Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of Risankizumab for Moderate-to-severe Plaque Psoriasis
Phase: PHASE2
Conditions: Psoriasis
Sponsor: Oregon Medical Research Center

 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
1 
ClinicalTrials.gov Submission 
Official Title: Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of 
Risankizumab for Moderate-to-Severe Plaque Psoriasis (Knockout) 
NCT Number: NCT05283135 
Document Date: Version 6 Dated 22FEB2024 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
2 
DECREASING RESIDENT MEMORY T CELLS WHILE INCREASING CLINICAL 
DURABILITY: HIGHER INDUCTION DOSES OF RISANKIZUMAB FOR 
MODERATE-TO-SEVERE PLAQUE PSORIASIS (KNOCKOUT) 
 
Protocol Number: B20-433  
Principal Investigator: Benjamin D. Ehst, MD, PhD 
IND Sponsor: Oregon Medical Research Center 
Funded by: AbbVie Inc. 
Version 6:   22 FEB 2024 
 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Throughout 
Protocol 
 
Format editing and update to both clinical 
site location and Principal Investigator. 
 
Oregon Medical Research Center 
relocated to a new address, and Dr. 
Andrew Blauvelt is retiring on 
05MAR2024 and Dr. Ehst is assuming 
the role of Principal Investigator. 
 

  
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
3 
Table of Contents 
 
STATEMENT OF COMPLIANCE ............................................................................................................................. 5 
1. 
PROTOCOL SUMMARY ............................................................................................................................... 5 
1.1. 
Synopsis ................................................................................................................................................ 5 
1.2. 
Schema ................................................................................................................................................. 7 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 8 
2. 
INTRODUCTION .......................................................................................................................................... 10 
2.1. 
Study Rationale .................................................................................................................................. 10 
2.2. 
Background......................................................................................................................................... 10 
2.3. 
Risk/Benefit Assessment .................................................................................................................. 11 
2.3.1. 
Known Potential Risks ................................................................................................... 11 
2.3.2. 
Known Potential Benefits .............................................................................................. 13 
2.3.3. 
Assessment of Potential Risks and Benefits .............................................................. 13 
3. 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 14 
4. 
STUDY DESIGN ........................................................................................................................................... 15 
4.1. 
Overall Design .................................................................................................................................... 15 
4.2. 
Scientific Rationale for Study Design.............................................................................................. 15 
4.3. 
Justification for Dose ......................................................................................................................... 15 
4.4. 
End of Study Definition ..................................................................................................................... 16 
5. 
STUDY POPULATION ................................................................................................................................ 16 
5.1. 
Inclusion Criteria ................................................................................................................................ 16 
5.2. 
Exclusion Criteria ............................................................................................................................... 16 
5.3. 
Lifestyle Considerations .................................................................................................................... 17 
5.4. 
Screen Failures .................................................................................................................................. 17 
5.5. 
Strategies for Recruitment and Retention ...................................................................................... 17 
5.6. 
Contraception recommendations .................................................................................................... 17 
6. 
STUDY INTERVENTION ............................................................................................................................ 18 
6.1. 
Study Intervention(s) Administration ............................................................................................... 18 
6.1.1. 
Study Intervention Description ..................................................................................... 18 
6.1.2. 
Dosing and Administration ............................................................................................ 18 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 18 
6.2.1. 
Acquisition and accountability ...................................................................................... 18 
6.2.2. 
Formulation, Appearance, Packaging, and Labeling ................................................ 18 
6.2.3. 
Product Storage and Stability ....................................................................................... 18 
6.2.4. 
Preparation ...................................................................................................................... 19 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 19 
6.4. 
Study Intervention Compliance ........................................................................................................ 19 
6.5. 
Concomitant Therapy ........................................................................................................................ 19 
6.5.1. 
Rescue Medicine ............................................................................................................ 19 
7. 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 20 

  
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
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7.1. 
Discontinuation of Study Intervention ............................................................................................. 20 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................................................... 20 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 20 
8.1. 
Efficacy Assessments ....................................................................................................................... 20 
8.2. 
Safety and Other Assessments ....................................................................................................... 22 
8.3. 
Adverse Events and Serious Adverse Events ............................................................................... 23 
9. 
STATISTICAL CONSIDERATIONS .......................................................................................................... 25 
9.1. 
Statistical Hypotheses ....................................................................................................................... 25 
9.2. 
SAMPLE SIZE DETERMINATION .................................................................................................. 25 
9.3. 
ANALYSIS SET ................................................................................................................................. 26 
9.4. 
HANDLING OF POTENTIAL INTERCURRENT EVENTS .......................................................... 26 
9.5. 
METHODS FOR ANALYSIS OF DEMOGRAPHICS AND BASELINE 
CHARACTERISTICS............................................................................................................................................ 26 
9.6. 
METHODS FOR ANALYSIS OF PRIMARY OUTCOMES .......................................................... 27 
9.7. 
METHODS FOR ANALYSIS OF SECONDARY OUTCOMES ................................................... 27 
9.8. 
METHODS FOR ANALYSIS OF SAFETY OUTCOMES ............................................................. 27 
9.9. 
MISSING DATA HANDLING ............................................................................................................ 27 
9.10. 
SENSITIVITY ANALYSES ............................................................................................................... 27 
9.11. 
MULTIPLICITY ADJUSTMENT ....................................................................................................... 27 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 28 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 28 
10.1.1. 
Informed Consent Process ........................................................................................... 28 
10.1.2. 
Confidentiality and Privacy ........................................................................................... 28 
10.1.3. 
Future Use of Stored Specimens and Data ............................................................... 29 
10.1.4 
Key Roles and Study Governance .............................................................................. 29 
10.1.5 
Data Handling and Record Keeping ............................................................................ 29 
10.1.6 
Protocol Deviations ........................................................................................................ 30 
10.1.7 
Publication and Data Sharing Policy ........................................................................... 30 
10.2. 
Abbreviations ...................................................................................................................................... 31 
10.3 
Protocol Amendment History ........................................................................................................... 34 
11 
REFERENCES ............................................................................................................................................. 35 
 
 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
5 
STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the Clinical Trial 
Agreement between Oregon Medical Research Center and AbbVie Inc. The Principal Investigator will 
assure that no deviation from, or changes to the protocol will take place without prior agreement from 
Oregon Medical Research Center (the Investigational New Drug (IND) sponsor), AbbVie (the funder of 
the study), and documented approval from the Institutional Review Board (IRB), except where necessary 
to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of 
this study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, Informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
1.  
PROTOCOL SUMMARY 
1.1. SYNOPSIS  
Title: 
“Decreasing resident memory T cells while increasing clinical durability: 
higher induction doses of risankizumab for moderate-to-severe plaque 
psoriasis (KNOCKOUT)” 
 
Study Description: 
 
This is a pilot study that explores whether higher induction doses of 
risankizumab (2x and 4x standard induction doses) can more effectively 
target resident memory (Trm) cells within psoriatic lesions, and whether 
more profound knock-down of Trm is associated with higher levels of 
complete clearance (i.e., PASI 100) and for longer periods of time. 
 
Objectives: 
 
Primary Objective: to determine whether the reduction in the number 
and/or effector function of epidermal CD8+CD103+ Trm cells at Week 52 
(compared to baseline numbers) in psoriasis patients treated with 4X 
standard induction doses of risankizumab (600 mg at Weeks 0, 4, and 16) 
is greater when compared to psoriasis patients treated with 2X standard 
induction doses of risankizumab (300 mg at Weeks 0, 4, and 16). 
 
Secondary Objectives:  
1) to compare the percentage of patients with PASI 100 (complete 
clearance) at Weeks 28, 40, 52 and 100 in patients receiving 4X standard 
induction doses of risankizumab vs. those receiving 2X standard induction 
doses of risankizumab and  
2) to compare safety events over 100 weeks in patients receiving 4X 
standard induction doses of risankizumab vs. those receiving 2X standard 
induction doses of risankizumab 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
6 
 
Endpoints: 
 
Primary Endpoint: change from baseline in number and/or effector 
function of epidermal CD8+CD103+ Trm cells at Week 52 in psoriasis 
patients treated with 4X standard induction doses of risankizumab (600 
mg at Weeks 0, 4, and 16) or 2X standard induction doses of risankizumab 
(300 mg at Weeks 0, 4, and 16). 
 
Secondary Endpoints:  
1) PASI 100 (complete clearance) response at Weeks 28, 40, 52, and 
100 in patients receiving 4X standard induction doses of 
risankizumab or those receiving 2X standard induction doses of 
risankizumab and  
2) safety events over 100 weeks in patients receiving 4X standard 
induction doses of risankizumab or those receiving 2X standard 
induction doses of risankizumab. 
 
Additional endpoints:  
1) Change from baseline in PASI and BSA at various timepoints, PASI 
75 response, PASI 90 response, PASI 100 response, and sPGA 0/1 
response at various study timepoints  
2) Change from baseline in DLQI at Weeks 28 and 52 and DLQI 0/1 
response at Weeks 28 and 52 
 
Study Population: 
 
20 patients with moderate-to-severe plaque psoriasis, males and females, 
18 years of age and older, good general health, Portland metropolitan area 
Phase: 
2 
Description of 
Sites/Facilities Enrolling 
Participants: 
Single center: Oregon Medical Research Center in Portland, Oregon 
 
 
Description of Study 
Intervention: 
 
This is a single-center, randomized, interventional, Phase 2 study 
(KNOCKOUT) consisting of a 52-week double-blind period followed by a 
48-week unblinded extension comparing tissue and clinical effects of 4X 
standard induction doses of risankizumab vs. 2X standard induction doses 
of risankizumab in patients with moderate-severe plaque psoriasis.  
Twenty patients with moderate-to-severe plaque psoriasis will be 
randomized in a 1:1 manner to receive either risankizumab 600 mg (4X 
dosing) or 300 mg (2X dosing), subcutaneous (SC), at Weeks 0, 4, and 16. 
All patients will receive four SC injections at Weeks 0, 4, and 16 (into right 
arm, left arm, right thigh, left thigh) by an unblinded pharmacist. For 
patients randomized into the highest induction dose arm, each shot will 
contain 150 mg of risankizumab; for patients randomized into the 2X 
induction dose arm, two shots will contain 150 mg of risankizumab each 
and 2 shots will contain placebo (sterile saline). 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
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Skin biopsies of lesional and/or non-lesional skin will be obtained at Week 
0, and an additional skin biopsy of lesional skin will be obtained at Week 
52. Lesional is defined as current lesion or prior lesional area. These 
samples will beprocessed for immunohistochemical staining and RNA seq 
analysis. Psoriasis severity clinical assessments (PASI, sPGA, BSA) and 
safety assessments (vital signs, history) will be assessed at screening and 
Weeks 0, 2, 4, 8, 12, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 
and 100 (to assess secondary endpoints). Routine labs will be performed at 
Screening and at Weeks 4, 8, 22, and 52. 
 
Study Duration: 
 
30 months 
 
Participant Duration: 
 
Screening period (up to 4 weeks) and then 100 weeks 
1.2. SCHEMA 
 
Note: screening visit to occur 0-4 weeks prior to randomization visit at Week 0. Double blinded period is 
Week 0 through Week 52, and patients will be additionally followed through week 100, post the double-
blind study period. 
 
 
*Patients will also be seen every 6 weeks, from Week 52 to Week 100 and assessed for safety 
and maintenance of clinical efficacy. 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
8 
1.3. SCHEDULE OF ACTIVITIES (SOA) 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
 
Day -28 to Day –1 
Day 0/BL/Wk 0 
Day 14/Wk 2 
Day 28/Wk 4 
Day 56/Wk 8 
Day 84/Wk 12 
Day 112/Wk 16 
Day 154/Wk 22 
Day 196/Wk 28 
Day 238Wk 34 
Day 280/Wk 40 
Day 322/Wk 46 
Day 364/Wk 52 
Day 406/Wk 58 
Day 448/Wk 64 
Day 490/Wk 70 
Day 532/Wk 76 
Day 574/Wk 82 
Day 616/Wk 88 
Day 658/Wk 94 
Day 700/Wk 100 
/Early Disc 
Visit window 
Plus or minus 7 days 
Interviews and Questionnaires 
Subject information and 
informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriasis history 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug, tobacco (including 
e-cigarettes), and alcohol 
history 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE assessment 
 
            
Prior/concomitant 
therapy 
 
            
TB screening 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Reported 
Outcomes (DLQI) 
 
 
 
 
 
 
 
 
 
 
 
 

 
Suicidal thoughts or 
actions screening (CSSRS) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Labs and Examinations 
Height 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
 
            
Complete physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 

 
Targeted physical 
examination 
 
 
 
 
  
 
             
 
Urine pregnancy test 
(females of childbearing 
potential only) 
 
 
 
         


 
TB test (QuantiFERON-TB 
Gold test) 
4mL/0.8 teaspoon of 
blood 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HBV, and HCV 
screening 
8mL/1.6 teaspoons of 
blood 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
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Day -28 to Day –1 
Day 0/BL/Wk 0 
Day 14/Wk 2 
Day 28/Wk 4 
Day 56/Wk 8 
Day 84/Wk 12 
Day 112/Wk 16 
Day 154/Wk 22 
Day 196/Wk 28 
Day 238Wk 34 
Day 280/Wk 40 
Day 322/Wk 46 
Day 364/Wk 52 
Day 406/Wk 58 
Day 448/Wk 64 
Day 490/Wk 70 
Day 532/Wk 76 
Day 574/Wk 82 
Day 616/Wk 88 
Day 658/Wk 94 
Day 700/Wk 100 
/Early Disc 
Visit window 
Plus or minus 7 days 
Hematology, clinical 
chemistry, and urinalysis  
8mL/1.6 teaspoons of 
blood 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PASI 
 
            
BSA 
 
            
sPGA 
 
            
Skin biopsies (6-mm punch 
samples) 
 
 
 
 
 
 
 
 
 
 
 
 

 
Treatment 
Randomization/drug 
assignment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study drug to 
subjects 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In-clinic post-dose 
monitoring (30 minutes) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
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2.  
INTRODUCTION 
2.1. STUDY RATIONALE 
We postulate that risankizumab, an anti-IL-23 biologic used to treat moderate-to-severe plaque 
psoriasis, may lead to high levels of prolonged skin clearance due to an effect on resident memory T 
(Trm) cells. Here, we describe a pilot study that explores whether higher induction doses of 
risankizumab (4X and 2X standard induction doses) can more effectively target Trm cells within psoriatic 
lesions, and whether more profound knock-down of Trm cells is associated with higher levels of 
complete clearance (i.e., PASI 100) and for longer periods of time. 
2.2. BACKGROUND 
Trm cells can develop within tissues in response to certain pathogens.1 They are long-lived and 
responsible for tissue protection from re-exposure to the original pathogen. When re-activated by re-
exposure to that pathogen, Trm cells amplify immune responses by recruiting additional immune cells 
from blood. Interestingly, Trm cells are also found in skin previously affected by active psoriasis, vitiligo, 
and fixed drug reaction skin, and are now believed to be the cells responsible for recurrences of 
psoriasis.2-6 In psoriatic skin, these cells are CD8+CD103+ epidermal T cells that produce IL-17A.2-6 It is 
unknown whether psoriatic Trm cells are under the control of IL-23, but recently, guselkumab, an IL-23 
blocker used to treat psoriasis, was shown to reduce Trm cells in skin after 6 months of dosing.7 Of note, 
similar IL-17A-producing cells (Th17 and Tc17 effector cells) in psoriasis are dependent upon IL-23 for 
survival.8 
Many excellent treatments exist for the treatment of patients with moderate-to-severe plaque psoriasis. 
Disease, however, recurs following withdrawal of these treatments. risankizumab, an anti-IL-23 biologic, 
is highly effective and safe for treating plaque psoriasis.9-11 The standard dose for this drug is 150 mg at 
Weeks 0 and 4, and then 150 mg every 12 weeks after two induction doses. Approximately 80% of 
patients reach PASI 90 and approximately 60% reach PASI 100 at 1 year, with few-to-no side effects.9-11 
In addition, the IMMhance study revealed that some patients undergoing risankizumab withdrawal 
demonstrated prolonged skin clearance long after their last dose; more specifically, 10-15% of patients 
with completely clear skin after only 3 risankizumab doses (at Weeks 0, 4, and 16) maintained 
completely clear skin for up to 1 year before psoriasis recurred.11 The combination of these prior clinical 
results suggests there is a need to scientifically explore the biologic basis of the duration of 
risankizumab’s therapeutic activity; specifically, there is a need to test higher doses at weeks 0, 4, and 
16 to determine whether more complete skin clearance at one year can be achieved. 
 
 
 

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11 
2.3. RISK/BENEFIT ASSESSMENT 
2.3.1. KNOWN POTENTIAL RISKS 
 
Risankizumab (Skyrizi) is FDA-approved for patients with moderate to severe plaque psoriasis. This 
information is derived largely from the product insert and is also the language placed into the patient 
informed consent form (ICF). 
 
Risankizumab has been given to healthy volunteers and patients with psoriasis (PsO), erythrodermic 
psoriasis (EP), generalized pustular psoriasis (GPP), psoriatic arthritis (PsA), Crohn’s disease (CD), 
ankylosing spondylitis, hidradenitis suppurativa (HS), and asthma. risankizumab has been given either by 
intravenous infusion (IV, slowly injected into a vein in the arm) or by subcutaneous injection (SC, 
injection into the deepest skin layer).  It has been tested in single doses as high as 1,800 mg IV and 300 
mg SC and in repeated doses as high as 1,200 mg IV and 180 mg SC. No new or different side effects 
were seen with higher doses of risankizumab. 
 
Taking the study drug in this study may cause you to have one or more of the side effects as listed 
below. 
 
Over 3,000 patients with psoriasis have been treated with risankizumab SC, predominantly with the 150 
mg dose. The rates of overall side effects and serious side effects were similar between risankizumab 
treatment and placebo treatment (an inactive substance). No new safety risks have been observed with 
risankizumab compared to the other antibody treatments that affect the immune system and were 
investigated in the risankizumab clinical development. In clinical trials that compared risankizumab to 
placebo and either ustekinumab or adalimumab, serious side effects occurred in 2.4% for the 
risankizumab group compared to 4.0% for the placebo group, 5.0% for the ustekinumab group, and 3.0% 
for the adalimumab group. 
 
In a Phase 2 completed psoriatic arthritis study, 185 patients received either 75 mg or 150 mg of 
risankizumab SC or placebo. The most frequent side effects reported in patients who received 
risankizumab were viral upper respiratory tract infection (common cold caused by a virus) (17.5%), 
upper respiratory tract infection (common cold) (5.6%), and headache (5.6%). 
 
In a Phase 2 completed CD study, 121 patients received 200 mg or 600 mg risankizumab or placebo by 
IV. Overall, the number of patients who reported side effects was similar between patients treated with 
risankizumab and patients treated with placebo. The most frequently reported side effects (equal to 5% 
or more of patients) in the risankizumab treatment group were arthralgia (joint pain) (17.1%), nausea 
(15.9%), headache (13.4%), abdominal pain (12.2%), asthenia (lack of energy) (7.3%), pyrexia (fever) 
(7.3%), vomiting (7.3%), and diarrhea (6.1%). 
 
Based on review of all the safety information to date, the following are known risks with risankizumab 
use: 
 
Very common (10% or more): may affect more than 1 in 10 people 
 
▪ 
upper respiratory infections with symptoms such as sore throat and stuffy nose (13%) 

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KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
12 
Common (1% or more and less than 10%): may affect up to 1 in 10 people 
▪ 
feeling tired (2.5%) 
▪ 
fungal skin infection (1.1%) 
▪ 
injection site reactions (1.5%) 
▪ 
headache (3.5%) 
 
Uncommon (0.1% or more and less than 1%): may affect up to 1 in 100 people 
 
▪ 
Infection of hair follicles (seen as small raised red bumps on the skin) 
 
Skin Biopsy Risk: You may have discomfort when the local anesthetic (numbing medicine) is injected to 
numb the area. The biopsy procedure may cause you to have a local infection that can be treated with 
an antibiotic. Other risks may include an allergic reaction to the local anesthetic. Symptoms of an allergic 
reaction are rash, difficulty breathing, and lightheadedness. If you think you are having an allergic 
reaction, call the study doctor right away. You may also have some bleeding after the biopsy. After the 
anesthesia wears off, there may be some temporary soreness at the biopsy sites. Biopsy wounds usually 
heal with a small scar, but sometimes a raised scar or visible lump may result. There is also a small 
chance that this biopsy may result in a wound that does not heal or that heals very slowly over time. 
Rarely, infection, bleeding, nerve damage, and darkening and lightening of the biopsied area may occur. 
 
Areas of Safety Interest: 
Infections: Drugs that affect the body’s immune system may increase the risk of infections, including 
tuberculosis (TB). No cases of active TB have been reported in patients treated with risankizumab. You 
will be screened for signs of active infection before you start on risankizumab. Talk to your study doctor 
before and during use of risankizumab if you: 
• 
currently have an infection or if you have an infection that keeps coming back. 
• 
have TB. 
• 
have recently received or plan to receive an immunization (vaccine); you should not be given 
certain types of vaccines while using risankizumab. 
 
Injection Site Reactions: Injection of study drug under the skin could result in redness, pain, swelling, or 
hardness at the site of the injection. Also, bleeding or bruising at the injection site may occur. Most 
injection site reactions are not severe and resolve without any treatment, but can be uncomfortable for 
a few hours to a few days. 
 
Liver Disease: A serious adverse reaction of drug-induced liver injury in conjunction with a rash that 
required hospitalization was reported in a patient with Crohn’s disease following two 600 mg 
intravenous doses of risankizumab. The liver test abnormalities resolved following administration of 
steroids. Risankizumab was subsequently discontinued. Patients with liver cirrhosis should not  
be treated with risankizumab. During risankizumab treatment, prompt investigation of the cause of liver 
enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Stopping 
treatment is recommended, if drug-induced liver injury is suspected. Patients should seek immediate 
medical attention if they experience symptoms suggestive of liver disease. 
 
Other Possible Risks: 
Some drugs that affect the immune response have been associated with side effects such as serious 
allergic reactions, and possible increased risk of malignancy (cancer). 

KNOCKOUT STUDY 
 
KNOCKOUT STUDY – VERSION 6, 22FEB2024 
 
13 
 
Allergic Reactions: All drugs have a potential risk of an allergic reaction. Allergic reactions may vary from 
mild (rash, hives, itching) to severe reactions such as anaphylaxis (which may include difficulty 
breathing, swelling of the face or throat, low blood pressure, or loss of consciousness). A severe allergic 
reaction requires immediate medical treatment and could result in permanent disability or death. It is 
important to tell your study doctor about any past allergic reactions that you may have had to other 
drugs including antibody drugs (which are usually given by IV or injection under the skin). If you seek 
medical care for a possible allergic reaction, please request the treating health care provider to contact 
the study physician. Serious hypersensitivity reactions, including anaphylaxis, have been reported with 
use of risankizumab. 
 
Malignancy (cancer): When an immune system pathway is blocked, there is a possibility of a decreased 
immune defense against malignancies. In the completed studies to date, risankizumab has not been 
associated with an increased risk of malignancies, but the risk with long term therapy is not known. 
 
Cardiovascular Events: Patients with inflammatory diseases such as psoriasis, psoriatic arthritis and 
inflammatory bowel disease have an increased risk of major cardiovascular events (such as heart 
attacks, strokes, or cardiovascular death). In the completed psoriasis studies to date, risankizumab has 
not shown an increased risk of these events. However, any new or worsening signs or symptoms such as 
chest, neck or arm pain, shortness of breath, sensation of rapid heart rate, new visual symptoms or 
muscle weakness should be immediately reported to your study site and/or primary health care 
provider. 
 
There is no antidote to risankizumab.  Any side effects occurring as a result of risankizumab will be 
treated symptomatically. 
2.3.2. KNOWN POTENTIAL BENEFITS  
Risankizumab, an anti-IL-23 biologic, is highly effective and safe for treating plaque psoriasis.9-11 The 
standard dose for this drug is 150 mg at Weeks 0 and 4, and then 150 mg every 12 weeks after two 
induction doses. Approximately 80% of patients reach PASI 90 and approximately 60% reach PASI 100 at 
1 year, with few-to-no side effects.9-11 In addition, the IMMhance study revealed that some patients 
undergoing risankizumab withdrawal demonstrated prolonged skin clearance long after their last dose.11  
2.3.3. ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
Doses of risankizumab higher than standard dosing used for psoriasis have been used to treat other 
diseases, such as Crohn’s disease. No new or different side effects were seen with higher doses of 
risankizumab in these studies. Thus, the side effect profile in the current proposed study is expected to 
be favorable. 
 
When testing higher doses of risankizumab, as described here, it is possible that efficacy will be higher 
than reported with standard dosing. It is also possible that disease remission following drug withdrawal 
will be longer than remission reported following drug withdrawal after standard dosing of risankizumab. 
 
 

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14 
3. OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary Objective: to determine 
whether the reduction in the 
number and/or effector function of 
epidermal CD8+CD103+ Trm cells 
at Week 52 (compared to baseline 
numbers) in psoriasis patients 
treated with 4X standard induction 
doses of risankizumab (600 mg at 
Weeks 0, 4, and 16) is greater when 
compared to psoriasis patients 
treated with 2X standard induction 
doses of risankizumab (300 mg at 
Weeks 0, 4, and 16). 
Primary Endpoint: change from 
baseline in number and/or effector 
function of epidermal CD8+CD103+ 
Trm cells at Week 52 in psoriasis 
patients treated with 4X standard 
induction doses of risankizumab (600 
mg at Weeks 0, 4, and 16) or 2X 
standard induction doses of 
risankizumab (300 mg at Weeks 0, 4, 
and 16). 
Trm cells are the primary 
cells within psoriatic lesions 
(and healed skin) that are 
responsible for psoriasis 
recurrences after skin 
lesions have cleared. 
Targeting these cells, as 
proposed here, may lead to 
prolonged remission of 
psoriasis. 
Secondary Objectives:  
1) to compare the percentage of 
patients with PASI 100 (complete 
clearance) at Weeks 28, 40, 52, and 
100 in patients receiving 4X 
standard induction doses of 
risankizumab vs. those receiving 2X 
standard induction doses of 
risankizumab and  
2) to compare safety events over 
100 weeks in patients receiving 4X 
standard induction doses of 
risankizumab vs. those receiving 2X 
standard induction doses of 
risankizumab. 
Secondary Endpoints:  
1)  PASI 100 (complete clearance) 
response at Weeks 28, 40, 52, and 
100 in patients receiving 4X standard 
induction doses of risankizumab or 
those receiving 2X standard induction 
doses of risankizumab and  
 
2) safety events over 100 weeks in 
patients receiving 4X standard 
induction doses of risankizumab or 
those receiving 2X standard induction 
doses of risankizumab. 
 
These are standard 
measures of efficacy and 
safety for psoriasis studies. 
Additional Objectives:  
1) to compare other standard 
measures of psoriasis efficacy in 
patients receiving 4X standard 
induction doses of risankizumab vs. 
those receiving 2X standard 
induction doses of risankizumab 
and  
2) to compare quality of life in 
patients receiving 4X standard 
induction doses of risankizumab vs. 
those receiving 2X standard 
induction doses of risankizumab. 
 
 
Additional Endpoints:  
1) Change from baseline in PASI 
and BSA at various 
timepoints, PASI 75 response, 
PASI 90 response, PASI 100 
response, and sPGA 0/1 
response at various 
timepoints   
2) Change from baseline in DLQI 
at Weeks 28 and 52 and DLQI 
0/1 response at Weeks 28 
and 52 
 
 
1) These are standard 
measures of efficacy for 
psoriasis studies. 
2) These are standard 
measures of quality of 
life for psoriasis studies. 

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15 
 
4. STUDY DESIGN 
4.1. OVERALL DESIGN 
The overall hypothesis for this study is to determine whether high-dose risankizumab, an anti-IL-23 
blocker approved for plaque psoriasis, can target Trm cells with psoriatic lesions, and whether a more 
marked reduction of Trm cells correlates with high levels of efficacy and longer periods of disease 
remission. 
In summary, this is single-center, randomized, interventional, Phase 2 study (KNOCKOUT) consisting of a 
52-week double-blind period followed by a 48-week unblinded extension comparing tissue and clinical 
effects of 4X standard induction doses of risankizumab vs. 2X standard induction doses of risankizumab 
in patients with moderate-severe plaque psoriasis. 
Twenty patients with moderate to severe plaque psoriasis will be randomized in a 1:1 manner to receive 
either risankizumab 600 mg (4X dosing) or 300 mg (2X dosing), SC, at Weeks 0, 4, and 16.  All patients 
will receive four SC injections at Weeks 0, 4, and 16 (into right arm, left arm, right thigh, left thigh) by an 
unblinded pharmacist.  For patients randomized into the highest induction dose arm, each shot will 
contain 150 mg of risankizumab; for patients randomized into the 2X induction dose arm, two shots will 
contain 150 mg of risankizumab each and 2 shots will contain placebo (sterile saline). 
Skin biopsies of lesional and/or non-lesional skin will be obtained at Week 0, and an additional skin 
biopsy of lesional skin will be obtained at Week 52. These samples will be processed for 
immunohistochemical staining and RNA seq analysis.  Psoriasis severity clinical assessments (PASI, sPGA, 
BSA) and safety assessments (vital signs, history) will be assessed at screening and Weeks 0, 2, 4, 8, 12, 
16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, and 100 (to assess secondary and additional 
endpoints).  Routine labs will be performed at Screening and at Weeks 4, 8, 22, and 52. 
4.2. SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We postulate that risankizumab, an anti-IL-23 biologic used to treat moderate to severe plaque 
psoriasis, may lead to high levels of prolonged skin clearance due to an effect on resident memory T 
(Trm) cells. Here, we describe a pilot study that explores whether higher induction doses of 
risankizumab (4X and 2X standard induction doses) can more effectively target Trm cells within psoriatic 
lesions, and whether more profound knock-down of Trm cells is associated with higher levels of 
complete clearance (i.e., PASI 100) and for longer periods of time. 
4.3. JUSTIFICATION FOR DOSE 
Risankizumab, an anti-IL-23 biologic, is highly effective and safe for treating plaque psoriasis.9-11 The 
standard dose for this drug is 150 mg at Weeks 0 and 4, and then 150 mg every 12 weeks after two 
induction doses. Approximately 80% of patients reach PASI 90 and approximately 60% reach PASI 100 at 
1 year, with few-to-no side effects.9-11 In addition, the IMMhance study revealed that some patients 
undergoing risankizumab withdrawal demonstrated prolonged skin clearance long after their last dose.11  

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16 
When testing higher doses of risankizumab (600 mg or 300 mg at Weeks 0, 4, and 16), as described here, 
it is possible that efficacy will be higher than reported with standard dosing. It is also possible that 
disease remission following drug withdrawal will be longer than remission reported following drug 
withdrawal after standard dosing of risankizumab. 
 
Indeed, doses of risankizumab higher than standard dosing used for psoriasis have been used to treat 
other diseases, such as Crohn’s disease. No new or different side effects were seen with higher doses of 
risankizumab in these studies. Thus, the side effect profile in the current proposed study is expected to 
be favorable. 
 
4.4. END OF STUDY DEFINITION 
 
Patients will be observed for 100 weeks after their first dose of risankizumab (84 weeks after their last 
dose of risankizumab). 
5. STUDY POPULATION 
5.1. INCLUSION CRITERIA 
 
1. Subject has provided written consent 
2. Subject has the ability to comply with all study visits and procedures 
3. Subject is at least 18 years of age 
4. Subject has chronic stable plaque psoriasis: 
a. For at least 6 months 
b. Severity of BSA 10 and PASI 12 
5. Female subjects of child-bearing potential must have a negative urine test at screening and 
baseline. Female subjects must be either postmenopausal, or permanently surgically sterile, or 
for women of child-bearing potential practicing at least one form of birth control (Section 5.6) 
5.2. EXCLUSION CRITERIA 
1. Breastfeeding or pregnant women, or women who plan to become pregnant during study 
period 
2. Participation in any other clinical trial 
3. Active infection with HIV, hepatitis B virus, or hepatitis C virus 
4. Active infection with tuberculosis or untreated latent tuberculosis 
5. History of known active cancer, other than non-melanoma skin cancer or cervical carcinoma in 
situ, in the past 3 years 
6. History of drug or alcohol abuse in the past 6 months, as per investigator’s assessment 
7. History of suicidal ideation or attempts in the past 6 months 
8. Presence of any concurrent illness, which in the opinion of the investigator, would place the 
patient at unnecessary safety risk during the trial or interfere with completion of the trial 
9. Treatment with topical medications for psoriasis in the past 2 weeks 
10. Treatment with oral medications for psoriasis in the past 4 weeks 
11. Phototherapy for psoriasis in the past 4 weeks 
12. Any prior treatment with risankizumab 

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17 
13. Treatment with biologic medications for psoriasis (other than risankizumab) in the past 4 
months 
 
5.3. LIFESTYLE CONSIDERATIONS 
 
None. 
 
5.4. SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or 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). Individuals who do not meet the 
criteria for participation in this trial (screen failure) may not be rescreened. Laboratory assessments 
used to determine subject eligibility may be repeated during the screening period before the subject is 
considered a screen failure. 
5.5. STRATEGIES FOR RECRUITMENT AND RETENTION 
 
OMRC, the sponsor of this trial, has a large database of psoriasis patients. We will recruit patients from 
this database as well as from general Google ads and referrals from community dermatologists.  
5.6. CONTRACEPTION RECOMMENDATIONS 
 
Female subjects of child-bearing potential must be ready and able to use highly effective methods of 
birth control, or subjects must have only vasectomized sexual partner(s) or be abstinent throughout the 
study.  Women of child-bearing potential are defined as: having experienced menarche, and are not 
postmenopausal (12 months with no menses without alternative medical cause), and are not 
permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy). 
The following is a list of accepted contraception methods: 
• 
Combined (estrogen and progesterone containing) hormonal contraception (oral, intravaginal, 
transdermal, injectable) associated with the inhibition of ovulation, initiated at least 1 month 
prior to study 
• 
Progestogen-only hormonal contraception (oral, injectable, implantable) associated with the 
inhibition of ovulation, initiated at least 1 month prior to study 
• 
Bilateral tubal occlusion/ligation 
• 
Vasectomized partner(s) 
• 
Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) 
• 
True abstinence (refraining from heterosexual intercourse when this is in line with the preferred 
and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable. 

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18 
6. STUDY INTERVENTION 
6.1. STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1. STUDY INTERVENTION DESCRIPTION 
The IB for risankizumab (Skyrizi), approved by the FDA for use in patients with moderate-to-severe 
psoriasis, is included with the IRB submission. 
6.1.2. DOSING AND ADMINISTRATION 
Twenty patients with moderate to severe plaque psoriasis will be randomized in a 1:1 manner to receive 
either risankizumab 600 mg (4X dosing) or 300 mg (2X dosing), SC, at Weeks 0, 4, and 16. All patients will 
receive four SC injections at Weeks 0, 4, and 16 (into right arm, left arm, right thigh, left thigh) by an 
unblinded pharmacist. For patients randomized into the highest induction dose arm, each shot will 
contain 150 mg of risankizumab; for patients randomized into the 2X induction dose arm, two shots will 
contain 150 mg of risankizumab each and 2 shots will contain placebo (sterile saline). 
6.2. PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1. ACQUISITION AND ACCOUNTABILITY 
 
All investigational product will be shipped to OMRC by AbbVie. Each supplied syringe will contain either 
150 mg of risankizumab or a matching placebo will be administered to patients at OMRC by an 
unblinded pharmacist at OMRC. All patients as well as physicians performing efficacy and safety 
assessments will be blinded to the treatment group (600 mg or 300 mg) during the initial 52-week 
period. Used syringes will be placed in sharps containers. The unblinded pharmacist will keep a record of 
administered drug. 
6.2.2. FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
SKYRIZI (risankizumab-rzaa) injection 150 mg/mL prefilled syringe and prefilled pen contain a sterile, 
preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each single-dose prefilled 
syringe or prefilled pen consists of a 1 mL glass syringe with a fixed 27- gauge ½ inch needle with needle 
guard. 
 
A copy of the drug labels prepared for this study are provided with this protocol for reference. 
6.2.3. PRODUCT STORAGE AND STABILITY 
 
Investigational product will be stored at 4 C (2-8 C range), in the original carton to protect from light, 
and in a locked and temperature-controlled refrigerator, one that only can be accessed by the unblinded 
pharmacist. 
 

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19 
6.2.4. PREPARATION 
 
Risankizumab injections will be prepared and administered in the clinic according to dosing instructions 
per the IB. 
 
• 
Before injecting, remove the carton with SKYRIZI from the refrigerator and without removing 
the prefilled pen or prefilled syringe(s) from the carton, allow SKYRIZI to reach room 
temperature out of direct sunlight (30 to 90 minutes for the prefilled pen and 15 to 30 minutes 
for the prefilled syringe(s)).  
• 
 Visually inspect SKYRIZI for particulate matter and discoloration prior to administration.  
o 
SKYRIZI 150 mg/mL is a colorless to yellow and clear to slightly opalescent solution. 
SKYRIZI 75 mg/0.83 mL is a colorless to slightly yellow and clear to slightly opalescent 
solution.  
o 
The solution may contain a few translucent to white particles. Do not use if the solution 
contains large particles or is cloudy or discolored. 
 
6.3. MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
To avoid unblinding of the patients and investigators as to treatment status during the double-blind 
period, all patients will be given 4 shots at Weeks 0, 4, and 16. An unblinded pharmacist will prepare and 
subcutaneously administer all drug and placebo (i.e., investigational product IP) to patients. This person 
will also be charged with accepting all IP shipments from AbbVie, storing IP in a locked refrigerator 
(maintained at 2-8 C), and recording all IP administrations to patients. IP will be delivered in the right 
arm, left arm, right thigh, and left thigh by the unblinded pharmacist at Weeks 0, 4, and 16. Monitoring 
will occur for 30 minutes post-dose. Patients will be shielded from viewing injections performed by the 
unblinded pharmacist. If an investigator believes the safety of a study subject is at risk due to study drug 
administrations, that investigator may unblind the treatment status to help direct/coordinate medical 
care of that patient. 
Once a subject reaches the end of the initial 52-week double blind period, the investigators, study staff 
and subject will be unblinded as to the treatment group. 
6.4. STUDY INTERVENTION COMPLIANCE 
 
6.5. CONCOMITANT THERAPY 
6.5.1. RESCUE MEDICINE 
 
No rescue medications or concomitant therapies for psoriasis will be allowed in this study. 
 
 

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20 
7. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. DISCONTINUATION OF STUDY INTERVENTION 
 
Subjects will be withdrawn from the study if, according to the investigator, safety of the subjects is 
compromised in any manner, or if subjects are no longer able to comply with study visits and 
procedures. Study subjects who are withdrawn will follow-up with their referring dermatologist, when 
possible. Study subjects who are withdrawn will not be replaced. 
 
The reason for withdrawal will be captured in the Case Report Form (CRF). 
 
7.2. PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request, including 
post the 52-week double blind period of the study. The reason for participant discontinuation or 
withdrawal from the study will be recorded on the CRF.  
8. STUDY ASSESSMENTS AND PROCEDURES 
8.1. EFFICACY ASSESSMENTS  
Clinical Assessments 
All assessments will be performed at Oregon Medical Research Center, P.C. At screening, Week 0, Week 
2, Week 4, and every visit thereafter until Week 100, the following will be done: 
1. Physical examination (*complete exam at screening, baseline, Week 4, Week 16, and Week 52; 
targeted exam at every other visit per Investigator discretion) 
2. Psoriasis Area and Severity (PASI) 
3. Body Surface Area (BSA) 
4. Static Physician’s Global Assessment (sPGA)  
5. DLQI (*at Weeks 0, 28, and 52 only) 
6. Vital signs (temperature, blood pressure, heart rate, respiratory rate, and weight) 
7. Past medical history, including past systemic treatments for psoriasis (*at screening visit only) 
8. Columbia Suicide Severity Rating Scale (*at screening visit only) 
9. Interim health history to assess for possible adverse events (*at all visits following the baseline 
visit) 
Laboratory Assessments 
At screening, Weeks 4, 8, 22, and 52, the following will be collected at Oregon Medical Research Center, 
P.C. and sent to a local laboratory: 

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21 
1. Complete blood count (CBC) w/differential 
2. Comprehensive metabolic panel 
3. Urinalysis 
4. Urine pregnancy test (*performed on-site only for women of child-bearing potential, at each 
visit up to Week 52, except Week 2) 
At screening only, the following will be collected at Oregon Medical Research Center, P.C. and sent to a 
local laboratory: 
1. HIV antibody 
2. Hepatitis B panel 
3. Hepatitis C antibody 
4. Quantiferon Gold 
At Weeks 0 and 52, the following will be collected at Oregon Medical Research Center, P.C. and shipped 
to the laboratory of Dr. Johann Gudjonsson at the University of Michigan: 
1. One 6 mm skin biopsy of lesional skin (at Weeks 0 and 52) and one 6 mm skin biopsy of peri-
lesional skin (at Week 0); both will be bisected and processed as follows: 
2. Single cell sequencing and CyTOF imaging: A 6 mm punch biopsy will be bisected with one half 
cryopreserved in CryoStor CS10 media (Millipore, Sigma) in a cryogenic vial, and the other 
formalin fixed for CyTOF imaging and IHC. The CryoStor CS10 media is an optimized preservation 
media, that is formulated to address the molecular and biological aspects of cells during the 
cryopreservation process thereby directly reducing the level of cryopreservation-induced 
delayed-onset cell death and improving post-thaw cell viability and function. Tissue will be 
stored at -80C until shipping and processing. At processing samples will be rapidly thawed in a 
water bath in a continuous agitation and placed onto 25mL of cold 1xHBSS (as described 
Guillaumet-Adkins A, Genome Biology, 45, 2017). Samples will be incubated in 0.4% dispase (Life 
Technologies) in Hank’s Balanced Saline Solution for 30 minutes. Epidermis and dermis are then 
separated. Epidermis is digested in 0.25% Trypsin-EDTA (Gibco) with 10U/mL DNase I (Thermo 
Scientific) for 1 hour at 37 °C, quenched with FBS (Atlanta Biologicals), and strained through a 70 
μM mesh. Dermis will be minced, digested in 0.2% Collagenase II (Life Technologies) and 0.2% 
Collagenase V (Sigma) in plain medium for 1.5 hours at 37°C, and strained through a 70μM 
mesh. Epidermal and dermal cells will be recombined, and libraries will be constructed by the 
University of Michigan Advanced Genomics Core on the 10X Chromium system. Libraries will 
then be sequenced on the Illumina NovaSeq 6000 sequencer to generate 151-bp paired end 
reads with a goal of 10,000 cells, each with approximately 10,000 reads per cell (100 million 
reads per sample). Data processing including quality control, read alignment, and gene 
quantification will be conducted using the 10X Cell Ranger software.  
3. Data Analysis: Initial processing of the sequencing reads will be performed using 10X Genomics 
Cell Ranger software, which performs sample de-multiplexing, barcode processing, and single 
cell 5’ gene counting. As recently summarized in an excellent review (Andrews TS, Mol Aspects 
Med 59, 114-122,2018), the key elements of scRNA-seq analysis include feature selection, 
dimensionality reduction, and clustering. Low quality reads and cells will be filtered by Seurat 
(Butler A, Nature Biotechnology 36, 411-420, 2018), and we will apply a scalable computational 
approach that utilizes the differences in expression values between cells shared across 
experiments to facilitate robust batch correction (Haghverdi L, Nature Biotechnology 36, 421-

KNOCKOUT STUDY 
 
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22 
427, 2018) and thus cell population (type) assignment. Data will be clustered using unique 
molecular identifier (UMI), and then each cell subpopulation will be analyzed, and characteristic 
gene expression determined. Furthermore, single-cell trajectory analyses (pseudotime) will be 
performed to quantify the state of individual cells. Our bioinformatic team will implement 
computational approaches to integrate single cell and bulk RNA-seq data. 
4. Bulk RNA-seq: For RNA seq, RNA 151 nucleotide paired-end read will be performed using the 
NovaSeq platform, which generates >800 million reads per sequencing run. We will use barcode 
oligo adapters to allow multiplexing of 15 samples per lane and expect to generate >20 million 
uniquely mapped reads/sample on average (assuming >75% mapping rate). We will use our in-
house analysis pipeline to perform adapter trimming and quality control procedures for the 
RNA-seq samples. Multiple testing correction will be used to identify statistically significant 
results (False Discovery Rate <10%). We will also conduct in silico analysis, including pathway, 
transcription factor, and co-expression analysis, to provide biological inference. 
5. CyTOF Imaging: Formalin-fixed, paraffin-embedded tissue slides will be heated for 2 hours at 
60°C, deparaffinized, and rehydrated. Slides will be placed in pH 9 Tris/EDTA antigen retrieval 
buffer and heated at 96°C for 30 minutes. After cooling, slides will be blocked in 3% BSA, and 
stained with a cocktail of metal-tagged antibodies overnight at 4 °C including CD45, E-Cadherin, 
CD4, CD8, collagen, and pan-actin, and TRM markers CD27 (Fluidigm #3171024D), CD127 
(Fluidigm # 3168026D). These have already been optimized in a panel for staining at our labs. 
For staining for CD69, CD103, CD49a, and circulating memory markers: CD62L, CCR7, we will 
optimize those using Imaging Mass Cytometry Staining Protocol for FFPE sections. The stained 
tissue is ablated, and raw data acquired on the Hyperion Imaging System (Fluidigm). 
6. Imaging CyTOF Data Analysis: Multiplexed imaging CyTOF data will be pre-processed using 
commercial acquisition software (Fluidigm) and converted to .TIFF images. These images will be 
segmented into individual cells using CellProfiler v3.1.8 for single-cell analysis.  The t-SNE 
dimensionality reduction algorithm and the Phenograph unsupervised clustering algorithm will 
be performed on TRM markers (CD4, CD8, CD69, CD103, CD49a, CD62L, CCR7) using HistoCAT 
v1.75 software. For t-SNE and PhenoGraph, the data will be normalized to the 99th percentile. 
The Heatmap will be generated to show z-scored mean marker expression of each cluster. P 
values will be computed using 2-tailed Student’s t tests assuming homoscedasticity. 
 
Remaining tissue samples will be stored at the University of Michigan laboratory until the end of trial or 
until arrangement for shipping to AbbVie is made. Patient ICF will include language for future use of 
remaining tissue samples by AbbVie in additional research. 
8.2. SAFETY AND OTHER ASSESSMENTS 
 
The Principal Investigator (PI) shall comply with applicable Laws pertaining to reporting of Adverse 
Events to the competent regulatory authorities. In addition, the PI shall comply with the reporting 
requirements that are specified for each event listed below: 
 
Event: 
Report to AbbVie within: 
Serious Adverse Events 
four (4) calendar days if reporting a death or life-
threatening event, and within eight (8) calendar days for 
all other Serious Adverse Events 

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23 
Adverse Events 
fifteen (15) calendar days 
Safety Signals 
fifteen (15) calendar days 
Negative outcomes or 
untoward events during the 
course of a Study subject's 
pregnancy or upon delivery 
fifteen (15) calendar days 
Pregnancies experienced by a 
Study subject or a partner of a 
Study subject receiving an 
AbbVie product 
fifteen (15) calendar days 
Special Situations 
fifteen (15) calendar days 
 
The PI or designee shall promptly make available to AbbVie such records as may be necessary and 
pertinent to investigate any Safety Information, if specifically requested by AbbVie. AbbVie's contact for 
reporting Serious Adverse Events, Adverse Events, pregnancies, pregnancy experiences, Safety Signals 
and Special Situations is PPDINDPharmacovigilance@AbbVie.com. 
 
"Product Complaint" means any suspected quality defect in an AbbVie product or its AbbVie-provided 
packaging, labeling or medical device component. Product Complaints may include, but are not limited 
to: 
1. damaged or broken product or packaging issues 
2. product appearance whose color/markings do not match the labeling 
3. labeling discrepancies/inadequacies in the labeling/instructions 
4. missing components/product 
5. any death of a patient 
6. device not working properly or use errors 
7. any illness, injury, or adverse event in the proximity of the device 
8. an adverse event that could be a result of using the device 
9. any event needing medical or surgical intervention, including hospitalization, while using the 
device 
In order for AbbVie to comply with all FDA requirements pursuant to 21 CFR 211 and 21 CFR 820, the 
PI or designee shall report to AbbVie within one (1) working day any Product Complaint. The PI or 
designee will report Product Complaints that involve an AbbVie product, whether AbbVie has supplied 
the AbbVie product used in the Study or not. AbbVie's contact for reporting Product Complaints is 
PPDINDPharmacovigilance@AbbVie.com.  
8.3. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
An adverse event (AE) is defined as any untoward medical occurrence in a patient, which does not 
necessarily have a causal relationship with their treatment. An adverse event can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal product, whether or not the event is 
considered causally related to the use of the product. 

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24 
Such an event can result from use of the drug as stipulated in the labeling, as well as from "special 
situations" as accidental or intentional overdose, medication error, occupational or accidental 
exposure, off-label use, drug abuse, drug misuse, lack of efficacy, or drug withdrawal, all which must 
be reported whether associated with an adverse event or not. 
If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): 
Death of Patient: 
An event that results in the death of a patient. 
Life-Threatening: 
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken. This does not include an event that would have been 
fatal if it had occurred in a more severe form. 
Hospitalization: 
An event that results in an admission to the hospital for any length 
of time. This does not include an emergency room visit or 
admission to an outpatient facility. 
Prolongation of Hospitalization: 
An event that occurs while the study patient is hospitalized 
and prolongs the patient's hospital stay. 
Congenital Anomaly: 
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss. 
Persistent or Significant 
Disability/Incapacity: 
An event that results in a condition that substantially interferes 
with the activities of daily living of a study patient. Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle). 
Important Medical Event Requiring 
Medical or Surgical Intervention to 
Prevent Serious Outcome: 
An important medical event that may not be immediately life-
threatening or result in death or hospitalization but based on 
medical judgment may jeopardize the patient and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of patient, life threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent 
or significant disability/incapacity). Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event, and suspected transmission of an infectious agent 
via a medicinal product if no other serious criterion is applicable. 
Examples of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug 
abuse. 
 
 

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The following definitions will be used to rate the severity for any adverse event being collected as an 
outcome/data point in the study and for all serious adverse events. 
Mild: 
The adverse event is transient and easily tolerated by the patient. 
Moderate: 
The adverse event causes the patient discomfort and interrupts the patient's usual 
activities. 
Severe: 
The adverse event causes considerable interference with the patient's usual activities 
and may be incapacitating or life threatening. 
The following definitions will be used to assess the relationship of the adverse event to the use 
of product: 
Reasonable Possibility 
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship. 
No Reasonable Possibility 
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship 
If no reasonable possibility of being related to product is given, an alternate etiology must be 
provided for the adverse event. 
 
9. STATISTICAL CONSIDERATIONS  
 
9.1. STATISTICAL HYPOTHESES 
The study is exploratory in nature and is not statistically powered to detect differences between the 
treatment arms. All analyses will be descriptive with the goal of developing hypothesis-generating data.  
The statistical analyses will be performed by AbbVie data and statistical sciences (DSS). Complete and 
specific details of the statistical analysis will be described and fully documented in the Statistical Analysis 
Plan (SAP). The statistical analyses will be performed using SAS (SAS Institute Inc., Cary, North Carolina, 
USA). 
 
9.2. SAMPLE SIZE DETERMINATION 
 The study is exploratory in nature and is not statistically powered for hypothesis testing. The sample 
size of 20 subjects is determined based on study feasibility. 

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9.3. ANALYSIS SET 
The Full Analysis Set (FAS) includes all randomized subjects who received at least 1 dose of study drug. 
The FAS will be used for all efficacy and Baseline analyses. Subjects will be grouped according to 
treatment as randomized. 
The Safety Analysis Set consists of all subjects who received at least 1 dose of study drug. For the Safety 
Analysis Set, subjects are assigned to a treatment group based on the treatment actually received, 
regardless of the treatment randomized. 
 
9.4. HANDLING OF POTENTIAL INTERCURRENT EVENTS 
There will be two major types of intercurrent events (ICE) in this study: risankizumab discontinuation 
due to lack of efficacy or intolerability, and risankizumab discontinuation due to other reasons. Each 
intercurrent event will be addressed by different strategies, specifically:  
 
Table ** Handling of Potential Intercurrent Events 
Intercurrent Event  
Strategy  
Description  
risankizumab or study 
discontinuation due to lack of 
efficacy or intolerability  
Composite variable strategy  
Data after risankizumab or 
study discontinuation due to 
lack of efficacy or intolerability 
will be set to non-responder for 
binary endpoints. For 
continuous endpoints, set to 
last observation before 
discontinuation.  
risankizumab discontinuation 
due to other reasons  
Treatment policy strategy  
Data after risankizumab 
discontinuation due to other 
reasons will be used regardless 
of whether the intercurrent 
event occurs.  
 
9.5. METHODS FOR ANALYSIS OF DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Demographics and baseline disease characteristics will be presented by descriptive statistics by 
treatment arm for the FAS. Medical history, prior therapy and medication, and concomitant medications 
will be summarized as well. Categorical variables will be summarized with frequency and percentage; 
percentages will be calculated with non-missing observations. Continuous variables will be summarized 
with descriptive statistics (number of non-missing observations, mean and standard deviation, median, 
minimum, and maximum). 

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9.6. METHODS FOR ANALYSIS OF PRIMARY OUTCOMES 
For the primary outcomes, after handling of intercurrent events as specified in Section 9.4, the change 
from baseline in the number and/or effector function of epidermal CD8+CD103+ Trm cells at Week 52 
will be summarized with mean, standard deviation, 95% confidence interval, and compared between the 
two treatment arms with t-test. Additional analysis with non-parametric test (e.g., Wilcoxon signed-rank 
test) will be performed, as appropriate. Details will be provided in the SAP.  
 
9.7. METHODS FOR ANALYSIS OF SECONDARY OUTCOMES 
For binary endpoints, after handling of intercurrent events in Section 9.4, the proportion will be 
summarized with percentage, 95% confidence interval, and compared between the two treatment arms 
with Fisher’s exact test. 
 
9.8. METHODS FOR ANALYSIS OF SAFETY OUTCOMES 
Treatment-emergent adverse events (TEAEs) are defined as those that began or worsened in severity 
after the first dose of the study drug but within 140 days after the last dose of the study drug. The 
number and percentage of subjects experiencing TEAEs will be tabulated by symptoms, severity, and 
relationship to the product as assessed by the investigator. Summaries (including percentages and 
events per 100 patient-years) of SAEs, deaths, and AEs leading to discontinuation will be provided as 
well. Pre-treatment AEs will be summarized separately, based on data availability. Note that missing 
safety data will not be imputed. Analysis details will be specified in the SAP. 
 
9.9. MISSING DATA HANDLING 
For the primary analysis, missing data will be assumed as missing completely at random (MCAR). Data 
after handling intercurrent events will be used as observed. 
 
For sensitivity analysis (as appropriate), missing data will be assumed as missing at random (MAR). 
Missing data after handling intercurrent events will be imputed by multiple imputation, as appropriate. 
Details will be documented in SAP. 
 
9.10. SENSITIVITY ANALYSES 
Analyses based on MAR, as appropriate, will be conducted as sensitivity analysis to handle missing data 
after handling of intercurrent events. Details of sensitivity analysis based on MAR will be provided in 
SAP. 
 
9.11. MULTIPLICITY ADJUSTMENT 
The study is exploratory in nature and there is no hypothesis testing for confirmatory purpose, thus no 
multiplicity adjustments is employed, and the results should be interpreted accordingly. 
 
 

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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1. INFORMED CONSENT PROCESS 
10.1.1.1. CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
All patients will sign and date an Informed Consent Form (ICF) prior to performing any study procedures. 
A copy of the completed ICF will be given to each patient.  
 
10.1.1.2. CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
10.1.2. CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the IND sponsors, investigators, and 
their staff. This confidentiality is extended to cover testing of biological samples in addition to the 
clinical information relating to participants. Therefore, the study protocol, documentation, data, and all 
other information generated will be held in strict confidence by the IND sponsor. No information 
concerning the study, or the data will be released to any unauthorized third party without prior written 
approval of the IND sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the IND sponsor, representatives of the 
Institutional Review Board (IRB), regulatory agencies or pharmaceutical company supplying study 
product may inspect all documents and records required to be maintained by the investigator, including 
but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants 

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in this study. The clinical study site will permit access to such records only in accordance with the 
informed consent form.   
The study participant's contact information will be securely stored at the IND sponsor’s site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location for 
as long a period as dictated by the reviewing IRB, Institutional policies, or IND sponsor requirements. 
Pseudonymized study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted by the IND sponsor to and stored at University of Michigan, AbbVie, and 
AbbVie’s Representatives. This will not include the participant's contact or identifying information. 
Rather, individual participants and their research data will be identified by a unique study identification 
number. The study data entry and study management systems used by the IND sponsor  [Oregon 
Medical Research Center] research staff will be secured, and password protected. At the end of the 
study, all study databases will be pseudonymized and archived by the IND sponsor [Oregon Medical 
Research Center]. 
10.1.3. FUTURE USE OF STORED SPECIMENS AND DATA  
 
Permission to transmit data and biological samples to the University of Michigan, AbbVie, and AbbVie’s 
representatives will be included in the informed consent.   
These data and samples could be used by IND sponsor, University of Michigan, AbbVie, and AbbVie’s 
representatives for future exploratory research in accordance with the informed consent form and 
applicable laws.  
10.1.4 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Benjamin D. Ehst, MD, PhD 
Investigator, Oregon Medical Research Center 
1750 S Harbor Way, Suite 330, Portland, OR  97201 
503-245-1525 
behst@oregonmedicalresearch.com 
 
10.1.5 DATA HANDLING AND RECORD KEEPING  
 
10.1.5.0 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All source documents should be completed in a neat, legible manner to 
ensure accurate interpretation of data.   
 
 
10.1.5.1 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harmonization (ICH) region and until there are no pending 

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or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform 
the investigator when these documents no longer need to be retained. 
 
10.1.6 PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonization Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and record 
deviations. Protocol deviations must be sent to the reviewing Institutional Review Board (IRB) per their 
policies. The site investigator is responsible for knowing and adhering to the reviewing IRB 
requirements.  
 
10.1.7 PUBLICATION AND DATA SHARING POLICY 
 
Each party is committed to fostering the highest standard of conduct related to Scientific Publications 
and transparency. Accordingly, the parties agree that the following shall apply to all Scientific 
Publications: 
1. Scientific publications should be published in a timely manner, in accordance with industry standards, and 
present scientific information in an accurate and balanced way that does not exclude or inappropriately 
downplay negative safety or health information. 
2. Authorship related to scientific publications shall be determined in accordance with and governed by the 
criteria defined by the International Committee Of Medical Journal Editors (ICMJE) "recommendations for 
the conduct, reporting, editing, and publication of scholarly work in medical journals" ("ICMJE 
recommendations"). 
3. Institution's and AbbVie's respective roles in the study and/or scientific publications shall be disclosed in 
all scientific publications. 

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10.2. ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
CBC 
Complete Blood Count 
CD 
Crohn’s Disease 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DLQI 
Dermatology Life Quality Index 
DSMB 
Data Safety Monitoring Board 
DSS 
Data and Statistical Sciences 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
EP 
Erythrodermic Psoriasis 
eCRF 
Electronic Case Report Forms 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GPP 
Generalized Pustular Psoriasis 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  

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HS 
Hidradenitis Suppurativa 
IB 
Investigator’s Brochure 
ICE 
Intercurrent Events 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IL 
Interleukin 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
IV 
Intravenous 
LSMEANS 
Least-squares Means 
MAR 
Missing at Random 
MCAR 
Missing Completely at Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mL 
Milliliter 
mm 
Millimeter 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
OMRC 
Oregon Medical Research Center 
PASI 
Psoriasis Area and Severity 
PI 
Principal Investigator 
PsA 
Psoriatic Arthritis 
PsO 
Psoriasis 

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QA 
Quality Assurance 
QC 
Quality Control 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
sPGA 
Static Physician’s Global Assessment 
TB 
Tuberculosis 
TEAE 
Treatment-emergent Adverse Events 
Trm 
Resident Memory T Cells 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.3 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
2 
 
25Jan2022 
Schedule of activities was revised, 
and administrative clarifications 
were added. 
Addressed typographical and 
administrative changes and 
clarifications.   
3  
 04Nov2022 
The Title Page was updated to 
include the AbbVie protocol number. 
 
 
 
 
The endpoints were revised.  
 
 
 
 
The Statistical Considerations 
Section of the protocol was revised. 
 
 
 
 
 
 
The abbreviations page was 
updated.   
 
Title Page did not have the 
assigned AbbVie protocol 
number listed on the original 
protocol or previous 
amendments. 
 
To clarify the endpoints for the 
study. 
 
 
 
Statistical Considerations 
Section was revised to clarify 
the role of AbbVie 
Statistics/Programming and to 
provide additional information 
for the statistical analysis. 
 
 
Added stats abbreviations 
based on the revised statistical 
considerations section. 
4  
14Feb2023 
The protocol was updated to extend 
the study for an additional year.  
Study was extended from Week 52 
to Week 100 throughout the 
protocol. Clinical assessments were 
also extended through Week 100. 
To follow up the subjects who 
are remaining in the study 
through Week 100.  
5 
27Mar2023 
Addition of unblinding plan and 
removal of non-lesional biopsy at 
Week 52. 
Subjects will be unblinded to 
their treatment group once 
they reach Week 52. 
6 
22Feb2024 
Update to site location and Principal 
Investigator.  
Oregon Medical Research 
Center relocated to a new 
address, Dr. Blauvelt is retiring 
on 05Mar2024, and Sub-I Dr. 
Ehst is assuming the role of PI. 
 
 
 

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