prox. Interphalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
11.  Prox. Interphalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
12.  Prox. Interphalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
13.  Prox. Interphalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
14.  Knee
0
1
0
1
9
NA
0
1
0
1
9
NA
TOTAL Joint Count

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX F. REPORTED OUTCOMES VAS

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX G. HEALTH ASSESSMENT QUESTIONNAIRE 
DISABILITY INDEX

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX H. 36-ITEM SHORT FORM HEALTH SURVEY SAMPLE

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX I.
RHEUMATOLOGY COMMON TOXICITY CRITERIA 
V.2.0
For designation of AE terms not shown in the Rheumatology Common Toxicity Criteria v.2.0 table, the 
approach described in the header row should be used.
Rheumatology Common Toxicity Criteria v.2.0
Based on Woodworth TG, et al.  Standardizing assessment of adverse effects in rheumatology clinical 
trials II.  Status of OMERACT Drug Safety Working Group May 2006:  OMERACT 8.  Standardizing 
Assessment and Reporting of Adverse Effects in Rheumatology Clinical Trials:  Enabling Description of 
Comparative Safety Profiles for Anti-Rheumatic Therapies.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
A.  Allergic/Immunologic
A1.  Allergic reaction/ 
hypersensitivity 
(includes drug fever)
Transient rash:  drug fever < 38°C:  
transient, asymptomatic 
bronchospasm
Generalised urticaria responsive to 
meds; or drug fever > 38°C, or 
reversible bronchospasm
Symptomatic bronchospasm 
requiring meds; symptomatic 
urticaria persisting with meds, 
allergy related oedema/angioedema
Anaphylaxis, laryngeal/pharyngeal 
oedema, requiring resuscitation
A2.  Autoimmune 
reaction
Seriologic or other evidence of 
autoimmune reaction, but patient 
asymptomatic:  all organ function 
normal and no treatment is 
required (e.g., vitiligo)
Evidence of autoimmune reaction 
involving a non-essential organ or 
functions, requiring treatment 
other than immunosuppressive 
drugs (e.g., hypothyroidism)
Reversible autoimmune reaction 
involving function of a major organ 
or toxicity requiring short term 
immunosuppressive treatment 
(e.g., transient colitis or anaemia)
Causes major organ dysfunction, or 
progressive, not reversible, or 
requires long term administration 
of high dose immunosuppressive 
therapy
A3.  Rhinitis (includes 
sneezing, nasal 
stuffiness, post nasal 
discharge)
Transient, non-prescription meds 
relieve
Prescription meds required, slow
Corticosteroids or other prescription 
med with persistent disabling 
symptoms such as impaired exercise 
tolerance
NA
A4.  Serum sickness
Transient, non-prescription meds 
relieve
Symptomatic, slow response to 
meds (e.g., oral corticosteroids)
Prolonged; symptoms only partially 
relieved by meds; parenteral 
corticosteroids required
Major organ dysfunction, requires 
long-term high-dose 
immunosuppressive therapy 
A5.  Vasculitis
Localised, not requiring treatment; 
or rapid response to meds; 
cutaneous
Symptomatic, slow response to 
meds (e.g., oral corticosteroids)
Generalised, parenteral 
corticosteroids required or/and 
short duration hospitalisation
Prolonged, hospitalisation, ischemic 
changes, amputation

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
B.  Cardiac
B1.  Arrhythmia
Transient, asymptomatic
Transient, but symptomatic or 
recurrent, responds to meds
Recurrent/persistent; maintenance 
prescription
Unstable, hospitalisation required, 
parenteral meds
B2.  Cardiac function 
decreased
Asymptomatic decline in resting 
ejection fraction by > 10%, but 
< 20% of baseline value
Asymptomatic decline of resting 
ejection fraction ≥ 20% of baseline 
value
CHF responsive to treatment
Severe or refractory CHF
B3.  Edema
Asymptomatic (e.g., 1 + 
feet/calves), self-limited, no 
therapy required
Symptomatic (e.g., 2 + 
feet/calves), requires therapy
Symptoms limiting function (e.g., 3 + 
feet/calves, 2 + thighs), partial relief 
with treatment prolonged
Anasarca; no response to treatment
B4.  Hypertension 
(new onset or 
worsening)
Asymptomatic, transient increase 
by > 20 mmHg (diastolic) or to 
> 150/100 if previously normal, no 
therapy required
Recurrent or persistent increase 
> 150/100 or by > 10 mmHg 
(diastolic), requiring and 
responding readily to treatment
Symptomatic increase > 150/100, 
> 20 mmHg, persistent, requiring 
multi agency therapy, difficult to 
control
Hypertensive crisis
B5.  Hypotension 
(without underlying 
diagnosis)
Transient, intermittent, 
asymptomatic, orthostatic 
decrease in blood pressure 
> 20 mmHg
Symptomatic, without 
interference with function, 
recurrent or persistent > 20 mmHg 
decrease, responds to treatment
Syncope or symptomatic, interferes 
with function, requiring therapy and 
sustained medical attention, dose 
adjustment or drug discontinuation
Shock
B6.  Myocardial 
ischaemia
Transient chest pain/ECG changes; 
rapid relief with nitro
Recurring chest pain, transient 
ECG ST-T changes; treatment 
relieves
Angina with infarction, no or 
minimal functional compromise, 
reduce dose or discontinue study 
drug
Acute myocardial infarction, 
arrhythmia or/and CHF
B7.  Pericarditis/ 
pericardial effusion
Rub heard, asymptomatic
Detectable effusion by 
echocardiogram, symptomatic 
NSAID required
Detectable on chest x-ray, dyspnoea; 
or pericardiocentesis; requires 
corticosteroids
Pulsus alternates with low cardiac 
output; requires surgery

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
B.  Cardiac (continued)
B8.  
Phlebitis/thrombosis/ 
Embolism (excludes 
injection sites)
Asymptomatic, superficial, 
transient, local, or no treatment 
required
Symptomatic, recurrent, deep vein 
thrombosis, no anticoagulant 
therapy required
Deep vein thrombosis requiring 
anticoagulant therapy
Pulmonary embolism
C.  General (Constitutional)
C1.  Fatigue/malaise 
(asthenia)
Increase over baseline; most usual 
daily functions maintained, short 
term
Limits daily function intermittently 
over time
Interferes with basic ADL, persistent
Unable to care for self, bed or 
wheelchair bound > 50% of day 
debilitating, hospitalisation
C2.  Fever (pyrexia) 
(note:  fever due to 
drug allergy should be 
coded as allergy)
Transient, few symptoms
37.7 – 38.5°C
Symptomatic, recurrent
38.6 – 39.9°C.  Relieved by meds
≥ 40°C; ≤ 24 h, persistent symptoms; 
partial response to meds.
≥ 40°C, debilitating, > 24 h, 
hospitalisation; no relief with meds
C3.  Headache
Transient or intermittent, no meds 
or relieved with OTC
Persistent, recurring, non-narcotic 
analgesics relieve
Prolonged with limited response to 
narcotic medicine
Intractable, debilitating, requires 
parenteral meds.
C4.  Insomnia
Difficulty sleeping, short term, no 
interfering with function
Difficulty sleeping interfering with 
function, use of prescription med.
Prolonged symptoms, with limited 
response to narcotic meds
Debilitating, hospitalisation; no 
relief with meds
C5.  Rigors, chills
Asymptomatic, transient, no meds, 
or non-narcotic meds relieve
Symptomatic, narcotic meds 
relieve.
Prolonged symptoms, with limited 
response to narcotic meds
Debilitating, hospitalisation; no 
relief with meds
C6.  Sweating 
(diaphoresis)
Episodic, transient
Frequent, short term
Frequent, drenching, disabling
Dehydration, requiring IV 
fluids/hospitalization > 24 hrs
C7.  Weight gain
5% – 9.9%
10% – 19.9%
20% – 30%
NA
C8.  Weight loss
5% – 9.9%
10% – 19.9%
20% – 30%
NA

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
D.  Dermatologic
D1.  Alopecia
Subjective, transient
Objective, fully reversible
Patchy, wig used, partly reversible
Complete, or irreversible even if 
patchy
D2.  Bullous eruption
Localised, asymptomatic
Localised, symptomatic, requiring 
treatment
Generalised, responsive to 
treatment; reversible
Prolonged, generalised, or requiring 
hospitalisation for treatment
D3.  Dry skin
Asymptomatic, controlled with 
emollients
Symptoms eventually (1 – 2 wks) 
controlled with emollients
Generalised, interfering with ADL 
> 2 wks, persistent pruritis, partially 
responsive to treatment
Disabling for extended period, 
unresponsive to ancillary therapy 
and requiring study drug 
discontinuation for relief
D4.  Injection site 
reaction
Local erythema, pain, pruritis, 
< few days
Erythema, pain, oedema, may 
include superficial phlebitis,
1 – 2 wks
Prolonged induration, superficial 
ulceration; includes thrombosis
Major ulceration necrosis requiring 
surgery
D5.  Petechiae 
(without vasculitis)
Few, transient asymptomatic
Dependent areas, persistent up to 
2 wks
Generalised, responsive to 
treatment; reversible
Prolonged, irreversible, disabling
D6.  Photosensitivity
Transient erythema
Painful erythema and oedema 
requiring topical treatment
Blistering or desquamation, requires 
systematic corticosteroids
Generalised exfoliation or 
hospitalisation
D7.  Pruritis
Localised, asymptomatic, transient, 
local treatment
Intense, or generalised, relieved 
by systematic medication
Intense or generalised; poorly 
controlled despite treatment
Disabling, irreversible
D8.  Rash (not 
bullous)
Erythema, scattered 
macular/popular eruption; pruritis 
transient; TOC or no meds
Diffuse macular/popular eruption 
or erythema with pruritus; dry 
desquamation; treatment 
required
Generalised, moist desquamation, 
requires systemic corticosteroids; 
responsive to treatment; reversible
Exfoliative or ulcerating; or requires 
hospitalisation; or parenteral 
corticosteroids

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
D.  Dermatologic (continued)
D9.  Induration/ 
fibrosis/Thickening 
(not sclerodermal)
Localized, high density on 
palpation, reversible, no effect on 
ADL and not disfiguring
Local areas < 50% body surface, 
not disfiguring, transient 
interference with ADL, reversible
Generalized, disfiguring, interferes 
with ADL, reversible
Disabling, irreversible, systemic 
symptoms
E.  Ear/Nose/Throat
E1.  Hearing loss
Transient, intermittent, no 
interference with function
Symptomatic, treatment required, 
reversible
Interferes with function; incomplete 
response to treatment
Irreversible deafness
E2.  Sense of smell
Slightly altered
Markedly altered
Complete loss, reversible
Complete loss, without recovery
E3.  Stomatitis
Asymptomatic
Painful, multiple, can eat
Interferes with nutrition, slowly 
reversible
Requires enteral support; residual 
dysfunction
E4.  Taste disturbance 
(dysgeusia)
Transiently altered; metallic
Persistently altered; limited effect 
on eating
Disabling, effect on nutrition
NA
E5.  Tinnitus
Intermittent, transient, no 
interference with function
Requires treatment, reversible
Disabling, or associated with hearing 
loss
Irreversible deafness
E6.  Voice changes 
(includes hoarseness, 
loss of voice, laryngitis)
Intermittent hoarseness, able to 
vocalise
Persistent hoarseness, able to 
vocalise
Whispered speech, slow return of 
ability to vocalise
Unable to vocalize for extended
E7.  Xerostomia (dry 
mouth)
Transient dryness
Relief with meds
Interferes with nutrition, slowly 
reversible
Extended duration interference 
with nutrition, requires parenteral 
nutrition

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
F.  Eye/Ophthalmologic
F1.  Cataract
Asymptomatic, no change in vision, 
non-progressive
Symptomatic, partial visual loss, 
progressive
Symptoms impairing function, vision 
loss requiring treatment, including 
surgery
NA
F2.  Conjunctivitis
Asymptomatic, transient, rapid 
response to treatment
Symptomatic, responds to 
treatment, changes not interfering 
with function
Symptoms prolonged, partial 
response to treatment, interferes 
with function
NA
F3.  Lacrimation 
increased (tearing, 
watery eyes)
Symptoms not requiring treatment, 
transient
Symptomatic, treatment required, 
reversible
Unresponsive to treatment with 
major effect on function
NA
F4.  Retinopathy
Asymptomatic, non-progressive, no 
treatment
Reversible change in vision; readily 
responsive to treatment
Disabling change in vision 
ophthalmological findings reversible, 
sight improves over time
Loss of sight
F5.  Vision changes 
(e.g., blurred, 
photophobia, night 
blindness, vitreous 
floaters)
Asymptomatic, transient, no 
treatment required
Symptomatic, vision changes not 
interfering with function, 
reversible
Symptomatic, vision changes 
interfering with function
Loss of sight
F6.  Xerophtalmia (dry 
eyes)
Mild scratchiness
Symptomatic without interfering 
with function, requires artificial 
tears
Interferes with vision/function, 
corneal ulceration
Loss of sight

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
G.  Gastrointestinal
G1.  Anorexia
Adequate food intake, minimal 
weight loss
Symptoms requiring oral 
nutritional supplementation
Prolonged, requiring iv support
Requires hospitalization for 
nutritional support
G2.  Constipation
Asymptomatic, transient, responds 
to stool softener, OTC laxatives
Symptomatic, requiring 
prescription laxatives, reversible
Obstipation requiring medical 
intervention
Bowel obstruction.  Surgery 
required.
G3.  Diarrhea
Transient, increase of
2 – 3 stools/day over pre-
treatment (no blood or mucus), 
OTC agents relieve
Symptomatic, increase
4 – 6 stools/day, nocturnal stools, 
cramping, requires treatment with 
prescription meds.
Increase > 6 stools/day, associated 
with disabling symptoms, 
e.g., incontinence, severe cramping, 
partial response to treatment.
Prolonged, dehydration, 
unresponsive to treatment, 
requires hospitalization.
G4.  Dyspepsia 
(heartburn)
Transient, intermittent, responds 
to OTC antacids, H-2 blockers
Prolonged, recurrent, requires 
prescription meds, relieved by 
meds
Persistent despite treatment, 
interferes with function, associated 
with GI bleeding
NA
G5.  GI bleed 
(gastritis, gastric or 
duodenal ulcer 
diagnosed-define 
aetiology)
Asymptomatic, endoscopic finding, 
haemocult + stools, no transfusion, 
responds rapidly to treatment
Symptomatic, transfusion ≤ 2 units 
needed; responds to treatment
Haematemesis, transfusion
3 – 4 units, prolonged interference 
with function
Recurrent, transfusion > 4 units, 
perforation, requiring surgery, 
hospitalisation
G6.  Haematochezia 
(rectal bleeding)
Haemorrhodial, asymptomatic, no 
transfusion
Symptomatic, transfusion
≤ 2 units, reversible
Recurrent, transfusion > 3 – 4 units
> 4 units, hypotension, requiring 
hospitalization
G7.  Hepatitis
Laboratory abnormalities, 
asymptomatic, reversible
Symptomatic laboratory 
abnormalities, not interfering with 
function, slowly reversible
Laboratory abnormalities persistent 
> 2 wks, symptoms interfere with 
function
Progressive, hepato-renal, 
anasarca, pre-coma or coma

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
G.  Gastrointestinal (continued)
G8.  Nausea, or 
nausea/vomiting (use 
diagnostic term)
Transient, intermittent, minimal 
interference with intake, rapid 
response to meds.
Persistent, recurrent, requires 
prescription meds, intake 
maintained
Prolonged, interferes with daily 
function and nutritional intake, 
periodic iv fluids
Hypotensive, hospitalization, 
parenteral nutrition, unresponsive 
to out-patient management
G9.  Pancreatitis
Anylase elevation, intermittent 
nausea/vomiting, transient, 
responds rapidly to treatment
Amylase elevation with abdominal 
pain, nausea, occasional vomiting, 
responsive to treatment
Severe, persistent abdominal pain 
with pancreatitic enzyme elevation, 
incomplete or slow response to 
treatment
Complicated by shock, 
haemorrhage (acute circulatory 
failure)
G10.  Proctitis
Perianal pruritus, haemorrhoids 
(new onset), transient, or 
intermittent, relieved by OTC meds
Tenesmus or ulcerations, anal 
fissure, responsive to treatment, 
minimal interference with 
function
Unresponsive to treatment, marked 
interference with function
Mucosal necrosis with 
haemorrhage, infection, surgery 
required.
H.  Musculoskeletal
H1.  Avascular 
necrosis
Asymptomatic MRI changes, non-
progressive
MRI changes and symptoms 
responsive to rest and analgesia
MRI changes, symptoms requiring 
surgical intervention
Wheelchair bound; surgical repair 
not possible
H2.  Arthralgia
Intermittent transient symptoms, 
no meds or relieved by OTC meds
Persistent or recurrent symptoms, 
resolve with meds, little effect on 
function
Severe symptoms despite meds 
impairs function
Debilitating, hospitalisation 
required for treatment
H3.  Leg cramps
Transient, intermittent, does not 
interfere with function
Recurrent symptoms, minimally 
interferes with function or sleep, 
responds to meds
Persistent, prolonged interference 
with function or sleep, partial or no 
response to meds
NA
H4.  Myalgia
Occasional; does not interfere with 
function
Frequent, requires meds (non-
narcotic); minor effects on 
function
Major change in function/lifestyle, 
narcotic pain meds
Debilitating, profound weakness, 
requires wheelchair, unresponsive 
to meds

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
I.  Neuropsychiatric
I1.  Anxiety or 
Depression (mood 
alteration)
Symptomatic, does not interfere 
with function; no meds
Frequent symptoms, responds to 
meds; interferes with ADL at times
Persistent, prolonged symptoms, 
partial or no response to meds, 
limits daily function
Suicidal ideation or danger to self
I2.  Cerebrovascular 
ischaemia
NA
Single transient ischaemic event, 
responsive to treatment
Recurrent transient ischaemic 
events
Cerebrovascular vascular accident 
with permanent disability
I3.  Cognitive 
disturbance
Subjective symptoms, transient, 
intermittent, not interfering with 
function
Objective symptoms, persisting, 
interferes with daily function 
occasionally
Persistent, or worsening objective 
symptoms; interferes with routine 
daily routine
Debilitating/disabling and 
permanent; toxic psychosis
I4.  Depressed 
consciousness 
(somnolence)
Observed, transient, intermittent, 
not interfering with function
Somnolence or sedation, 
interfering with function
Persistent, progressive, obundation, 
stupor
Coma
I5.  Inability to 
concentrate
Subjective symptoms, does not 
interfere with function
Objective findings, interferes with 
function
Persistent, prolonged objective 
findings or organic cause
NA
I6.  Insomnia (in 
absence of pain)
Occasional difficulty sleeping, 
transient intermittent, not 
interfering with function
Recurrent difficulty sleeping; 
requires meds for relief; 
occasional interference with 
function
Persistent or worsening difficulty 
sleeping; severely interferes with 
routine daily function
NA
I7.  Libido decreased
Decrease in interest
Loss of interest; influences 
relationship
Persistent, prolonged interfering 
with relationship
NA
I8.  Peripheral motor 
neuropathy
Subjective or transient loss of deep 
tendon reflexes; function 
maintained
Objective weakness, persistent, no 
significant impairment of daily 
function
Objective weakness with substantial 
impairment of function
Paralysis

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
I.  Neuropsychiatric (continued)
I9.  Peripheral sensory 
neuropathy (sensory 
disturbance)
Subjective symptoms without 
objective findings, transient, not 
interfering with function
Objective sensory loss, persistent, 
not interfering with function
Prolonged sensory loss or 
paraethesias interfering with 
function
NA
I10.  Seizure
NA
Recurrence of old seizures, 
controlled with adjustment of 
meds
Recurrence/exacerbation with 
partial response to medication
Recurrence not controlled, 
requiring hospitalization; new 
seizures
I11.  Vertigo 
(dizziness)
Subjective symptoms, transient, 
intermittent, no treatment
Objective findings, recurrent, 
meds relieve, occasionally 
interfering with function
Persistent, prolonged, interfering 
with daily function; partial response 
to medication
Debilitating without response to 
medication, hospitalization
J.  Pulmonary
J1.  Asthma
Occasional wheeze, no interference 
with activities
Wheezing, requires oral meds, 
occasional interference with 
function
Debilitating, requires nasal O2
Requires ventilator assistance
J2.  Cough
Transient, intermittent, occasional 
OTC meds relieve
Persistent, requires narcotic or 
other prescription meds for relief
Recurrent, persistent coughing 
spasms without consistent relief by 
meds, interferes with function
Interferes with oxygenation; 
debilitating
J3.  Dyspnea
Subjective, transient, no 
interference with function
Symptomatic, intermittent or 
recurring, interferes with 
exertional activities
Symptomatic during daily routine 
activities, interferes with function, 
treatment with intermittent nasal O2
relieves
Symptomatic at rest, debilitating, 
requires constant nasal O2
J4.  Pleuritic pain 
(pleurisy)
Transient, intermittent symptoms, 
no treatment or OTC meds relieve
Persistent symptoms, requires 
prescription meds for relief
Prolonged symptoms, interferes 
with function, requires frequent 
narcotic pain relief
Debilitation, requiring 
hospitalisation

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
J.  Pulmonary (continued)
J5.  Pneumonitis 
(pulmonary 
infiltrates)
Asymptomatic radiographic 
changes, transient, no treatment 
required
Symptomatic, persistent, requiring 
corticosteroids
Symptomatic, requiring treatment 
including O2
Debilitating, not reversible; or 
requiring assisted ventilation
J6.  Pulmonary 
function decreased 
(FVC or carbon 
monoxide diffusion 
capacity – DLCO)
76% – 90% of pre-treatment value
51% – 75% of pre-treatment value
26% – 50% of pre-treatment value
≤ 25% of pre-treatment value
Laboratory Data
K.  Haematology
K1.  Hgb (g/dl) 
decrease from pre-
treatment
1.0 – 1.4
1.5 – 2.0
2.1 – 2.9, or Hgb < 8.0, > 7.0
≥ 3.0; or Hgb < 7.0
K2.  Leukopenia (total 
WBC) × 1000
3.0 – 3.9
2.0 – 2.9
1.0 – 1.9
< 1.0
K3.  Neutropenia 
(× 1000)
1.5 – 1.9
1.0 – 1.4
0.5 – 0.9
< 0.5
K4.  Lymphopenia 
(× 1000)
1.5 – 1.9
1.0 –1.4
0.5 – 0.9
< 0.5
K5.  Platelets (× 1000)
75 – LLN
50 – 74.9
20 – 49.9; platelet transfusion required
< 20; recurrent platelet transfusions

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
L.  Chemistry
L1.  Hypercalcaemia 
(mg/dl)
1.1 × ULN – 11.5
11.6 – 12.5
12.6 – 13.5; or symptoms present
> 13.5; or associated coma
L2.  Hyperglycemia 
(mg/dl) Fasting
140 – 160
161 – 250
251 – 500
> 500, or associated with 
ketoacidosis
L3.  Hyperkalaemia 
(mg/dl)
5.5 – 5.9
6.0 – 6.4
6.5 – 7.0 or any ECG change
> 7.0 or any arrhythmia
L5.  Hypocalcaemia 
(mg/dl)
0.9 × LLN – 7.8
7.7 – 7.0
6.9 – 6.5; or associated with 
symptoms
< 6.5 or occurrence of tetany
L6.  Hypoglycemia 
(mg/dl)
55 – 64 (no symptoms)
40 – 54 (or symptoms present)
30 – 39 (symptoms impair function)
< 30 or coma
L7.  Hyponatraemia 
(mg/dl)
--
125 – 129
120 – 124
< 120
L8.  Hypokalaemia 
(mg/dl)
--
3.0 – 3.4
2.5 – 2.9
< 2.5
L9.  CPK (also if 
polymyositis-disease)
1.2 – 1.9 × ULN
2.0 – 4.0 × ULN
4.0 × ULN with weakness but 
without life-threatening signs or 
symptoms
> 4.0 × ULN with signs or symptoms 
of rhabdomyolysis or life-
threatening
L10.  Serum uric acid
1.2 – 1.6 × ULN
1.7 – 2.9 × ULN
3.0 – 5.0 × ULN or gout
NA
L11.  Creatinine 
(mg/dL)
1.1 – 1.3 × ULN
1.3 – 1.8 × ULN
1.9 – 3.0 × ULN
> 3.0 × ULN
L12.  SGOT (AST)
1.2 – 1.5 × ULN
1.6 – 3.0 × ULN
3.1 – 8.0 × ULN
> 8.0 × ULN
L13.  SGPT (ALT)
1.2 – 1.5 × ULN
1.6 – 3.0 × ULN
3.0 – 8.0 × ULN
> 8.0 × ULN

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 – Mild
No medication or OTC
Asymptomatic, or transient
Short duration (< 1 week)
No change in life style
2 – Moderate
Symptomatic
Duration (1 – 2 weeks)
Alter lifestyle occasionally
Meds relieve (may be 
prescription)
Study drug continued
3 – Severe
Prolonged symptoms, reversible, 
major functional impairment
Prescription meds/partial relief
May be hospitalized < 24 hr
Temporary study drug 
discontinuation or/and dose 
reduced
4 – Includes Life Threatening
At risk of death
Substantial disability, especially if 
permanent
Multiple meds
Hospitalized > 24 hr
Study drug discontinued
L.  Chemistry (continued)
L14.  Alkaline 
phosphatase
1.1 – 2.0 × ULN
1.6 – 3.0 × ULN
3.0 – 5.0 × ULN
> 5.0 × ULN
L15.  T. bilirubin
1.1 – 1.4 × ULN
1.5 – 1.9 × ULN
2.0 – 3.0 × ULN
> 3.0 × ULN
L16.  LDH
1.3 – 2.4 × ULN
2.5 – 5.0 × ULN
5.1 – 10 × ULN
> 10 × ULN
M.  Urinalysis
M1.  Haematuria
Micro only
Gross, no clots
Clots, transfusion < 2 units 
Transfusion required
M2.  Proteinuria (per 
24 h)
300 – 500 mg (tr/1+)
501 – 1999 mg (2+)
2 – 5.0 g (3+) nephrotic syndrome
5.0 g (4+) anasarca
M3.  WBC in urine
NA
NA
Indicating acute interstitial nephritis
Associated with acute renal failure
M4.  Uric acid crystals
Present without symptoms
NA
With stones or symptoms of stones 
(e.g., renal colic)
Causing renal outflow obstruction 
and hospitalization
ADL = activities of daily living; ANA = antinuclear antibodies; CHF = congestive heart failure; ECG = electrocardiogram; FVC = forced vital capacity; H-2 blockers = histamine-2 blockers 
IV = intravenous; LLN = lower limit of normal; MRI = magnetic resonance imaging; OTC = over-the-counter medication; SLE = systemic lupus erythematosus; ULN = upper limit of 
normal; WBC = white blood cells

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX J.
ACTIVITY SCHEDULE
The following table shows the required activities the subject encounters.  The individual activities are 
described in detail in Appendix K, the Operations Manual.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX K. SUMMARY OF CHANGES
Previous Protocol Versions
Protocol 
Date
Version 1.0
18 October 2018
Version 1.1 (Germany Only)
07 November 2019
Version 1.1.1 (Germany Only)
20 November 2019
Version 2.0
20 November 2019
Version 3.0
20 November 2019
Version 4.0
11 March 2020
Version 4.1 (Germany Only)
12 March 2020
The purpose of this version is to remove the 
 cohort.  Minor clerical edits have been made as 
needed for consistency and clarity throughout the protocol.
Summary of Protocol Changes:
!
Title Page, removed 
 from the Title Page.
Rationale:  
 is not being studied in this protocol.
!
Synopsis, removed 
 language from the Synopsis.
Rationale:  
 is not being studied in this protocol.
!
Section 2.1, removed 
 language from this section and the clinical hypothesis.
Rationale:  
 is not being studied in this protocol.
!
Section 2.2, removed 
 language, and added language regarding COVID-19 related risks.
Rationale:  
 is not being studied in this protocol.  COVID-19 language added to indicate 
that no change to the benefit/risk balance for subjects in this study is expected.
!
Section 3.1, removed the primary and secondary objectives for the 
 cohort.
Rationale:  To clarify that the 
 cohort is not being studied in this protocol.
!
Section 3.5, revised PK and immunogenicity endpoints to remove 
Rationale:  
 is not being studied in this protocol.
!
Section 3.6, removed 
 with regard to assessment of changes in cortisol level.
Rationale:  
 is not being studied in this protocol.
!
Section 4.1, revised overall study design, including study schematic, and plan to exclude the 
 cohort.
Rationale:  
 is not being studied in this protocol.
!
Section 4.2, removed details of study conduct related to

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Rationale:  
 is not being studied in this protocol.
!
Section 5.1, removed prior and concomitant medication criteria and expectations for the 
 cohort.
Rationale:  
 is not being studied in this protocol.
!
Section 5.1, removed washout times for prior biologics/tsDMARDs for the 
 cohort, and 
shortened duration of treatment with any investigational drug prior to first dose of study drug 
to 30 days.
Rationale:  
 is not being studied in this protocol.  Thirty days is the correct duration; 
the change to 70 days in the last amendment was made in error.
!
Section 5.4, removed reference to 
 Investigator Brochure and 
 wash out 
times before baseline.
Rationale:  
 is not being studied in this protocol.
!
Section 5.7, removed details for 
 cohort dosing.
Rationale:  
 is not being studied in this protocol.
!
Section 5.8, removed information about randomization for the 
 cohort.
Rationale:  
 is not being studied in this protocol.
!
Section 6.2, removed drug administration information for 
Rationale:  
 is not being studied in this protocol.
!
Section 7.3, removed statistical analyses for efficacy for 
Rationale:  
 is not being studied in this protocol.
!
Section 7.4, removed "of each cohort" regarding the Safety Analysis Set.
Rationale:  
 is not being studied in this protocol.
!
Section 7.5, removed 
 from statistical analysis of PK and immunogenicity data.
Rationale:  
 is not being studied in this protocol.
!
Section 7.7, removed interim analysis for 
Rationale:
 is not being studied in this protocol.
!
Section 12, reference list updated.
Rationale:  References that are no longer applicable have been removed.
!
Appendix J:  revised to remove assessment/procedures related to 
 cohort.
Rationale:  
 is not being studied in this protocol.
Summary of Operations Manual Changes:
!
Title Page, removed 
 from Title Page.
Rationale:  
 is not being studied in this protocol.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
!
Section 1, added section description for clarity, and removed 
 from Pharmacokinetic 
Lab section.
Rationale:  
 is not being studied in this protocol.
!
Section 2.1, removed study activities for 
.
Rationale:  
 is not being studied in this protocol.
!
Section 3.5, removed sections for PK and immunogenicity sampling for 
.
Rationale:  
 is not being studied in this protocol.
!
Section 3.6, removed biomarker sampling for 
.
Rationale:  
 is not being studied in this protocol.
!
Section 3.12, removed clinical laboratory testing for the 
 cohort.
Rationale:  
 is not being studied in this protocol.
!
Section 5.1, removed 
 for SUSAR reporting.
Rationale:  
 is not being studied in this protocol.
!
Section 6.1, removed section for 
 treatment administration.
Rationale:  
 is not being studied in this protocol.
!
Section 6.2, removed information on for 
 drug supply, storage, and disposition.
Rationale:  
 is not being studied in this protocol.
!
Section 6.3, removed the section for method of assigning subjects to treatment groups for the 
 cohort.
Rationale:  
 is not being studied in this protocol.
!
Section 6.4, removed the section for timing of study drug in the 
 cohort.
Rationale:  
 is not being studied in this protocol.

STUDY M16-560  |  Version 5.0 | EudraCT 2018-003053-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX L.
OPERATIONS MANUAL