Conditions: Plaque Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 24
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of 3 doses of AGN-242428 in adult participants with moderate to severe plaque-type psoriasis.

Detailed description:

Arms:
arm 1: Placebo-matching AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. arm 2: AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. arm 3: AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. arm 4: AGN-242428 capsule and placebo-matching AGN-242428 capsule, oral administration, once-daily for up to 12 weeks.

Interventions: intervention 1: AGN-242428 intervention 2: Placebo
Intervention descriptions: intervention 1: AGN-242428 administered as an oral capsule(s) once daily. intervention 2: Placebo administered as an oral capsule(s) once daily.

Protocol document:
Prot_000.pdf: 
 
   
 
 
 
         NCT 03339999 
 
Study ID: 1957-201-001 
 
 
Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Assess 
the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AGN-
242428 in Patients With Plaque Psoriasis 
 
                                  Protocol Date: December 21, 2017 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
AGN-242428 
 
GRD-CLN-T-01-01 Protocol Template v1.0 
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TITLE PAGE 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Assess the 
Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AGN-242428 in Patients 
With Plaque Psoriasis 
Amendment Number: Amendment 2 
Brief Protocol Title: AGN-242428 in the treatment of plaque psoriasis 
Product: AGN-242428 
Sponsor Name and Legal Registered Address: 
Vitae Pharmaceuticals Inc., a subsidiary of Allergan plc 
2525 Dupont Drive 
Irvine, California USA 92612 
Regulatory Agency Identifying Number(s): U.S. FDA IND 124698 
Emergency Telephone Number 
Refer to the study contacts page 
SAE Reporting Fax Number/Email: 
 
 
Allergan 
 
 
 
Sponsor Signatory: 
Refer to the final page of this protocol for electronic signature and date of approval. 
 
 
 
Date 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
AGN-242428 
 
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Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2 
December 2017 
Amendment 1 
September 2017 
Original Protocol 
June 2017 
 
Amendment 2 (December 2017) 
Overall Rationale for the Amendment: 
The overall rationale for the changes implemented in Protocol Amendment 2 was to modify 
alcohol intake and food consumption during the study, clarify prohibited medications, and 
describe pharmacokinetic analyses. 
 


 
 
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Section No. and 
Name 
Description of Change 
Brief Rationale 
1 Synopsis 
(Objectives and 
Endpoints) 
Deleted “across scheduled postbaseline visits” and 
“Plasma concentrations of AGN-242428 at randomly 
selected times relative to last dose at the Week 6 and 
Week 10 visits” and replaced them with “and 
pharmacokinetic parameters” 
To modify the pharmacokinetic 
objective 
2 Schedule of 
 
 
 
 
 
 
 
 
 
 
 
3.3 Benefit/Risk 
Assessment 
Added strong CYP3A4 inhibitors and inducers 
To update based on in vitro 
studies 
4 Objectives and 
Endpoints 
For consistency, the change that was made in 
Section 1 Synopsis (as described above) was also 
made here 
To modify the pharmacokinetic 
objective 
 
 
 
 
 
6.2 Exclusion 
Criteria 
Added “with any anti-TNFα biologic therapy within 
3 months or 5 half-lives of study, and/or all other” to 
2.03. Note: Made this change throughout the protocol, 
where applicable 
To clarify exclusion criteria 
 
 
 
 
 
 
 
 
 
 
 
 
6.3.1 Meals and 
Dietary Restrictions 
Added a grapefruit and Seville orange restriction for 
the entire study population 
To modify verbiage regarding 
dietary restrictions 
6.3.1 Meals and 
Dietary Restrictions 
Removed the fruit restriction in the PK subset 
To modify verbiage regarding 
dietary restrictions 
6.3.2 Caffeine, 
Alcohol, and 
Tobacco 
Deleted caffeine paragraph 
To eliminate caffeine 
restrictions 
6.3.2 Caffeine, 
Alcohol, and 
Tobacco 
Deleted the following phrase from the Alcohol 
subsection: “no alcohol for the first month and then no 
more than a total of 3 drinks per week.” 
To modify verbiage regarding 
alcohol intake during the study 
 
 
 
6.4 Screen Failures 
Deleted “Participants who rescreen for the study must 
be reconsented.” Replaced the text with “A participant 
who is rescreened is not required to sign another ICF 
To modify verbiage regarding 
consent during rescreening 


 
 
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Section No. and 
Name 
Description of Change 
Brief Rationale 
if the rescreening occurs within 28 days from the 
previous ICF signature date.” 
7.7.1 Prohibited 
Treatments and 
Washout Before the 
Study 
Added “Any previous use of systemic psoriasis 
medications/treatments used by the participant prior to 
enrollment must be recorded on the eCRF.” 
To clarify what medication 
should be captured on the 
eCRF 
 
 
 
 
 
 
 
 
 
 
 
 
8.1.1 Temporary 
Discontinuation 
Deleted this section and replaced it with “The DMC 
allows for temporary discontinuation of dosing 
pending further analysis of possible safety issues (an 
option open to the DMC).” 
To clarify temporary 
discontinuation 
9.1.4 Photograph of 
Primary Lesion 
Added “The images can be captured before or after 
the study medication is administered.” 
To clarify when the images can 
be captured 
9.1.4 Photograph of 
Primary Lesion 
Added “Participants may decline permission for use 
of their study photographs for advertising, publicity, 
and promotional purposes.” 
To clarify that participation is 
optional 
 
 
 
 
 
 
9.4.4 Clinical Safety 
Laboratory 
Assessments 
Deleted the local laboratory paragraph and replaced it 
with “All laboratory tests should be sent to the central 
laboratory for the study.” 
To clarify that the central 
laboratory should be used 
9.5 
Pharmacokinetics 
Added additional pharmacokinetics text 
To provide additional details 
on the pharmacokinetics 
9.6 
Pharmacodynamics 
Deleted “Participants will consent to these additional 
analyses.” 
To reflect additional consent is 
not required 
9.8 Biomarkers 
Updated this section 
To reflect biomarkers will be 
evaluated 
10.3.1 Disposition 
and Baseline 
Demographic 
Characteristics 
Analyses 
Deleted “and the safety analysis set” 
Safety analysis set is similar to 
the mITT analysis set 
10.3.4 
Pharmacokinetic 
Analyses 
Updated text to describe the pharmacokinetic analyses 
To provide more detail on the 
analyses 
10.3.5 
Pharmacodynamic 
Analyses 
Added “and Pharmacokinetic-Pharmacodynamic 
Analyses” to the title and text to this section 
To provide additional detail on 
the pharmacokinetic-
pharmacodynamic analyses 
12.6 Liver Safety 
Deleted HPLC assay and associated reference. Note: 
HPLC is not necessary 


 
 
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Section No. and 
Name 
Description of Change 
Brief Rationale 
The reference was also deleted from Section 11 
12.8 List of 
Prohibited 
Medications 
Added “sensitive” before substrates. Updated the 
medication in the table and added strong CYP3A4 
inhibitors and inducers 
To provide more clarification 
on what is prohibited 
12.9 Protocol 
Amendment History 
Moved Amendment 1 text here 
To allow for Amendment 2 text 
to be in the beginning of this 
protocol 
Throughout 
Minor editorial revisions 
Minor, therefore, have not been 
summarized 
 
 
 


 
 
Approval Date: 
 
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Table of Contents 
TITLE PAGE ...................................................................................................................................1 
Protocol Amendment Summary of Changes Table .........................................................................2 
Table of Contents .............................................................................................................................6 
List of Tables ...................................................................................................................................8 
1. 
Synopsis ..........................................................................................................................10 
 
 
3. 
Introduction .....................................................................................................................26 
3.1. 
Study Rationale ...............................................................................................................26 
3.2. 
Background .....................................................................................................................26 
3.2.1. 
VTP-43742-001: Single-Ascending Dose Study ............................................................26 
3.2.2. 
VTP-43742-002 Part 1: Multiple-Ascending Dose Study ..............................................27 
3.2.3. 
VTP-43742-002 Part 2: Proof-of-Concept Study ...........................................................28 
3.3. 
Benefit/Risk Assessment ................................................................................................28 
4. 
Objectives and Endpoints ...............................................................................................32 
5. 
Study Design ...................................................................................................................34 
5.1. 
Overall Design ................................................................................................................34 
5.2. 
Participant and Study Completion ..................................................................................35 
5.3. 
End of Study Definition ..................................................................................................35 
5.4. 
Scientific Rationale for Study Design ............................................................................36 
5.5. 
Justification for Dose ......................................................................................................36 
6. 
Study Population .............................................................................................................38 
6.1. 
Inclusion Criteria ............................................................................................................38 
6.2. 
Exclusion Criteria ...........................................................................................................39 
6.3. 
Lifestyle Restrictions ......................................................................................................43 
6.3.1. 
Meals and Dietary Restrictions .......................................................................................43 
6.3.2. 
Alcohol and Tobacco ......................................................................................................44 
6.4. 
Screen Failures ................................................................................................................44 
7. 
Treatments ......................................................................................................................45 
7.1. 
Treatments Administered ................................................................................................45 
7.1.1. 
Medications and Administration .....................................................................................45 
7.1.2. 
Study Supplies ................................................................................................................46 
7.2. 
Dose Modification ..........................................................................................................46 
7.3. 
Method of Treatment Assignment ..................................................................................46 
7.4. 
Blinding/Masking ...........................................................................................................46 
7.5. 
Preparation/Handling/Storage/Accountability ................................................................47 
7.5.1. 
Study Medication Accountability ...................................................................................48 
7.5.2. 
Study Medication Handling and Disposal ......................................................................48 


 
 
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7.6. 
Treatment Compliance ....................................................................................................48 
7.7. 
Concomitant Therapy .....................................................................................................48 
7.7.1. 
Prohibited Treatments and Washout Before the Study ...................................................48 
7.7.2. 
Permitted Treatments ......................................................................................................51 
7.7.3. 
Rescue Medicine .............................................................................................................51 
7.7.4. 
Prohibited Medications During the Study.......................................................................51 
7.8. 
Treatment After the End of the Study .............................................................................51 
8. 
Discontinuation/Withdrawal Criteria ..............................................................................52 
8.1. 
Discontinuation of Study Treatment ...............................................................................52 
8.1.1. 
Temporary Discontinuation ............................................................................................53 
8.1.2. 
Criteria for Study Termination ........................................................................................53 
8.2. 
Withdrawal from the Study.............................................................................................54 
8.3. 
Lost to Follow-Up ...........................................................................................................54 
9. 
Study Assessments and Procedures ................................................................................55 
9.1. 
Efficacy Assessments .....................................................................................................55 
9.1.1. 
Determination of Percent Body Surface Area ................................................................55 
9.1.2. 
Psoriasis Area and Severity Index ..................................................................................56 
9.1.3. 
Physician’s Global Assessment ......................................................................................58 
9.1.4. 
Photograph of Primary Lesion ........................................................................................59 
 
 
9.2. 
Adverse Events ...............................................................................................................61 
9.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................61 
9.2.2. 
Method of Detecting AEs and SAEs ..............................................................................61 
9.2.3. 
Follow-up of AEs and SAEs ...........................................................................................62 
9.2.4. 
Regulatory Reporting Requirements for SAEs ...............................................................62 
9.2.5. 
Cardiovascular and Death Events ...................................................................................62 
9.2.6. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................................63 
9.2.7. 
Pregnancy ........................................................................................................................63 
9.2.8. 
Adverse Events of Special Interest .................................................................................63 
9.2.9. 
Medication Errors ...........................................................................................................64 
9.3. 
Treatment of Overdose ...................................................................................................65 
9.4. 
Safety Assessments .........................................................................................................65 
9.4.1. 
Physical Examinations ....................................................................................................65 
9.4.2. 
Vital Signs .......................................................................................................................66 
9.4.3. 
Electrocardiograms .........................................................................................................66 
9.4.4. 
Clinical Safety Laboratory Assessments ........................................................................67 
9.4.5. 
Suicidal Risk Monitoring ................................................................................................68 
9.5. 
Pharmacokinetics ............................................................................................................69 
9.6. 
Pharmacodynamics .........................................................................................................70 
9.7. 
Genetics ..........................................................................................................................71 


 
 
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9.8. 
Biomarkers ......................................................................................................................71 
9.9. 
Medical Resource Utilization and Health Economics ....................................................71 
10. 
Statistical Considerations ................................................................................................72 
10.1. 
Sample Size Determination ............................................................................................72 
10.2. 
Populations for Analyses ................................................................................................72 
10.3. 
Statistical Analyses .........................................................................................................72 
10.3.1.  Disposition and Baseline Demographic Characteristics Analyses .................................72 
10.3.2.  Efficacy Analyses ...........................................................................................................73 
10.3.3.  Safety Analyses ...............................................................................................................74 
10.3.4.  Pharmacokinetic Analyses ..............................................................................................74 
10.3.5.  Pharmacodynamic and Pharmacokinetic-Pharmacodynamic 
Analyses ..........................................................................................................................75 
10.3.6.  Interim Analyses .............................................................................................................75 
11. 
References .......................................................................................................................76 
12. 
Appendices......................................................................................................................77 
12.1. 
Appendix 1: Abbreviations and Trademarks ..................................................................77 
12.2. 
Appendix 2: Study Governance Considerations .............................................................81 
12.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................85 
12.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................90 
12.5. 
Appendix 5: Standard Discontinuation Criteria..............................................................94 
12.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessment......................................................................................................................96 
12.7. 
Appendix 7: Study Tabular Summary ..........................................................................100 
12.8. 
Appendix 8: Partial List of Prohibited Medications Which Are 
Sensitive Substrates for BCRP, OATP1B3, CYP2D6, and 
CYP2C8 and Strong Inhibitors or Inducers of CYP3A4 ..............................................103 
12.9. 
Appendix 9: Protocol Amendment History ..................................................................104 
 
List of Tables 
 
 
Table 4-1 
Objectives and Endpoints ..................................................................................32 
Table 6-1 
Inclusion Criteria ...............................................................................................38 
Table 6-2 
Exclusion Criteria ..............................................................................................39 
Table 7-1 
Treatments Administered ..................................................................................45 
 
 


 
 
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Table 8-1 
Safety Criteria for Individual Participants Stopping Study Treatment .............53 
Table 9-1 
Score Assignment for Body Region based on Body Surface Area (BSA) 
(Surface Area Involvement Score) ....................................................................56 
Table 9-2 
Psoriasis Area and Severity Index (PASI) calculator ........................................58 
Table 9-3 
Physician’s Global Assessment (PGA) Scoring ................................................59 
Table 9-4 
Clinical Laboratory Tests ..................................................................................68 
Table 9-5 
Allowable Windows for Pharmacokinetic (PK) Sampling Times ....................70 
Table 10-1 
Analysis Populations .........................................................................................72 
Table 10-2 
Fitzpatrick Skin Phototype ................................................................................73 
 


 
 
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1. 
Synopsis 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy, 
Safety, Pharmacokinetics and Pharmacodynamics of AGN-242428 in Patients With Plaque 
Psoriasis 
Protocol Number: 1957-201-001 
Brief Title: AGN-242428 in the treatment of plaque psoriasis 
Study Phase: Phase 2b 
Study Rationale: 
This study will evaluate the efficacy, safety, tolerability, pharmacokinetics and 
pharmacodynamics of 3 doses of AGN-242428, 
 
 and 
 once-daily, relative 
to placebo, in participants with moderate to severe plaque-type psoriasis. A previous 
proof-of-concept (POC) study (VTP-43742-002 Part 2) evaluated efficacy and safety of 
AGN-242428 over a 28-day treatment period. The treatment duration is increased to 16 weeks in 
the current trial to allow evaluation of efficacy and safety over the longer term. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
• 
To compare the efficacy of AGN-242428 with 
placebo, administered orally once-daily for a period 
of 16 weeks, in participants with moderate to severe 
plaque psoriasis 
• 
The percentage of participants achieving a 
reduction (improvement) in Psoriasis Area and 
Severity Index (PASI) score of ≥ 75% from 
baseline to Week 16 
Secondary 
 
• 
To compare the efficacy of AGN-242428 with 
placebo, with respect to the Physician’s Global 
Assessment (PGA) score 
• 
Percentage of participants achieving ≥ 2-point 
improvement in PGA score at Week 16 
• 
Percentage of participants achieving a clear (0) or 
almost clear (1) score in PGA at Week 16 
• 
To compare the efficacy of AGN-242428 with 
placebo, with respect to PASI score 
• 
Percentages of participants achieving reductions of 
50% and 90% from baseline in PASI score at 
Week 16 
• 
To assess the safety and tolerability of AGN-242428 
in participants with moderate to severe plaque 
psoriasis  
• 
Incidence of adverse events (AEs) including 
severity and causality of AEs, as well as AEs 
leading to discontinuation 
• 
Change from baseline in clinical laboratory tests, 
vital signs and electrocardiogram (ECG) 


 
 
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Objectives 
Endpoints 
• 
To characterize the pharmacokinetics of 
AGN-242428 in participants with moderate to 
severe plaque psoriasis 
• 
Plasma concentrations of AGN-242428 and 
pharmacokinetic parameters 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Overall Study Design: 
This is a double-blind, randomized, placebo-controlled trial to evaluate the efficacy, safety, 
tolerability, pharmacokinetics and pharmacodynamics of AGN-242428 when administered 
once-daily for 16 weeks to adults with moderate to severe plaque psoriasis. The study consists of 
3 periods, as described below. Details of individual assessments to be completed at each study 
visit are included in Section 2. 
Screening Period: The purpose of the screening period is to evaluate potential study participants 
and to qualify them for enrollment into the study. This period begins at the point of informed 
consent and ends when the participant is randomized to treatment. The screening period will be 
up to 4 weeks (≤ 28 days) in duration. 
Treatment Period: Participation in the study begins at the point the participant is randomized. 
The treatment starts after his/her first dose of study medication and ends after 16 weeks of 
treatment or at the point of permanent study medication withdrawal should the participant 
discontinue treatment prior to completion of Week 16.  
On Day 1 of the treatment period, qualified participants will be randomly assigned to receive 
16 weeks of once-daily oral treatment with 
 AGN-242428, 
 AGN-242428, 
AGN-242428, or placebo. Baseline data for evaluation of participant efficacy and safety 
will be obtained on Day 1, prior to receiving the first dose. Participants will complete study visits 
on the first day of treatment and following 2, 4, 6, 8, 10, 12 and 16 weeks of treatment for 
evaluation of efficacy, safety and tolerability assessments.  
A subset of approximately 14 to 18 participants in each treatment group (includes placebo), who 
have provided consent, will have sequential blood samples collected at scheduled times before 
and up to 24 hours after study medication administration during the Week 4 visit to establish 
AGN-242428 pharmacokinetic (PK) concentration versus time profiles. All participants will 
have blood samples collected to determine trough AGN-242428 concentrations obtained on Day 


 
 
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1 and at the Week 4, 8, 12 and 16/early termination visits. Random time PK sampling at Weeks 6 
and 10 (in addition to other assessments eg, select laboratory tests [see Table 9-4] and AEs 
[Section 9.2]) will also be obtained in all participants. 
Any participant who exhibits a predefined change in clinical laboratory parameters may be 
required to complete unscheduled visits to further monitor abnormal safety laboratory test 
results. See Section 2 for testing criteria. Investigators may complete unscheduled study visits at 
any point they feel necessary to monitor and ensure participant safety. 
 
 
  
Follow-up Period: Participants will return for a follow-up visit 14 ± 3 days after completion or 
premature discontinuation of study medication for end-of-study assessments. 
A Data Monitoring Committee (DMC) will review select safety and exposure data (as needed), 
when approximately 10%, 30%, 60% and 80% of the total participants have completed treatment 
through Week 4. Ad-hoc meetings of the DMC may be scheduled to evaluate potential safety 
signals, as indicated. The DMC will review blinded data. If there is a significant safety signal, 
then unblinded data may be reviewed in a closed session by DMC members designated as 
unblinded reviewers. Policies, procedures and composition of the DMC are described in the 
DMC charter for this trial. 
Key inclusion criteria: Male or female participants who have a confirmed diagnosis of plaque 
psoriasis, diagnosed at least 6 months before study, with a PGA score ≥ 3 at screening and 
baseline. Severity of disease must be at least moderate, defined as Psoriasis Area and Severity 
Index (PASI) ≥ 12 and % body surface area (BSA) ≥ 10. Participant is a candidate for 
phototherapy or systemic therapy for psoriasis. 
Key exclusion criteria: Non-plaque forms of psoriasis (erythrodermic, guttate, pustular) or 
drug-induced psoriasis. Psoriasis which has not been stable for the 4 weeks prior to screening 
and which is unstable at Study Day 1. History of Gilbert’s, Rotor, or Dubin-Johnson syndromes 
or any other disorder of bilirubin metabolism. History of active mycobacterium tuberculosis 
(TB) infection or untreated or inadequately treated latent TB. Positive QuantiFERON test for TB 
infection. Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months prior to 
baseline. Positive drug and/or alcohol test at screening (with the exception of marijuana). 
Retesting in the case of a positive alcohol test is allowed at the discretion of the sponsor. Current 
treatment or history of treatment for psoriasis with any anti-TNFα biologic therapy within 
3 months or 5 half-lives of study, and/or all other biologics within 6 months of study (Day 1) is 
prohibited. Efficacy failure on 2 or more biologic agents for the treatment of psoriasis when the 
failures occurred within 1 year of the initiation of the therapy of the first biologic agent. Alanine 
aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBL) exceeding 
1.5 times the upper limit of normal (ULN) at screening (may be repeated once to confirm value). 
Values that are above the ULN and ≤ 1.5 x ULN must be repeated to confirm that the value is 
stable. 


 
 
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Number of Participants: 
Participants will be screened to achieve approximately 200 randomly assigned to study 
medication and an estimated total of 160 evaluable participants who will complete the study 
(estimated 40 evaluable participants per treatment group). 
Number of Sites:  
Approximately 40 study centers in the United States 
Treatment Groups and Study Duration: 
The trial will consist of a screening period of up to 4 weeks (≤ 28 days), a treatment period of 
once-daily administration for 16 weeks and a follow-up period of 14 ± 3 days after completion of 
study medication, or after early withdrawal. Thus, the trial duration for each participant will be 
up to 22 weeks ± 3 days from screening to follow-up. 
Approximately 200 participants will be randomly assigned (1:1:1:1) to once-daily study 
medication (50 participants to AGN-242428 
 50 participants to AGN-242428
, 
50 participants to AGN-242428 
 and 50 participants to placebo) to provide an estimated 
total of 160 evaluable participants who will complete the study. 


 
 
 
 
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3. 
Introduction 
AGN-242428 (formerly Vitae Pharmaceuticals compound VTP-43742) is an orally active small 
molecule inhibitor of RORγt activity that is being pursued as a potential treatment for psoriasis 
and other autoimmune disorders. Increased production of the inflammatory cytokine interleukin-
17A (IL-17A) appears to be a critical part of the pathophysiology in certain autoimmune 
disorders. RORγt is a nuclear hormone receptor that is essential for the formation of T helper 17 
(Th17) cells and for the synthesis of IL-17A. It is expected that inhibition of RORγt activity in 
Th17 and other cells will be beneficial for the treatment of multiple autoimmune disorders. 
Summaries and detailed results of individual studies and assays included in the nonclinical 
investigational program are included in the investigator’s brochure (IB). Clinical investigators 
must read and use the IB in conjunction with this protocol. 
3.1. 
Study Rationale 
This study will evaluate the efficacy, safety, tolerability, pharmacokinetics and 
pharmacodynamics of 3 doses of AGN-242428, 
, 
 and 
 once-daily, relative 
to placebo, in participants with moderate to severe plaque-type psoriasis. A previous 
proof-of-concept (POC) study (VTP-43742-002 Part 2) evaluated efficacy and safety of 
AGN-242428 over a 28-day treatment period. The treatment duration is increased to 16 weeks in 
the current trial to allow evaluation of efficacy and safety over the longer term.  
3.2. 
Background 
Brief summaries of topline results from a single ascending-dose study (VTP-43742-001) and a 
multiple-ascending dose study (VTP-43742-002) in healthy volunteers are provided in this 
protocol. Preliminary data from a POC study conducted in patients with moderate to severe 
plaque psoriasis are also summarized. Additional results of each study are provided in the IB 
which must be read and used in conjunction with this protocol. 
 
 
 
 
 
  
 
 
 
 
 


 
 
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4. 
Objectives and Endpoints 
Table 4-1 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To compare the efficacy of AGN-242428 with 
placebo, administered orally once-daily for a period 
of 16 weeks, in participants with moderate to severe 
plaque psoriasis 
• 
The percentage of participants achieving a reduction 
(improvement) in Psoriasis Area and Severity Index 
(PASI) score of ≥ 75% from baseline to Week 16 
Secondary 
 
• 
To compare the efficacy of AGN-242428 with 
placebo, with respect to the Physician’s Global 
Assessment (PGA) score 
• 
Percentage of participants achieving ≥ 2-point 
improvement in PGA score at Week 16 
• 
Percentage of participants achieving a clear (0) or 
almost clear (1) score in PGA at Week 16 
• 
To compare the efficacy of AGN-242428 with 
placebo, with respect to PASI score 
• 
Percentages of participants achieving reductions of 
50% and 90% from baseline in PASI at Week 16 
• 
To assess the safety and tolerability of 
AGN-242428 in participants with moderate to 
severe plaque psoriasis  
• 
Incidence of adverse events (AEs) including 
severity and causality of AEs, as well as AEs 
leading to discontinuation 
• 
Change from baseline in clinical laboratory tests, 
vital signs and electrocardiogram (ECG) 
• 
To characterize the pharmacokinetics of 
AGN-242428 in participants with moderate to 
severe plaque psoriasis 
• 
Plasma concentrations of AGN-242428 and 
pharmacokinetic parameters 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Clinical Hypotheses 
1. The percentage of participants achieving ≥ 75% reduction (improvement) in PASI score will 
be higher for AGN-242428-treated participants relative to placebo-treated participants. 
2. AGN-242428 
, 
 and 
 doses administered for 16 weeks will decrease 
clinical scores (eg, PASI, Physicians Global Assessment [PGA]) in participants with 
psoriasis to a greater extent than in participants receiving placebo. 
3. AGN-242428 
 dose administered for 16 weeks may decrease clinical scores in 
participants with psoriasis to a greater extent than treatment with 
 AGN-242428. 
4. AGN-242428 at all 3 doses will be generally safe and well tolerated.  


 
 
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5. 
Study Design 
5.1. 
Overall Design 
This is a double-blind, randomized, placebo-controlled trial to evaluate the efficacy, safety, 
tolerability, pharmacokinetics and pharmacodynamics of AGN-242428 when administered 
once-daily for 16 weeks to adults with moderate to severe plaque psoriasis. The study consists of 
3 periods, as described below. Details of individual assessments to be completed at each study 
visit are included in Section 2.  
Screening Period: The purpose of the screening period is to evaluate potential study participants 
and to qualify them for enrollment into the study. This period begins at the point of informed 
consent and ends when the participant is randomized to treatment. The screening period will be 
up to 4 weeks (≤ 28 days) in duration. 
Treatment Period: Participation in the study begins at the point the participant is randomized. 
The treatment starts after his/her first dose of study medication and ends after 16 weeks of 
treatment or at the point of permanent study medication withdrawal should the participant 
discontinue treatment prior to completion of Week 16. 
On Day 1 of the treatment period, qualified participants will be randomly assigned to receive 
16 weeks of once-daily oral treatment with 
 AGN-242428,
 AGN-242428, 
 AGN-242428, or placebo. Baseline data for evaluation of participant efficacy and safety 
will be obtained on Day 1, prior to receiving the first dose. Participants will complete study visits 
on the first day of treatment and following 2, 4, 6, 8, 10, 12 and 16 weeks of treatment for 
evaluation of efficacy safety and tolerability assessments.  
A subset of approximately 14 to 18 participants in each treatment group (includes placebo), who 
have provided consent, will have sequential blood samples collected at scheduled times before 
and up to 24 hours after study medication administration during the Week 4 visit to establish 
AGN-242428 PK concentration versus time profiles. All participants will have blood samples 
collected to determine trough AGN-242428 concentrations obtained on Day 1 and at the Week 4, 
8, 12 and 16/early termination visits. Random time PK sampling at Weeks 6 and 10 (in addition 
to other assessments eg, select laboratory tests [see Table 9-4] and AEs [Section 9.2]) will also 
be obtained in all participants. 
Photography of primary lesions will be taken in a subset of participants that consent to have their 
photos taken. A primary lesion that is representative of the severity of the PGA and PASI scores 
at baseline (Day 1) will be selected and photographed at scheduled visits (see Section 2). 
Any participant who exhibits a predefined change in clinical laboratory parameters may be 
required to complete unscheduled visits to further monitor abnormal safety laboratory test 
results. See Section 2 for testing criteria. Investigators may complete unscheduled study visits at 
any point they feel necessary to monitor and ensure participant safety. 
 


 
 
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. 
Follow-up Period: Participants will return for a follow-up visit 14 ± 3 days after completion of 
study medication or after early withdrawal for end-of-study assessments.  
A DMC will review select safety and exposure data when approximately 10%, 30%, 60% and 
80% of the total participants have completed treatment through Week 4. Ad-hoc meetings of the 
DMC may be scheduled to evaluate potential safety signals, as indicated. The DMC will review 
blinded data. If there is a significant safety signal, then unblinded data may be reviewed in a 
closed session by DMC members designated as unblinded reviewers. Policies, procedures and 
composition of the DMC are described in the DMC charter for this trial. 
5.2. 
Participant and Study Completion 
The study will be conducted at approximately 40 study centers in the United States. 
Approximately 200 participants will be randomly assigned (1:1:1:1) to study medication 
(50 participants to AGN-242428 
, 50 participants to AGN-242428 
 
50 participants to AGN-242428
 and 50 participants to placebo) to provide an estimated 
total of 160 evaluable participants who will complete the study (estimated 40 evaluable 
participants per treatment group). 
If an inadequate number of participants complete the study, and the decrease in evaluable 
participant data compromise the statistical validity of the primary endpoint, the sponsor may 
elect to enroll additional participants to ensure sufficient data. Participants who withdraw due to 
an AE will not be replaced. 
The treatment period ends after 16 weeks of treatment or at the point of permanent study 
medication discontinuation should the participant discontinue treatment prior to completion of 
the 16th week.  
5.3. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the schedule of activities for the last participant in the study 
globally. A participant is considered to have completed the study if he/she has completed all 
phases of the study including the follow-up visit. In addition, all SAEs must be reported from the 
date of participant’s written consent until 30 days post-discontinuation of study medication or 
participation in the study if the last scheduled visit occurs at a later time. 


 
 
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5.4. 
Scientific Rationale for Study Design  
This study is designed to address the following main questions: 
1. Is AGN-242428 efficacious, relative to placebo, in treating participants with moderate to 
severe plaque psoriasis after 16 weeks of treatment? 
2. Is AGN-242428 generally safe and well tolerated with long-term dosing? 
Participant selection: Entry criteria are designed to select a population that is representative of 
participants with moderate to severe plaque psoriasis. Prohibited medications and diseases that 
may interact with AGN-242428 are excluded. Participants who have failed treatment for 
psoriasis with biologics targeting IL-17 and IL-23 are also excluded from the study.  
Trial design: A randomized, double-blind, placebo-controlled design is used to reduce bias in 
the estimation of treatment effects. Participants are informed of the probability of being 
randomized to placebo and they may discontinue the trial at any time they choose.  
Efficacy and safety assessments are standardized and performed regularly throughout the 
16-week treatment period. Clearly defined processes for evaluation and follow-up of hepatic 
enzyme elevations and signs and symptoms of hepatic impairment are also included to enhance 
safety monitoring in the study. 
5.5. 
Justification for Dose 
The doses of AGN-242428 selected for this study are
 once-daily for 
16 weeks. 
The 
 dose of AGN-242428 has been evaluated previously in healthy participants and 
patients for up to 28 days, and was shown to be generally safe and well tolerated. Administration 
for 28 days to patients with psoriasis resulted in an improvement in disease as measured by 
percent change from baseline in PASI scores. The
 dose provided a plasma exposure that 
was ≥ IC90 for inhibition of IL-17 secretion in an ex vivo whole blood assay of IL-17 secretion, 
and this inhibition was sustained over a full 24 hours duration with chronic dosing. Previous 
studies with multiple agents have demonstrated that it takes 12 to 16 weeks to see full efficacy 
for improvement in psoriasis. Thus, improvement from baseline in the PASI score at 28 days 
most likely does not represent the full potential for clinical efficacy. The current study 
(1957-201-001) extends the treatment duration to 16 weeks of once-daily dosing, providing the 
opportunity to more completely assess clinical efficacy at the 350 mg per day dose level. 
The
 and
 doses of AGN-242428 allow for evaluation of a dose response. The 
dose is expected to demonstrate improvement in disease as measured by change from 
baseline in the PASI score while maintaining a larger safety margin. The
 dose is 
expected to demonstrate a greater improvement in disease than the lowest (
 dose) as 
measured by change from baseline in the PASI score. 
During the 4-week POC trial in participants with moderate to severe psoriasis (VTP-43742-002), 
elevations of ALT/AST were noted at a dose level of 
 but not at a dose level of 
 
 


 
 
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Selection of the 
dose for evaluation in the current study thus provides a dose that has 
previously been demonstrated to be efficacious and to not have a liver function test (LFT) signal. 
Modeling of exposure and hepatic transaminase data from the VTP-43742-002 study suggest that 
a 
 dose is unlikely to result in elevations of hepatic transaminase levels greater than 
3 x ULN for most participants. Given that the higher dose results in greater exposure, the 
 
 
dose is expected to be more efficacious than the lower doses of 
 and 
.  


 
 
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6. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
6.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Table 6-1 
Inclusion Criteria 
1. 
Age 
1.01 
Participant must be 18 to 75 years of age inclusive, at the time of signing the 
informed consent. 
2. 
Type of Participant and Disease Characteristics 
2.01 
Participants who have a confirmed diagnosis of plaque psoriasis, diagnosed at least 
6 months before study, with a PGA score ≥ 3 at screening and baseline. 
2.02 
Severity of disease must be at least moderate, defined as Psoriasis Area and Severity 
Index (PASI) ≥ 12 and % body surface area (BSA) ≥ 10. 
2.03 
Participant is a candidate for phototherapy or systemic therapy for psoriasis. 
2.04 
Participants who are overtly healthy as determined by medical evaluation. Includes 
medical history, physical examination, laboratory tests, and cardiac monitoring. 
3. 
Weight and Body Mass Index 
3.01 
Body weight of at least 55 kg (121 lbs). 
4. 
Sex 
4.01 
Male or female. 
 
 


 
 
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Table 6-1 
Inclusion Criteria 
5.01 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
Participants who do not meet the criteria for participation in this study (screen failures) may be 
rescreened (Section 6.4).  
6.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Table 6-2 
Exclusion Criteria 
1. 
Medical Conditions 
1.01 
Non-plaque forms of psoriasis (erythrodermic, guttate, pustular) or drug-induced 
psoriasis. 
1.02 
Psoriasis which has not been stable for the 4 weeks prior to screening and which is 
unstable at Study Day 1. 


 
 
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Table 6-2 
Exclusion Criteria 
1.03 
History or presence of significant and/or not well controlled cardiovascular, pulmonary, 
hepatic, renal, hematologic, coagulation, gastrointestinal, endocrine, immunologic, 
dermatologic (other than psoriasis), neurologic or psychiatric disease. Significant is 
defined as any disease that, in the assessment of the investigator, would put the safety of 
the patient at risk through participation, or which would prevent or confound protocol 
specified assessments. 
1.04 
History of Gilbert’s, Rotor, or Dubin-Johnson syndromes or any other disorder of 
bilirubin metabolism. 
1.05 
 
. 
1.06 
 
 
 
1.07 
History of active mycobacterium tuberculosis (TB) infection or untreated or inadequately 
treated latent TB. Adequacy of treatment will be determined by the investigator based 
upon local standards. Individuals treated for TB must have completed treatment prior to 
screening. 
1.08 
Positive QuantiFERON test for TB infection at screening. Two successive indeterminate 
test results will be considered a positive result. 
1.09 
Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months prior to 
baseline or intend to have this vaccination with BCG during the course of the study, or 
within 12 months of completing treatment in this study. 
1.10 
 
1.11 
Positive drug and/or alcohol test at screening (with the exception of marijuana). 
Participants with a documented medical condition and a current prescription to a 
medication for which they have tested positive, may be allowed at the discretion of the 
sponsor. Retesting in the case of a positive alcohol test is allowed at the discretion of the 
sponsor. 
1.12 
 
  


 
 
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Table 6-2 
Exclusion Criteria 
 
 
 
 
 
 
 
 
 
 
 
2.03 
Current treatment or history of treatment with any anti-TNFα biologic therapy within 
3 months or 5 half-lives of study, and/or all other biologics within 6 months of study 
(Day 1). Treatment with biologics is further prohibited for the duration of the study (see 
Section 7.7.4). 
 
 
2.05 
Efficacy failure on 2 or more biologic agents for the treatment of psoriasis when the 
failures occurred within 1 year of the initiation of the therapy of the first biologic agent 
(see Section 7.7.1). Efficacy failure is defined as a treatment or treatment regimen that 
was administered as prescribed and which did not result in a therapeutic effect or 
beneficial change in the disease signs and symptoms. The treatment did not produce the 
projected outcomes as stated in the product labeling. 
 
 
 
 
 
 
 
 
 


 
 
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Table 6-2 
Exclusion Criteria 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 
 
4.07 
ALT, AST or TBL exceeding 1.5 times the testing laboratory’s ULN at screening (may 
be repeated once to confirm value). Values that are above the ULN and ≤ 1.5 x ULN 
must be repeated to confirm that the value is stable. 
 
 
 
 
. 


 
 
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Table 6-2 
Exclusion Criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.3. 
Lifestyle Restrictions 
6.3.1. 
Meals and Dietary Restrictions 
Fasting: Participants should fast for at least 8 hours before study visits when clinical laboratory 
specimens are collected with the exception of the Screening Visit and Week 6 and Week 10 
visits, when participants are not required to fast. Water is allowed during the fast for all clinical 
laboratory specimens, including the PK samples. 


 
 
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All participants in the study should refrain from consuming grapefruit, grapefruit juice, Seville 
oranges, and Seville orange juice during the treatment period. 
In addition, in the PK subset of approximately 14 to 18 participants per treatment arm who have 
provided consent, at the Week 4 visit the following restrictions apply: 
• Participants in the PK subset will fast for at least 8 hours prior to dosing and continue to 
fast until after collection of the 0.5 hour postdose blood sample has been collected at the 
Week 4 visit. Water (240 mL) will be administered with the study medication at the time 
of dosing. 
• A light meal will be served after all assessments scheduled at 0.5 hour are completed. 
Participants may only consume the food and beverages provided by the study staff. The 
meals provided must not contain prohibited or restricted foods and beverages. 
• Participants will remain at the clinic until after collection of the 8-hour postdose sample 
and will return for collection of the 24-hour postdose sample which is collected BEFORE 
administration of study medication on Day 29. 
6.3.2. 
Alcohol and Tobacco 
Alcohol: Consumption of alcohol should be limited to no more than 1 drink per day. A drink is 
defined as 12 ounces of beer, 8 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of distilled 
spirits or liquor. 
Tobacco: Tobacco users are to keep use stable over the course of the study. 
6.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to treatment/entered in the study. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and 
to respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
Participants who do not meet the criteria for participation in this study (screen failures) may be 
rescreened. A participant who is rescreened is not required to sign another ICF, if the rescreening 
occurs within 28 days from the previous ICF signature date. 


 
 
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7. 
Treatments 
Study medication is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
7.1. 
Treatments Administered 
The study medications in this study are:  
• 
AGN-242428 capsules 
• 
Placebo to match AGN-242428 capsules 
Table 7-1 
Treatments Administered 
Study Treatment Name 
AGN-242428/Placebo 
Dosage Formulation 
Capsule 
(White, opaque, size 00 capsule) 
Unit Dose Strength 
, Placebo 
Route of Administration  
Oral 
Dosing Instructions 
Two capsules taken in the morning with 240 mL of water and approximately 
30 minutes before the participant consumes food (see Section 7.4) 
Packaging and Labeling 
Study medication will be provided in blister cards for individual participant use 
and will be labeled as required per country requirement. 
7.1.1. 
Medications and Administration 
Administration in the clinic: On days when study medication is administered during a clinic 
visit (Section 2), the study medication will be administered in the morning and under fasted 
conditions. The study medication will be administered from the remainder of the study 
medication blister cards returned by the participant (Week 4, 8, 12, and 16 visits). Participants 
will receive AGN-242428 and/or placebo administered as 2 capsules with 240 mL of water. The 
time of dosing will be recorded on the electronic case report form (eCRF). 
Administration outside the clinic: On days when the study medication is self-administered by 
the participant, the study medication will be administered in the morning with 240 mL of water 
and approximately 30 minutes before the participant consumes food. Participants will be 
counseled to take their daily dose of study medication at approximately the same time each day 
in the morning. 


 
 
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7.1.2. 
Study Supplies 
AGN-242428 and matching placebo will be packaged in blister cards for individual participant 
use, each containing a sufficient number of capsules to support once-daily dosing for 28 days 
with an overage appropriate to accommodate the visit window schedule at each designated visit 
when study medication is dispensed. Study medication will be clearly labeled with the contents, 
directions for use, storage condition, protocol identification, and all required regulatory caution 
statements including a caution to ‘Keep away from children’. The labeling for the placebo and 
AGN-242428 will be identical. 
7.2. 
Dose Modification 
A participant’s randomized dose of study medication may not be adjusted (increased or 
decreased) during the trial. 
Retreatment Criteria 
If a participant is required to discontinue their study medication (eg, protocol defined safety 
stopping criteria are met), re-challenge will not be permitted.  
7.3. 
Method of Treatment Assignment 
Participants will be randomized to receive either AGN-242428 or placebo according to a 
computer-generated randomization schedule, prepared and validated in advance of the study 
start. A central randomization will be used for the study with a ratio of 1:1:1:1 (
 
AGN-242428: 
 AGN-242428: 
 AGN-242428: placebo). 
All participants will be centrally assigned to randomized study medication using an interactive 
response system (IxRS). Before the study is initiated, access and instructions for use of the study 
medication will be provided to each site. 
Study medication will be dispensed at the study visits summarized in the SoA (Section 2).  
Returned study medication should not be re-dispensed to the participants. 
7.4. 
Blinding/Masking 
The investigator, site staff, participant, and sponsor will be blinded to randomized treatment 
allocation. Only the unblinded staff of the Allergan Global Clinical Supplies Management 
(GCSM) Group will be aware of treatment assignment. To maintain the blind, AGN-242428 and 
placebo will be provided as capsules that are identical in appearance and that are packaged and 
labeled identically. Participants will take the same number of capsules each day, irrespective of 
treatment allocation. 
If randomized to 
 AGN-242428 treatment: 
• Daily dose = one (1) 
 AGN-242428 capsule AND one (1) placebo capsule 


 
 
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If randomized to 
 AGN-242428 treatment: 
• Daily dose = two 
 AGN-242428 capsules 
If randomized to 450 mg AGN-242428 treatment: 
• Daily dose = two 
 AGN-242428 capsules 
If randomized to placebo: 
• Daily dose = two (2) placebo capsules 
A unique identification number will be printed on the study medication label to maintain the 
blind of the treatment allocation at the participant- and site-level. This identification number will 
be traceable to randomized treatment allocation available only to the unblinded Allergan GCSM 
Group. 
Blinding is critical to the integrity of the clinical trial. However, in the event of a medical 
emergency for an individual participant and for which the knowledge of the study medication 
allocation is essential to the participant’s medical management, the blind for that participant may 
be broken by the investigator.  
Before breaking the blind of an individual participant’s treatment, the investigator should have 
determined that the information is necessary (ie, that it will alter the participant’s immediate 
management). In many cases, particularly when the emergency is not likely to be related to 
investigational treatment, the problem may be properly managed by assuming that the participant 
is receiving active product without the need for unblinding. 
The need to break the blind for an individual participant must first be discussed with the 
responsible Medical Safety Physician (MSP), unless not possible to do so in advance of the 
break. If such unblinding occurs, the investigator shall notify the MSP immediately or as soon as 
reasonably possible.  
Procedures for breaking of the blind are provided to the investigator independent of this protocol. 
The date, time and reason for breaking the blind must be recorded. 
7.5. 
Preparation/Handling/Storage/Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study medication received and any discrepancies are 
reported and resolved before use of the study medication. 
2. Only participants enrolled in the study may receive study medication, and only authorized 
site staff may supply or administer study medication. All study medications must be stored in 
a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 


 
 
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3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study medication accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study medication are 
provided in the study reference manual.  
7.5.1. 
Study Medication Accountability 
Adequate records of all study medication receipt, storage conditions, dispensing to participants, 
return from participants and reconciliation of dose administration will be maintained by the study 
site. Participant level compliance will be recorded.  
7.5.2. 
Study Medication Handling and Disposal 
AGN-242428 and matching placebo will be stored in a secure area with restricted access and 
according to local regulations. It is the responsibility of the investigator to ensure that the study 
medication is dispensed only to study participants. The study medication must only be dispensed 
from official study sites by authorized personnel according to local regulations.  
Any study medication remaining at the end of the study, including original containers (even if 
empty), should be returned to sponsor or designee at study completion. 
7.6. 
Treatment Compliance 
The first dose of study medication will be administered at the study site on Day 1 and after 
collection of the baseline blood samples for AGN-242428 and IL-17 concentrations. During the 
intervals between study visits, participants will take their study medication as instructed. On days 
of clinic visits (Weeks 4, 8, 12, and 16), participants will withhold taking their daily dose of 
study medication and will take their daily dose after collection of trough blood samples for 
AGN-242428 and IL-17 concentrations (see Section 2). The date and time of study medication 
administration during clinic visits will be recorded in the eCRF. During scheduled study visits, 
designated study staff will inspect the returned study medication and reconcile the amount of 
study medication dispensed with the amount of study medication returned.  
Participants who show poor compliance with study medication administration will be counseled 
on the importance of medication compliance.  
7.7. 
Concomitant Therapy 
The use of any concomitant, prescription or OTC medication, is to be recorded on the 
participant’s eCRF at each visit along with the reason the medication is taken. In addition, 
concurrent procedures are to be recorded on the participant’s eCRF. 
7.7.1. 
Prohibited Treatments and Washout Before the Study 
Any previous use of systemic psoriasis medications/treatments used by the participant prior to 
enrollment must be recorded on the eCRF. Topical treatments for psoriasis used by the 


 
 
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participant within 2 years prior to enrollment must be recorded on the eCRF. The psoriasis 
medication or therapy, the dose and regimen, the duration of treatment, and the reason for 
discontinuation of the therapy will be recorded on the eCRF. All other medications (prescription, 
OTC, vitamins, or herbal) taken within 4 weeks prior to enrollment must be recorded on the 
eCRF. Investigational medications taken within 4 weeks or 6 half-lives (if known), whichever 
period is longer, will also be recorded on the eCRF. 
 
 


 
 
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7.7.2. 
Permitted Treatments 
Any medication or vaccine (including OTC or prescription medicines, vitamins, and/or herbal 
supplements) that the participant is receiving at the time of enrollment or receives during the 
study must be recorded along with: 
• Indication 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The sponsor or designee should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Please refer to Section 7.7.1,Section 7.7.4, and Appendix 8, Section 12.8 for details of prohibited 
treatments prior to and during the study. 
7.7.3. 
Rescue Medicine 
The study site or sponsor will not provide rescue medication. 
7.7.4. 
Prohibited Medications During the Study 
Participants are prohibited from using prescription, OTC, and herbal products for the duration of 
the study unless the medication has been approved by the investigator and sponsor, with the 
exception of prescribed hormonal contraceptives. Participants are also prohibited from using 
treatments/therapies for psoriasis, with the exception of study medication, for the duration of the 
study. 
Participants may be discontinued if they take a prohibited medication that has not been 
previously approved by the investigator and sponsor. 
Please refer to Section 7.7.1 for prohibited treatments and the washout period prior to the study.  
7.8. 
Treatment After the End of the Study  
No study medication will be provided following the end of the study.  


 
 
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8. 
Discontinuation/Withdrawal Criteria  
Withdrawn participants are those who do not complete all evaluations and procedures outlined in 
the protocol. Participants who discontinue taking study medication for any reason must also be 
withdrawn from the study. All AEs that are present when the participant withdraws from the 
study will be followed as described in Section 9.2. 
Participants may voluntarily withdraw from the study at any time. 
Notification of early participant discontinuation from the study and the reason for 
discontinuation will be made to the sponsor and will be clearly documented on the appropriate 
eCRF. 
Reasons for discontinuation from the study treatment and/or the study may include the 
following: 
• AE 
• Death 
• Lost to follow-up 
• Non-compliance with study drug 
• Meets study defined stopping criteria 
• Investigator decision 
• Pregnancy 
• Protocol deviation 
• Screen failure 
• Site terminated by sponsor 
• Study terminated by sponsor 
• Withdrawal by subject 
• Completed 
• Other 
8.1. 
Discontinuation of Study Treatment  
Participants may stop study medication on the basis of intolerability, as determined by AE, vital 
sign or physical examination findings, clinically important laboratory or ECG findings, or 
investigator opinion. If a participant does not tolerate study medication, the participant will be 
observed until the intolerable AE has either resolved or satisfactorily stabilized in the judgment 
of the investigator, and the participant will be withdrawn from the study.  


 
 
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A participant will be permanently withdrawn from study medication if any of the criteria 
in Table 8-1 are met and considered related to AGN-242428. Re-challenge with AGN-242428 
will not be permitted. 
Table 8-1 
Safety Criteria for Individual Participants Stopping Study Treatment 
Parameter 
Definition 
Study treatment-related serious adverse event 
(SAE) 
Study treatment-related SAE, as assessed by investigator 
Increased liver transaminasesa 
Aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) increased to ≥ 5 × upper limit of normal 
(ULN)c 
Increased liver transaminases with increased 
total bilirubin (TBL) or increased INR 
AST and/or ALT increased to ≥ 3 x ULN AND TBL increased 
to ≥ 2 x ULN or INR > 1.5c 
Increased liver transaminases with symptomsa,b 
AST and/or ALT increased to ≥ 3 x ULN with symptomsc 
Decreased total leukocyte counta 
Leukopenia to < 3000/µL [< 3.0 × 109/L] 
Decreased total neutrophil counta 
Neutropenia to < 1000/µL [< 1.0 × 109/L]  
Decreased lymphocyte counta 
Lymphopenia to < 500/µL [< 0.5 × 109/L] 
Decreased platelet counta 
Thrombocytopenia to < 100,000/µL [< 100 × 109/L] 
Increased serum creatininea 
Serum creatinine increased to ≥ 2 x ULN 
Unspecified 
Based on medical judgment of sponsor’s Medical Safety 
Physician, Medical Expert and investigator 
a To be confirmed by a repeat of the test within 2 to 5 calendar days. 
b New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper quadrant pain 
or tenderness or jaundice) or hypersensitivity (such as fever, rash or eosinophilia > 5%) 
c Discontinuation of study treatment for abnormal liver function should be considered by the investigator when a participant 
meets one of the conditions outlined, or if the investigator believes that it is in best interest of the participant. 
 
Liver Safety Suggested Actions and Follow-up Assessments Section can be found in 
Appendix 6, Section 12.6. 
See the SoA (Section 2) for data to be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that need to be completed. 
8.1.1. 
Temporary Discontinuation  
The DMC allows for temporary discontinuation of dosing pending further analysis of possible 
safety issues (an option open to the DMC). 
8.1.2. 
Criteria for Study Termination 
The study may be terminated for any of the following reasons: 
• Sponsor decides to terminate the trial for any reason. 


 
 
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• There are multiple similar AEs or SAEs that are deemed by the sponsor and its medical 
experts as a safety signal that poses a medically unacceptable risk to patients. 
8.2. 
Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. If the participant withdraws consent for disclosure of future information, 
the sponsor may retain and continue to use any data collected before such a withdrawal of 
consent. If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study records. 
See the schedule of activities (Section 2) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
Participants withdrawn due to AEs will not be replaced. Participants who are withdrawn for 
other reasons may be replaced at the discretion of the sponsor if deemed necessary to ensure 
sufficient data are obtained at each dose level to adequately assess safety.  
8.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain whether or not the participant wishes to and/or should continue in the study. 
Before a participant is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up.  


 
 
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9. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the schedule of activities (Section 2).  
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the schedule of 
activities, is essential and required for study conduct. 
To be eligible to take part in the study, all screening evaluations must be completed and 
reviewed to confirm that potential participants meet all eligibility criteria. The investigator will 
maintain a screening log to record details of all participants screened and to confirm eligibility or 
record reasons for screening failure, as applicable.  
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 440 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples.  
9.1. 
Efficacy Assessments 
Efficacy assessments and data will be collected for all participants receiving AGN-242428 or 
placebo. Efficacy will be assessed by medical review of PASI, total BSA and PGA scores and 
changes from baseline values. PD measures including IL-17A and IL-17F plasma concentrations 
will be determined, but the assessment of efficacy will be determined primarily by clinical signs 
and symptoms and improvement in clinical psoriasis scores.  
9.1.1. 
Determination of Percent Body Surface Area 
The % body surface area (BSA) will be determined using the participant’s palm area to 
approximate 1% of BSA (handprint method). To the extent possible, the same trained and 
qualified dermatologist will complete estimation of % BSA for a participant at all study 
timepoints when % BSA is assessed including screening and baseline. The same trained and 
qualified dermatologist must determine the baseline and Week 16 % BSA.  
The palmar surface of the participant’s hand (entire palmar surface including fingers) will 
approximate 1% of BSA: 
• 
Head and neck = 10% (10 palms) 
• 
Upper extremities = 20% (20 palms) 
• 
Trunk (axillae and groin) = 30% (30 palms) 
• 
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Estimate the total BSA affected and record in the eCRF. If multiple small lesions are present, 
combine several to equal 1 participant palm. If there is central clearing, include only the edge 
and not the areas that have cleared. 
9.1.2. 
Psoriasis Area and Severity Index 
The PASI score will be determined by the same trained and qualified dermatologist, to the extent 
possible, at all study timepoints when PASI score is assessed including the screening and 
baseline visits. Assessment of PASI at Day 1 (baseline) and Week 16 will be completed by the 
same trained and qualified dermatologist. 
The PASI score combines the severity (erythema, induration, and desquamation) and percentage 
of affected area. Each of 4 body regions will be assessed for surface area involvement and 
graded for erythema, thickness (induration) and scaling (desquamation). By combining the 
individual scores from each body region, the total PASI score is determined.  
9.1.2.1. 
Surface Area Involvement by Body Regions 
The 4 body regions to be assessed are:  
• 
Head and neck – 10% of total BSA 
• 
Upper extremities – 20% of total BSA 
• 
Trunk including axillae and groin – 30% of total BSA 
• 
Lower extremities including buttocks – 40% of total BSA  
The surface area covered by plaques in each body region is determined using the palm method 
(handprint method) and assigned a score for that body region according to the scoring criteria 
tabulated below. Surface area involvement of each of the 4 anatomic regions is scored on a scale 
of 0 (no involvement of that specific body region) to 6 (90% to 100% involvement of that 
specific body region). 
Table 9-1 
Score Assignment for Body Region based on Body Surface Area (BSA) (Surface 
Area Involvement Score) 
Score to Assign 
Percent of Body Region Involvement 
0 
No involvement 
1 
1% to 9% 
2 
10% to 29% 
3 
30% to 49% 
4 
50% to 69% 
5 
70% to 89% 
6 
90% to 100% 
 


 
 
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9.1.2.2. 
Erythema, Thickness and Scaling Intensity Grading 
Erythema: Each of the 4 body regions is given an erythema score ranging from 0 to 4: 
• 
0 = none 
• 
1 = slight 
• 
2 = moderate 
• 
3 = marked 
• 
4 = very marked 
Thickness (induration): Each of the 4 body regions is given an induration score ranging from 
0 to 4:  
• 
0 = none 
• 
1 = slight 
• 
2 = moderate 
• 
3 = marked 
• 
4 = very marked 
Scaling (desquamation): Each of the 4 body regions is given a scaling score ranging from 
0 to 4:  
• 
0 = none 
• 
1 = slight 
• 
2 = moderate 
• 
3 = marked 
• 
4 = very marked 
9.1.2.3. 
Calculate the PASI score 
Body region score: First sum the intensity grading for erythema, thickness and scaling for each 
of the body regions. The intensity score for each body region will fall within the range of 0 to 12 
(see Section 9.1.2.2). Next multiply the intensity body region score by the surface area 
involvement score. The surface area involvement score will fall within the range of 0 to 6 
(see Section 9.1.2.1). Finally, multiply by the total % of BSA accounted for by each body region 
and this will be the body region score. 
Individual intensity and surface area involvement scores will be recorded for each body region. 
The eCRF will calculate the body region and total PASI scores. The total PASI score will fall 
within the range of 0 to 72. A PASI calculator is provided below. 


 
 
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Table 9-2 
Psoriasis Area and Severity Index (PASI) calculator 
Body Regions 
Head and Neck 
Body Region Score 
(E + T + Sc) x surface area involvement score x 0.1  
(__+__+__) x _____________ x ___ 
 
Upper Extremities 
Body Region Score 
(E + T + Sc) x surface area involvement score x 0.2 
(__+__+__) x _____________ x ___ 
 
Trunk (includes axillae and 
groin) 
Body Region Score 
(E + T + Sc) x surface area involvement score x 0.3 
(__+__+__) x _____________ x ___ 
 
Lower Extremities (includes 
buttocks) 
Body Region Score 
(E + T + Sc) x surface area involvement score x 0.4  
(__+__+__) x _____________ x ___ 
PASI =  
Head and neck + Upper extremities + Trunk + Lower extremities 
____________+____________+____________+____________ 
PASI = Psoriasis Area and Severity Index 
E = erythema; T = thickness; Sc = scaling 
 
9.1.3. 
Physician’s Global Assessment 
The PGA will be completed by the same trained and qualified dermatologist, to the extent 
possible, at all study timepoints when PGA is assessed, including the screening and baseline 
visits. The same trained and qualified dermatologist must determine the baseline and Week 16 
PGA. A 5-point scale (0 to 4) will be used and is described in Table 9-3.  


 
 
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Table 9-3 
Physician’s Global Assessment (PGA) Scoring 
Score 
Severity 
Description 
0 
Clear 
Plaque elevation = 0 (no elevation over normal skin); 
Scaling = 0 (no evidence of scaling); 
Erythema = 0 (except for residual hyperpigmentation 
/hypopigmentation) 
1 
Almost clear 
Plaque elevation = ± (possible but difficult to ascertain whether 
there is a slight elevation above normal skin); 
Scaling = ± (surface dryness with some desquamation); 
Erythema = ± (fading, diffuse pink or slight red coloration) 
2 
Mild 
Plaque elevation = slight (slight but definite elevation, 
typically edges are indistinct or sloped); 
Scaling = fine (fine scale partially or mostly covering lesions); 
Erythema = mild (light red coloration) 
3 
Moderate 
Plaque elevation = marked (marked definite elevation with 
rough or sloped edges); 
Scaling = coarser (coarser scale covering most or all of the 
lesions); 
Erythema = moderate (definite red coloration). 
4 
Severe 
Plaque elevation = marked (marked elevation typically with 
hard or sharp edges); 
Scaling = coarser (coarse, non-tenacious scale predominates 
covering most or all of the lesions); 
Erythema = severe (very bright red coloration) 
 
For PGA scores recorded after initiation of treatment, the assessment of overall severity will 
include areas that have already been cleared (scores of 0) and will not be scored only on 
remaining lesions. The severity will be averaged across all areas of involvement including 
cleared lesions. When severities differ across the disease parameters evaluated (erythema, 
scaling and induration), the parameter that is the predominant feature of the disease should be 
used to determine the PGA score. 
9.1.4. 
Photograph of Primary Lesion 
Photography of primary lesions will be taken in a subset of participants that consent to have their 
photos taken. A primary lesion that is representative of the severity of the PGA and PASI scores 
at baseline (Day 1) will be selected and photographed at scheduled visits (Section 2). The images 
can be captured before or after the study medication is administered. Conditions of photography 
will be standardized across all photos including camera equipment, exposure, background, 
lighting and focal length. Ideally, the same photographer will take all required photos.  
A qualified third party vendor will provide instructions for taking photographs and processing 
digital photographs. Photographs will be transferred to sponsor on a periodic basis and all digital 
images will be transferred to sponsor at the end of the study. Participants will provide consent to 


 
 
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be photographed and by consenting to have photographs taken, participants are indicating their 
understanding that they give permission for use of their study photographs for general research, 
education or informational purposes. Participants may decline permission for use of their study 
photographs for advertising, publicity, and promotional purposes. 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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9.2. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3 (Section 12.3). 
AEs will be reported by the participant (or, when appropriate, by a caregiver or surrogate).  
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and any other study-specific terms as relevant 
and remain responsible for following up AEs that are serious, considered related to the study 
treatment or study procedures, or that caused the participant to discontinue the study treatment 
and/or study (see Section 8).  
9.2.1. 
Time Period and Frequency for Collecting AE and SAE Information  
All AEs (serious and non-serious) from the signing of the informed consent form (ICF) until the 
follow-up visit will be collected at the timepoints specified in the schedule of activities 
(Section 2), and as observed or reported spontaneously by study participants. 
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the AE section of the eCRF. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours, as indicated 
in Appendix 3 (Section 12.3). The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE information in former study 
participants. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the investigator must promptly notify the 
sponsor. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3, 
Section 12.3.  
9.2.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.  


 
 
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9.2.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All AEs, SAEs, and adverse events of special interest (AESI), 
including out of reference range laboratory test results, will be followed until resolution, 
stabilization, until the event is otherwise explained, or the participant is lost to follow-up (as 
defined in Section 8.3).  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation with 
other health care professionals. 
If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings including 
histopathology. 
New or updated information will be recorded in the originally completed eCRF. 
The investigator will submit any updated SAE data to the sponsor within 24 hours of receipt of 
the information. 
9.2.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, institutional review boards (IRBs)/independent ethics committees 
(IECs), and investigators.  
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it, 
along with the IB, and will notify the IRB/IEC, if appropriate according to local requirements. 
9.2.5. 
Cardiovascular and Death Events 
Not applicable. 


 
 
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9.2.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Progression of the treatment indication (ie, the disease under investigation), including new 
occurrence or worsening of anticipated clinical signs or symptoms collected as clinical efficacy 
variables and assessed as unequivocally associated with the disease progression and /or lack of 
efficacy, should NOT be reported as an adverse event unless the disease progression is greater 
than anticipated in the natural course of the disease. 
9.2.7. 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study treatment and until 30 days after the last dose. 
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 4 (Section 12.4).  
Abnormal pregnancy outcomes (eg, spontaneous abortion, elective termination of a pregnancy, 
fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs 
(Appendix 3, Section 12.3). 
9.2.8. 
Adverse Events of Special Interest 
All of the following are AESI: 
• AST and/or ALT increased to ≥ 5 ULN  
• AST and/or ALT increased to ≥ 3 x ULN AND TBL increased to ≥ 2 x ULN or 
INR > 1.5. Typically, all analytes will be obtained from the same sample, but they may 
come from multiple samples taken within a 24-hour period.  
• AST and/or ALT increased to ≥ 3 x ULN with symptoms believed to be related to liver 
injury (eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness or jaundice) 
or hypersensitivity (such as fever, rash or eosinophilia > 5%) 
• For any participant who meets one of the above liver criteria resulting in study treatment 
discontinuation, the following must be performed (See Appendix 3, Section 12.3, for 
additional details regarding the reporting of AESIs):  
1) 
The lab abnormality captured as an AESI  
2) 
Non-serious AESIs should be reported to the sponsor within 72 hours and serious 
AESIs should be reported to the sponsor within 24 hours 
3) 
The AESI form, which is the Adverse Event of Interest Abnormal Liver Function 
Reporting Form, should be completed and used for reporting the AESI even if a 
serious outcome may not apply, and  


 
 
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4) 
Every effort to determine the cause of the liver enzyme abnormalities must be made 
(in conjunction with the MSP and in accordance with the FDA Guidance for Industry, 
Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009). 
In addition, a potential Hy’s Law case is also an AESI. Criteria for potential Hy’s Law cases are 
as follows:  
• ALT and/or AST ≥ 3 × ULN AND  
• TBL ≥ 2 × ULN AND 
• Alkaline phosphatase < 2 × ULN 
Study site personnel must report every participant who meets these potential criteria. Typically, 
all 3 analytes will be obtained from the same sample, but they may come from multiple samples 
taken within a 24-hour period. This requirement applies from the time the participant signs the 
ICF for the study until 30 days after the final protocol-defined study visit or the last known dose 
of study treatment (if the final visit does not occur).  
A laboratory alert for potential Hy’s Law cases will be in place, and must notify investigators 
and the sponsor immediately when the above criteria have been met. A potential Hy’s law case 
must be reported as a SAE by completing an Adverse Event of Interest Abnormal Liver Function 
Reporting Form and sent to IR-Clinical-SAE@allergan.com (or faxed to the SAE fax number) as 
soon as possible (within 24 hours of learning of the potential Hy’s Law case). The eCRF for 
potential Hy’s Law cases must be completed within 7 calendar days. Every effort to determine 
the cause of the liver enzyme abnormalities must be made, and close monitoring should be 
initiated in conjunction with the MSP and in accordance with the FDA Guidance for Industry, 
Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009. 
Suggested actions and follow-up assessments for liver safety are described in Appendix 6 
(Section 12.6). 
9.2.9. 
Medication Errors 
Medication error refers to any unintended error in the dosing and/or administration of the study 
treatment as per instructions in the protocol. Medication errors generally fall into 4 categories as 
follows: 
Wrong study treatment/device 
Wrong dose (including dosing regimen, strength, form, concentration, amount) 
Wrong route of administration 
Wrong participant (ie, not administered to the intended participant) 
Medication errors include occurrences of overdose and underdose of the study treatment. 
Overdose: Unintentional administration of a quantity of the study treatment given per 
administration or per day that is above the maximum recommended dose according to the 


 
 
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reference safety information or protocol for the study treatment or comparator as applicable. This 
also takes into account cumulative effects due to overdose. An overdose for this study treatment 
is any dose of AGN-242428 greater than 
 taken within 1 calendar day with less than 
8 hours between doses will be considered an overdose.  
Underdose: Unintentional administration of a quantity of the study treatment given per 
administration or per day that is under the minimum recommended dose according to the 
reference safety information or protocol. An underdose for this study will be any dose of 
AGN-242428 less than the randomized study treatment. 
9.3. 
Treatment of Overdose 
For this study, any dose of AGN-242428 greater than 
 taken within 1 calendar day with 
less than 8 hours between doses will be considered an overdose. 
Sponsor does not recommend specific treatment for an overdose.  
In the event of an overdose, the investigator/treating physician should: 
1. Contact the sponsor immediately. 
2. Closely monitor the participant for AEs/SAEs and laboratory abnormalities until study 
treatment can no longer be detected systemically (at least 5 days). 
3. Obtain a plasma sample for PK analysis within 2 days from the date of the last dose of study 
medication. 
4. Document the quantity of the excess dose of the overdose in the eCRF. 
Decisions regarding dose interruptions will be made by the investigator in consultation with the 
MSP based on the clinical evaluation of the participant. 
9.4. 
Safety Assessments 
All participants receiving study medication (AGN-242428 or placebo) will be included in the 
safety summary. Safety will be assessed by medical review of AE reports, clinical laboratory 
findings, ECG data, physical examinations, and vital signs. Any skin findings will be carefully 
assessed and reviewed. 
Planned timepoints for all safety assessments are provided in the schedule of activities 
(Section 2). 
9.4.1. 
Physical Examinations 
A full physical examination, including but not limited to, evaluation of the head, eyes, ears, nose, 
throat, neck, heart, chest, lungs, abdomen, extremities, neurological status, skin, and any other 
notable conditions, will be performed at screening, Day 1, and Week 16.  
Abbreviated physical examinations including skin, heart, chest, lungs, and abdomen will be 
conducted at all other scheduled visits during the study. For the skin examination performed at 


 
 
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screening and baseline, a careful examination for and documentation of possible pre-existing 
cutaneous infections, including fungal infections, or scarring will be included. Screening and 
baseline skin findings for psoriatic participants will be carefully noted in the eCRF.  
The physical examination must be performed by a qualified healthcare professional [eg, medical 
doctor (MD) ie, physician, Doctor of Osteopathy (DO), physician assistant (PA)]. Whenever 
possible, the same qualified healthcare professional should conduct the physical examination at 
all scheduled times throughout the study. Skin evaluations associated with physical examinations 
for psoriatic participants will be completed by the same qualified dermatologist throughout the 
study. Assessment of PASI and PGA will follow the procedures outlined in Section 9.1.  
Height and weight will be measured in full indoor clothing without shoes at the Screening Visit. 
A BMI will be calculated using the screening height and weight values. Additional weight 
measurement will be taken at baseline and the end of the study.  
9.4.2. 
Vital Signs 
All vital sign measurements will be taken after a participant has been in a sitting position for a 
minimum of 5 minutes (participant in a quiet setting without distractions eg, television, cell 
phones). Vital signs will include blood pressure, pulse, respiration rate, and body temperature. 
Radial or brachial pulse will be measured over a 30 second interval, if performed manually and 
respiration rate will be measured over a 60 second interval. Body temperature may be oral or 
aural. An electronic or manual sphygmomanometer or an electronic oscillometric device may be 
used. The method of assessment should be consistent throughout the study. 
9.4.3. 
Electrocardiograms 
Standard 12-lead ECGs will be performed after the participant has been resting quietly supine for 
at least 10 minutes at scheduled visits throughout the study (see Section 2).  
At the time that the ECG is obtained, the investigator or medically qualified subinvestigator will 
inspect the ECG tracing to confirm the QT interval provided by the ECG machine is accurate so 
that a repeat tracing may be performed, if needed. ECG results will be classified by the 
investigator as normal, having a clinically significant (CS) abnormality, or having a not clinically 
significant (NCS) abnormality.  
ECGs will be assessed by an external vendor through central reading of ECGs. Standardized 
equipment and instructions will be provided by the ECG vendor and data will be received and 
over-read by the external vendor. Central ECG over-read and interval measurements will be 
provided by experienced, qualified, and certified cardiac safety specialists (primary reader). The 
readers will be blinded to participant details and a single reader will read all ECGs of a given 
participant. In addition, the ECGs will also be reviewed by a US board-certified Cardiologist 
from the vendor who will evaluate the ECG from a morphological perspective and who will 
confirm the interval measurements performed by the primary reader. 
If a clinically significant finding is identified (including, but not limited to changes from baseline 
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enrollment, the investigator or qualified designee will determine if the participant can continue in 
the study and if any change in participant management is needed. This review of the ECG 
printed at the time of collection must be documented. Any new clinically relevant finding should 
be reported as an AE. 
The ECG printout should be kept in the source documentation file. If potentially clinically 
significant findings are detected by the site investigator, the MSP should be consulted. All 
communications and diagnoses should be filed in the source documentation file.  
The investigator is responsible for maintaining participant’s safety throughout the study. 
Investigators will review ECGs and may discontinue participants with clinically significant 
abnormal ECG findings. 
9.4.4. 
Clinical Safety Laboratory Assessments 
See Table 9-4 for a listing of laboratory tests utilized during the screening period to qualify 
patients for study participation and throughout the study to monitor participant safety. PK 
(Section 9.5) and PD (Section 9.6) assessments are listed separately.  
Specimens for serum hematology, chemistry, coagulation and urinalysis will be drawn at the 
times indicated in the schedule of activities (Section 2). All clinical laboratory testing will be 
performed in the fasting state with the exception of laboratory testing at the Screening Visit and 
Week 6 and Week 10 visits, which will not require fasted samples. Additional guidance on 
monitoring of liver function tests is provided in Section 8 and Appendix 6, Section 12.6.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 30 days after the last dose of study medication should be repeated until the 
values return to normal or baseline, or are no longer considered clinically significant by the 
investigator or MSP. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified. 
All protocol-required laboratory assessments must be conducted in accordance with the 
laboratory manual and the schedule of activities.  
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE), then the results must be recorded in the 
eCRF.  
The tests detailed in Table 9-4 will be performed by the central laboratory. All laboratory tests 
should be sent to the central laboratory for the study. 


 
 
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Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 6. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Laboratory/analyte results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded. 
Table 9-4 
Clinical Laboratory Tests 
Categorya 
Parameters 
Hematology and 
Coagulationa 
Hematocrit (HCT), hemoglobin (HGB), red blood cell (RBC) count, RBC indices, 
total leukocyte (or white blood cell [WBC]) count including differential, and platelet 
count with mean platelet volume, activated partial thromboplastin time (aPTT), 
prothrombin time (PT), international normalized ratio (INR) 
Serum Chemistry 
 
Electrolytes 
Sodium (Na), potassium (K), chloride, bicarbonate 
Renal function 
Blood urea nitrogen (BUN), creatinine (Cr) 
Liver functiona 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), total, direct, and indirect bilirubin (TBL, DBL, IBL), gamma-
glutamyl transferase (GGT), lactate dehydrogenase (LDH) 
Pancreatic function 
Lipase and amylase 
Othera 
(selected tests at Week 6 
and Week 10) 
Calcium (Ca), magnesium (Mg), phosphorus (P), total proteina, albumina, globulins, 
glucose, uric acid, creatine phosphokinase (CK)a, cholesterol (total and fractionated) 
and triglycerides  
Urinalysis 
Appearance, bilirubin, color, ketones, glucose, leukocyte esterase, nitrites, pH, blood, 
protein, specific gravity and urobilinogen with microscopic examination of the 
sediment if blood, protein or leukocyte esterase is positive. 
Other Analyses 
Serum for hepatitis B (hepatitis B surface antigen [HbsAG] and hepatitis B core 
antibodies [Anti-HBc]), hepatitis C antibodies (HCV Ab), and HIV (screening only) 
 
Urine pregnancy (women of childbearing potential [WOCBP] only)b 
 
Urine drug and alcoholc 
 
Mycobacterium tuberculosis (TB) by QuantiFERON 
a Visits on Week 6 and Week 10 need random blood draws. Participants can be fasting or non-fasting and only the following 
laboratory tests will be performed at those visits: Hematology and Coagulation, Liver function, and Other (Total protein, 
albumin, and CK). For example, urinalysis is not collected at these visits. 
b Urine pregnancy tests will be done on site with kits provided by the central laboratory. 
c As referenced in the laboratory manual. 
 
9.4.5. 
Suicidal Risk Monitoring 
Not applicable.  


 
 
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9.5. 
Pharmacokinetics 
Blood samples for the analysis of AGN-242428 plasma concentrations will be collected at 
scheduled times (Section 2). Instructions for the collection and handling of biological samples 
will be provided by the central laboratory. The actual date and time (24-hour clock time) of each 
sample will be recorded. Trough and random PK blood samples will be drawn from all 
participants; sequential PK samples will be drawn in a subset of participants. The participants 
will be asked to provide the date and time of administration of the 3 doses taken prior to the visit 
when PK samples are to be drawn. This date and time information will be recorded in the eCRF. 
Trough PK samples: Trough PK samples will be collected from all study participants. Samples 
that are designated as trough (Day 1 and Weeks 4, 8, 12 and 16) will be collected before on-site 
administration of the morning dose of study medication. In case of early termination, a blood 
sample for AGN-242428 plasma concentration will be drawn at the early termination visit. The 
date and time of PK sample collection will be recorded in the eCRF. Deviations to sample 
collection such as failure to collect the sample, collection of the sample after dose administration, 
or deviations to dose administration in the 3 days prior to sample collection will be recorded in 
the eCRF. 
Profile (Sequential) PK samples: A subset of approximately 14 to 18 participants per treatment 
arm will provide sequential blood samples at the Week 4 visit to allow evaluation of PK 
concentration versus time profiles and PK parameters. Participants must not take the study 
medication at home as it will be administered on site. Participants will fast for at least 8 hours 
prior to dosing and continue to fast until after collection of the 0.5 hour postdose blood sample 
has been collected. Sequential blood samples will be obtained immediately before the 
administration of study medication at the Week 4 visit and at the following times after study 
medication administration: 0.5, 2, 6, 8, and 24 hours (Day 29). Allowable collection windows to 
sampling times are summarized in Table 9-5. The date and time of PK sample collection and the 
date and time of dosing during this visit will be recorded in the eCRF. Deviations to sample 
collection such as failure to collect the sample, collection of the predose sample after dose 
administration, or deviations to dose administration in the 3 days prior to sample collection will 
be recorded in the eCRF. Participants will remain at the clinical site until after collection of the 
8 hour postdose sample and will return to the clinical site for collection of the 24 hour postdose 
sample on the following morning. The 24 hour postdose sample will be collected BEFORE the 
participant takes their morning dose of randomized study medication on Day 29. 


 
 
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Table 9-5 
Allowable Windows for Pharmacokinetic (PK) Sampling Times 
Scheduled Time 
Allowable Collection Windows 
Predose (0 hour) 
Within 15 minutes prior to dose administration 
0.5 hour 
± 3 minutes 
2 hour 
± 15 minutes 
6 hour 
± 30 minutes 
8 hour 
± 30 minutes 
24 hour 
± 1 hour but before dose administration 
 
Random Time PK samples: Random PK samples will be collected from all study participants. 
Samples that are designated as random will be collected during the Week 6 and Week 10 visits. 
All participants will self-administer their morning dose of study medication and then report to 
the clinic to have a sample collected no sooner than 1 hour, but no later than 2 hours after 
self-administration. The participant will self-administer their morning dose of study medication 
at home as normally instructed in advance of the Week 6 and Week 10 visits. The date and time 
that the blood sample for AGN-242428 concentration was collected will be recorded in the 
eCRF. Deviations to sample collection such as failure to collect the sample or deviations to dose 
administration in the 3 days prior to sample collection will be recorded in the eCRF.  
Required blood collection tubes, processing instructions, storage instructions and processing 
instructions will be provided in the laboratory manual. 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
Any changes in the timing or addition of timepoints for any planned study assessments must be 
documented and then archived in the sponsor and site study files, but will not constitute a 
protocol amendment. The IRB/IEC will be informed of any safety issues that require alteration 
of the safety monitoring scheme or amendment of the ICF. 
9.6. 
Pharmacodynamics 
Blood samples for the analysis of IL-17A and IL-17F plasma concentrations will be collected 
from all participants before dose administration at scheduled times (Section 2). The date and 
time of sample collection will be recorded in the eCRF. Deviations to sample collection such as 
failure to collect the sample, collection of the sample after dose administration or deviations to 
dose administration in the 3 days prior to sample collection will be recorded in the eCRF.  
Additional cytokines, chemokines, or proteins may be measured from samples collected. 
Required blood collection tubes, processing instructions, storage instructions and processing 
instructions will be provided in the laboratory manual.  


 
 
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9.7. 
Genetics 
Genetics are not evaluated in this study. 
9.8. 
Biomarkers 
As discussed in Section 9.6, biomarkers will include, but not be limited to, the following: IL-17A 
and IL-17F.  
9.9. 
Medical Resource Utilization and Health Economics 
Health economics and medical resource utilization parameters are not evaluated in this study. 


 
 
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10. 
Statistical Considerations 
10.1. 
Sample Size Determination 
A responder is a participant with ≥ 75% reduction in PASI from baseline to Week 16. The 
sample size of 200 participants (50 per treatment arm) will provide 90% power to detect a 
response rate difference of 27% between each AGN-242428 and placebo group at Week 16, with 
an assumed response rate of 6% in the placebo group, a 5% type 1 error rate, and 20% 
dropout rate. 
10.2. 
Populations for Analyses 
The analysis populations will consist of participants as defined in Table 10-1.  
Table 10-1 
Analysis Populations 
Population 
Definition 
Study Treatment 
Modified intent-to-
treat (mITT) 
All randomized participants with at least 1 postbaseline PASI 
assessment. This population will be used for all efficacy analysis. 
Randomized assignment 
Pharmacokinetic 
(PK) 
All participants who received AGN-242428 and had available 
plasma concentration data. The PK analysis set will be used for 
all PK analyses.  
Actual received 
Pharmacodynamic 
(PD) 
All participants for whom PD measurements are available at 
baseline and at least one postbaseline visit.  
Actual received 
Safety 
All participants who received ≥ 1 administration of study 
treatment.  
Actual received 
PASI = Psoriasis Area and Severity Index 
 
10.3. 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the participant populations to be included in the analyses, and procedures for accounting 
for missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints. 
10.3.1. 
Disposition and Baseline Demographic Characteristics Analyses 
Disposition: The number and percentage of participants screened or randomized, included in 
each analysis population, completing the study, and withdrawing from the study (together with 
the reasons for withdrawal) will be summarized by treatment group. 
Baseline demographic characteristics: Demographic data (age, sex, race, ethnicity), and 
baseline characteristics (weight, height, BMI, Fitzpatrick skin phototype (Table 10-2), baseline 
PASI, % BSA, and PGA) will be summarized by treatment for the mITT analysis set. 


 
 
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Continuous variables will be summarized using descriptive statistics. Categorical variables will 
be tabulated using frequency distributions.  
Table 10-2 
Fitzpatrick Skin Phototype 
Type 
Description 
I 
Always burns easily; never tans (sensitive) 
II 
Always burns easily; tans minimally (sensitive) 
III 
Burns moderately; tans gradually (light brown) (normal) 
IV 
Burns minimally; always tans well (moderate brown) (normal) 
V 
Rarely burns; tans profusely (dark brown) (insensitive) 
VI 
Never burns; deeply pigmented (insensitive) 
Source: Federal Register 1999 
10.3.2. 
Efficacy Analyses 
10.3.2.1. Primary and Secondary Endpoints 
The following key primary and secondary efficacy endpoints will be analyzed for the mITT 
population. All other efficacy endpoints and analyses will be defined in the SAP. 
The primary efficacy endpoint is the percentage of participants achieving a reduction 
(improvement) in PASI score of ≥ 75% from baseline to Week 16 (responder). The null 
hypothesis is that the population responder rates of the AGN-242428 and placebo groups are 
the same. The alternative hypothesis is that the rates differ:  
• H0: rv = rp  
• Ha: rv ≠ rp 
where rv and rp are the population rates in the AGN-242428 and placebo groups, respectively. 
The difference between each of the AGN-242428 groups and placebo in the proportion of 
participants with a reduction in PASI of ≥ 75% from baseline to Week 16 will be analyzed using 
a Chi-square test. 
Frequency counts of participants achieving a 50%, 75%, and 90% reduction in PASI score 
relative to baseline will be tabulated by treatment at each postbaseline visit. Frequency counts of 
participants achieving ≥ 2-point improvement in PGA score will be tabulated by treatment at 
each postbaseline visit. Frequency counts of participants who achieve a PGA score of clear or 
almost clear will be tabulated by treatment at each postbaseline visit. 
Other efficacy measures will be summarized by visit and treatment.  


 
 
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10.3.3. 
Safety Analyses 
The following safety categories will be summarized as appropriate for the safety population and 
will be fully defined in the SAP. 
AEs: A by-participant listing of all AEs and of all TEAEs, including verbatim term, preferred 
term, treatment, as well as severity and relationship to treatment as per investigator assessment, 
will be provided. The number of participants experiencing TEAEs will be summarized by 
treatment using frequency counts and percentages. TEAEs will also be summarized by severity, 
and causality. A listing of TEAEs leading to study discontinuation will be provided.  
A TEAE is defined as a postbaseline AE in which: 
• the onset date is on or after the date of the first study treatment, or 
• the onset date is prior to the date of the first study treatment, and 
• the severity worsened on or after the date of the first study treatment, or 
• the event became serious on or after the date of the first study treatment. 
Clinical laboratory evaluations: Descriptive summaries (mean, SD, median, minimum, and 
maximum) of changes from baseline will be presented for clinical laboratory values by treatment 
group and visit. 
Vital signs: Descriptive summaries (mean, SD, median, minimum, and maximum) of actual 
values and changes from baseline will be calculated for vital signs (systolic and diastolic blood 
pressure, pulse and respiration rate). These summaries will be presented by treatment and by 
visit. 
ECG: ECG data will be summarized by treatment and by visit. 
10.3.4. 
Pharmacokinetic Analyses  
Listings will be provided for trough, random, and sequential (profile) plasma concentrations for 
the PK population. Additionally, trough and sequential plasma concentrations will be 
summarized by using appropriate descriptive statistics. 
Sequential PK samples will be analyzed using noncompartmental methods based on a PK 
analysis plan. The following PK parameters will be determined from this analysis: area under the 
plasma concentration versus time curve from time 0 to the end of the dosing interval, tau, at 
steady state (AUC0-tau.ss), maximum plasma drug concentration at steady state (Cmax,ss), minimum 
plasma drug concentration at steady state (Cmin,ss), and time of maximum plasma drug 
concentration at steady state (Tmax,ss). The PK parameters will be summarized using appropriate 
descriptive statistics. 
All plasma PK samples (trough, sequential, and random) obtained in the study will be analyzed 
using a population PK model. Individual predictions of AGN-242428 exposure (including, but 
not limited to, steady state AUC0-tau,ss and Cmin,ss) will be determined based on the population PK 


 
 
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model. A stand alone pharmacometric analysis plan will be written and the analyses will be 
reported separately from the integrated clinical trial report. 
10.3.5. 
Pharmacodynamic and Pharmacokinetic-Pharmacodynamic Analyses 
Descriptive statistics will be calculated for IL-17A and IL-17F levels in plasma for the PD 
population. 
The relationship of systemic exposure parameters such AUC0-tau,ss and Cmin,ss with efficacy, 
safety and/or biomarker endpoints will be evaluated graphically. If graphical evaluation 
identifies possible trends, exploratory PK/PD analyses will be performed for the evaluation and 
quantification of potential relationships via nonlinear mixed effects modeling. These analyses 
will be prespecified in the pharmacometrics analysis plan. 
10.3.6. 
Interim Analyses 
No formal interim analyses are planned. Ongoing review of safety data will be completed along 
with blinded review of select safety data when approximately 10%, 30%, 60% and 80% of the 
total participants have completed treatment through Week 4. 


 
 
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11. 
References 
Federal Register 1999: Volume 64(98); Friday, May 21, 1999 
https://www.gpo.gov/fdsys/pkg/FR-1999-05-21/html/99-12643.htm 
FDA Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical Evaluation, 
July 2009. https://www.fda.gov/downloads/Drugs/.../guidances/UCM174090.pdf. 
 
 
 


 
 
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12. 
Appendices 
12.1. 
Appendix 1: Abbreviations and Trademarks 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
Anti-HBc 
Hepatitis B core antibody 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration curve 
AUC∞ 
area under the plasma concentration curve from time 0 to 
infinity 
AUCtau 
area under the plasma concentration curve from 0 hours to 
the time of next dosing 
AUC0-tau.ss 
area under the plasma concentration versus time curve from 
time 0 to the end of the dosing interval, tau, at steady state 
BCG 
Bacillus Calmette-Guérin vaccine 
BCRP 
Breast Cancer Resistance Protein alternately known as 
ABCG2 (ATP binding cassette sub-family G member 2) 
BMI 
body mass index 
BSA 
body surface area 
BUN 
blood urea nitrogen 
Ca 
calcium 
CFR 
Code of Federal Regulations (United States of America) 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatinine phosphokinase – also known as CPK 
Cmax  
maximum plasma concentration 
Cmax,ss 
maximum plasma drug concentration at steady state 
Cmin,ss 
minimum plasma drug concentration at steady state 


 
 
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Abbreviation or Specialist Term 
Explanation 
CONSORT 
Consolidated Standards of Reporting Trials 
Cr 
creatinine 
CS 
clinically significant 
CYP2C8 
cytochrome P450 family 2 subfamily C member 8 
CYP2D6 
cytochrome P450 family 2 subfamily D member 6 
CYP3A4 
cytochrome P450 family 3 subfamily A member 4 
DDIs 
drug-drug interactions 
 
 
DMC 
Data Monitoring Committee 
DO 
Doctor of Osteopathy 
EAE 
experimental autoimmune encephalomyelitis 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ET 
early termination 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GCSM 
Global Clinical Supplies Management 
hERG 
human ether-a-go-go-related gene 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
HRT 
hormonal replacement therapy 
IB 
investigator’s brochure 
IBL 
indirect bilirubin 
IC50 
inhibitory concentration producing 50% inhibition 
IC90 
inhibitory concentration producing 90% inhibition 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IL-12 
interleukin 12 


 
 
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Abbreviation or Specialist Term 
Explanation 
IL-17 
interleukin 17 family inclusive of IL-17A and IL-17F 
IL-23 
interleukin 23 
IND 
investigational new drug application 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ITT 
intent to treat population 
IxRS 
interactive response system 
K 
potassium 
Ki 
inhibition constant 
LBD 
ligand binding domain 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
mAb 
monoclonal antibody 
MAD 
multiple-ascending dose 
MCS 
Mental component summary 
MD 
medical doctor (physician) 
Mg 
magnesium 
mITT 
modified intent to treat population 
mIU/mL 
milli-international units per milliliter 
MSP 
Medical Safety Physician 
Na 
sodium 
NOAEL 
no observed adverse effect level 
NCS 
not clinically significant 
OATP1B3 
organic anion-transporting polypeptide 1B3 also known as 
SLCO1B3 (solute carrier organic anion transporter family 
member 1B3) 
OTC 
over-the-counter 
P 
phosphorus 
PA 
Physician’s Assistant 
PASI 
Psoriasis Area and Severity Index 
PCS 
physical component summary 


 
 
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Abbreviation or Specialist Term 
Explanation 
PD 
pharmacodynamics 
 
 
PGA 
Physician’s Global Assessment 
PK 
pharmacokinetics 
POC 
proof-of-concept 
PT 
prothrombin time 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
 
 
SF-36 
36-item Short Form 
SoA 
schedule of activities 
SUSAR 
suspected unexpected serious adverse reaction  
TB 
tuberculosis (mycobacterium tuberculosis) 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
Th17 
T helper 17 
tmax  
time at which Cmax occurs  
Tmax,ss 
time of maximum plasma drug concentration at steady state 
TNFα 
Tumor Necrosis Factor alpha 
ULN 
upper limit of normal 
WOCBP 
women of childbearing potential 


 
 
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12.2. 
Appendix 2: Study Governance Considerations 
Regulatory and Ethical Considerations  
This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
o Applicable ICH Good Clinical Practice (GCP) guidelines 
o Applicable laws and regulations 
The protocol, protocol amendments, ICF, investigator’s brochure, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.  
The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the overall conduct of the study at the site and adherence to 
requirements of applicable local regulations, for example 21 CFR, ICH guidelines, the 
IRB/IEC, and European regulation 536/2014 for clinical studies (if applicable) 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant 
and answer all questions regarding the study.  


 
 
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Participants must be informed that their participation is voluntary. Participants will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center.  
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
A copy of the ICF(s) must be provided to the participant.  
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred.  
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
Committees Structure 
A Data Monitoring Committee (DMC) will review select safety and exposure data (as needed) at 
scheduled times during the conduct of the study. Ad-hoc meetings of the DMC may be scheduled 
to evaluate potential safety signals, as needed. The DMC will review blinded data. If there is a 
significant safety signal, then unblinded data may be reviewed in a closed session by DMC 
members designated as unblinded reviewers. Policies, procedures, and composition of the DMC 
are described separately in the DMC charter for this study.  
Publication Policy 
Allergan as the sponsor has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and Allergan 
personnel. Authorship will be established prior to the writing of the manuscript. As this study 
involves multiple centers, no individual publications will be allowed prior to completion of the 
final report of the multicenter study except as agreed with Allergan. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 


 
 
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multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements.  
Dissemination of Clinical Study Data 
Study information and tabular study results will be posted to the US National Institutes of Health 
website .  
Study data and information may be published in non-promotional, peer-reviewed publications 
either by or on behalf of Allergan.  
Clinical study reports, safety updates and annual reports will be provided to regulatory 
authorities as required.  
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRFs unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.  
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.  
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 3 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor.  
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 


 
 
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Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
Source data are defined as: Original documents, data, and records (eg, hospital records, clinical 
and office charts, diaries or evaluation checklists, pharmacy dispensing records, recorded data 
from automated instruments (eg, ECGs), copies or transcriptions certified after verification as 
being accurate and complete, microfiche, photographic negatives, microfilm or magnetic media, 
x-rays, participant files, and records kept at the pharmacy, at the laboratories, and at medico-
technical departments involved in the clinical study). These records include, but are not limited 
to, original signed and dated consent forms, relevant observations including records of adverse 
events and records of all exposure to study treatments. 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor’s procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study treatment development 


 
 
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12.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
An AE is any untoward medical occurrence in a participant or clinical study participant, 
temporally associated with the use of study treatment, whether or not considered related to the 
study treatment.  
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study treatment.  
AE of Special Interest (AESI) 
An adverse event of special interest (serious or nonserious) is one of scientific and medical 
concern specific to the sponsor’s study treatment/device or program, which warrants ongoing 
monitoring and rapid communication by the investigator to the sponsor. Such an event might 
warrant further investigation in order to characterize and understand it.  
The following AESI(s) have been identified for the study treatment(s) in this protocol:  
• 
AST and/or ALT ≥ 5 ULN  
• 
AST and/or ALT ≥ 3 x ULN AND TBL ≥ 2 x ULN or INR > 1.5. Typically, all analytes 
will be obtained from the same sample, but they may come from multiple samples taken 
within a 24-hour period.  
• 
AST and/or ALT ≥ 3 x ULN with symptoms believed to be related to liver injury (eg, 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness or jaundice) or 
hypersensitivity (such as fever, rash or eosinophilia > 5%) 
• 
Changes in hepatic laboratory test results that meet potential Hy’s Law 
• 
ALT and/or AST ≥ 3 x ULN AND 
• 
TBL ≥ 2 x ULN AND 
• 
Alkaline phosphatase < 2 x ULN 
Typically, all 3 analytes will be obtained from the same sample, but they may come from 
multiple samples taken within a 24-hour period. Non-serious AESIs should be reported to the 
sponsor within 72 hours and serious AESIs should be reported to the sponsor within 24 hours. 
The AESI form, which is the Adverse Event of Interest Abnormal Liver Function Reporting 
Form, should be used for reporting the AESI even if a serious outcome may not apply. Of note, 
all potential Hy’s Law cases are to be reported as SAEs. 
 


 
 
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Events Meeting the AE Definition  
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECGs, radiological scans, vital signs measurements), including those that 
worsen from baseline, considered clinically significant in the medical and scientific judgment of 
the investigator (ie, not related to progression of underlying disease) 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition 
New condition detected or diagnosed after study treatment administration even though it may 
have been present before the start of the study 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae 
Lack of efficacy or failure of expected pharmacological action per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE 
if they fulfill the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
Any clinically significant abnormal laboratory findings or other abnormal safety assessments that 
are associated with the underlying disease, unless judged by the investigator to be more severe 
than expected for the participant’s condition 
The disease/disorder being studied or expected progression, signs, or symptoms (clearly defined) 
of the disease/disorder being studied, unless more severe than expected for the participant’s 
condition 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital) 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected 
at the start of the study that do not worsen.  
 


 
 
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Definition of SAE 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease).  
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. 
Results in death 
b. 
Is life threatening 
The term life threatening in the definition of serious refers to an event in which the participant was at risk 
of death at the time of the event. It does not refer to an event, which hypothetically might have caused 
death, if it were more severe.  
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious.  
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE.  
d. 
Results in persistent disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions.  
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption.  
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.  
Examples of such events include invasive or malignant cancers, intensive treatment in an 


 
 
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emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization, or development of drug dependency or drug abuse.  
As discussed in Section 9.2.7, abnormal pregnancy outcomes (eg, spontaneous abortion, elective 
termination of a pregnancy, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs. 
All events of AST and/or ALT ≥ 3 x ULN and TBL ≥ 2 x ULN and alkaline phosphatase 
< 2 x ULN indicate severe liver injury (potential ‘Hy’s Law’) and must be reported as an SAE. 
 
Recording an AE and/or SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event.  
The investigator will then record all relevant AE/SAE information in the eCRF.  
It is not acceptable for the investigator to send photocopies of the participant’s medical records 
to the sponsor in lieu of completion of the AE/SAE eCRF page.  
There may be instances when copies of medical records for certain cases are requested by the 
sponsor. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to the sponsor.  
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE.  
Assessment of Severity as per Investigator 
MILD 
A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual activities of daily living.  
MODERATE 
A type of adverse event that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant.  
SEVERE 
A type of adverse event that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention.  
An event is defined as serious when it meets at least one of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe.  


 
 
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Assessment of Causality as per Investigator 
The investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE.  
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.  
The investigator will use clinical judgment to determine the relationship.  
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study treatment administration will be 
considered and investigated.  
The investigator will also consult the investigator’s brochure (IB) and/or product information, for 
marketed products, in his/her assessment.  
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality.  
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the sponsor.  
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment.  
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.  
 
SAE Reporting to the sponsor via Paper CRF 
Facsimile transmission of the SAE Reporting Form is the preferred method to transmit SAE 
information to the sponsor.  
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier service.  
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the SAE Reporting Form within the designated reporting time frames.  
Contacts for SAE reporting can be found in the protocol title page. 
 


 
 
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12.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal  
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
 
Contraception Guidance 
Male Participants 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the study and for 30 days following the last dose of study 
treatment:  
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent  
• 
Agree to use a male condom plus partner use of a contraceptive method with a failure rate of 
< 1% per year when having penile-vaginal intercourse with a WOCBP who is not currently 
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Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration during the study and 
for 30 days following the last dose of study treatment. 
In addition, male participants must refrain from donating sperm for the duration of the study and 
for 30 days following the last dose of study treatment. 
The same highly effective method of contraception must be used consistently and correctly 
throughout the study. 
Female Participants 
Female participants of childbearing potential are eligible to participate if they agree to use 
2 forms of birth control, in which at least 1 form must be a highly effective method of 
contraception, consistently and correctly as tabulated below. Of note, both forms can be highly 
effective if preferred, but at least 1 form must be highly effective. 
Highly Effective Contraceptive Methods That Are User Dependenta 
Failure rate of < 1% per year when used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
• 
Oral  
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Oral  
• 
Injectable  
Highly Effective Methods That Are User Independenta
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Etonogestrel implant (ie, Nexplanon®) 
Bilateral tubal occlusion 
Intrauterine copper contraceptive (ie, ParaGard®) 
Vasectomized Partner  
A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner 
of the women of childbearing potential (WOCBP) and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
Sexual Abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
The list in this table is not all inclusive. 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with local 
regulations regarding the use of contraceptive methods for participants participating in clinical studies.
 
Acceptable birth control methods that result in a failure of more than 1% per year (and are thus, 
not classified as highly effective) include the following noted below. One of these methods can 
be used as the required second method of contraception, if desired: 


 
 
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• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
• Male or female condom with or without spermicide 
• Cap, diaphragm, or sponge with spermicide 
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double 
barrier methods) are also considered acceptable, but not highly effective, birth control methods. 
 
Pregnancy Testing 
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test.  
Additional pregnancy testing should be performed as outlined in schedule of activities during the 
treatment period and at the follow-up visit or upon early termination. Pregnancy testing will be 
performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected at 
the investigator’s discretion.  
Pregnancy testing, with a sensitivity of at least 25 mIU/mL will be performed at the study site 
with testing materials provided by the central laboratory.  
Collection of Pregnancy Information  
Male Participants with Partners Who Become Pregnant  
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study medication. 
After obtaining the necessary site specific signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the sponsor. Generally, the follow-up will be 
no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of fetal status (presence or absence of anomalies) or 
indication for the procedure.  
Female Participants Who Become Pregnant  
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate form 
and submitted to the sponsor within 24 hours of learning of a participant’s pregnancy.  
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 


 
 
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forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure.  
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication will 
be reported as an AE or SAE. A spontaneous abortion and an elective termination of a pregnancy 
are always considered to be SAEs and will be reported as such. Any poststudy pregnancy-related 
SAE considered reasonably related to the study treatment by the investigator will be reported to 
the sponsor as described in Section 9.2. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.  
Any female participant who becomes pregnant while participating in the study will discontinue 
study treatment immediately and be withdrawn from the study.  


 
 
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12.5. 
Appendix 5: Standard Discontinuation Criteria 
CDISC Submission Value 
CDISC Definition 
Adverse event 
Any untoward medical occurrence in a patient or 
clinical investigation participant administered a 
pharmaceutical product and which does not 
necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be 
any unintended sign (including an abnormal 
laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal 
(investigational) product, whether or not related to 
the medicinal (investigational) product. For further 
information, see the ICH Guideline for Clinical 
Safety Data Management: Definitions and 
Standards for Expedited Reporting. [Modified from 
ICH E2A] Synonyms: side effect, adverse 
experience. See also serious adverse event, serious 
adverse experience. (CDISC glossary) 
Completed 
To possess every necessary or normal part or 
component or step; having come or been brought to 
a conclusion (National Cancer Institute [NCI]) 
Death 
The absence of life or state of being dead (NCI) 
Disease relapse 
The return of a disease after a period of remission 
Failure to meet randomization criteria 
An indication that the participant has been unable 
to fulfill/satisfy the criteria required for assignment 
into a randomized group 
Lack of efficacy 
The lack of expected or desired effect related to a 
therapy (NCI) 
Lost to follow-up 
The loss or lack of continuation of a participant to 
follow-up 
Non-compliance with study treatment 
An indication that a participant has not agreed with 
or followed the instructions related to the study 
medication (NCI) 
Other 
Different than the one(s) previously specified or 
mentioned (NCI) 
Physician decision 
A position, opinion or judgment reached after 
consideration by a physician with reference to 
participant (NCI) 
Pregnancy 
Pregnancy is the state or condition of having a 
developing embryo or fetus in the body (uterus), 
after union of an ovum and spermatozoon, during 
the period from conception to birth (NCI) 
Progressive disease 
A disease process that is increasing in extent or 
severity (NCI) 


 
 
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CDISC Submission Value 
CDISC Definition 
Protocol deviation 
An event or decision that stands in contrast to the 
guidelines set out by the protocol (NCI) 
Recovery 
A healing process and/or an outcome implying 
relative health. The term is typically used in the 
context of direct and indirect effects of sickness or 
injury (NCI) 
Screen failure 
The potential participant who does not meet one or 
more criteria required for participation in a trial 
Site terminated by sponsor 
An indication that a clinical study was stopped at a 
particular site by its sponsor (NCI) 
Study terminated by sponsor 
An indication that a clinical study was stopped by 
its sponsor (NCI) 
Technical problems 
A problem with some technical aspect of a clinical 
study, usually related to an instrument (NCI) 
Withdrawal by parent/guardian 
An indication that a study participant has been 
removed from the study by the parent or legal 
guardian 
Withdrawal by participant 
An indication that a study participant has removed 
itself from the study (NCI) 
 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
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96 
12.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessment 
Phase II liver chemistry stopping criteria are designed to assure participant safety and to 
evaluate liver event etiology. 
Phase II Liver Chemistry Stopping Criteria and Follow-Up Assessments 
 
 
Liver Chemistry Stopping Criteria 
AST and/or ALT-absolute 
AST and/or ALT ≥ 5 x ULN 
AST and/or ALT Increase 
AST and/or ALT ≥ 3 x ULN persists for ≥ 4 weeks 
Bilirubin or INR 
AST and/or ALT ≥ 3 x ULN and TBL ≥ 2 x ULN or INR > 1.5 
Cannot Monitor 
AST and/or ALT ≥ 3 x ULN and cannot be monitored weekly 
for 4 weeks 
Symptomatica 
AST and/or ALT ≥ 3 x ULN associated with symptoms (new or 
worsening) believed to be related to liver injury or 
hypersensitivity 
Potential Hy’s Law cases 
AST, ALT, and Bilirubinb 
AST and/or ALT ≥ 3 x ULN and TBL ≥ 2 x ULN and alkaline 
phosphatase < 2 x ULN 


 
 
Approval Date: 
 
21-Dec-2017
 
 
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GRD-CLN-T-01-01 Protocol Template v1.0 
97 
Required Actions and Follow-up Assessments  
Actions 
Follow-Up Assessments 
• Immediately discontinue study treatment.  
• Report the event to the sponsor within 24 hours. 
• Complete the liver event eCRF, and complete a 
serious adverse event (SAE) data collection tool if 
the event also met the criteria for an SAE.b 
• Perform liver chemistry follow-up assessments.  
• Monitor the participant until liver chemistry test 
abnormalities resolve, stabilize, or return to 
baseline (see MONITORING). 
• Do not restart/rechallenge participant with study 
treatment  
• As restart/rechallenge is not allowed per protocol, 
permanently discontinue study treatment and 
continue participant in the study for any protocol 
specified follow-up assessments  
 
 
MONITORING: 
If AST and/or ALT ≥ 3 x ULN AND bilirubin 
≥ 2 x ULN:  
• Repeat liver chemistry tests (include alanine 
transferase (ALT), aspartate transaminase [AST], 
alkaline phosphatase [ALP], total, direct, and 
indirect, bilirubin [TBL, DBL, IBL], gamma-
glutamyl transferase [GGT], and lactate 
dehydrogenase [LDH]) and perform liver event 
follow-up assessments within 24 hours. 
• Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, or 
return to baseline. 
• A specialist or hepatology consultation is 
recommended. 
If AST and/or ALT ≥ 3 x ULN AND bilirubin 
< 2 x ULN:  
• Viral hepatitis serology and other 
laboratory testing, as well as anti-
nuclear antibody and anti-smooth 
muscle antibodyc 
• 
Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show 
downward trend 
• 
Obtain blood sample for 
pharmacokinetic (PK) analysis 
48 hours after the most recent dosed 
• Serum creatine phosphokinase 
(CPK) and lactate dehydrogenase 
(LDH) 
• Fractionate bilirubin, if 
TBL ≥ 2 x ULN 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening 
of clinical symptoms of liver injury, 
or hypersensitivity, on the adverse 
event (AE) report form 
• Record use of concomitant 
medications (including 
acetaminophen, herbal remedies, and 
other over-the-counter medications) 
on the concomitant medications 
eCRF. 
• Record alcohol use on the liver 
event alcohol intake eCRF 
If AST and/or ALT ≥ 3 x ULN AND 
bilirubin ≥ 2 x ULN: 
• Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total 
immunoglobulin G (IgG) or gamma 


 
 
Approval Date: 
 
21-Dec-2017
 
 
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GRD-CLN-T-01-01 Protocol Template v1.0 
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• Repeat liver chemistry tests (include ALT, AST, 
ALP, TBL, DBL, IBL, GGT, and LDH) and 
perform liver chemistry follow-up assessments 
within 24 to 72 hours. 
• Monitor participants weekly until liver chemistry 
abnormalities resolve, stabilize, or return to 
baseline. 
globulins. 
• Liver imaging (ultrasound, magnetic 
resonance, or computerized 
tomography) and/or liver biopsy to 
evaluate liver disease; complete the 
Hy’s Law eCRF form and the AESI 
Form, which is the Adverse Event of 
Interest Abnormal Liver Function 
Reporting Form. 
AESI = adverse event of special interest; ALT = alanine aminotransferase; AST = aspartate aminotransferase; eCRF = electronic 
case report form: TBL = total bilirubin; ULN = upper limit of normal 
a = New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia). 
b = All events of AST and/or ALT ≥ 3 x ULN and TBL ≥ 2 x ULN and alkaline phosphatase < 2 x ULN indicate severe liver 
injury (potential ‘Hy’s Law’) and must be reported as both an AESI and an SAE by completing the AESI Form, which is the 
Adverse Event of Interest Abnormal Liver Function Reporting Form, and and sending it to IR-Clinical-SAE@allergan.com (or 
faxing it to the SAE fax number) within 24 hours of learning of the potential Hy’s Law case.  
c = Includes:Hepatitis A immunoglobulin M (IgM) antibody; hepatitis B surface antigen and hepatitis B Core Antibody 
(HBcAb); hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
heterophile antibody or monospot testing); hepatitis E IgM antibody; anti-nuclear antibody; and anti-smooth muscle antibody.  
d = PK sample may not be required for participants known to be receiving placebo or non-comparator treatments. Record the 
date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to the blood sample draw on the 
eCRF. If the date or time of the last dose is unclear, provide the participant’s best approximation. If the date/time of the last dose 
cannot be approximated OR a PK sample cannot be collected in the time period indicated above, do not obtain a PK sample. 
Instructions for sample handling and shipping are in the Laboratory Manual. 
 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
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GRD-CLN-T-01-01 Protocol Template v1.0 
99 
Phase II Liver Chemistry Increased Monitoring Criteria with Continued Therapy 
Liver Chemistry Increased Monitoring Criterion and Follow-Up 
Criterion 
Actions 
ALT ≥ 3 x ULN and < 5 x ULN and 
bilirubin < 2 x ULN, without 
symptoms believed to be related to 
liver injury or hypersensitivity, and 
who can be monitored weekly for 
4 weeks 
• Notify the sponsor within 24 hours of learning of 
the abnormality to discuss participant safety.  
• Participant can continue study treatment 
• Participant must return weekly for repeat liver 
chemistry tests (ALT, AST, alkaline phosphatase, 
bilirubin) until the abnormalities resolve, stabilize 
or return to baseline.  
• If at any time, the participant meets liver chemistry 
stopping criteria, proceed as described in Section 8. 
• If, after 4 weeks of monitoring, ALT < 3 x ULN 
and bilirubin < 2 x ULN, monitor participants twice 
monthly until liver chemistry tests resolve, 
stabilize, or return to baseline. 
 
 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
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100 
12.7. 
Appendix 7: Study Tabular Summary 
 
Parameter Group 
Parameter 
Value 
Trial information 
Trial Title 
A Randomized, Double-Blind, Placebo-
Controlled, Study to Assess the Efficacy, 
Safety, Pharmacokinetics and 
Pharmacodynamics of AGN-242428 in 
Patients With Plaque Psoriasis 
 
Clinical Study sponsor 
Vitae Pharmaceuticals Inc., an Allergan 
affiliate
 
Trial Phase Classification 
Phase 2b Trial 
 
Trial Indication 
Plaque psoriasis 
 
Trial Indication Type 
Treatment 
 
Trial Type 
Efficacy 
Safety 
 
Trial Length 
22 weeks ± 3 days from screening to 
follow-up 
 
Planned Country of Investigational Sites 
United States 
 
Planned Number of Participants 
200
 
FDA-Regulated Device Study Indicator 
No 
 
FDA-Regulated Drug Study Indicator 
Yes 
 
Pediatric Study Indicator 
No 
Participant 
information 
Diagnosis Group 
Moderate to severe plaque psoriasis 
defined as PASI ≥ 12, % BSA ≥ 10 and 
PGA of ≥ 3
 
Healthy Participant Indicator 
No 
 
Planned Minimum Age of Participants 
18
 
Planned Maximum Age of Participants 
75
 
Sex of Participants 
Male/Female
 
Stable Disease Minimum Duration 
6 months 


 
 
Approval Date: 
 
21-Dec-2017
 
 
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GRD-CLN-T-01-01 Protocol Template v1.0 
101 
Parameter Group 
Parameter 
Value 
Treatments 
Investigational Therapy or Treatment 
AGN-242428 
 
Intervention Type 
Drug 
 
Pharmacological Class of Invest. Therapy 
Selective, orally active small molecule 
inhibitor of RORγt activity 
 
Dose per Administration 
 
 
Dose Units 
 and 
 capsules 
 
Dosing Frequency 
Once-daily 
 
Route of Administration 
Oral 
 
Current Therapy or Treatment 
Current treatment or history of treatment 
with immunosuppressive therapy, for any 
condition, within 4 weeks of study, unless 
otherwise stated is prohibited. Current 
treatment or history of treatment with any 
anti-TNFα biologic therapy within 
3 months or 5 half-lives of study, and/or all 
other biologics within 6 months of study 
(Day 1) is prohibited. Current treatment or 
history of treatment for psoriasis with 
non-biologic systemic medications or UV 
therapy within 4 weeks of Day 1 and 
treatment with topical agents within 
2 weeks of Day 1 is prohibited. 
 
Added on to Existing Treatments 
No 
 
Control Type 
Placebo 
 
Comparative Treatment Name 
Not applicable 
Trial design 
Study Type 
Interventional 
 
Intervention Model 
Parallel 
 
Planned Number of Arms 
4
 
Trial is Randomized 
Yes 
 
Randomization Quotient 
1:1:1:1 (
 AGN-242428: 
 
AGN-242428: 
 AGN-242428: 
placebo).
 
Trial Blinding Schema 
Double blind 
 
Stratification Factor 
No 
 
Adaptive Design 
No 
 
Study Stop Rules 
A participant will be permanently 
withdrawn from study treatment if any of 
the criteria below are met and considered 
related to AGN-242428: 


 
 
Approval Date: 
 
21-Dec-2017
 
 
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AGN-242428 
 
GRD-CLN-T-01-01 Protocol Template v1.0 
102 
Parameter Group 
Parameter 
Value 
Study Treatment-related SAE  
Decreased total leukocyte count; 
Leukopenia < 3000/µL (< 3.0 x 109/L) 
Decreased total neutrophil count; 
Neutropenia < 1000/µL (< 1.0 x 109/L) 
Decreased total lymphocyte count; 
Lymphopenia < 500/µL (< 0.5 x 109/L) 
Decreased platelet count; 
Thrombocytopenia < 100,000/µL 
(< 100 x 109/L) 
Increased serum creatinine ; Serum 
creatinine > 2 x ULN 
Unspecified safety concern; Upon request 
by investigator or Medical Safety 
Physician 
Increased liver enzymes: 
•ALT and/or AST ≥ 5 x ULN 
•ALT and/or AST ≥ 3 x ULN AND TBL 
≥ 2 x ULN or INR > 1.5 
•ALT and/or AST ≥ 3 x ULN with 
symptoms
 
 
 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
AGN-242428 
 
GRD-CLN-T-01-01 Protocol Template v1.0 
103 
12.8. 
Appendix 8: Partial List of Prohibited Medications Which Are 
Sensitive Substrates for BCRP, OATP1B3, CYP2D6, and CYP2C8 
and Strong Inhibitors or Inducers of CYP3A4 
This list of prohibited medications is provided as a guidance. Use of these medications is 
prohibited unless approved by the investigator or sponsor. This list is not comprehensive and the 
investigators will consult with the sponsor before allowing concomitant medication use during 
the trial. 
 
Partial List of Prohibited Substrates 
BCRP 
Substrates 
OATP1B3 
Substrates 
CYP2D6  
Substrates 
CYP2C8 
Substrates 
CYP3A4 
Inhibitors 
CYP3A4 
Inducers 
Apixaban 
Atorvastatin 
Amitriptyline 
Amiodarone 
Bitter Orange sup-
plement 
Carbamazepine 
Methotrexate 
Methotrexate 
Aripiprazole 
Pioglitazone 
Clarithromycin 
Guggul (Commiphora 
mukul) 
Rivaroxaban 
Pravastatin 
Atomoxetine 
Repaglinide 
Grapefruit 
Phenobarbital 
Rosuvastatin 
Rifampin 
Carvedilol 
 
Grapefruit Juice 
Phenytoin 
Sulfasalazine 
Rosuvastatin 
Chlorpheniramine 
 
Itraconazole 
Primidone 
 
 
Desipramine 
 
Ketoconazole 
Rifampin 
 
 
Dextromethorphan 
 
Resveratrol 
St. John’s Wort 
 
 
Doxepin 
 
Seville oranges 
 
 
 
Fluoxetine 
 
Seville orange 
juice 
 
 
 
Imipramine 
 
 
 
 
 
Metoprolol 
 
 
 
 
 
Mirtazapine 
 
 
 
 
 
Nortriptyline 
 
 
 
 
 
Paroxetine 
 
 
 
 
 
Propafenone 
 
 
 
 
 
Propranolol 
 
 
 
 
 
Risperidone 
 
 
 
 
 
Tolterodine 
 
 
 
Use of drugs or substances known to be sensitive cytochrome P450 CYP2D6 or CYP2C8 substrates, strong CYP3A4 inhibitors, strong 
CYP3A4 inducers, or transported by specific liver transporters (ie, breast cancer resistance protein [BCRP] and/or organic anion 
transporting polypeptide 1B3 [OATP1B3]) is prohibited unless approved by the investigator and sponsor. 
 


 
 
Approval Date: 
 
21-Dec-2017
 
 
Protocol 1957-201-001 Amd 2 
AGN-242428 
 
GRD-CLN-T-01-01 Protocol Template v1.0 
104 
12.9. 
Appendix 9: Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment (Amendment 2) 
is located directly before the table of contents. 
The rationale and the protocol amendment summary of changes table for Amendment 1 is 
located below: 
Overall Rationale for Amendment 1: 
The overall rationale for the changes implemented in the protocol amendment was 1) to align the 
inclusion/exclusion criteria with industry precedence for similar psoriasis studies, 2) to add INR 
monitoring to the stopping criteria to adhere to FDA Guidance for DILI 2009, and 3) to add INR 
monitoring to the Adverse Events of Special Interest for additional safety surveillance. 
 
Section No. and 
Name 
Description of Change 
Brief Rationale 
6.1 Inclusion 
Criteria 
Removed the following phrase from Inclusion 
Criterion 3.01: “and body mass index (BMI) within 
the range 18 to 35 kg/m2 inclusive” 
To align the 
inclusion/exclusion criteria 
with industry precedence for 
similar psoriasis studies 
6.2 Exclusion 
Criteria 
Removed the following statement from Exclusion 
Criterion 1.02: “Stable is defined as psoriasis that has 
not worsened or improved resulting in a 1% change in 
total body surface area (BSA) or a 2-point change in 
total Psoriasis Area and Severity Index (PASI) score.” 
To align the 
inclusion/exclusion criteria 
with industry precedence for 
similar psoriasis studies 
Table 7-1 
Deleted “Manufactured for Allergan by Frontage 
Laboratories, Inc.” 
In the event there is a change 
in the manufacturer 
Table 8-1 Safety 
Criteria for 
Individual 
Participants 
Stopping Study 
Treatment 
Added INR to stopping criteria here and throughout 
the protocol 
Adhere to FDA Guidance for 
DILI 2009 
9.1.1 Determination 
of Percent Body 
Surface Area 
Added “(handprint method)” 
Clarified the BSA 
methodology 
9.1.2 Psoriasis Area 
and Severity Index 
Added “(handprint method)” and text on the surface 
area involvement of each of the 4 anatomic regions 
and how they are scored. 
Clarified the PASI 
methodology and aligned the 
PASI descriptors with industry 
precedents 
Section 9.2.8 
Adverse Events of 
Special Interest 
Added INR to Adverse Events of Special Interest here 
and throughout the protocol 
Additional safety surveillance 
12.4 Contraceptive 
Guidance 
Deleted footnote b from the table, which stated: 
“Hormonal contraception may be susceptible to 
interaction with the study treatment, which may 
Deleted for clarity to match the 
text in the protocol, which 
states: “…agree to use 2 forms 


 
 
Approval Date: 
 
21-Dec-2017
 
 
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Section No. and 
Name 
Description of Change 
Brief Rationale 
reduce the efficacy of the contraceptive method. In 
this case, 2 highly effective methods of contraception 
should be utilized during the treatment period and for 
30 days after the last dose of study treatment.” 
of birth control, in which at 
least 1 form must be a highly 
effective method of 
contraception.” 
Throughout 
Minor editorial revisions 
Minor, therefore have not been 
summarized 
 


 
 
Approval Date: 
 
21-Dec-2017
ALLERGAN 
 
 
 
 
 
 
 
 
 
Date (DD/MMM/YYYY)/Time (PT) 
Signed by: 
Justification 
  
 
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Protocol 1957-201-001 Amd 2

SAP_001.pdf: 
 
   
 
 
 
         NCT 03339999 
 
Study ID: 1957-201-001 
 
 
Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Assess 
the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AGN-
242428 in Patients With Plaque Psoriasis 
 
                Statistical Analysis Plan Date: May 16, 2018 


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Controlled, 
amics of AG
Psoriasis 
SIS PLAN -
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Clinical Stu
     SAP 19
 
ssess the Ef
in Patients W
udy Report
57-201-001 
fficacy, Safe
With Plaque
 
1 
ety, 
e 


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     SAP 1957-201-001 
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2.0 
TABLE OF CONTENTS 
1.0 
TITLE PAGE .................................................................................................................................... 1 
2.0 
TABLE OF CONTENTS .................................................................................................................. 2 
3.0 
LIST OF ABBREVIATIONS ........................................................................................................... 4 
4.0 
INTRODUCTION ............................................................................................................................. 5 
5.0 
OBJECTIVES ................................................................................................................................. 17 
6.0 
PATIENT POPULATIONS ............................................................................................................ 17 
6.1 
Modified Intent-to-Treat Population ................................................................................. 17 
6.2 
Safety Population .............................................................................................................. 17 
7.0 
PATIENT DISPOSITION ............................................................................................................... 17 
8.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................................ 18 
8.1 
Demographics and Baseline Characteristics ..................................................................... 18 
8.2 
Medical History ................................................................................................................ 18 
8.3 
Prior and Concomitant Medications .................................................................................. 19 
9.0 
EXTENT OF EXPOSURE AND TREATMENT COMPLIANCE ................................................ 20 
9.1 
Extent of Exposure ............................................................................................................ 20 
9.2 
Measurement of Treatment Compliance ........................................................................... 20 
10.0 
EFFICACY ANALYSES ................................................................................................................ 21 
10.1 
Primary Efficacy Parameter(s) .......................................................................................... 21 
10.2 
Secondary Efficacy Parameter(s) ...................................................................................... 21 
 
 
11.0 
SAFETY ANALYSES .................................................................................................................... 23 
11.1 
Adverse Events ................................................................................................................. 23 
11.1.1 
Adverse Events of Special Interest ..................................................................... 23 
11.2 
Clinical Laboratory Parameters ......................................................................................... 24 
11.3 
Vital Signs ......................................................................................................................... 27 
11.4 
Electrocardiogram ............................................................................................................. 28 
 
 
13.0 
INTERIM ANALYSIS.................................................................................................................... 29 
14.0 
DETERMINATION OF SAMPLE SIZE ........................................................................................ 29 
15.0 
STATISTICAL SOFTWARE ......................................................................................................... 29 
16.0 
DATA HANDLING CONVENTIONS .......................................................................................... 29 
 
 
16.2 
Derived Variables ............................................................................................................. 30 
16.3 
Repeated or Unscheduled Assessments of Safety Parameters .......................................... 31 
16.4 
Missing Severity Assessment for Adverse Events ............................................................ 31 
16.5 
Missing Causal Relationship to study Treatment for Adverse Events .............................. 31 


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16.6 
Missing Date Information for Adverse Events.................................................................. 31 
16.7 
Missing Date Information for Prior or Concomitant Medications .................................... 32 
16.8 
Character Values of Clinical Laboratory Parameters ........................................................ 32 
17.0 
REFERENCES ................................................................................................................................ 34 
 


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3.0 
LIST OF ABBREVIATIONS  
 
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
analysis of covariance 
BSA 
Body Surface Area 
CMH 
Cochran-Mantel-Haenszel 
CRF 
case report form 
ECG 
electrocardiogram, electrocardiographic 
mITT 
modified intent to treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
PASI 
Psoriasis Area and Severity Index 
PGA 
Physician’s Global Assessment 
PRO 
Patient Reported Outcomes 
PT 
Preferred Term 
QTc 
QT interval corrected for heart rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC 
System Organ Class 
TEAE 
treatment-emergent adverse event 


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     SAP 1957-201-001 
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4.0 
INTRODUCTION 
This statistical analysis plan (SAP) provides a more technical and detailed elaboration of the 
statistical analyses of the efficacy and safety data as outlined and/or specified in the final 
protocol of Study 1957-201-001 (dated 29 Jun 2017) and the most recent amendment 2 (dated 
21 Dec 2017). Specifications of tables, figures, and data listings are contained in a separate 
document. The SAP for pharmacokinetic/pharmacodynamic and health economics and outcomes 
research data will be prepared separately. 
Study 1957-201-001 is a Phase 2b, double-blind, randomized, placebo-controlled trial to evaluate 
the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of AGN-242428 
when administered once daily for 16 weeks to adults with moderate to severe plaque psoriasis.  
Approximately 200 participants were planned to be randomly assigned (1:1:1:1) to once-daily 
study medication (50 participants to AGN-242428 225 mg, 50 participants to AGN-242428 350 
mg, 50 participants to AGN-242428 450 mg and 50 participants to placebo) to provide an 
estimated total of 160 evaluable participants who will complete the study. The study consists of 3 
periods, as described below.  
Screening Period: The purpose of the Screening period is to evaluate potential study 
participants and to qualify them for enrollment into the study. This period begins at the point of 
informed consent and ends when the participant is randomized to treatment. The screening 
period will be up to 4 weeks (≤ 28 days) in duration. 
Treatment Period: Participation in the study begins at the point the participant is randomized. 
The treatment starts after his/her first dose of study medication and ends after 16 weeks of 
treatment or at the point of permanent study medication withdrawal should the participant 
discontinue treatment prior to completion of Week 16.  
On Day 1 of the treatment period, qualified participants will be randomly assigned to receive 
16 weeks of once-daily oral treatment with 
 AGN-242428, 
 AGN-242428, 
 AGN-242428, or placebo. Baseline data for evaluation of participant efficacy and safety 
will be obtained on Day 1, prior to receiving the first dose. Participants will complete study visits 
on the first day of treatment and following 2, 4, 6, 8, 10, 12, and 16 weeks of treatment for 
evaluation of efficacy, safety, and tolerability assessments.  
Any participant who exhibits a predefined change in clinical laboratory parameters may be 
required to complete unscheduled visits to further monitor abnormal safety laboratory test 
results. Investigators may complete unscheduled study visits at any point they feel necessary to 


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     SAP 1957-201-001 
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6 
monitor and ensure participant safety. 
 
 
 
 
  
Follow-up Period: Participants will return for a follow-up visit 14 ± 3 days after completion of 
study medication or after early withdrawal for end-of-study assessments. 
The schedule of evaluations for Study 1957-201-001 is presented in Table 4-1.  
 


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5.0 
OBJECTIVES 
The objectives of this study are: 
• To compare the efficacy of AGN-242428 with placebo, with respect to Psoriasis 
Area and Severity Index (PASI) score and Physician’s Global Assessment (PGA) 
score, in participants with moderate to severe plaque psoriasis 
• To assess the safety and tolerability of AGN-242428 in participants with 
moderate to severe plaque psoriasis 
• To characterize the pharmacokinetics of AGN-242428 in participants with 
moderate to severe plaque psoriasis 
6.0 
PATIENT POPULATIONS 
The patient populations will be summarized in total and by treatment group for all 
randomized or treated participants. 
6.1 
MODIFIED INTENT-TO-TREAT POPULATION 
The modified Intent-to-Treat (mITT) Population will consist of all randomized 
participants with at least 1 postbaseline PASI assessment.  
6.2 
SAFETY POPULATION 
The Safety Population will consist of all participants who received at least 1 
administration of study treatment. 
7.0 
PATIENT DISPOSITION 
Participant disposition encompasses the distribution of participants screened, randomized, 
treated, and who completed or discontinued the study (along with reasons for 
withdrawal/discontinuation). Participant disposition will be summarized for all screened 
participants in total and by treatment group. 


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8.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
8.1 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Demographic parameters (age; age group; sex; race; ethnicity), baseline characteristics 
(weight; height; body mass index, calculated as weight [kg]/(height [m])2; Fitzpatrick 
skin phototype [Table 8-1], baseline PASI, % Body Surface Area (BSA), and PGA) will 
be summarized descriptively for the mITT Population by treatment group and in total. 
Continuous variables will be summarized by number of participants and mean, SD, 
median, minimum, and maximum values. Categorical variables will be summarized by 
number and percentage of participants. 
Table 8-1 
Fitzpatrick Skin Phototype 
Type 
Description 
I 
Always burns easily; never tans (sensitive) 
II 
Always burns easily; tans minimally (sensitive) 
III 
Burns moderately; tans gradually (light brown) (normal) 
IV 
Burns minimally; always tans well (moderate brown) (normal) 
V 
Rarely burns; tans profusely (dark brown) (insensitive) 
VI 
Never burns; deeply pigmented (insensitive) 
Source: Federal Register 1999 
8.2 
MEDICAL HISTORY 
Medical history, encompassing abnormalities and surgeries reported as occurring before 
Day 1, will be coded using the Medical Dictionary for Regulatory Activities (MedDRA), 
version 20.1 or newer. Unique participants who report medical history events will be 
summarized by MedDRA system organ class (SOC) and preferred term (PT) for the 
mITT Population by treatment group. Medical history will be summarized separately for 
those ongoing at Day 1 and those not ongoing at Day 1. 


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8.3 
PRIOR AND CONCOMITANT MEDICATIONS 
Medications will be coded using the World Health Organization (WHO) Drug 
Dictionary. Prior medications are medications taken ≥ 1 time before the study treatment 
start date, regardless of medication end date. Concomitant medications are medications 
taken ≥ 1 time on or after the study treatment start date, regardless of medication start 
date. Unique participants who reported medications will be summarized by WHO Drug 
class and preferred drug name for the mITT Population by treatment group. Prior and 
concomitant medications will be summarized separately. 


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9.0 
EXTENT OF EXPOSURE AND TREATMENT COMPLIANCE 
9.1 
EXTENT OF EXPOSURE 
Exposure to the investigational product for the Safety Population during the double-blind 
treatment period will be summarized in terms of treatment duration, calculated as the 
number of days from the date of the first dose of double-blind investigational product to 
the date of the last dose of double-blind investigational product during the double-blind 
treatment period, inclusive. Descriptive statistics (number of participants, mean, SD, 
median, minimum, and maximum) will be presented by treatment group.  
Patient-years, defined as total exposure to double-blind investigational product in years 
will be summarized by treatment group for the Safety Population. 
9.2 
MEASUREMENT OF TREATMENT COMPLIANCE 
Dosing compliance for the study period is defined as the total number of capsules (Row 1 
+ Row 2) actually taken by a participant during the study (from first treatment start date 
until the last treatment end date) divided by the number of capsules prescribed (2 
capsules a day) for the same period multiplied by 100. If the total number of capsules for 
any week is missing, that week will be excluded from the compliance calculation. This 
information will be obtained from study treatment record of the participant’s eCRF. 
Descriptive statistics for study drug compliance will be presented by treatment group for 
the whole double-blind treatment period, for the Safety Population. 
 


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10.0 
EFFICACY ANALYSES 
The efficacy analyses will be based on the mITT Population, defined as randomized 
participants with at least 1 postbaseline PASI assessment. Baseline for efficacy is defined 
as the last non-missing efficacy assessment before the first dose of study treatment. All 
efficacy analyses will be conducted using observed data. All statistical tests will be 
2-sided hypothesis tests performed at the 5% level of significance for main effects. All 
confidence intervals will be 2-sided 95% confidence intervals, unless stated otherwise. 
10.1 
PRIMARY EFFICACY PARAMETER 
The primary efficacy endpoint will be percentage of participants achieving a reduction 
(improvement) in PASI score of ≥ 75% from baseline to Week 16.  
The null hypothesis is that the population responder rates of the AGN-242428 and 
placebo groups are the same. The alternative hypothesis is that the rates differ:  
• H0: rv = rp  
• Ha: rv ≠ rp 
where rv and rp are the population rates in the AGN-242428 and placebo groups, 
respectively. 
Frequency counts of participants achieving a ≥ 75% reduction in PASI score relative to 
baseline will be tabulated by treatment at each postbaseline visit. The difference between 
each of the AGN-242428 groups and placebo in the proportion of participants with a 
reduction in PASI of ≥ 75% from baseline, will be analyzed using a Chi-Square test.  
10.2 
 SECONDARY EFFICACY PARAMETERS 
The following are considered secondary endpoints of the study: 
• Percentage of participants achieving ≥ 2-point improvement in PGA score at 
Week 16 
• Percentage of participants achieving a clear (0) or almost clear (1) score in PGA 
at Week 16 


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• Percentages of participants achieving reductions of 50% from baseline in PASI 
score at Week 16  
• Percentages of participants achieving reductions of 90% from baseline in PASI 
score at Week 16 
 
Frequency counts of participants achieving ≥ 2-point improvement in PGA score will be 
tabulated by treatment at each postbaseline visit. Frequency counts of participants who 
achieve a PGA score of clear or almost clear will be tabulated by treatment at each 
postbaseline visit. Frequency counts of participants achieving a 50% and 90% reduction 
in PASI score relative to baseline will be tabulated by treatment at each postbaseline 
visit. 
The difference between each of the AGN-242428 groups and placebo in the proportion of 
participants achieving each of the secondary endpoints above will be analyzed using a 
Chi-Square test.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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11.0 
SAFETY ANALYSES 
The safety analysis will be performed using the Safety Population. The safety parameters 
will include adverse events (AEs) and clinical laboratory, vital sign, and 
electrocardiographic (ECG) parameters. For each safety parameter of the clinical 
laboratory, vital sign, and ECG parameters, the last nonmissing safety assessment before 
the first dose of study treatment will be used as the baseline for all analyses of that safety 
parameter. Continuous variables will be summarized by number of participants and 
mean, SD, median, minimum, and maximum values. Categorical variables will be 
summarized by number and percentage of participants. 
11.1 
ADVERSE EVENTS 
Adverse events will be coded by SOC and PT using the MedDRA, version 20.1 or newer. 
An AE will be considered a treatment-emergent adverse event (TEAE) if the AE began or 
worsened (increased in severity or became serious) on or after the date of the first dose of 
study intervention.  Per case report form instructions, a new AE record will be created for 
any AE that worsens; therefore, TEAEs can be identified as those AEs with recorded 
onset date on or after the date of the first dose of study intervention  
The number and percentage of participants reporting TEAEs will be summarized by 
treatment group using MedDRA PT nested within SOC. Events will be in alphabetic 
order of SOC and by descending frequency of PTs within each SOC. Treatment-related 
TEAEs will be tabulated by descending frequency of PTs within the SOC. If more than 1 
AE is coded to the same PT for the same patient, the patient will be counted only once for 
that PT using the greatest severity and strictest causality for the summarization by 
severity and causal relationship. 
The number and percentage of participants who have treatment emergent serious adverse 
events (TESAEs) will be summarized by PT and treatment group.  
The number and percentage of participants in the Safety Population who have TEAEs 
leading to premature discontinuation of the study treatment will be summarized by PT 
and treatment. 


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11.1.1 
Adverse Events of Special Interest 
The following adverse events of special interest (AESI) will be summarized by treatment 
group: 
• aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 5 x 
upper limit of normal (ULN) 
• AST and/or ALT ≥ 3 x ULN AND total bilirubin (TBL) ≥ 2 x ULN or 
international normalized ratio (INR) > 1.5  
• AST and/or ALT ≥ 3 x ULN with symptoms believed to be related to liver injury 
(eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness or 
jaundice) or hypersensitivity (such as fever, rash, or eosinophilia > 5%) 
• Changes in hepatic laboratory test results that meet potential Hy’s Law 
• ALT and/or AST ≥ 3 x ULN AND 
• TBL ≥ 2 x ULN AND 
• Alkaline phosphatase < 2 x ULN  
 
Potential Hy’s Law criteria within a 24-hour window is defined by a postbaseline 
elevation of ALT and/or AST ≥ 3x ULN, along with TBL ≥ 2 x ULN and a non-elevated 
alkaline phosphatase (ALP) < 2 x ULN, all based on blood draws collected within a 
24-hour period.  
 
A graphical representation of liver function, known as eDISH, will be generated by 
plotting the maximum postbaseline TBL elevation at any timepoint during the study vs 
maximum postbaseline ALT elevation at any timepoint. Note that the maximum ALT 
may be from a different visit than when the maximum TBL was observed. A plot of 
maximum TBL vs maximum AST will be generated separately. 
 
11.2 
CLINICAL LABORATORY PARAMETERS 
Descriptive statistics (mean, SD, median, Q1, Q3, minimum, and maximum) for clinical 
laboratory values (in SI units) and changes from the baseline values at each assessment 
timepoint will be presented by treatment group for the following laboratory parameters: 


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Table 11.2-1 
Clinical Laboratory Tests 
Categorya 
Parameters 
Hematology and 
Coagulationa 
Hematocrit (HCT), hemoglobin (HGB), red blood cell (RBC) count, RBC 
indices, total leukocyte (or white blood cell [WBC]) count including 
differential, and platelet count with mean platelet volume, activated partial 
thromboplastin time (aPTT), prothrombin time (PT), international normalized 
ratio (INR) 
Serum Chemistry 
 
Electrolytes 
Sodium (Na), potassium (K), chloride, bicarbonate 
Renal function 
Blood urea nitrogen (BUN), creatinine (Cr) 
Liver functiona 
ALT, AST, ALP, total, direct, and indirect bilirubin (TBL, DBL, IBL), 
gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH) 
Pancreatic function 
Lipase and amylase 
Othera 
(selected tests at Week 
6 and Week 10) 
Calcium (Ca), magnesium (Mg), phosphorus (P), total proteina, albumina, 
globulins, glucose, uric acid, creatine phosphokinase (CK)a, cholesterol (total 
and fractionated) and triglycerides  
Urinalysis 
Appearance, bilirubin, color, ketones, glucose, leukocyte esterase, nitrites, 
pH, blood, protein  
a Visits on Week 6 and Week 10 need random blood draws. Participants can be fasting or non-fasting and only the 
following laboratory tests will be performed at those visits: Hematology and Coagulation, Liver function, and 
Other (Total protein, albumin, and CK) 
 
Clinical laboratory test values will be considered potentially clinically significant (PCS) 
if they meet either the lower-limit or higher-limit PCS criteria listed in Table 11.2-2. A 
listing of patients with PCS postbaseline values will be provided, including the 
participant identification (PID) number, baseline, and all postbaseline (including 
non-PCS) values. 
Table 11.2-2 
Criteria for Potentially Clinically Significant Laboratory Results 
Parameter 
Unit 
Lower Limit 
Higher Limit 
CHEMISTRY 
Albumin 
g/dL 
  ≤ 2.0  
 ≥ 7.1 
Alanine aminotransferase 
U/L 
— 
≥ 3 x ULN 
Alkaline phosphatase  
U/L 
— 
> 2 x ULN 


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Table 11.2-2 
Criteria for Potentially Clinically Significant Laboratory Results 
Parameter 
Unit 
Lower Limit 
Higher Limit 
Amylase  
U/L 
— 
> 1.5 x ULN 
Aspartate 
aminotransferase  
U/L 
— 
≥ 3 x ULN 
Bicarbonate  
mEq/L 
≤ 15 
≥ 40 
Bilirubin, total 
mg/dL 
— 
≥ 2.75 x ULN 
Calcium 
mg/dL 
< 7.0  
> 12.5  
Chloride 
mEq/L 
 ≤ 74  
≥ 131  
Cholesterol 
 mg/dL 
— 
> 400 
CPK  
U/L 
— 
> 2.5 x ULN 
Creatinine  
mg/dL 
— 
≥ 2 x ULN 
GGT  
U/L 
— 
≥ 2.5xULN 
Glucose 
 mg/dL 
< 55 
 > 250 
LDH  
U/L 
— 
≥ 2 x ULN 
Lipase 
U/L 
— 
> 2 x ULN 
   Magnesium 
mEq/L 
< 1.0 
> 2.5 
Potassium 
mEq/L 
< 3.0 
> 6.0 
Phosphorus 
mg/dL 
< 2.0 
≥ 9.4 
Protein, total  
g/dL 
≤ 3.9 
≥ 10.1  
Sodium 
mEq/L 
< 130 
> 155 
Triglycerides 
mg/dL 
— 
> 300 
BUN 
mg/dL 
— 
> 31  
Uric acid  
mg/dL 
— 
> ULN 
HEMATOLOGY 
Eosinophils, absolute cell 
count 
x10E3/uL 
— 
> ULN 
Eosinophils 
% 
— 
> ULN 
Neutrophils, absolute cell 
count 
x10E3/uL 
 < 1.5 
≥ 2 x ULN 
Neutrophils 
% 
< LLN 
> ULN 


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Table 11.2-2 
Criteria for Potentially Clinically Significant Laboratory Results 
Parameter 
Unit 
Lower Limit 
Higher Limit 
  Lymphocytes, absolute  
count 
x10E3/uL 
< 0.8 
> 4 
Lymphocytes  
% 
< LLN 
> ULN 
Haematocrit  
% 
< 20 
> 60 
Haemoglobin 
g/dL 
< 8.0 
≥ 19 
INR 
— 
— 
> 1.5 
Platelet count 
x10E3/uL  
< 100   
> 999      
White blood cell count 
x10E3/uL 
< 3.0    
≥ 22 
URINALYSIS 
pH 
— 
< LLN 
> ULN 
Specific gravity 
— 
< LLN 
> ULN 
Blood  
— 
— 
≥ 2+ 
Protein 
— 
— 
≥ 2+ 
Glucose 
— 
— 
≥ 2+ 
LLN = lower limit of normal value provided by the laboratory; ULN = upper limit of normal value provided by the 
laboratory. 
 
11.3 
VITAL SIGNS 
Descriptive statistics (mean, SD, median, Q1, Q3, minimum, and maximum) for vital 
signs (systolic and diastolic blood pressures, pulse rate, and weight) and changes from 
baseline values at each visit and at the end of study will be presented by treatment group. 
Vital sign values will be considered PCS if they meet both the observed-value criteria and 
the change-from-baseline criteria listed in Table 11.3-1. A listing of patients with PCS 
postbaseline values will be provided, including the PID number, baseline and all 
postbaseline (including non-PCS) values. 


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Table 11.3–1 
Criteria for Potentially Clinically Significant Vital Signs 
Parameter 
Flag 
Criteriaa 
Observed Value 
Change From Baseline 
Sitting systolic blood 
pressure, mm Hg 
High 
≥ 180 
Increase of ≥ 20 
Low 
≤ 90 
Decrease of ≥ 20 
Sitting diastolic blood 
pressure, mm Hg 
High 
≥ 105 
Increase of ≥ 15 
Low 
≤ 50 
Decrease of ≥ 15 
Sitting pulse rate, bpm 
High 
≥ 120 
Increase of ≥ 15 
Low 
≤ 50 
Decrease of ≥ 15 
Weight, kg 
High 
— 
Increase of ≥ 7% 
Low 
— 
Decrease of ≥ 7% 
a A postbaseline value is considered potentially clinically significant if it meets both the observed-value 
and the change-from-baseline criteria. 
bpm = beats per minute. 
11.4 
ELECTROCARDIOGRAM 
Descriptive statistics (mean, SD, median, Q1, Q3, minimum, and maximum) for ECG 
parameters (heart rate, RR interval, PR interval, QRS interval, QT interval, and QTc) and 
changes from baseline values at each assessment timepoint to the end of study will be 
presented by treatment group.  
Electrocardiographic parameter values are considered PCS if they meet or exceed the 
higher-limit PCS criteria listed in Table 11.4–1. A listing of patients with PCS 
postbaseline values will be provided, including the PID number, baseline, all postbaseline 
(including non-PCS) values, and change from baseline. 
Table 11.4–1 
Criteria for Potentially Clinically Significant Electrocardiograms 
Parameter 
Unit 
Higher Limit 
QRS interval 
msec 
≥ 150 
PR interval 
msec 
≥ 250 
QTc  
msec 
>500 or Change from baseline (increase of 
> 60) 
QTc = QT interval corrected for heart rate. 


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. 
13.0 
INTERIM ANALYSIS 
No formal interim analyses are planned for this study. 
14.0 
DETERMINATION OF SAMPLE SIZE 
A responder is a participant with ≥ 75% reduction in PASI from baseline to Week 16. 
The sample size of 200 participants (50 per treatment arm) was selected to provide 90% 
power to detect a response rate difference of 27% between each AGN-242428 and 
placebo group at Week 16, with an assumed response rate of 6% in the placebo group, a 
5% type 1 error rate, and 20% dropout rate. 
15.0 
STATISTICAL SOFTWARE 
Statistical analyses will be performed using 
 
. 
16.0 
DATA HANDLING CONVENTIONS 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 


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If the assessment date is on or after the date of the first dose of study treatment, the 
study day is calculated by assessment date – date of the first dose of study treatment + 1. 
If the assessment date is before the date of the first dose of study treatment, the study day 
is calculated by assessment date – date of the first dose of study treatment. Therefore, a 
negative day indicates a day before the start of the study treatment. If the assessment date 
is unavailable, use the visit date instead. 
If a participant has 2 or more visits within the same window, the last visit with a 
nonmissing value will be used for analysis. 
16.2 
DERIVED VARIABLES 
Not applicable. 


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16.3 
REPEATED OR UNSCHEDULED ASSESSMENTS OF SAFETY 
PARAMETERS 
If a participant has repeated assessments before the start of the first treatment, the results 
from the final nonmissing assessment made prior to the start of the study treatment will 
be used as baseline. If end-of-study assessments are repeated or if unscheduled visits 
occur, the last nonmissing postbaseline assessment will be used as the end-of-study 
assessment for generating summary statistics. If more than one lab assessment is 
conducted on the same day during the study, the last nonmissing value on that day will be 
used for analysis. If more than one ECG assessment is conducted on the same day during 
the study, the value corresponding to the scheduled visit on the CRF will be used for 
analysis as the valid reading will be assigned the scheduled visit label as opposed to 
being labeled as an unscheduled visit.  
16.4 
MISSING SEVERITY ASSESSMENT FOR ADVERSE EVENTS 
If severity is missing for an AE that started before the date of the first dose of study 
treatment, an intensity of mild will be assigned. If severity is missing for an AE that 
started on or after the date of the first dose of study treatment (based on date, and time if 
known), an intensity of severe will be assigned. The imputed values for severity 
assessment will be used for the incidence summary; the values will be shown as missing 
in the data listings. 
16.5 
MISSING CAUSAL RELATIONSHIP TO STUDY TREATMENT 
FOR ADVERSE EVENTS 
If the causal relationship to study treatment is missing for an AE that started before first 
dose of study treatment, a causality of no will be assigned. If the causal relationship to the 
study treatment (per the investigator) is missing for an AE that started on or after the date 
of the first dose of study treatment (based on date, and time if known), a causality of yes 
will be assigned. The imputed values for causal relationship to study treatment will be 
used for the incidence summary; the values will be shown as missing in the data listings. 
16.6 
MISSING DATE INFORMATION FOR ADVERSE EVENTS 
Missing/incomplete AE start dates will be imputed on a case by case basis. 


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Imputed partial AE dates will only be used to determine if an AE is a TEAE. All partial 
dates will be listed “as is” in the data listings. 
16.7 
MISSING DATE INFORMATION FOR PRIOR OR 
CONCOMITANT MEDICATIONS 
For prior or concomitant medications, including incomplete (ie, partly missing) start 
dates and/or stop dates will not be imputed.  
If start or stop dates for medications are only partially reported but can be classified as 
prior to Day 1, then the medications will be included as prior medications. 
If start or stop dates for medications are only partially reported and cannot be definitively 
classified as having stopped prior to Day 1, then the medications will be included as 
concomitant medications. 
16.8 
CHARACTER VALUES OF CLINICAL LABORATORY 
PARAMETERS 
If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table because, for example, a character string is reported for a parameter of the 
numeric type, a coded value must be appropriately determined for use in the statistical 
analyses. The actual values, however, as reported in the database will be presented in the 
data listings. 
Table 16.8–1 shows examples of how some possible laboratory results should be coded 
for the analysis. 


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Table 16.8–1 
Examples of Coding Special Character Values for Clinical Laboratory 
Parameters 
Laboratory Test, 
SI Unit 
Possible Laboratory Results 
Coded Value for Analysis 
CHEMISTRY 
ALT, U/L 
< 5 
5 
AST, U/L 
< 5 
5 
Bilirubin, total, µmol/L 
< 2 
2 
URINALYSIS 
Glucose, mmol/L 
= OR > 55, ≥ 55, > 0 
Positive 
≤ 0, negative 
Negative 
pH 
> 8.0, ≥ 8.0 
8.0 
≥ 8.5 
8.5 
Protein 
= OR > 3.0, ≥ 3.0, > 0 
Positive 
≤ 0 
Negative 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; SI = Le Système International d’Unités 
(International System of Units). 
 


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17.0 
REFERENCES 
Federal Register 1999: Volume 64(98); Friday, May 21, 1999 
https://www.gpo.gov/fdsys/pkg/FR-1999-05-21/html/99-12643.htm 


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Date (DD/MMM/YYYY)/Time (PT) 
Signed by: 
Justification 
  
 
           
 
            
 
           
 
            
 
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
1957-201-001 Statistical Analysis Plan