Clinical trial NCT04856917
Conditions: Acne Vulgaris
Keywords: LI-36 Receptor Interleukin 36 Imsidolimab
Sponsor: AnaptysBio, Inc.
Start date: 2021-05-15; Completion date: 2022-03-29
Enrollment: 123 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Efficacy and Safety of Imsidolimab in Participants with Acne Vulgaris

Detailed description:
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of imsidolimab in adolescent and adult participants with acne vulgaris (AV). This study also will characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to imsidolimab in participants with AV.

Arms: arm 1: Participants received imsidolimab 400 milligrams (mg) by subcutaneous (SC) injection on Day 1, followed by 200 mg on Days 29 and 57. arm 2: Participants received imsidolimab 200 mg by SC injection on Day 1, followed by 100 mg on Days 29 and 57. arm 3: Participants received imsidolimab matching placebo by SC injection on Days 1, 29, and 57.
Interventions: intervention 1: Imsidolimab intervention 2: Placebo
Intervention descriptions: intervention 1: Humanized Monoclonal Antibody intervention 2: Placebo

Protocol documents:
Prot_000.pdf: 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
1 
A Phase 2, Randomized, Double-Blind, 
Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Imsidolimab (ANB019) in the Treatment of 
Subjects with Acne Vulgaris 
 
Protocol Number: ANB019-209 
Investigational New Drug (IND) Number: 136145 
 
 
Sponsor Name: AnaptysBio, Inc. 
Sponsor Address: 10421 Pacific Center Court, Suite 200 
San Diego, CA 92121, United States 
 
Sponsor Medical Expert and Signatory: 
MD, PhD 
 
 
 
 
 
 
Original Protocol (Version 1.0) 
11 February 2021
AnaptysBio, ANB019
IND 136145, SN 0043












Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
6 
Tmax 
time to maximum observed concentration 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
URTI 
upper respiratory tract infection 
W 
week 
WHO 
World Health Organization 
WOCBP 
woman of childbearing potential 
 
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IND 136145, SN 0043




Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
8 
 
Study Treatment Compliance .................................................................................................. 47 
 
Concomitant Therapy .............................................................................................................. 47 
 
Permitted Therapies .......................................................................................................... 48 
 
Prohibited Medications or Procedures .............................................................................. 48 
 
Rescue Treatment .................................................................................................................... 50 
 
Dose Modification ................................................................................................................... 50 
 
Treatment After the End of the Study ..................................................................................... 50 
7 
STUDY TREATMENT DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ................................................................................................... 51 
 
Discontinuation of Study Treatment ....................................................................................... 51 
 
Temporary Interruption ..................................................................................................... 51 
 
Re-Challenge .................................................................................................................... 51 
 
Subject Discontinuation/Withdrawal from the Study .............................................................. 51 
 
Lost to Follow-Up ................................................................................................................... 52 
8 
STUDY ASSESSMENTS AND PROCEDURES .......................................................................... 54 
 
Efficacy Assessments .............................................................................................................. 54 
 
Patient Global Impression of Severity .............................................................................. 54 
 
Patient Global Impression of Change ............................................................................... 55 
 
Index Questionnaire ................................................................................................... 55 
 
Subject Satisfaction Questionnaire ................................................................................... 55 
 
Subject Satisfaction Rating Scale ..................................................................................... 56 
 
 .......................................................................... 56 
 
 ........................................................................... 56 
 
Facial Inflammatory/Noninflammatory Lesion Count ..................................................... 56 
 
Safety Assessments ................................................................................................................. 57 
 
Adverse Events and Serious Adverse Events ................................................................... 57 
8.2.1.1 
Definition of Adverse Events ..................................................................................... 57 
8.2.1.1.1 
Events Meeting the Adverse Event Definition .............................................. 57 
8.2.1.1.2 
Events Not Meeting the Adverse Event Definition ....................................... 58 
8.2.1.2 
Definition of Serious Adverse Events ........................................................................ 58 
8.2.1.3 
Classification of an Adverse Event ............................................................................ 59 
8.2.1.3.1 
Severity of Event ........................................................................................... 59 
8.2.1.3.2 
Relationship to Study Treatment ................................................................... 60 
8.2.1.3.3 
Expectedness ................................................................................................. 61 
8.2.1.4 
Time Period and Frequency for Event Assessment and Follow-Up .......................... 61 
8.2.1.5 
Adverse Event Reporting ........................................................................................... 62 
8.2.1.6 
Serious Adverse Event Reporting .............................................................................. 63 
8.2.1.6.1 
Reporting via an Electronic Data Collection Tool ........................................ 64 
8.2.1.6.2 
Reporting via Paper Case Report Form ......................................................... 64 
8.2.1.7 
Reporting Events to Subjects ..................................................................................... 64 
8.2.1.8 
Reporting of Pregnancy .............................................................................................. 64 
8.2.1.9 
Treatment of Overdose ............................................................................................... 65 
 
Height and Weight ............................................................................................................ 66 
 
Physical Examinations ...................................................................................................... 66 
 
Vital Signs......................................................................................................................... 66 
 
Electrocardiograms ........................................................................................................... 66 
AnaptysBio, ANB019
IND 136145, SN 0043


Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
9 
 
Clinical Safety Laboratory Assessments .......................................................................... 67 
 
Other Assessments .................................................................................................................. 67 
 
Photography ...................................................................................................................... 67 
 
Pharmacokinetics .............................................................................................................. 68 
 
Immunogenicity Assessments ........................................................................................... 69 
 
Biomarker Analysis .......................................................................................................... 70 
8.3.4.1 
Tape Stripping ............................................................................................................ 70 
9 
STATISTICAL CONSIDERATIONS ............................................................................................ 71 
 
Statistical Hypotheses .............................................................................................................. 71 
 
Sample Size Determination ..................................................................................................... 71 
 
Populations for Analyses ......................................................................................................... 72 
 
Statistical Analyses.................................................................................................................. 72 
 
General Approach ............................................................................................................. 72 
 
Subject Disposition ........................................................................................................... 73 
 
Baseline Descriptive Statistics .......................................................................................... 73 
 
Concomitant Medication ................................................................................................... 74 
 
Analysis of the Primary Efficacy Endpoint ...................................................................... 74 
 
Analysis of the Secondary Efficacy Endpoints ................................................................. 74 
9.4.6.1 
Categorical Endpoints ................................................................................................ 75 
9.4.6.2 
Continuous Endpoints ................................................................................................ 75 
 
Analysis of the Exploratory Efficacy Endpoints............................................................... 75 
 
Safety Analyses ................................................................................................................. 76 
9.4.8.1 
Adverse Events and Serious Adverse Events ............................................................. 76 
9.4.8.2 
12-Lead Electrocardiogram, Vital Signs, and Clinical Safety Laboratory Tests ....... 77 
 
Pharmacokinetic Analyses ................................................................................................ 77 
9.4.9.1 
Derivation of Pharmacokinetic Parameters ................................................................ 77 
9.4.9.2 
Pharmacokinetic Concentration Data Analysis .......................................................... 77 
9.4.9.3 
Pharmacokinetic Parameter Data Analysis ................................................................ 78 
9.4.9.4 
Population Pharmacokinetics Analysis ...................................................................... 78 
9.4.9.5 
Immunogenicity Analyses .......................................................................................... 78 
 
Biomarker Analyses .......................................................................................................... 79 
 
Planned Interim Analysis .................................................................................................. 79 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .................. 80 
 
Regulatory, Ethical, and Study Oversight Considerations ...................................................... 80 
 
Informed Consent Process ................................................................................................ 80 
10.1.1.1 
Consent and Other Informational Documents Provided to Subjects .......................... 80 
10.1.1.2 
Consent Procedures and Documentation .................................................................... 80 
 
Study Discontinuation and Closure .................................................................................. 81 
 
Confidentiality and Privacy .............................................................................................. 81 
 
Future Use of Stored Specimens and Data ....................................................................... 83 
 
Medical Monitor ............................................................................................................... 83 
 
Safety Oversight ............................................................................................................... 83 
 
Clinical Monitoring ........................................................................................................... 83 
 
Quality Assurance and Quality Control ............................................................................ 84 
 
Data Handling and Record Keeping ................................................................................. 85 
10.1.9.1 
Data Collection and Management Responsibilities .................................................... 85 
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IND 136145, SN 0043


Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
10 
10.1.9.2 
Study Records Retention ............................................................................................ 86 
 
Protocol Deviations ........................................................................................................... 87 
 
Publication and Data Sharing Policy ................................................................................ 88 
 
Conflict of Interest Policy ................................................................................................. 88 
 
Additional Considerations ....................................................................................................... 89 
 
Ethics and Responsibility .................................................................................................. 89 
 
Amendment Policy ........................................................................................................... 89 
 
Insurance ........................................................................................................................... 89 
11 
REFERENCES ................................................................................................................................ 90 
12 
APPENDICES ................................................................................................................................. 92 
Appendix 1: Contraceptive Guidance and Collection of Pregnancy Information ................................... 92 
Appendix 2: Patient Global Impression of Severity ................................................................................ 96 
Appendix 3: Patient Global Impression of Change ................................................................................. 97 
Appendix 4: Dermatology Life Quality Index ........................................................................................ 98 
 .................................................................... 100 
Appendix 6: Subject Satisfaction Questionnaire ................................................................................... 102 
Appendix 7: Subject Satisfaction Rating Scale ..................................................................................... 103 
Appendix 
 .......................................................................... 104 
Appendix 
 ........................................................................................ 105 
Appendix 10: Clinical Laboratory Tests ............................................................................................... 106 
 
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
14 
For scheduled on-site study visits, subjects will come to the study site on 
7 occasions: Screening and Days 1, 15, 29, 57, 85, and 141 (end of study 
[EOS])/early termination [ET]). All procedures will be conducted in accordance 
with the Schedule of Activities (SoA) in Section 1.3. 
Disease activity will be evaluated for all subjects using facial inflammatory and 
noninflammatory lesion count, Facial 
 Global Assessment (IGA), 
Truncal (chest, neck, and back) 
PGA]), 
s of 
age, Patient Global Impression of Severity (PGIS), Patient Global Impression of 
Change (PGIC), Subject Satisfaction Questionnaire (SSQ), and Subject 
Satisfaction Rating Scale (SSRS). 
Safety assessments will include adverse event (AE)/serious adverse event (SAE) 
monitoring, vital signs, physical examination, electrocardiograms (ECGs), and 
clinical laboratory tests (hematology, biochemistry, and urinalysis). 
Facial photography will be conducted at each study visit. Optional truncal 
photography will be performed at selected sites.  
Blood samples will be collected during the study to determine PK and 
immunogenicity (presence of anti-drug antibodies [ADA] to imsidolimab) on 
Day 1 before the administration of the study treatment and at the other time 
points specified in the SoA (Section 1.3). Any remaining serum/plasma from 
samples collected for PK/PD immunogenicity endpoints may be retained for 
assay method development, troubleshooting, or validation. The samples will not 
be used for any type of genetic analyses.  
Tape strips will be collected at Day 1, Week 4, and Week 12 to study key 
biomarkers.  
Interim analyses (IA) may be performed for assessment of all primary and 
secondary efficacy endpoints and evaluation of all safety data available. 
Objectives: 
Primary Objective:   
 To evaluate the efficacy of imsidolimab in subjects with AV  
 
Secondary Objective:   
 To evaluate the safety of imsidolimab in subjects with AV 
 To evaluate the effect of imsidolimab on AV signs and symptoms and 
quality of life in subjects with AV 
AnaptysBio, ANB019
IND 136145, SN 0043


Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
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15 
Exploratory Objectives: 
 To further evaluate the effect of imsidolimab on AV signs and symptoms 
and quality of life in subjects with AV 
 To explore the effect of imsidolimab on cutaneous biomarkers 
 To test for immunogenicity to imsidolimab 
 To describe the PK profile of imsidolimab in subjects with AV 
Endpoints: 
Primary Endpoint: 
 Change from Baseline in facial inflammatory lesion counts at Week 12 
 
Secondary Efficacy Endpoints:  
 Change from Baseline in facial inflammatory lesion counts at visits other 
than Week 12 
 Percent change from Baseline in facial inflammatory lesion counts at each 
visit 
 Change from Baseline in facial noninflammatory lesion counts at each 
visit 
 Percent change from Baseline in facial noninflammatory lesion counts at 
each visit 
 Change from Baseline in total facial lesion (inflammatory and 
noninflammatory lesions) counts at each visit 
 Percent change from Baseline in total facial lesion (inflammatory and 
noninflammatory lesions) counts at each visit 
 Change from Baseline in Facial IGA at each visit 
 Proportion of subjects achieving a Facial IGA of clear (0) or almost clear 
(1) with at least a 2-grade decrease from Baseline at each visit 
 Proportion of subjects in each response category for the PGIS at each visit
 Proportion of subjects in each response category for the PGIC at each post-
Baseline visit 
 Change from Baseline in DLQI/CDLQI at each visit 
Safety Endpoint: 
 Incidence of AEs, SAEs, and AEs leading to withdrawals, as well as 
changes in vital signs, clinical laboratory parameters (hematology, 
biochemistry, and urinalysis), and 12-lead ECGs  
Exploratory Endpoints:  
 Two-point decrease from Baseline in Facial IGA at each visit 
 Change from Baseline in Truncal PGA for chest at each visit 
 Change from Baseline in Truncal PGA for neck at each visit 
 Change from Baseline in Truncal PGA for back at each visit 
AnaptysBio, ANB019
IND 136145, SN 0043


Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
16 
 Proportion of subjects achieving a Truncal PGA for chest of clear (0) or 
almost clear (1) with at least a 2-grade decrease from Baseline at each visit
Proportion of subjects achieving a Truncal PGA for neck of clear (0) or 
almost clear (1) with at least a 2-grade decrease from Baseline at each visit
 Proportion of subjects achieving a Truncal PGA for back of clear (0) or 
almost clear (1) with at least a 2-grade decrease from Baseline at each visit
 Proportion of subjects in each response category for the SSQ at each visit 
 Proportion of subjects in each response category for the SSRS at Week 12
and Week 20 
 Change from Baseline in lesion counts based on blinded photographic 
assessment at each visit 
 Assessment of biomarkers in tape strips  
 Assessment of PK of imsidolimab in AV subjects 
 Assessment of ADA concentrations following administration of 
imsidolimab 
Study 
Population: 
Approximately 120 male and female subjects aged 12 to 45 years with clinically 
confirmed diagnosis of AV 
Inclusion 
Criteria: 
1. Male and female aged 12 to 45 years (inclusive) at the time of signing the 
informed consent/assent. 
2. Moderate to severe facial AV at Screening and Day 1, defined as follows: 
a. Facial IGA score of 3 (moderate) or 4 (severe)  
b. At least 20 and no more than 100 inflammatory lesions on the face  
c. No more than 100 noninflammatory lesions on the face. 
d. 
 
3. Subject agrees to use Cetaphil Skin Cleanser on a regular basis (ideally once 
or twice daily) for at least 1 week prior to Day 1 and agrees to continue using 
Cetaphil Skin Cleanser at the same frequency throughout the study. 
4. Subject must meet the following laboratory criteria at screening: 
a. 
 
 g/dL) 
b. 
 × 109
 × 103/µL) 
c. 
 × 109
 × 103/µL) 
d. Serum creatinine <132.6 µmol/L (< 1.5 mg/dL) 
e. Alanine aminotransferase (ALT) and aspartate aminotransferase 
(AST)  2 upper limit of normal (ULN) 
f. 
 × 
have serum bilirubin < 3 × ULN may be included 
5. Body weight  40 kg and body mass index (BMI) within the range of 18 to 40 
kg/m2 for adults and 16 to 40 kg/m2 for adolescents, inclusive {BMI = weight 
(kg)/[height (m)]2}). 
AnaptysBio, ANB019
IND 136145, SN 0043


Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
Confidential and proprietary. Permission should be obtained before any reproduction.  
17 
6. Contraceptive use by men and women should be consistent with local 
regulations regarding the methods of contraception for those participating in 
clinical studies. 
Contraception and pregnancy: 
a. A male subject must agree to use contraception as detailed in 
Appendix 1 of this protocol during the treatment period and for at 
least 200 days (which includes the duration of relevant exposure plus 
the duration of sperm cycle) after the last study treatment 
administration and refrain from donating sperm during this period. 
b. Female subjects: 
i. A woman of childbearing potential (WOCBP) is eligible to 
-human 
chorionic gonadotropin) at screening and a negative urine 
pregnancy test at Day 1 (see Appendix 1), is not breastfeeding, 
and agrees to follow the contraceptive guidance in Appendix 1 
during the treatment period and for at least 6 months after 
receiving the study treatment, and refrains from donating oocytes 
selected form of contraception must be effective by the time the 
female subject enters into the study at Day 1 (eg, hormonal 
contraception should be initiated at least 12 Weeks before Day 1. 
For WOCBP, hormonal contraceptives must be used without 
schedule changes and in steady doses during the study treatment. 
Starting hormonal contraceptives during the study is not 
permitted. Use of any hormonal contraceptives containing 
drospirenone, chlormadinone acetate, or cyproterone acetate is 
prohibited unless part of a stable contraceptive regimen as 
described in Section 6.5.1. 
ii. A woman not of childbearing potential as defined in Appendix 1, 
must have a follicle-stimulating hormone (FSH) test confirming 
nonchildbearing potential. 
iii. An adolescent subject who experiences menarche during the trial 
will be considered a WOCBP and will be required to follow the 
contraceptive guidance for WOCBP in Appendix 1 and undergo 
pregnancy testing as detailed in the SoA (Section 1.3). 
7. Willing to participate and capable of giving written informed consent, which 
must be personally signed and dated by the subject and obtained prior to any 
trial-related activities. Subjects who need to provide assent, as per local 
requirement, need to have their parent(s) or legal representative read and sign 
the informed consent form prior to any study-related procedures. Adolescent 
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
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18 
subjects who reach 18 years of age during the study must be reconsented as 
adults. 
8. Willing to comply with all study procedures and lifestyle considerations, and 
must be available for the duration of the study. 
Exclusion 
Criteria: 
1. Has acne fulminans or conglobate or secondary acne, including drug induced 
acne (steroids, cloracne, lithium, epidermal growth factor receptor inhibitors 
[EGFRi, eg, cetuximab, erlotinib, panitumumab, gefitinib], associated with 
acneiform eruptions, including PRIDE [papulopustules and/or paronychia, 
regulatory abnormalities of hair growth, itching, and dryness due to EGFRi]) 
syndrome). 
2. Acne associated with known hormonal imbalances such as polycystic 
ovaries, Cushing syndrome, congenital adrenal hyperplasia (CAH), 
androgen-secreting tumors, and acromegaly. Patients with signs/symptoms of 
hyperandrogenism such as hirsutism should undergo hormonal status 
assessment at the discretion of the Investigator. 
3. Acne as part of a known genetic syndrome, such as SAPHO, PAPA, PASH 
or other variants possibly associated with PSTPIP1 gene. 
4. Extensive (acne) keloids and hypertrophic scarring making clinical 
evaluation difficult. 
5. Hidradenitis suppurativa also called acne inversa. 
6. Other forms of acne rosacea, peri-oral dermatitis and gram-negative 
folliculitis. 
7. Concomitant dermatological condition (skin burn, sun burn, extensive 
scarring), or excessive facial hair or beard that may interfere with the 
  
8. Clinically significant medical condition or physical/laboratory/ECG/vital 
signs abnormality that would, in the opinion of the Investigator, put the 
subject at undue risk or interfere with interpretation of study results. 
9. Any evidence of active infection that required systemic treatment within 
4 weeks of Day 1 (eg, bronchopulmonary, urinary, or gastrointestinal). 
Note: Subjects with localized oral or genital herpes simplex that, in the 
opinion of the Investigator, is well-controlled may participate in the study. 
10. Opportunistic infection (eg, Pneumocystis carinii, aspergillosis, or 
mycobacteria other than tuberculosis [TB]) or parasitic infections (eg, 
helminths, protozoa, Trypanosoma cruzi) within 6 months prior to screening. 
11. Herpes zoster infection within 8 weeks prior to screening. 
12. Known or suspected congenital or acquired immunodeficiency state, or 
splenectomy). 
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
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19 
13. History of cancer or lymphoproliferative disease within 5 years prior to 
Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous 
cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix 
are not to be excluded. 
14. Any major surgery within 4 weeks prior to Day 1 or has a major surgery 
planned during the study. 
15. Any significant drug allergy or reaction (such as anaphylaxis or 
hepatotoxicity) and reactivity to polysorbate-20, a component of imsidolimab 
formulation, or the inactive ingredients (excipients). 
16. Has taken the following drugs or had the following procedures within the 
specified period prior to Day 1: 
a. Over-the-counter (OTC) topical medication for the treatment of AV, 
including benzoyl peroxide, topical anti-inflammatory medications, 
-hydroxy/glycolic, or 
antibacterial/antiseptic soap or wash within 2 weeks prior to Day 1. 
b. Prescription topical retinoids (eg, tretinoin, tazarotene, adapalene, 
dapsone) or antimicrobials (eg, clindamycin, erythromycin), or other 
prescription topical medications for the treatment of AV within 4 
weeks prior to Day 1. Topical antibiotics may be used to treat non-acne 
skin lesions not on the face. 
c. Systemic anti-acne drugs not mentioned in other exclusion criteria 
within 4 weeks prior to Day 1. 
d. Oral or injectable corticosteroids within 4 weeks prior to Day 1 or 
require them during the study.  
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. 
Eye and ear drops containing corticosteroids are also allowed. 
e. Use of any systemic hormonal treatment (in particular anti-androgens, 
such as spironolactone, finasteride, flutamide) within 4 weeks before 
Day 1. Oral contraceptives can be continued if stable for the last 
12 weeks before Day 1 and if stable in dose and dosing regimen and 
type (brand), and if the subject plans to continue throughout the study 
period. 
f. Drospirenone, chlormadinone acetate, or cyproterone acetate within 
12 weeks prior to Day 1, unless part of a stable contraceptive regimen 
as described in Section 6.5.1. 
g. Previous surgical, 
blue or UV light, photodynamic therapy [PDT]) or laser therapy within 
12 weeks prior to Day 1. 
h. Cryodestruction, chemodestruction, dermabrasion, acne surgery, 
intralesional steroids, X-ray therapy procedures performed on the face 
within 12 weeks prior to Day 1. 
i. Systemic antibiotics (including tetracyclines) within 4 weeks prior to 
Day 1. 
j. Systemic antiviral medication (except for prevention of localized oral 
or genital herpes simplex) within 4 weeks prior to Day 1. 
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
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20 
k. Any nonbiologic investigational drug within 4 weeks or 5 half-lives, 
whichever is longer prior to Day 1. 
l. Marketed or investigational biological agent within 12 weeks or 5 half-
lives (whichever is longer) prior to Day 1. 
m. Live attenuated vaccine within 12 weeks prior to Day 1 , including any 
approved for COVID-19. Live attenuated vaccines may be utilized after 
the subjects complete the 8-week standard safety follow-up period of 
the study. Note: Non-live-attenuated vaccines for COVID-19 (eg, 
RNA-based vaccines, protein-based vaccines) are allowed during the 
study.  
n. Previous treatment with anti-IL-36R, anti-IL-36, anti-tumor necrosis 
factor (TNF)/ IL-12/IL-23/ IL-17, or any other mAbs within 12 weeks 
or 5 half-lives (whichever is longer) prior to Day 1. 
o. Oral retinoid (eg, isotretinoin) or vitamin A supplements > 10,000 U/d 
within 26 weeks prior to Day 1. 
p. Previous treatment with imsidolimab. 
17. Has had excessive sun exposure, is planning a trip to a sunny climate, or has 
used tanning booths within 4 weeks prior to Day 1 or is not willing to 
minimize natural and artificial sunlight exposure during the study. Use of 
sunscreen products and protective apparel are recommended when sun 
exposure cannot be avoided. 
18. Active TB or latent TB infection as indicated by a positive 
QuantiFERON®-TB Gold test at screening or within 6 months prior to 
screening (if the test is indeterminate, it can be repeated only once; chest 
X-ray will be administered per local standards, as required), and/or clinical 
examination, or has had active TB disease at any time in the past. 
19. Clinically significant drug or alcohol abuse in the last year prior to Day 1, or 
other factors limiting the ability to cooperate and to comply with the study 
protocol, as determined by the Investigator. 
20. Subject is a pregnant or lactating woman, or a woman who intends to become 
pregnant during the study period. 
21. Any other physical, mental, or medical conditions, which, in the opinion of 
the Investigator, make study participation inadvisable or could confound 
study assessments. 
22. Positive blood screen for hepatitis C antibody and hepatitis C RNA, 
antibodies to hepatitis B core antigens, hepatitis B surface antigen, or human 
immunodeficiency virus 1 and 2 antibodies. 
23. Is not able to tolerate SC drug administration. 
Phase: 
2 
Study 
Centers 
Approximately 12 study centers are expected to participate in this study.   
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
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Enrolling 
Subjects: 
Description 
of Study 
Treatments: 
Imsidolimab (ANB019) will be provided in a glass vial as a sterile, colorless to 
yellow, and clear to slightly opalescent solution for injection. The placebo 
contains no active ingredient and will be provided as a sterile, colorless to 
slightly yellowish, and clear to very slightly opalescent solution for injection. 
Imsidolimab will be administered as SC injection. Placebo will also be 
administered as SC injection in the same volumes as imsidolimab. 
Rescue 
Medication: 
Not applicable 
Subject 
Duration: 
The maximum study duration per subject included in this study is approximately 
24 weeks from first visit to last visit.  
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
Version 1.0 
Protocol ANB019-209
11 February 2021
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25 
Table 1: Schedule of Activities (continued) 
Abbreviations: ADA, anti-drug antibody; AE, adverse event; CDLQI
 
D, day; DLQI, Dermatology Life Quality Index; ECG, electrocardiogram; EOS, end of study; ET, early termination, 
FSH, follicle-
PGIC, Patient Global Impression of Change; PGIS, Patient Global Impression of Severity; PK, pharmacokinetic; 
SAE, serious adverse event; SC, subcutaneous; SoA, Schedule of Activities; SSRS, Subject Satisfaction Rating 
Scale; SSQ, Subject Satisfaction Questionnaire; TB, tuberculosis; W, week; WOCBP, woman of childbearing 
potential. 
a The ET visit will include all procedures to be done at the EOS visit (Day 141 [Week 20]).  
b Adolescent subjects who reach 18 years of age during the study must be reconsented as adults.  
c Height will be measured at screening only. Subjects below the age of 18 at the start of the study will have height 
measured at Week 12. 
d Refer to Section 8.2.3 for details regarding the complete physical examination.  
e Refer to Section 8.2.4 for details and instructions regarding vital signs. 
f Refer to Section 8.2.5 for details and instructions regarding the ECG. In addition to the time points specified in the 
SoA, ECGs may be performed at any time during the study if, in the opinion of the Investigator, it is clinically 
warranted. 
g If a negative QuantiFERON®-TB Gold test result was obtained within 6 months of screening, it can be skipped at 
screening. A chest X-ray will be administered per local standards, as required. The FSH testing is performed for 
women not of childbearing potential (postmenopausal women with at least 12 months of amenorrhea without an 
alternative medical cause). An adolescent subject who experiences menarche during the trial will be considered a 
WOCBP (refer to Appendix 1 for definition of WOCBP) and will be required to follow the contraceptive 
guidance in Appendix 1 and undergo scheduled pregnancy testing. Additional pregnancy testing may be 
performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected. Refer to Appendix 10 
for instructions regarding clinical laboratory parameters. 
h Refer to Section 8.1 for details and instructions regarding facial lesion count, facial IGA, truncal (chest, neck, and 
back) IGA, PGI-S, PGI-C, DLQI (subjects  16 years of age)/CDLQI (subjects < 16 years of age), SSQ, and 
SSRS. Facial IGA must be performed before facial lesion count.  
i On Day 1, samples for PK will be collected at predose and 2 hr (± 10 min) post SC administration. See Table 5. 
j Tape stripping will be performed for all randomized subjects as part of this study (not optional). Tape strips will 
be collected from non-lesional and lesional skin at Day 1 and Week 12 and from lesional skin at Week 4. 
k During the treatment period, subjects will receive either imsidolimab or placebo SC administered as follows: 400 
mg imsidolimab, 200 mg imsidolimab, or placebo on Day 1; followed by 200 mg imsidolimab, 100 mg 
imsidolimab, or placebo on Days 29 and 57.  
l At screening, prior medications should be reviewed and documented. Refer to Section 6.5. 
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could be due to treatment-related immune modulation. However, data published on IL-36R 
deficient humans shows no deleterious effect on general health, and normal immune function is 
broadly preserved, indicating that inhibition of IL-36R, does not generally compromise host 
defenses. Similar to other immune-modulating treatment paradigms, subjects should be closely 
monitored for any clinical gastrointestinal manifestations including infections and evaluated on 
an ongoing basis. If a gastrointestinal infection is suspected, the subject should be treated as 
clinically indicated. 
In the ANB019-001 study in healthy adults, single doses of imsidolimab up to 750 mg 
administered by IV infusion or SC injection to 32 healthy adults in the SAD part of the Phase 1 
study were generally well tolerated with a similar number of treatment-emergent adverse event 
(TEAEs) reported in subjects receiving imsidolimab or placebo, 29 subjects (81%) and 11 
subjects (92%), respectively. The most frequently reported AEs were upper respiratory tract 
infection (URTI; 10 [28%] imsidolimab; 6 [50%] placebo), headache (10 [28%] imsidolimab; 3 
[25%] placebo), and viral URTI (4 [11%] imsidolimab; 1 [8%] placebo). Additionally, multiple 
doses of imsidolimab up to 300 mg administered by IV infusion once weekly for 4 weeks to 18 
healthy adults were also well tolerated. Overall, TEAEs occurred in 16 subjects (89%) receiving 
imsidolimab and in 3 subjects (50%) receiving the placebo. The most common AEs were 
headache (7 [39%] imsidolimab; 1 [17%] placebo) and URTI (3 [17%] imsidolimab; 1 [17%] 
placebo). 
In ANB019-005, single doses of imsidolimab up to 750 mg administered by IV infusion or SC 
injection to 32 healthy Japanese and Caucasian adults were generally well tolerated. The most 
common TEAEs were alanine aminotransferase (ALT) increased (3 subjects [9.4%]) and 
aspartate aminotransferase (AST) increased (2 subjects [6.3%]).  
One SAE of sepsis was reported in the ongoing ANB019-002 study in subjects with GPP; the 
SAE was considered possibly related to the study drug. The subject had a medical history of 
sepsis and experienced the SAE after the 750 mg IV dose administration. Antibiotic treatment 
rapidly resolved the sepsis episode with complete subject recovery. Further details of 
imsidolimab clinical studies are in the IB.  
As allergic or anaphylactic reactions may occur in any subjects treated with mAbs, subjects 
should be observed during study drug administration and for a period of 2 hr after study drug 
administration. Subjects with true allergic/anaphylactic reactions should not receive further doses 
of the monoclonal antibody. Symptoms of an apparent allergic reaction to the drug, also known 
 
 Mild to moderate fever, chills, headache, nausea, and vomiting 
 Moderate to severe symptoms such as edema, hypotension, and pulmonary infiltrates (eg, 
blood and mucus in the lung) 
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Such reactions should be managed as clinically indicated and according to standard clinical 
practice. 
 
KNOWN POTENTIAL BENEFITS  
Subjects with AV may or may not receive direct benefit from participating in this study. 
Participation in this study also may help generate future benefit for larger groups of patients with 
AV if imsidolimab proves to be successful in treating this disease.  
 
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
All quality, pharmacology and toxicology data, and satisfactory safety and tolerability data 
demonstrated in nonclinical and clinical studies are considered sufficient to expect a positive 
benefit/risk ratio for the treatment of AV with imsidolimab, and therefore to initiate this study. 
The risk to subjects in this trial will be minimized by compliance with the eligibility criteria, 
proper study design, and close monitoring. 
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During the COVID period, if any data is collected at a home visit, it will be recorded by 
the home nurse in the source documents and the originals will be sent back to the site for 
data entry into the electronic data capture system for storage/archiving. 
 Clinical laboratory tests (chemistry and hematology) and pregnancy tests may be 
performed by local laboratory if home nursing visits are not possible and sample collection 
cannot be performed at the study site due to COVID 19-related limitations, including but 
not limited to site closure. Abnormal laboratory results should be promptly communicated 
results to the Medical Monitor.   
 At home study drug administration by home health nurses may be done. 
 Source documentation should note that the visit was performed virtually (not face-to-face), 
and note the name of the local laboratory where laboratory tests were done. 
 If certain study procedures or assessments cannot be completed per the schedule of events, 
the reason for the missed assessment (ie, laboratory, vital signs, physical exams, etc.) must 
be noted in the source documentation (eg, COVID-19), captured in the protocol deviations 
documentation, and reported to the IRB/Ethics Committee, as applicable. 
A detailed assessment of COVID-19 related risk and mitigation measures will be documented in 
the appropriate study plans. 
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acromegaly. Patients with signs/symptoms of hyperandrogenism such as hirsutism should 
undergo hormonal status assessment at the discretion of the Investigator. 
3. Acne as part of a known genetic syndrome, such as SAPHO, PAPA, PASH or other variants 
possibly associated with PSTPIP1 gene. 
4. Extensive (acne) keloids and hypertrophic scarring making clinical evaluation difficult. 
5. Hidradenitis suppurativa also called acne inversa. 
6. Other forms of acne rosacea, peri-oral dermatitis and gram-negative folliculitis. 
7. Concomitant dermatological condition (skin burn, sun burn, extensive scarring), or excessive 
response to therapy.  
8. Clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality 
that would, in the opinion of the Investigator, put the subject at undue risk or interfere with 
interpretation of study results. 
9. Any evidence of active infection that required systemic treatment within 4 weeks of Day 1 
(eg, bronchopulmonary, urinary, or gastrointestinal). 
Note: Subjects with localized oral or genital herpes simplex that, in the opinion of the 
Investigator, is well-controlled may participate in the study. 
10. Opportunistic infection (eg, Pneumocystis carinii, aspergillosis, or mycobacteria other than 
tuberculosis [TB]) or parasitic infections (eg, helminths, protozoa, Trypanosoma cruzi) 
within 6 months prior to screening. 
11. Herpes zoster infection within 8 weeks prior to screening. 
12. Known or suspected congenital or acquired immunodeficiency state, or condition that would 
 
13. History of cancer or lymphoproliferative disease within 5 years prior to Day 1. Subjects with 
successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or 
localized carcinoma in situ of the cervix are not to be excluded. 
14. Any major surgery within 4 weeks prior to Day 1 or has a major surgery planned during the 
study. 
15. Any significant drug allergy or reaction (such as anaphylaxis or hepatotoxicity) and reactivity 
to polysorbate-20, a component of imsidolimab formulation, or the inactive ingredients 
(excipients). 
16. Has taken the following drugs or had the following procedures within the specified period 
prior to Day 1: 
a. Over-the-counter (OTC) topical medication for the treatment of AV, including benzoyl 
peroxide, topical anti-
-
hydroxy/glycolic, or antibacterial/antiseptic soap or wash within 2 weeks prior to Day 
1. 
b. Prescription topical retinoids (eg, tretinoin, tazarotene, adapalene, dapsone) or 
antimicrobials (eg, clindamycin, erythromycin), or other prescription topical 
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medications for the treatment of AV within 4 weeks prior to Day 1. Topical antibiotics 
may be used to treat non-acne skin lesions not on the face. 
c. Systemic anti-acne drugs not mentioned in other exclusion criteria within 4 weeks prior 
to Day 1. 
d. Oral or injectable corticosteroids within 4 weeks prior to Day 1 or require them during 
the study.  
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear 
drops containing corticosteroids are also allowed. 
e. Use of any systemic hormonal treatment (in particular anti-androgens, such as 
spironolactone, finasteride, flutamide) within 4 weeks before Day 1. Oral 
contraceptives can be continued if stable for the last 12 weeks before Day 1 and if 
stable in dose and dosing regimen and type (brand), and if the subject plans to continue 
throughout the study period. 
f. Drospirenone, chlormadinone acetate, or cyproterone acetate within 12 weeks prior to 
Day 1, unless part of a stable contraceptive regimen as described in Section 6.5.1. 
g. 
photodynamic therapy [PDT]) or laser therapy within 12 weeks prior to Day 1. 
h. Cryodestruction, chemodestruction, dermabrasion, acne surgery, intralesional steroids, 
X-ray therapy procedures performed on the face within 12 weeks prior to Day 1. 
i. Systemic antibiotics (including tetracyclines) within 4 weeks prior to Day 1. 
j. Systemic antiviral medication (except for prevention of localized oral or genital herpes 
simplex) within 4 weeks prior to Day 1. 
k. Any nonbiologic investigational drug within 4 weeks or 5 half-lives, whichever is 
longer prior to Day 1. 
l. Marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever 
is longer) prior to Day 1. 
m. Live attenuated vaccine within 12 weeks prior to Day 1 , including any approved for 
COVID-19. Live attenuated vaccines may be utilized after the subjects complete the 8-
week standard safety follow-up period of the study. Note: Non-live-attenuated vaccines 
for COVID-19 (eg, RNA-based vaccines, protein-based vaccines) are allowed during 
the study.  
n. Previous treatment with anti-IL-36R, anti-IL-36, anti-tumor necrosis factor (TNF)/ 
IL-12/IL-23/ IL-17, or any other mAbs within 12 weeks or 5 half-lives (whichever is 
longer) prior to Day 1. 
o. Oral retinoid (eg, isotretinoin) or vitamin A supplements > 10,000 U/d within 26 weeks 
prior to Day 1. 
p. Previous treatment with imsidolimab. 
17. Has had excessive sun exposure, is planning a trip to a sunny climate, or has used tanning 
booths within 4 weeks prior to Day 1 or is not willing to minimize natural and artificial 
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Study Treatment 
Name: 
Imsidolimab (ANB019) 
Anti-interleukin 36 receptor monoclonal 
antibody 
Placebo 
 
For SC injections, imsidolimab and placebo should be prepared by drawing up the required 
dosing volume into suitable sized syringe and attaching a dosing needle. No further dilution 
is required. Syringes should be covered in tape by an unblinded pharmacist to obscure color 
and volume. 
The preferred anatomical site of SC administration is the abdomen; however, the injection 
may be made in the upper arm, if needed. 
A 30-minute observation period should be included after the first dose administered. 
The same anatomical site should be used throughout the entire study for a given subject (ie, 
do not administer one dose into the upper arm and at a subsequent visit or dose, administer 
the next dose into the abdomen). 
Subsequent doses should be rotated within an anatomical site (ie, if the upper left abdominal 
quadrant is used as the initial site of administration, then the next administration at a 
subsequent visit should be rotated to the upper right quadrant). 
Subcutaneous injections should not be given into moles, scars, tattoos, or areas where the 
skin is tender, bruised, red, hard, or not intact. 
Prior to SC needle insertion, the skin will be pinched between the thumb and index finger to 
separate the subcutaneous layer from the muscle. 
The needle is to be injected at a 90-degree angle to the fat pad. 
The plunger will be pressed gently until the entire dose is delivered to the SC space and the 
needle will be held in place (fully depressed) for 10 seconds after the injection is 
administered.  
The needle will be removed and then the skin pinch released; any leakage or backflow of 
fluid from the administration site onto the surface of the skin will be noted and documented 
in the eCRF. 
The site of administration is NOT to be massaged by either the clinic staff or by the subject 
for at least 60 minutes after drug administration. 
Abbreviations: eCRF, electronic case report form; NaCl, sodium chloride; SC, subcutaneous. 
The contents of the label will be in accordance with all applicable regulatory requirements. 
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PERMITTED THERAPIES 
Cetaphil Skin Cleanser is the only permitted skin cleanser during the conduct of the study. 
Subject should use Cetaphil Skin Cleanser on a regular basis (ideally once or twice daily) for at 
least 1 week prior to Day 1 and at the same frequency throughout the study. 
Topical bland emollients (without pharmacological active ingredients) are allowed during the 
study, except within 3 hr prior to study visits. Make-up, facial moisturizers, creams, lotions, 
and/or sunscreens are also allowed during the study, except within 3 hr prior to the study visit.   
Oral contraceptives should be continued if stable for the last 12 weeks before Day 1 and if stable 
in dose and dosing regimen and type (brand) and if the subject plans to continue throughout the 
study period. 
Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and eardrops containing 
corticosteroids are also allowed. 
Non-live-attenuated vaccines for COVID-19 (eg, RNA-based vaccines, protein-based vaccines) 
are allowed during the study. The Medical Monitor should be consulted to confirm that the 
vaccine received is allowed and that subject participation in the study should be continued. Of 
note, COVID-19 vaccines should be captured as a concomitant medication and any related 
symptoms documented as AEs. 
 
PROHIBITED MEDICATIONS OR PROCEDURES 
Prohibited medications/therapy are listed in Table 4. The use of a prohibited medication/therapy 
is a protocol violation and must be recorded in the eCRF. Subjects who start prohibited 
medications or therapies that have been demonstrated to be effective for treatment of AV during 
the study will be withdrawn from study treatment. Subjects who start any other prohibited 
medications or therapies during the study may be withdrawn from study treatment if an impact 
on efficacy assessment or safety of the subjects is expected. If in any doubt, Investigator is 
advised to discuss medications with the Medical Monitor. In addition, the Investigator must 
notify the Medical Monitor in order to make a decision as to whether the subject will be 
withdrawn from the study.  
All treatments likely to have efficacy in AV need to be discontinued prior to treatment initiation 
(prior to Day 1). All medications listed below are also restricted during the study period. If 
treatment with any of these prohibited treatments is essential, then the subject must notify the 
study team. 
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 Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
 
or study file. 
 Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study. 
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The PGIS will be completed by the subject on a worksheet prior to any safety and efficacy 
evaluations. The questionnaire is self-explanatory and handed to the subject who is asked to fill it 
in without the need for a detailed explanation. The PGIS (modified from Yalcin 2003) is 
presented in Appendix 2. 
 
PATIENT GLOBAL IMPRESSION OF CHANGE  
The PGIC will be assessed at the visits specified in the SoA (Section 1.3). The PGIC is a 
single-item, self-administered questionnaire, which asks the subject to rate the change in their 
 
The PGIC will be completed by the subject on a worksheet prior to any safety and efficacy 
evaluations. The questionnaire is self-explanatory and handed to the subject who is asked to fill it 
in without the need for a detailed explanation. The PGIC (modified from Yalcin 2003) is 
presented in Appendix 3. 
 
DERMATOLOGY LIFE QUALITY INDEX 
QUESTIONNAIRE
GY LIFE QUALITY 
INDEX QUESTIONNAIRE 
The DLQI/CDLQI questionnaires will be assessed at the visits specified in the SoA 
(Section 1.3). They are simple 10-question validated questionnaires (Finlay 1994; Lewis-Jones 
1995). 
 The aim of these subject-reported questionnaires is to measure 
 
The CDLQI will be administered to subjects < 16 years old and the DLQI will be administered to 
Subjects will be administered the same questionnaire during the entire 
study based on their age at Day 1. 
The DLQI/CDLQI will be completed by the subject on a worksheet prior to any safety and 
efficacy evaluations. The questionnaires are self-explanatory and will be filled in by the subjects 
without the need for a detailed explanation. The DLQI and CDLQI are presented in Appendix 4 
and Appendix 5, respectively. 
 
SUBJECT SATISFACTION QUESTIONNAIRE 
The SSQ asks subjects to rate their satisfaction with their acne condition on a 7-point scale from 
0 (extremely dissatisfied) to 6 (extremely satisfied) (Appendix 6). It will be administered at 
Week 1 and all subsequent study visits.  
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SUBJECT SATISFACTION RATING SCALE 
The SSRS asks subjects to rate their satisfaction with their study treatment on a 7-point scale 
from 0 (extremely dissatisfied) to 6 (extremely satisfied) (Appendix 7). It will be administered at 
Week 12 and Week 20 (EOS). 
 
S GLOBAL ASSESSMENT 
The Facial IGA is a global assessment that will be used to assess the current state of AV on the 
face at each visit. It is a 5-point morphological assessment ranging from 0 (clear) to 4 (severe). 
distance from the subject and must be performed before the acne lesion count. The Facial IGA is 
presented in Appendix 8.  
 
TRUNCAL 
 GLOBAL ASSESSMENT 
The truncal PGA is a global assessment that will be used to assess the current state of AV on the 
chest, neck, and back at each visit. Each area will be evaluated and scored separately on a scale 
ranging from 0 (clear) to 4 (severe). The Truncal PGA is an overall global evaluation of acne that 
The Truncal PGA scale is 
presented in Appendix 9.   
 
FACIAL INFLAMMATORY/NONINFLAMMATORY LESION COUNT 
The number of acne inflammatory lesions (pustules, papules, and nodular lesions) and 
noninflammatory lesions (open and closed comedones) will be counted at Baseline, and at each 
visit and recorded separately. At Baseline, the total of both inflammatory and noninflammatory 
lesions will also be calculated. 
Subjects will be examined in a well-lit room and without the aid of magnifying instruments. 
Facial inflammatory lesion counts will be made at the forehead, left and right cheeks, nose, and 
chin. Noninflammatory lesion counts will be made at the forehead, left and right cheeks, and 
chin. 
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 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. 
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. 
8.2.1.1.2 EVENTS NOT MEETING THE ADVERSE EVENT DEFINITION 
Events not meeting the AE definition include: 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
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. 
8.2.1.2 
DEFINITION OF SERIOUS ADVERSE EVENTS  
An AE or suspected adverse reaction is considered "serious" if, in the view of either the 
Investigator or AnaptysBio, it results, at any dose, in any of the following outcomes:  
 Death 
 Life-threatening adverse event  
-
event. It does not refer to an event, which hypothetically might have caused death, if it 
were more severe. 
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 Inpatient hospitalization or prolongation of existing hospitalization  In general, 
hospitalization signifies that the subject has been admitted (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that 
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 
serious. Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from Baseline is not considered an AE. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions  
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. 
 Congenital anomaly/birth defect 
 Other important medical events  Events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition. Examples 
of such medical events include invasive or malignant cancers, 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.  
8.2.1.3 
CLASSIFICATION OF AN ADVERSE EVENT 
8.2.1.3.1 SEVERITY OF EVENT 
The intensity of an AE is an estimate of the relative severity of the event. The Investigator will 
make an assessment of intensity for each AE and SAE reported during the study based on his or 
her clinical experience and familiarity with the literature. The following definitions are to be 
used to rate the severity of an AE: 
 Mild  Events require minimal or no treatment, is easily tolerated by the subject, causing 
 
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 Moderate  Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning and sufficient 
discomfort to the subject. 
 Severe  Events interrupt 
therapy or other treatment. Severe events are usually potentially life-threatening or 
AE that is assessed as severe should not be confused with a SAE. Severe is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
8.2.1.3.2 RELATIONSHIP TO STUDY TREATMENT 
All AEs must have their relationship to study treatment assessed by the Investigator who 
examines and evaluates the subject based on temporal relationship and his or her clinical 
judgment. 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 IB in his or her assessment. 
The degree of certainty about causality will be graded using the categories below. In a clinical 
study, the study treatment must always be suspect.  
 Unrelated  Clinical event incontrovertibly not related to the study treatment.  
 Unlikely to be related  Clinical event with an incompatible time relationship to study 
treatment administration which makes a causal relationship improbable, and in which an 
underlying condition or other drugs or chemicals provides plausible explanations.  
 Possibly related  Clinical event with a reasonable time relationship to study treatment 
administration, and that is unlikely to be attributed to concurrent condition or other drugs 
or chemicals.  
 Related  Clinical event with plausible time relationship to study treatment 
administration and that cannot be explained by concurrent condition or other drugs or 
chemicals.  
For each AE/SAE, the Investigator must document in the medical notes that he or 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 pharmacovigilance unit. However, it is very 
important that the Investigator always make an assessment of causality for every event before the 
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initial transmission of the SAE data to the pharmacovigilance unit within 24 hr of awareness of 
the event. 
The Investigator may change his or her opinion of causality in light of follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
8.2.1.3.3 EXPECTEDNESS  
The pharmacovigilance unit will be responsible for determining whether an AE is expected or 
unexpected as interpreted through the IB. An AE will be considered unexpected if the nature, 
severity, or frequency of the event is not consistent with the risk information previously 
described for the study treatment. 
8.2.1.4 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study subject presenting for medical care, or upon review by a study 
monitor. 
All AEs including local and systemic reactions will be captured on the appropriate eCRF. 
Informat
severity, seriousness, relationship to study treatment (assessed only by those with the training 
and authority to make a diagnosis), action taken, and outcome of the event. All AEs occurring 
while on study must be documented appropriately regardless of relationship (see Section 
8.2.1.3.2). All AEs will be followed to adequate resolution. 
present prior to the informed consent signature in the appropriate section of the source document 
and eCRF. During the study, site personnel will note any change in the condition(s) and the 
occurrence and nature of any AE. Care will be taken not to introduce bias when detecting AEs 
and/or SAEs. Open-ended and nonleading verbal questioning of the subject is the preferred 
method to inquire about AE occurrences. 
Should a subject experience an AE at any time after the screening visit informed consent 
signature until the end of participation in the study, the event will be recorded as an AE in the 
source document and eCRF. Any SAE related to the study participation (eg, screening 
procedure) will be recorded in the source document and eCRF from the time consent is given to 
participate in the study until the end of participation in the study (EOS/ET visit).  
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Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he or she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the 
pharmacovigilance unit.  
Any medical condition that is present at the time that the subject is screened will be considered 
as medical history and not reported as an AE
deteriorates at any time during the study, it will be recorded as an AE.  
Changes in the severity of an AE/SAE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
The Investigator is responsible for appropriate medical care of subjects during the study. After 
the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. The Investigator also remains responsible for following through with 
an appropriate health care option for all AEs that are ongoing at the end of the study. The subject 
should be followed until the event is resolved or stable. If an AE is ongoing at the end of study, 
the follow-up duration is left to the discretion of the Investigator. Follow-up frequency will be 
performed at the discretion of the Investigator.  
Whenever possible, clinically significant abnormal laboratory results are to be reported using the 
diagnostic that resulted in the clinically significant abnormal laboratory results and not the actual 
abnormal test. 
8.2.1.5 
ADVERSE EVENT REPORTING  
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 (including event term, start 
and stop dates, severity, relationship to study treatment, outcome, if serious or non-serious) in the 
eCRF. Each event must be recorded separately. 
the pharmacovigilance unit 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 
pharmacovigilance unit. In this case, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records before submission to the 
pharmacovigilance unit. 
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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. 
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 
pharmacovigilance unit 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. 
New or updated information will be recorded in the originally completed eCRF. 
8.2.1.6 
SERIOUS ADVERSE EVENT REPORTING  
Prompt notification by the Investigator to the pharmacovigilance unit of an SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of subjects and the safety of a 
study treatment under clinical investigation are met. All SAEs will be recorded and reported to 
the pharmacovigilance unit within 24 hr of awareness. The Investigator will submit any updated 
SAE data to the pharmacovigilance unit within 24 hr of receipt of the information as outlined in 
the Safety Reporting Instructions that will be provided to the sites and in the study Safety 
Management Plan. 
The pharmacovigilance unit will inform the Medical Monitor, AnaptysBio, and Innovaderm 
within 1 business day of awareness of a new SAE. The pharmacovigilance unit will process and 
evaluate all SAEs as soon as the reports are received. For each SAE received, the 
pharmacovigilance unit, in consultation with AnaptysBio if needed, will make a determination as 
to whether the criteria for expedited reporting to relevant regulatory authorities have been met. 
AnaptysBio or designee 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. 
AnaptysBio or designee will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IRB/EC, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected SAEs according to local 
regulatory requirements and pharmacovigilance unit policy, and forwarded to Investigators as 
necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the pharmacovigilance unit will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.  
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If a subject dies while participating in the study, the Investigator will provide the 
pharmacovigilance unit with a copy of any postmortem findings.  
8.2.1.6.1 REPORTING VIA AN ELECTRONIC DATA COLLECTION TOOL  
The primary mechanism for reporting an SAE to the pharmacovigilance unit will be the EDC 
clinical database. 
If the electronic system is unavailable, then the study site will use the back-up paper SAE Report 
Form. The study site will then enter the SAE data into the EDC system as soon as it becomes 
available. 
After the study is completed and the database is locked, the tooled system will be taken off-line 
to prevent the entry of new data or changes to existing data. 
If a study site receives a report of a new SAE from a subject or receives updated data on a 
previously reported SAE after the EDC system is locked, then the study site can report this 
information on a paper SAE form and email the form to the pharmacovigilance unit. 
Contacts for SAE reporting can be found in SAE form and Safety Reporting Instructions that 
will be provided to the sites. 
8.2.1.6.2 REPORTING VIA PAPER CASE REPORT FORM  
In rare circumstances, and in the absence of EDC or email, notification by telephone is 
acceptable for notifying the pharmacovigilance unit of an SAE. Once the EDC is available, the 
SAE must be reported in the system within 24 hr of it becoming available. 
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
Contacts for SAE reporting can be found in Safety Reporting Instructions that will be provided 
to the sites. 
8.2.1.7 
REPORTING EVENTS TO SUBJECTS  
Not applicable. 
8.2.1.8 
REPORTING OF PREGNANCY  
If a female subject or a female partner of a male subject becomes pregnant during the study and 
up to 28 days after the end of the study, the subject should inform the study site as soon as 
possible. 
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If a pregnancy is reported, the Investigator should inform the pharmacovigilance unit within 24 
hours of learning of the pregnancy and should follow the procedures outlined in Appendix 1. 
If a pregnancy occurs, it will be followed up to determine the outcome, but no longer than 6 to 8 
weeks after the estimated delivery date, where consent has been obtained to do so. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, and ectopic pregnancy) are considered SAEs and must be reported within 24 hours of 
awareness as described in Section 8.2.1.6. 
8.2.1.9 
TREATMENT OF OVERDOSE  
For this study, any dose of imsidolimab or placebo administered in a volume exceeding the 
planned dosing detailed in Table 3 (Dose Strength[s]/Dosage Level[s]) will be considered an 
overdose. 
In the improbable event of a suspected overdose, the following procedures should be executed: 
 Administration is to be discontinued. 
 The subject is to be monitored clinically. 
 Supportive measures are to be undertaken as clinically indicated. 
 Electrocardiography and clinical laboratory evaluations (ie, blood glucose, hepatic 
enzymes, creatinine, blood urea nitrogen, creatine kinase (CK), and complete blood 
count) are to be performed and followed until all values return to Baseline levels and AEs 
subside, if applicable. 
No information on overdose, maximum tolerated dose, or dose-limiting toxicities for 
imsidolimab has been established at this time and since there are no known antidotes for 
imsidolimab
 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the subject for any AE/SAE and laboratory abnormalities and follow-up 
until resolution. 
3. Obtain a serum sample for PK analysis soon after the dose for SC administration. 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the subject. 
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HEIGHT AND WEIGHT 
Height (cm) and weight (kg) will be collected to calculate the BMI. Height and weight will be 
measured at the time points specified in the SoA (Section 1.3). 
 
PHYSICAL EXAMINATIONS 
Complete physical examinations will be performed at the time points indicated in the SoA 
(Section 1.3). 
A complete physical examination will include assessments of general appearance; skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, lymphatic, and musculoskeletal system; 
extremities; eyes; nose; throat; and neurologic status. 
A detailed examination of the skin should be performed at the time points indicated in the SoA 
for the efficacy assessments (eg, lesion count). 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
 
VITAL SIGNS 
Body temperature (°C), pulse rate (bpm), blood pressure (mmHg), and respiratory rate 
(breath/min) will be assessed at the time points specified in SoA (Section 1.3).   
Blood pressure and pulse rate will be assessed in a seated position with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse rate measurements should be preceded by at least 5 minutes of rest for 
the subject in a quiet setting without distractions (eg, television, cell phones). 
Vital signs including body temperature, respiratory rate, and pulse rate (after at least 5 minutes 
rest) should be measured once. Arterial blood pressure should be measured twice (at intervals of 
at least 5 minutes), using a validated device. 
 
ELECTROCARDIOGRAMS 
A single 12-lead ECG will be obtained at the time points specified in the SoA (Section 1.3) using 
a validated ECG machine that automatically calculates the heart rate and measures RR, PR, 
QRS, QT, and QTcF intervals. 
Additional information will be provided in a separate manual. 
The ECG will be reviewed by the Investigator or an authorized representative who is 
experienced in the evaluation of ECGs and assessed for clinical significance. 
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Additional information on photography will be described in the manual provided to sites.  
Optional truncal photography will be performed at selected sites. 
 
PHARMACOKINETICS 
Whole blood will be obtained for the determination of imsidolimab concentration in human 
serum. Samples will be collected according to the SoA (Section 1.3) and Table 5. Whole blood 
will be obtained from each subject for PK assessments during the study. Each serum sample will 
be divided into 2 aliquots (1 each for primary and a back-up). Samples collected for analyses of 
imsidolimab serum concentration also may be used to correlate exposure to safety or efficacy as 
well as supportive analysis for dose justification.  
The actual date and time (24-hour clock) of the blood sample collection will be recorded in the 
preparation, storage, and shipping procedures will be described in a separate laboratory manual. 
The measurement of the concentrations of imsidolimab will be performed using a validated assay 
method under the supervision of AnaptysBio. The analytical methods used to measure 
concentrations of imsidolimab will be described in a separate bioanalytical report. 
Only samples within the stability window of the assay will be analyzed.   
While PK samples must be collected from subjects randomized to the placebo arm to maintain 
the blinding of treatment assignment, PK assay results for these subjects are not needed for the 
safe conduct or proper interpretation of this study. These samples may not be analyzed unless 
needed to investigate if a dosing error has occurred. Personnel at the bioanalytical laboratory 
performing PK assays will be unblinded, the clinical study team members, and study site staff 
(with the exception of the unblinded Pharmacist) will remain blinded to treatment for the 
duration of the study. Data may be de-identified for quality review. Additional details on de-
identification or unblinding of the PK data, if applicable, will be described in a separate plan. 
Drug concentration information that may unblind the study will not be reported to study sites or 
blinded personnel until the study has been unblinded.  
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BIOMARKER ANALYSIS 
8.3.4.1 
TAPE STRIPPING 
Tape strip samples will be collected from non-lesional and lesional skin according to the SoA 
(Section 1.3) to measure cutaneous biomarkers including but not limited to IL-36R, Th-17 
cytokines such as IL-17A, and markers of neutrophils and dendritic cell infiltration. 
details of tape strip collection, sample tube labeling, sample preparation, storage, and shipping 
procedures will be described in a separate Laboratory Manual. 
The measurement of tape strip biomarkers may be performed by an additional third party (eg, a 
university Investigator) designated by AnaptysBio. 
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The default summary statistics for continuous variables include number of contributing 
observations, mean, SD, median, minimum, and maximum. For PK parameters, coefficient of 
variation (CV) and geometric mean will also be presented, as appropriate. 
For categorical variables, the number and percentage (percentage of subjects in each category 
relative to the total number of subjects in the relevant analysis set or relative to the total number 
of subjects in the relevant analysis set with assessments available [where appropriate]) in each 
category will be the default summary presentation. 
interest prior to the first intake of study treatment (this includes unscheduled visits). For 
numerical variables, change from Baseline will be calculated as the difference between the value 
of interest and the corresponding Baseline value. 
Unless otherwise specified, all formal statistical tests will be 2-sided at the 10% significance 
level. Point estimates of treatment differences will be accompanied with 2-sided 90% confidence 
intervals (CIs), where applicable. 
In the case of normality assumption violations, appropriate nonparametric methods may be used 
for analysis. 
All data will be presented in by-subject listings. 
 
SUBJECT DISPOSITION 
A tabular presentation of the subject disposition will be provided. It will include the number of 
subjects screened, randomized, treated, completed as well as the number of dropouts with 
reasons for discontinuation, and major protocol deviations or violations. 
A listing will be presented to describe dates of screening, assigned treatment, screen failed with 
reason, completion or early withdrawal, and the reason for early discontinuation, if applicable, 
for each subject. A list of protocol deviations/violations will be identified and discussed with the 
Investigator/AnaptysBio in dry run to categorize as major or minor with decisions of exclusion 
from analysis sets prior to unblinding. 
During the COVID-19 pandemic, protocol deviations related to COVID-19 will be documented 
and information on how they will be handled in the analyses will be detailed in the SAP. 
 
BASELINE DESCRIPTIVE STATISTICS 
Subject characteristics obtained at Baseline will be summarized for all subjects taking 
imsidolimab or placebo. 
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Summaries will include descriptive statistics for continuous variables (sample size [n], mean, 
SD, median, minimum, and maximum) and for categorical variables (n, frequency, and 
percentage). 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
latest version and listed for all subjects. 
 
CONCOMITANT MEDICATION 
All medications will be coded using the World Health Organization (WHO) Drug Dictionary and 
Anatomical Therapeutic Chemical (ATC) system. Each medication will be classified as prior 
medication if it is stopped prior to the first dose of study treatment, or as concomitant medication 
if it is ongoing at the time of the first dose or is started after the first dose of study treatment. 
Prior, concomitant, and rescue medications will be summarized descriptively with a by-subject 
listing. 
To handle the issue of rescue medication use, the efficacy data on and after the use rescue 
medication will be set to missing in the efficacy analysis. 
 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT 
The primary efficacy endpoint is the change from Baseline in facial inflammatory lesion count at 
Week 12. 
A general linear mixed model repeated measures (MMRM) analysis will be used to estimate the 
least-squares means (LSM) and associated standard errors for the change from Baseline in facial 
inflammatory lesion count to Week 12. The model will include change from Baseline in facial 
inflammatory lesion count at Week 12 as the dependent variable, fixed effects for treatment arm, 
categorical time point, and the treatment by time point interaction, and the Baseline facial 
inflammatory lesion count and the stratification factor (ie, facial IGA score at baseline) as 
covariates. An unstructured covariance structure will be used.  The difference between LSMs 
(imsidolimab  placebo) at Week 12 will be presented along with the associated 90% CI and p-
value. 
Possible effect of any other covariates as well as investigation of variables through sub-group 
analysis may also be investigated.  
 
ANALYSIS OF THE SECONDARY EFFICACY ENDPOINTS 
Following are the secondary efficacy endpoints: 
 Change from Baseline in facial inflammatory lesion counts at visits other than Week 12 
 Percent change from Baseline in facial inflammatory lesion counts at each visit 
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 Change from Baseline in facial noninflammatory lesion counts at each visit 
 Percent change from Baseline in facial noninflammatory lesion counts at each visit 
 Change from Baseline in total facial lesion (inflammatory and noninflammatory lesions) 
counts at each visit 
 Percent change from Baseline in total facial lesion (inflammatory and noninflammatory 
lesions) counts at each visit 
 Change from Baseline in Facial IGA at each visit 
 Proportion of subjects achieving a Facial IGA of clear (0) or almost clear (1) with at least 
a 2-grade decrease from Baseline at each visit 
 Proportion of subjects in each response category for the PGIS at each visit 
 Proportion of subjects in each response category for the PGIC at each post-Baseline visit 
 Change from Baseline in DLQI/CDLQI at each visit 
9.4.6.1 
CATEGORICAL ENDPOINTS 
Frequency and percentages for each response Yes/No for categorical endpoints will be presented 
separately by visit for each treatment arm. Estimates of the difference between treatments 
(imsidolimab  placebo) will be presented along with exact 90% CIs. Treatment arms will be 
compared using an exact test. 
9.4.6.2 
CONTINUOUS ENDPOINTS 
Summary statistics will be provided by visit and treatment arm. A by-subject listing will be 
presented for each assessment, by visit. 
 
ANALYSIS OF THE EXPLORATORY EFFICACY ENDPOINTS  
Following are the exploratory efficacy endpoints: 
 Two-point decrease from Baseline in Facial IGA at each visit 
 Change from Baseline in Truncal PGA for chest at each visit 
 Change from Baseline in Truncal PGA for neck at each visit 
 Change from Baseline in Truncal PGA for back at each visit 
 Proportion of subjects achieving a Truncal PGA for chest of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit Proportion of subjects achieving 
a Truncal PGA for neck of clear (0) or almost clear (1) with at least a 2-grade decrease 
from Baseline at each visit 
 Proportion of subjects achieving a Truncal PGA for back of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit 
 Proportion of subjects in each response category for the SSQ at each visit 
 Proportion of subjects in each response category for the SSRS at Week 12 and Week 20 
 Change from Baseline in lesion counts based on blinded photographic assessment at each 
visit 
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Methods for analyzing the above categorical and continuous efficacy endpoints will mirror the 
methods described in Section 9.4.6.1 and 9.4.6.2, respectively. 
 
SAFETY ANALYSES 
Following are the primary safety and tolerability endpoints: 
 Assessment of AEs, SAEs, and AEs leading to treatment discontinuation and study 
withdrawal. 
 Vital signs. 
 12-Lead ECG. 
 Clinical safety laboratory tests (hematology, biochemistry, and urinalysis). 
All safety analyses will be performed on the safety analysis set. 
9.4.8.1 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
A TEAE is defined as: 
 A new event that occurs during or after first dose of study treatment or, 
 Any event present at Baseline that worsens in either intensity or frequency after first dose 
of study treatment. 
Adverse events will be coded using the MedDRA and only TEAEs will be summarized. Number 
of events and percentage will be tabulated by preferred term (PT) and primary system organ 
class (SOC). Multiple occurrences of an AE for a subject will only be counted once per primary 
SOC and PT. Percentages will be determined relative to the subjects in the safety analysis set for 
the given treatment arm. 
If the intensity or seriousness of the AE changes, the overall intensity or seriousness will be the 
maximum intensity or seriousness of the multiple occurrences. The TEAEs, SAEs, TEAEs 
leading to treatment discontinuation, and TEAEs leading to withdrawal of subject will be 
tabulated for each treatment arm. 
All AE data will be listed for each subject. 
Summaries over SOC and PT of TEAEs, TEAEs leading to death, SAEs, and TEAEs that led to 
discontinuation from the study or study treatment will be presented by treatment. Summaries will 
also be presented by relatedness to the study treatment and the severity of the TEAE. 
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9.4.8.2 
12-LEAD ELECTROCARDIOGRAM, VITAL SIGNS, AND CLINICAL 
SAFETY LABORATORY TESTS 
Summaries and listings of data for vital signs and safety laboratory tests result (hematology, 
biochemistry, and urinalysis) will be presented. Appropriate descriptive statistics will be 
summarized for the observed value at each scheduled assessment and for the corresponding 
change from Baseline. 
For hematology and biochemistry tests, listings of subject data will also flag any abnormal or 
out-of-range values. Clinically significant changes in the laboratory test parameters will be 
summarized and listed. Hematology and biochemistry data will be reported in System 
International units. 
Descriptive statistics will be used to present the safety outcomes including, weight, BMI, 12-
Lead ECG, vital signs, and clinical laboratory test results. 
Change from Baseline will also be summarized for vital signs, and clinical laboratory tests 
results. 
All ECG data results (normal/abnormal) will be summarized using frequency and percentage, 
and parameter values will be summarized descriptively. Clinically significant abnormalities will 
be presented in by-subject listings. 
 
PHARMACOKINETIC ANALYSES 
Limited imsidolimab PK parameter analysis will be evaluated by assessment of drug 
concentrations in serum. These drug concentrations will be listed and summarized for each 
sampling time point using appropriate descriptive statistics. The PK parameters will be 
summarized using appropriate descriptive statistics. 
9.4.9.1 
DERIVATION OF PHARMACOKINETIC PARAMETERS 
Where possible, PK parameters will be derived using noncompartmental methods. The actual 
sampling times will be used in the PK parameter calculations. Further details of PK analysis, 
data handling, analysis procedures, and data reporting will be detailed in a separate analysis plan. 
9.4.9.2 
PHARMACOKINETIC CONCENTRATION DATA ANALYSIS 
A subject listing of all concentration-time data following SC injections will be presented by 
subject and scheduled sample collection time. 
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Concentration data of imsidolimab will be summarized by day and nominal time point using the 
number of observations, arithmetic mean, SD, CV, minimum, median, maximum, and geometric 
mean. 
Graphs for mean concentration-time data following SC administration will be presented. 
Individual subject concentration-time plots will also be presented. 
Mean trough concentrations-time data will be graphically displayed for samples collected at the 
visits specified in the SoA (Section 1.3) to visually assess time to attainment of steady state. 
Time to steady state may also be explored by using inferential statistics, if deemed appropriate. 
Other presentations of data may be added at the discretion of the PK scientist, as appropriate, and 
will be described in detail in a separate analysis plan. 
9.4.9.3 
PHARMACOKINETIC PARAMETER DATA ANALYSIS 
Where possible, PK parameters will be summarized using number of observations, arithmetic 
mean, SD, CV, minimum, median, maximum, geometric mean, and geometric CV, with the 
exception of time to maximum observed concentration (Tmax), which should be reported with n, 
minimum, median, and maximum only. 
Graphs of parameters may be added at the discretion of the PK scientist, as appropriate, and will 
be described in detail in a separate analysis plan. 
9.4.9.4 
POPULATION PHARMACOKINETICS ANALYSIS 
Pharmacokinetic data from the study may also be used for population PK and PK/response 
analyses. The data may be combined with PK data from other imsidolimab studies, if needed, to 
conduct the population PK analysis.  If done, a separate analysis plan will be prepared, and 
results will be reported separately from the Clinical Study Report (CSR). 
9.4.9.5 
IMMUNOGENICITY ANALYSES 
Observed values for ADA levels/status will be listed by-subject and summarized with descriptive 
statistics based on the safety analysis set. If data permits, correlation will be analyzed between 
ADA levels, serum concentration, and safety and efficacy endpoints. 
Frequency and percentage of ADA response will be presented and listed and correlated to safety 
and PK endpoints. 
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BIOMARKER ANALYSES 
Tape strip samples will be collected from nonlesional and lesional skin according to the SoA 
(Section 1.3) to measure cutaneous biomarkers including but not limited to IL-36R, Th-17 
cytokines such as IL-17A, and markers of neutrophils and dendritic cell infiltration. 
details of tape strip collection, sample tube labeling, sample preparation, storage, and shipping 
procedures will be described in a separate Laboratory Manual. 
The measurement of tape strips biomarkers may be performed by an additional third party (eg, a 
university Investigator) designated by AnaptysBio. 
 
PLANNED INTERIM ANALYSIS  
Interim analyses (IA) may be performed for assessment of all primary and secondary efficacy 
endpoints, and evaluation of all safety data available.  
The rationale for these analyses is to assist in making decisions for potential future development 
of this treatment. No adjustments to the current protocol are planned as a result of the interim 
analyses; therefore, overall alpha in the analyses of the primary analysis is expected to be 
maintained at 0.10, two-sided. 
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Subjects 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/assent document will be 
given to the subjects 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 subject 
undergoes any study-specific procedures. The rights and welfare of the subjects 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. 
The medical record must include a statement that written informed consent was obtained before 
the subject was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF/assent. 
Subjects must be re-consented to the most current version of the ICF(s)/assent(s) during their 
participation in the study. Subjects who are rescreened are required to sign a new ICF/assent. 
 
STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study subjects, 
Investigator, the IND sponsor, and regulatory authorities, as applicable. If the study is 
prematurely terminated or suspended, the Investigator will promptly inform study subjects and 
the IRB/EC and will provide the reason(s) for the termination or suspension. Study subjects will 
be contacted, as applicable, and be informed of changes to study visit schedule.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to subjects 
 Insufficient compliance to protocol requirements 
 Data that are not sufficiently complete and/or evaluable 
 Scientific or corporate reasons 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy AnaptysBio, IRB/EC and/or regulatory authorities. 
 
CONFIDENTIALITY AND PRIVACY  
Subject confidentiality and privacy are strictly held in trust by the participating Investigators, 
their staff, and AnaptysBio and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
subjects. Therefore, the study protocol, documentation, data, and all other information generated 
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will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of AnaptysBio.  
All research activities will be conducted in a setting as private as possible. The Investigator must 
from unauthorized parties. On CRFs or other documents submitted to AnaptysBio, subjects 
should not be identified by their names, but by an identification code. The Investigator should 
keep a subject log relating codes with the names of subjects. The Investigator should maintain in 
strict confidence documents not for submission to AnaptysBio 
forms). 
The study monitor, other authorized representatives of AnaptysBio, and representatives of the 
IRB/EC, regulatory agencies, or pharmaceutical company supplying study treatment 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 subjects in 
this study. The clinical study site will permit access to such records. 
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 applicable legal or regulatory requirements, the 
reviewing IRB/EC, Institutional policies, or AnaptysBio requirements. 
Study subject research data, which are for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at the data management company responsible for data 
information. Rather, individual subjects and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by 
clinical study sites and by data management research staff will be secured and password 
protected. At the end of the study, all study databases will be de-identified and archived by 
AnaptysBio.  
All information generated in this study must be considered highly confidential and must not be 
disclosed to any persons not directly concerned with the study without written prior permission 
from AnaptysBio. Authorized regulatory officials and AnaptysBio personnel (or their 
representatives) will be allowed full access to inspect and copy the records. All study 
investigational product, subject bodily fluids, and/or other materials collected shall be used 
solely in accordance with this protocol, unless otherwise agreed to in writing by AnaptysBio. 
Subjects will only be identified by unique subject numbers on eCRFs. Every subject will be 
given a copy of each version of the ICF that he or she signs before and during the study. Each 
ICF may also include authorization allowing the institution, Investigator, and AnaptysBio to use 
and disclose personal health information in compliance with the Health Information Portability 
and Accountability Act (HIPAA). 
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FUTURE USE OF STORED SPECIMENS AND DATA  
-identified biological samples will be 
stored at a certified, licensed central laboratory. During the conduct of the study, a subject may 
choose to withdraw consent to have biological specimens stored for future research. Once 
samples have been analyzed specimens will be destroyed. If no analyses have been completed 
within 5 years following EOS, samples will be destroyed.  
Any remaining serum/plasma from samples collected for PK/PD immunogenicity endpoints may 
be retained for assay method development, troubleshooting, or validation. These samples may 
also be used for research purposes, but will not be used for any type of genetic analyses. 
 
MEDICAL MONITOR 
Medical monitoring will be conducted to ensure the early recognition, identification and 
-being throughout the trial. Details of 
medical monitoring with contact information of the Medical Monitors will be documented in a 
Medical Monitoring Plan. 
 
SAFETY OVERSIGHT 
No data and safety monitoring board is required as part of this study. 
 
CLINICAL MONITORING 
All aspects of the study will be monitored by AnaptysBio or authorized representatives of 
AnaptysBio according to GCP and Standard Operating Procedures (SOPs) for compliance with 
applicable government regulations, (ie, Informed Consent Regulations [US 21CFR, Part 50] and 
Institutional Review Board regulations [US 21CFR, Part 56.103]).  
Access to all records, both during the study and after study completion, should be made available 
to AnaptysBio at any time for review and audit to ensure the integrity of the data. The 
Investigator must notify AnaptysBio immediately if the responsible IRB/EC has been 
disqualified or if proceedings leading to disqualification have begun.  
The Investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines; applicable informed consent regulations (US 21CFR, Part 50); and in compliance 
with the Declaration of Helsinki. Every attempt must be made to follow the protocol and to 
obtain and record all data requested for each subject at the specified times. If data are not 
recorded per protocol, the reasons must be clearly documented on the eCRF/records.  
Before study initiation, at a study site initiation visit or at a meeting with the Investigator(s), a 
representative from AnaptysBio will review the protocol and study eCRFs with the 
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Investigator(s) and their staff. During the study, the study monitor will visit the study site 
regularly to check the completeness of subject records, the accuracy of entries on the eCRFs, the 
adherence to the protocol and to GCP, the progress of enrollment, and to ensure that consent is 
being sought and obtained in compliance with applicable regulations, and that the study drug is 
being stored, dispensed and accounted for according to specifications.  
The Investigator and key study personnel must be available to assist the monitor during these 
visits. The Investigator must give the monitor access to relevant hospital or clinical records, to 
confirm their consistency with the eCRF entries. No information in these records about the 
identity of the subjects will leave the study site.  
Monitoring standards require full verification for the presence of informed consent, adherence to 
the inclusion/exclusion criteria, documentation of SAEs, and the recording of primary efficacy 
and safety variables. Additional checks of the consistency of the source data with the eCRFs will 
be performed according to the study-specific Monitoring Plan.  
responsible for reviewing them and clarifying and resolving any data queries. A copy of the 
eCRFs will be retained by the Investigator who must ensure that it is stored in a secure place 
with other study documents, such as the protocol, the IB, and any protocol amendments.  
The Investigator must provide AnaptysBio and the responsible IRB/EC with a study summary 
shortly after study completion, or as designated by AnaptysBio. 
 
QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.   
Quality control (QC) procedures will be implemented beginning with the data entry system, and 
data QC checks, which will be run on the database, will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated and biological specimens are collected, documented (recorded), and reported in 
compliance with the protocol, ICH GCP, and applicable regulatory requirements (eg, GLP, Good 
Manufacturing Practices [GMP]).  
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by AnaptysBio, and inspection by 
IRB/EC and local and regulatory authorities. 
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DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
All protocol-specified data will be recorded in site source documents. Study data will be entered 
completion of the study, the Investigator is required to sign and affirm the data entered in the 
subject CRF along with a statemen
reviewed. All Investigator data attestation signatures will be made through the 21 CFR Part11 
 
It is AnaptysBio  policy that study data be verifiable with the source data which necessitates 
access to all original recordings, laboratory reports, and other records for each subject. The 
e data must be 
made available for all study data. Subjects (or their legal representatives) must also allow access 
to their medical records. Subjects will be informed of the importance of increased record access 
and permission granted by signature on the informed consent document prior to screening.  
Checks will be performed to ensure quality, consistency, and completeness of the data. Instances 
of missing or uninterpretable data will be resolved with the Investigator or study coordinator. 
Data queries, documented within the clinical database, will be accessible to the research facility 
through the EDC system. Study site personnel will be responsible for providing resolutions to the 
data queries and for correcting the eCRFs, as appropriate. 
The Investigator must keep written or electronic source documents for every subject participating 
in the clinical study. for the appropriate document retention period. The subject file that 
identifies the study in which the subject is participating must include the subject
demographic and medical information including:  
 Name 
 Contact information 
 Year of birth 
 Sex 
 Medical history 
 Concomitant therapies/medication 
 Study visit dates 
 Performed examinations, evaluations, and clinical findings 
 Investigational product administration 
 AEs, SAEs, or pregnancy (as applicable)  
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Additionally, any other documents with source data, especially original printouts of data that 
laboratory v
the date of the evaluation.  
The data recorded during the course of the study will be documented in the eCRF and/or the 
study-specific forms. Before or at study termination, all data must be forwarded to AnaptysBio. 
The data will then be recorded, evaluated, and stored in anonymous or coded form in accordance 
with data-protection regulations.  
Subjects will authorize the use of their protected health information during the informed consent 
process in accordance with the applicable privacy requirements. Subjects who deny permission 
to use and disclose protected health information will not be eligible to participate in the study.  
The Investigator will ensure that the study documents forwarded to AnaptysBio, and any other 
documents, contain no mention of subject names. Any amendments and corrections necessary 
will be undertaken in both the source documents and eCRFs (as appropriate), and countersigned 
by the Investigator, or documented designee, stating the date of the amendment/correction. 
Errors must remain legible and may not be deleted with correction aids. The Investigator must 
state his/her reason for the correction of any data. In the case of missing data/remarks, the entry 
spaces provided in the eCRF should be cancelled out so as to avoid unnecessary follow-up 
inquiries.  
Electronic CRFs will be kept by AnaptysBio or an authorized designee in a secured area. Clinical 
data will be recorded in a computer format for subsequent statistical analyses. Data files will be 
stored on electronic media with a final master data file kept by AnaptysBio after descriptive and 
statistical analyses and reports have been generated and are complete.  
It is the responsibility of the Investigator to ensure that the study site file is maintained in 
accordance with the ICH Guidance for Industry E6(R2) GCP: Consolidated Guidance, Section 8 
 Essential Documents for the Conduct of a Clinical Trial. 
10.1.9.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region, and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study treatment. These documents should be 
retained for a longer period, however, if required by local regulations or as specified in the study 
agreement, whichever retention period is longer.  
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If the Investigator withdraws from the study (eg, relocation, retirement) all study-related records 
should be transferred to a mutually agreed upon designee. Notice of such transfer will be 
provided to AnaptysBio in writing. No records will be destroyed without the written consent of 
AnaptysBio, if applicable. It is the responsibility of AnaptysBio to inform the Investigator when 
these documents no longer need to be retained.  
 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP 
requirements. The noncompliance may be either on the part of the subject, the Investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site 
and implemented promptly. Protocol deviations related to COVID-19 pandemic will be 
identified and documented accordingly. 
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 Investigator to use continuous vigilance to identify and report 
deviations as soon as possible. All deviations must be addressed in study source documents, and 
applicable deviations must be sent to the reviewing IRB/EC per their policies. The Investigator is 
responsible for knowing and adhering to the reviewing IRB/EC requirements. Further details 
about the handling of protocol deviations will be included in the Protocol Deviation Management 
Plan, Data Management Plan, Medical Monitoring Plan, blind data review documentation, and 
SAP.  
This study will be conducted as described in this protocol, except for an emergency situation in 
which the protection, safety, and well-being of the subject requires immediate intervention, 
based on the judgment of the Investigator (or a designee, appropriately trained professional 
designated by the Investigator). In the event of a significant deviation from the protocol due to an 
emergency, accident, or mistake, the Investigator or designee must contact the Medical Monitor 
and AnaptysBio at the earliest possible time by telephone. This will allow an early joint decision 
Investigator and the Medical Monitor. Please refer to Section 4.5 for allowable, as necessary, 
modifications to the protocol due to COVID-19 restrictions. 
The monitor must ensure that a prompt action is taken to secure compliance. If a noncompliance 
that significantly affects or has the potential to significantly affect human subject protection or 
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88 
reliability of trial results is discovered, the CRO and AnaptysBio should perform a root cause 
analysis and implement appropriate corrective and preventive actions. 
 PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: It is understood by the Investigator that the information generated in 
this study will be used by AnaptysBio in connection with the development of the product. To 
allow for the use of information derived from the study, it is understood that the Investigator is 
obliged to provide the AnaptysBio with complete test results, all study data, and access to all 
study records.  
Any results of medical investigations with AnaptysBio
publication/lecture/manuscripts based thereon, shall be exchanged and discussed by the 
Investigator and AnaptysBio representative(s), 30 days before submission for publication or 
presentation. Due regard shall be given to AnaptysBio
manuscript authorship, obtaining optimal patent protection, coordinating and maintaining the 
proprietary nature of submissions to health authorities, coordinating with other ongoing studies 
in the same field, and protecting confidential data and information. AnaptysBio shall be 
furnished with a copy of any proposed publication. Comments shall be rendered without undue 
delay.  
In cases of publications or presentations of material arising from multicenter clinical 
investigations, the AnaptysBio is to serve as coordinator and referee. Individual Investigators 
who are part of a multicenter investigation may not publish or present data that are considered 
common to a multicenter investigation without the consent of the other participating 
Investigators and the prior review of AnaptysBio.  
Results from investigations shall not be made available to any third party by the investigating 
team outside the publication procedure as outlined previously. AnaptysBio will not quote from 
publications by Investigators in its scientific information and/or promotional material without 
full acknowledgment of the source (ie, author and reference). 
 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any 
actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, 
financial interest, or any aspect of this trial will be disclosed and managed. Furthermore, persons 
who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this study. AnaptysBio 
has established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. 
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Efficacy and Safety of Imsidolimab in Subjects with Acne Vulgaris 
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91 
Jemec GB. Hidradenitis suppurativa. N Engl J Med 2012;366:158-164 
Kimball AB, Jemec GB, Yang M et al. Assessing the validity, responsiveness and meaningfulness of the 
hidradenitis suppurativa clinical response (HiSCR) as the clinical endpoint for hidradenitis suppurativa 
treatment. Br J Dermatol 2014; 171: 1434 42. 
Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC et al. Two Phase 3 Trials 
of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016 Aug 4;375(5):422-34. doi: 
10.1056/NEJMoa1504370. PMID: 27518661. 
Kirby, J., Thorlacius, L., Villumsen, B., Ingram, J., Garg, A., Christensen, K., Butt, M., Esmann, S., Tan, 
J. and Jemec, G. The Hidradenitis Suppurativa Quality of Life (HiSQOL) score: development and 
validation of a measure for clinical trials. Br J Dermatol 2020, 183: 340-
348. https://doi.org/10.1111/bjd.18692 
Micheletti RG. Natural history, presentation, and diagnosis of hidradenitis suppurativa. Semin Cutan Med 
Surg. 2014 Jun;33(3 Suppl):S51-3. doi: 10.12788/j.sder.0092. PMID: 
25188458https://pubmed.ncbi.nlm.nih.gov/25188458/ 
Nagy I, Pivarcsi A, Koreck A, Széll M, Urbán E, Kemény L. Distinct strains of Propionibacterium acnes 
induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-
like receptors. J Invest Dermatol. 2005 May;124(5):931-8. doi: 10.1111/j.0022-202X.2005.23705.x. 
PMID: 15854033. 
Sartorius K, Emtestam L, Jemec GB et al. Objective scoring of hidradenitis suppurativa reflecting the role 
of tobacco smoking and obesity. Br J Dermatol 2009; 161: 831 839. 
Suh D, Kwon H. What's new in the physiopathology of acne? Br J Dermatol 2015 172: 13-19. 
https://doi.org/10.1111/bjd.13634 
Thomi R, Kakeda M, Yawalkar N, Schlapbach C, Hunger RE. Increased expression of the interleukin-36 
cytokines in lesions of hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2017 Dec;31(12):2091-
2096. doi: 10.1111/jdv.14389. Epub 2017 Aug 29. PMID: 28602023. 
Von Der Werth, J. and Williams, H. (2000), The natural history of hidradenitis suppurativa. Journal of 
the European Academy of Dermatology and Venereology, 14: 389-392. https://doi.org/10.1046/j.1468-
3083.2000.00087.x 
Yalcin I, Bump R. Validation of two global impression questionnaires for incontinence. Am J Obstet 
Gynecol. 2003;189:98-101. 
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93 
 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 pregnant. 
In addition, male subjects must refrain from donating sperm for the duration of the study and for 
200 days after the last dose of study treatment. 
Male subjects 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 for 
the duration of the study and for 200 days after the last dose of study treatment. 
Female subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use highly 
effective methods of contraception consistently and correctly as described in the table below and 
during the protocol-defined time frame in Section 5.1, and refrain from donating oocytes for 
assisted reproduction during this period. For WOCBP, hormonal contraceptives must be used 
without schedule changes and in steady doses during the study treatment. Starting hormonal 
contraceptives during the study is not permitted. Use of any hormonal contraceptives containing 
drospirenone, chlormadinone acetate and cyproterone acetate is prohibited unless part of a stable 
contraceptive regimen as described in Section 6.5.1. 
 
 
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95 
Collection of Pregnancy Information 
Male subjects with partners who become pregnant: 
partner who becomes pregnant while the male subject is in this study. This applies only to male 
subjects who receive study treatment. 
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the Investigator will record pregnancy information on the appropriate pregnancy form and 
submit it to the pharmacovigilance unit within 24 hr 
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 AnaptysBio. 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.  
Any SAEs associated with the pregnancy in the male subj
the pharmacovigilance unit within 24 hr of the event using the back-up Paper Report Form. 
Female subjects who become pregnant  
The Investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate form 
and submitted to the pharmacovigilance unit within 24 hr 
The subject will be followed to determine the outcome of the pregnancy. The Investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the AnaptysBio. Generally, follow-up will not be required for longer than 6 to 
8 weeks after the 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 or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is 
always considered to be an SAE 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 AnaptysBio as described in Section 8.2.1.8. While the 
Investigator is not obligated to actively seek this information in former subjects, he or she may 
learn of an SAE through spontaneous reporting.  
Any female subject who becomes pregnant while participating in the study will be withdrawn 
from the study. 
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101 
 
other people calling you names, teasing, 
 
 
Only a little 
 
 
 
bullying, asking questions or avoiding you? 
 
 
Not at all 
 
 
 
9. 
Over the last week, how much has your sleep  
 
 
Very much 
 
 
 
been affected by your skin problem? 
 
 
 
Quite a lot 
 
 
 
 
 
 
 
 
 
 
 
Only a little 
 
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
 
10. 
Over the last week, how much of a  
 
 
 
Very much 
 
 
 
problem has the treatment for your  
 
 
 
Quite a lot 
 
 
 
skin been? 
 
 
 
 
 
 
Only a little 
 
 
 
 
 
 
 
 
 
 
  
Not at all 
 
 
 
Please check that you have answered EVERY question. Thank you.  
 
©M.S. Lewis-Jones, A.Y. Finlay, May 1993. This must not be copied without the permission of the authors. 
 
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107 
Laboratory 
Assessments 
Parameters 
Follicle stimulating 
hormone (FSH) 
In women of nonchildbearing potential only (postmenopausal woman with at least 12 
months of amenorrhea without an alternative medical cause) 
Urinalysis 
Bilirubin  
pH 
Blood 
Protein 
Glucose 
Specific gravity 
Ketones 
Urobilinogen 
Leukocytes 
 
Nitrites 
 
Microscopy (At discretion of Investigator 
based on urinalysis results) 
 
 
Viral serology and 
testing 
Antibodies to hepatitis B core antigens
Hepatitis B surface antigen 
Hepatitis C antibody and reflex RNA 
 
Human immunodeficiency virus 
antibodies 
 
Tuberculosis (TB) 
screening 
QuantiFERON-TB Gold® In-Tube, the third-generation test (If the test indeterminate 
it can be retested only once).  
NOTES: Please see SoA for laboratory tests time points. 
All blood samples must be drawn prior to administration of the study treatment, unless otherwise specified. The 
date and exact time of sample collection must be recorded. 
 
AnaptysBio, ANB019
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SAP_001.pdf: 
 
 
 
 
 
Clinical Study Report 
Protocol Number: ANB019-209 
Sponsor: AnaptysBio, Inc. 
 
______________________________________________________________________________ 
 
16.1.9 
Documentation of Statistical Methods 
16.1.9.1 
Statistical Analysis Plan for Study ANB019-209 – Version 1.0 (28 Feb 2022) 
 
Page 1 of 50


 
 
 
CONFIDENTIAL 
Page 1 of 49 
 
 
STATISTICAL ANALYSIS PLAN 
FOR STUDY ANB019-209 
 
Trial Sponsor: 
Protocol Number: 
AnaptysBio, Inc. 
ANB019-209 
IND Number: 
136145
Investigational Drug: 
Indication: 
Anti-interleukin 36 receptor monoclonal antibody 
Subjects with Acne Vulgaris 
Drug Number: 
ANB019 (Imsidolimab) 
Dosage Form/Strength/Dose: 
Solution for Injection/100 mg/400, 200 or 100 mg 
 Imsidolimab 400 mg on Day 1, followed by 200 mg on 
Days 29 and 57. 
 Imsidolimab 200 mg on Day 1, followed by 100 mg on 
Days 29 and 57. 
 Placebo on Days 1, 29, and 57
 
 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and 
Safety of Imsidolimab (ANB019) in the Treatment of Subjects with Acne Vulgaris 
 
Version: 
v1.0 
Sign-off Date: 
 
Archive Date: 
 
 
 
  
 
 
 
Page 2 of 50






 
Statistical Analysis Plan 
Protocol No. ANB019-209
Last Revision Date: 28 FEB 2022 
 
CONFIDENTIAL 
Page 4 of 49 
CHANGE LOG FOR CHANGES MADE AFTER THE INITIAL APPROVAL 
Revision 
Date* 
Section(s) 
Modified 
Brief Description of Revision(s) or 
Reason(s) for Revision 
Modifications Reviewed and 
Approved by** 
AnaptysBio, Everest 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Update the Last Revision Dates on the cover page and the document header. 
** 
 
 
 
  
 
 
 
 
 
 
Page 5 of 50


 
Statistical Analysis Plan 
Protocol No. ANB019-209
Last Revision Date: 28 FEB 2022 
 
CONFIDENTIAL 
Page 5 of 49 
TABLE OF CONTENTS 
SIGNATURES .............................................................................................................................................................. 2 
CHANGE LOG FOR CHANGES MADE AFTER THE INITIAL APPROVAL ................................................. 4 
TABLE OF CONTENTS ............................................................................................................................................. 5 
GLOSSARY OF ABBREVIATIONS ......................................................................................................................... 7 
1. 
INTRODUCTION ............................................................................................................................................. 9 
2. 
STUDY OBJECTIVES..................................................................................................................................... 9 
2.1 PRIMARY OBJECTIVE ................................................................................................................................... 9 
2.2 SECONDARY OBJECTIVES ............................................................................................................................ 9 
2.3 EXPLORATORY OBJECTIVES ........................................................................................................................ 9 
3. 
STUDY DESIGN ............................................................................................................................................... 9 
3.1 STUDY DESIGN ............................................................................................................................................ 9 
3.2 RANDOMIZATION ....................................................................................................................................... 10 
3.3 HYPOTHESIS TESTING ................................................................................................................................ 10 
3.4 INTERIM ANALYSIS .................................................................................................................................... 11 
3.5 SAMPLE SIZE ............................................................................................................................................. 11 
3.6 STUDY PROCEDURES AND SCHEDULE OF ACTIVITIES ................................................................................ 12 
4. 
DATA AND ANALYTICAL QUALITY ASSURANCE ............................................................................. 15 
5. 
ANALYSIS SETS ............................................................................................................................................ 15 
5.1 INTENT-TO-TREAT ANALYSIS SET ............................................................................................................. 15 
5.2 SAFETY ANALYSIS SET .............................................................................................................................. 15 
5.3 PER PROTOCOL ANALYSIS SET .................................................................................................................. 15 
5.4 PHARMACOKINETIC ANALYSIS SET ........................................................................................................... 15 
5.5 POPULATIONS FOR PRIMARY ANALYSES ................................................................................................... 15 
6. 
SPECIFICATION OF ENDPOINTS AND VARIABLES .......................................................................... 16 
6.1 DEMOGRAPHIC AND BASELINE CHARACTERISTICS ................................................................................... 16 
6.1.1 
Demography and Physical Characteristics................................................................................ 16 
6.1.2
Medical and Surgical History ................................................................................................... 17
6.1.3 
Prior and Concomitant Medications ......................................................................................... 17 
6.2 EFFICACY .................................................................................................................................................. 17 
6.2.1 
Study Day and Visit Window Definitions ................................................................................ 17 
6.2.2 
Primary Efficacy Variable ........................................................................................................ 18 
6.2.3 
Secondary Efficacy Variables ................................................................................................... 18 
6.2.4 
Exploratory Efficacy Variables................................................................................................. 21 
6.3 PHARMACOKINETIC VARIABLES ................................................................................................................ 28 
6.4 IMMUNOGENICITY VARIABLES .................................................................................................................. 28 
6.5 BIOMARKER VARIABLES .. ........................................................................................................................ 29 
6.6 SAFETY ...................................................................................................................................................... 29 
6.6.1 
Study Day and Visit Window Definitions ................................................................................ 29 
6.6.2 
Extent of Exposure to Study Medication and Compliance ....................................................... 30 
6.6.3 
Adverse Events ......................................................................................................................... 30 
6.6.4 
Laboratory Data ........................................................................................................................ 31 
6.6.5 
Vital Signs ................................................................................................................................. 31 
6.6.6 
Electrocardiogram (ECG) ......................................................................................................... 31 
6.6.7 
Other Safety Assessments......................................................................................................... 31 
  
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7. 
STATISTICAL ANALYSIS........................................................................................................................... 31 
7.1 DATA HANDLING RULES AND DEFINITIONS, INCLUDING HANDLING OF MISSING DATA .......................... 31 
7.2 SUBJECT DISPOSITION ............................................................................................................................... 34 
7.3 DEVIATIONS .............................................................................................................................................. 34 
7.4 DEMOGRAPHIC AND BASELINE CHARACTERISTICS ................................................................................... 34 
7.4.1 
Demography and Physical Characteristics................................................................................ 34 
7.4.2 
Medical and Surgical History ................................................................................................... 34 
7.4.3 
Prior and Concomitant Medications ......................................................................................... 35 
7.5 EFFICACY ANALYSES ................................................................................................................................ 35 
7.5.1 
Primary Efficacy Analysis ........................................................................................................ 35 
7.5.2 
Secondary Efficacy Analyses ................................................................................................... 36 
7.5.3 
Exploratory Efficacy Analyses ................................................................................................. 38 
7.5.4
Sensitivity Analyses.................................................................................................................. 38
7.5.5 
Subgroup Analyses ................................................................................................................... 39 
7.6 PHARMACOKINETIC ANALYSES ................................................................................................................. 40 
7.7 IMMUNOGENICITY ANALYSES ................................................................................................................... 40 
7.8 BIOMARKER ANALYSES ............................................................................................................................. 40 
7.9 SAFETY ANALYSES .................................................................................................................................... 40 
7.9.1 
Extent of Exposure to Study Medication and Compliance ....................................................... 40 
7.9.2 
Adverse Events ......................................................................................................................... 41 
7.9.3 
Laboratory Data ........................................................................................................................ 42 
7.9.4 
Vital Signs ................................................................................................................................. 42 
7.9.5 
Electrocardiogram (ECG) ......................................................................................................... 42 
7.9.6 
Other Safety Assessments......................................................................................................... 42 
8. 
CHANGES FROM METHODS PLANNED IN THE PROTOCOL ......................................................... 42 
9. 
STATISTICAL SOFTWARE ........................................................................................................................ 43 
10. 
REFERENCES ................................................................................................................................................ 43 
11. 
APPENDIX 1 DATA HANDLING RULES.................................................................................................. 44 
12. 
APPENDIX 2 SAS CODE FOR STATISTICAL ANALYSES ................................................................... 46 
13. 
APPENDIX 3 MOCKUP TABLES, LISTINGS, AND GRAPHS (TLGS) ................................................ 49 
 
 
  
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GLOSSARY OF ABBREVIATIONS
Abbreviation
Term 
ADA 
Anti-drug antibody 
AE
Adverse event
ATC 
Anatomical Therapeutic Chemical
AV 
Acne Vulgaris 
BDRM
Blinded data review meeting
BMI 
Body mass index 
BLQ 
Below the limit of quantitation 
CDLQI 
 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case report form 
CV 
Coefficient of variation 
DLQI
Dermatology Life Quality Index 
ECG 
Electrocardiograms
eCRF 
Electronic case report forms 
Everest 
Everest Clinical Research 
FCS 
Fully Conditional Specification 
FSH
Follicle-stimulating hormone 
IGA 
Investigator Global Assessment 
GEE 
Generalized estimating equations 
IND 
Investigational new drug  
ITT 
Intention-to-treat 
LS 
Least squares 
MCMC 
Monte Carlo Markov Chain 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed model for repeated measures 
  
 
 
 
 
 
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GLOSSARY OF ABBREVIATIONS
Abbreviation
Term 
NCA
Non-compartmental analysis 
PAS
Parametric Acne Severity 
PGA 
 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK 
Pharmacokinetic 
PP 
Per Protocol 
Prob 
Probability 
SAE 
Serious adverse event 
SAP
Statistical analysis plan 
SAS
Statistical analysis system 
SC 
Subcutaneous/subcutaneously 
SD 
Standard deviation 
SoA 
Schedule of Activities 
SOC 
System organ class 
SOP
Standard operating procedure 
SSQ
Subject Satisfaction Questionnaire 
SSRS 
Subject Satisfaction Rating Scale 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
WHO Global 
World Health Organization Drug Dictionary 
WOCBP 
Woman of childbearing potential 
  
 
 
 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the pre-specified statistical methods for the display, 
summary, and analysis of data collected within the scope of the latest version of the ANB019-209 
Protocol (Version 1.0 dated 12 February 2021). As with any SAP, the proposed methods and approaches 
to the data analysis should be deemed as flexible. The analysis of the data should allow changes in the 
plan to the extent that deviations from the original plan would provide a more reliable and valid analysis 
of the data. As such, the statistical analysis to a certain degree is iterative since much of the planning is 
based on assumptions that require verification. The purpose of this plan is to provide general guidelines 
from which the analysis will proceed. Nevertheless, deviations from these guidelines must be 
substantiated by a sound statistical rationale. 
The SAP should be read in conjunction with the study protocol and the Case Report Forms (CRFs). This 
version of the SAP has been developed using the final version of the protocol mentioned above. 
This study is designed to evaluate the efficacy and safety of imsidolimab in the treatment of subjects with 
acne vulgaris (AV). (See Protocol Sections 2.1 to 2.3 for details.) 
2. STUDY OBJECTIVES 
2.1 
Primary Objective 
 
To evaluate the efficacy of imsidolimab in subjects with AV 
2.2 
Secondary Objectives 
 
To evaluate the safety of imsidolimab in subjects with AV 
 
To evaluate the effect of imsidolimab on AV signs and symptoms and quality of life in subjects 
with AV 
2.3 
Exploratory Objectives 
 
To further evaluate the effect of imsidolimab on AV signs and symptoms and quality of life in 
subjects with AV 
 
To explore the effect of imsidolimab on cutaneous biomarkers 
 
To test for immunogenicity to imsidolimab 
 
To describe the PK profile of imsidolimab in subjects with AV 
3. STUDY DESIGN 
3.1 
Study Design 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of imsidolimab in adolescent and adult subjects with AV. This study also will 
characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to 
imsidolimab in subjects with AV. This study will be conducted at approximately 15 sites, contributing 
approximately 8-12 subjects per site. Approximately 120 adult male and female subjects, aged 12 to 45 
years with clinically confirmed diagnosis of AV will be enrolled in this study. At the screening and Day 1 
visits, the subjects will need to have a facial Investigator Global Assessment (IGA) score of 3 (moderate) 
or 4 (severe), at least 20 and no more than 100 inflammatory lesions on the face, no more than 100 
noninflammatory lesions on the face, and no more than 5 
 mm) on the face. Eligible subjects 
  
 
 
 
 
 
 
 
 
 
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will be randomized (1:1:1) to receive either imsidolimab (at 1 of 2 different regimens) or placebo, 
subcutaneously (SC) administered on 3 occasions: Day 1, Day 29 (Week 4), and Day 57 (Week 8). The 
randomization will be stratified based on facial IGA score at baseline (3 [moderate] vs. 4 [severe]). The 
maximum study duration per subject is approximately 24 weeks, which includes a screening period of up 
to 30 days followed by a 12-week treatment period and an 8-week safety follow-up period. 
The overall study design is summarized and illustrated in Figure 1. 
 
Abbreviations: D, day; SC, subcutaneously; W, week. 
a Study treatment will be administered according to the following schedule: 
Arm 1: Imsidolimab 400 mg on Day 1, 200 mg on Days 29 and 57
Arm 2: Imsidolimab 200 mg on Day 1, 100 mg on Days 29 and 57
Arm 3: Placebo on Days 1, 29, and 57 
Study treatment will be administered as 2 × 2 mL injections on Day 1 and 1 x 2 mL injection on Days 29 and 57, according to 
Protocol Table 3. 
Figure 1 
Study Schema
3.2 
Randomization 
On Day 1, after verification that all inclusion and no exclusion criteria have been met, the subjects will be 
stratified by facial IGA score at baseline (3 [moderate] vs. 4 [severe]) and randomized in a 1:1:1 ratio to 
receive imsidolimab at one of two doses or placebo. 
3.3 
Hypothesis Testing 
The primary analysis for this study is to compare the mean facial inflammatory lesion count for 
imsidolimab at each dose with placebo during the treatment period, at a two-sided alpha = 0.10 level. Any 
  
 
 
 
 
 
 
  
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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testing being performed for secondary or exploratory endpoints will be considered exploratory in nature 
based on a 2-sided alpha = 0.10. 
H0
imsidolimab - 
Placebo = 0 vs. HA
imsidolimab - 
Placebo 
 
3.4 
Interim Analysis 
A primary analysis, considered as the interim analysis of this study, will be performed when all 
randomized subjects have reached Week 12 or discontinued. The purpose of the primary analysis is to 
assist AnaptysBio executive management in making decisions for potential future development of this 
compound. No adjustments to the protocol are planned as a result of the primary analysis; as such, the 
type I error will not be adjusted in the primary analysis and is expected to be maintained at 0.10, 
two-sided. 
Only data collected on or prior to the data cut-off date will be included in the primary analyses. 
Generation of Blinded Reports
In the primary analysis, blinded tables, listings, and graphs will be produced by the Everest Clinical 
Research Corporation (Everest) study statistician and study programmer based upon dummy 
randomization codes. Blinded reports may be shared with the study team for review of ongoing data, 
production of dry run results, or other reasons as Everest standard operating procedures (SOPs) and 
AnaptysBio SOPs allow. 
Generation of Unblinded Reports 
The subject, clinical site personnel, and AnaptysBio will be unaware of the randomized treatment 
assigned to a subject. However, the primary analysis itself will be unblinded. At Everest, only the 
Unblinded Statistician and the Unblinded Programmer(s) responsible for the primary analysis will be 
aware of the treatment assigned to a subject. The Unblinded Statistician and Unblinded Programmer(s) 
will both be appointed by Everest, a company external to AnaptysBio. The Unblinded Statistician and 
Unblinded Programmer(s) will not be involved in writing the SAP, or in decisions about how the 
statistical analyses will be conducted, or in daily activities of this study other than those involved in 
preparing and performing unblinded primary analysis; however, these individuals may be involved in the 
generation of the randomization list for this study. The Unblinded Statistician and Unblinded 
Programmer(s) will function independently of the investigators and AnaptysBio/Innovaderm clinical 
study team members. All unblinded roles and responsibilities of these individuals, the sources of the 
unblinded information, and the processes to maintain the blind are detailed in the Unblinded Data 
Management Plan. 
The Unblinded Statistician and Unblinded Programmer(s) will be in possession of unblinding treatment 
codes produced for the Interactive Web-based Response System (IWRS) which is used to randomize 
subjects to treatment, and managed by a separate team at Everest. Upon successful generation of the 
blinded versions of the datasets and analyses, the Unblinded Statistician and Unblinded Programmer(s) 
will be responsible for generating unblinded datasets and analyses according to this SAP. The unblinded 
primary analysis results will be provided to a designated member of AnaptysBio executive management 
by the Unblinded Statistician. 
3.5 
Sample Size 
Approximately 120 subjects will be stratified based on facial IGA score at baseline (3 [moderate] vs. 
4 [severe]) and randomized in a 1:1:1 ratio to receive one of the following study treatments: 
 
Imsidolimab 400 mg on Day 1, 200 mg on Days 29 and 57 
  
 
 
 
 
 
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Imsidolimab 200 mg on Day 1, 100 mg on Days 29 and 57 
 
Placebo on Days 1, 29, and 57 
Assuming a total of 10% of subjects will discontinue prior to Week 12, there will be approximately 
108 evaluable subjects (36 subjects in each arm) at the end of Week 12. 
The study has 80% power to detect a between-group treatment difference of 6.1 lesions in the primary 
endpoint of mean change from baseline in the facial inflammatory lesion count at Week 12, using a 2-
sided, equal-variance two-sample t-
deviation (SD) of 10.4 lesions. The assumption was based on Arazlo (tazarotene) acne Phase 3 Study 
Trial-301 results.1 Table 1 shows more information on power from a set of scenarios of variability and 
between-group mean differences. 
Table 1
Power Exploration for Different Scenarios of Variability and Between-group Mean 
Differences 
Common Standard 
Deviation 
Between-group Mean 
Difference 
Power (%) 
1-sided Test 
2-sided Test 
8 
3 
62 
48 
 
4 
80 
68 
 
5 
92 
84 
 
6 
97 
94 
10 
3 
50 
36 
 
4 
66 
52 
 
5 
80 
68 
 
6 
90 
82 
12 
3 
41 
28 
 
4 
55 
41 
 
5 
69 
55 
 
6 
80 
68 
Note: An equal variance two-sample t-test at alpha=0.10 is used for the power calculations. 
3.6 
Study Procedures and Schedule of Activities 
Study procedures and their timing are summarized in the Schedule of Activities (Table 2).
  
 
 
  
    
 
 
 
 
 
  
 
 
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Table 2
Schedule of Activities 
 
Screening 
Period 
Treatment Period 
Follow-Up 
Period 
Concomitant medication reviewl 
X 
Continuously 
Abbreviations: ADA, anti-drug antibody; AE, adverse event; CDLQI, 
 D, day; 
DLQI, Dermatology Life Quality Index; ECG, electrocardiogram; EOS, end of study; ET, early termination, FSH, follicle-
essment; PGI-C, Patient Global 
Impression of Change; PGI-S, Patient Global Impression of Severity; PK, pharmacokinetic; SAE, serious adverse event; SC, 
subcutaneous; SoA, Schedule of Activities; SSRS, Subject Satisfaction Rating Scale; SSQ, Subject Satisfaction Questionnaire; 
TB, tuberculosis; W, week; WOCBP, woman of childbearing potential. 
a The ET visit will include all procedures to be done at the EOS visit (Day 141 [Week 20]).  
b Adolescent subjects who reach 18 years of age during the study must be reconsented as adults.  
c Height will be measured at screening only. Subjects below the age of 18 at the start of the study will have 
height measured at Week 12. 
d Refer to Protocol Section 8.2.3 for details regarding the complete physical examination.  
e Refer to Protocol Section 8.2.4 for details and instructions regarding vital signs. 
f Refer to Protocol Section 8.2.5 for details and instructions regarding the ECG. In addition to the time points 
specified in the SoA, ECGs may be performed at any time during the study if, in the opinion of the Investigator, 
it is clinically warranted. 
g If a negative QuantiFERON®-TB Gold test result was obtained within 6 months of screening, it can be skipped 
at screening. A chest X-ray will be administered per local standards, as required. The FSH testing is performed 
for women not of childbearing potential (postmenopausal women with at least 12 months of amenorrhea 
without an alternative medical cause). An adolescent subject who experiences menarche during the trial will be 
considered a WOCBP (refer to Protocol Appendix 1 for definition of WOCBP) and will be required to follow 
the contraceptive guidance in Protocol Appendix 1 and undergo scheduled pregnancy testing. Additional 
pregnancy testing may be performed whenever a menstrual cycle is missed or when pregnancy is otherwise 
suspected. Refer to Protocol Appendix 10 for instructions regarding clinical laboratory parameters. 
h Refer to Protocol Section 8.1 for details and instructions regarding facial lesion count, facial IGA, truncal 
(chest, neck, and back) IGA, PGI-S, PGI-C, DLQI 
/CDLQI (subjects < 16 years of 
age), SSQ, and SSRS. Facial IGA must be performed before facial lesion count.  
i On Day 1, samples for PK will be collected at predose and 2 hr (± 10 min) post SC administration. See 
Table 7. 
j Tape stripping will be performed for all randomized subjects as part of this study (not optional). Tape strips 
will be collected from non-lesional and lesional skin at Day 1 and Week 12 and from lesional skin at Week 4. 
k During the treatment period, subjects will receive either imsidolimab or placebo SC administered as follows: 
400 mg imsidolimab, 200 mg imsidolimab, or placebo on Day 1; followed by 200 mg imsidolimab, 100 mg 
imsidolimab, or placebo on Days 29 and 57.  
l At screening, prior medications should be reviewed and documented. Refer to Protocol Section 6.5. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
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4. DATA AND ANALYTICAL QUALITY ASSURANCE 
The overall quality assurance procedures for the study data, statistical programming, and analyses are 
described in 
s. Detailed data management procedures are documented in the Data 
Management Plan, Data Validation Check Specifications, and Data Review Plan. Detailed statistical and 
programming quality control and quality assurance procedures are documented in the Statistical Analysis 
and Programming Quality Control/Quality Assurance Plan. 
The study endpoints and analytic approaches are both prospectively defined and documented in the 
protocol and in this SAP. The SAP will be finalized prior to the primary analysis data snapshot, and 
protocol deviations will be identified and decisions for inclusion and exclusion of subjects from the Per 
Protocol Analysis Set (Section 5.3) will be made prior to the final database lock and data analysis. 
5. ANALYSIS SETS 
5.1 
Intent-to-Treat Analysis Set 
The Intent-to-Treat (ITT) Analysis Set will include all randomized subjects. In this analysis set, treatment 
will be assigned based upon the treatment arm to which subjects were randomized regardless of which 
treatment they receive. ITT Analysis Set will be used for primary, secondary, and exploratory efficacy 
analyses. 
5.2 
Safety Analysis Set 
The Safety Analysis Set will include all randomized subjects who receive at least 1 dose of imsidolimab 
or placebo. The Safety Analysis Set will be used for all safety analyses. Subjects will be analyzed as 
treated. If a subject receives both treatments, they will be analyzed in the imsidolimab group. 
5.3 
Per Protocol Analysis Set 
The Per Protocol (PP) Analysis Set will include all subjects in the ITT Analysis Set who do not have 
important protocol violations that would affect the evaluation of the primary efficacy endpoint. Further 
details on the determination of protocol deviations are described in Section 7.3. 
5.4 
Pharmacokinetic Analysis Set 
The PK Analysis Set will include all imsidolimab-treated subjects in the Safety Analysis Set who have at 
least 1 quantifiable post-dose PK sample available and who do not have events or protocol deviations 
with the potential to affect PK concentrations. The PK Analysis Set will be used for all PK analyses. 
The PK Analysis Set will be determined after review of the clinical study data (e.g., concomitant 
medications, study drug dosing information, and adverse events [AEs]). Prior to the final PK analysis, 
subject data as well as protocol deviations will be reviewed in a blinded manner by Everest, AnaptysBio, 
and Innovaderm at the blinded data review meeting (BDRM) for inclusion/exclusion into the PK Analysis 
Set.
5.5 
Populations for Primary Analyses
Demographics will be summarized on the ITT Analysis Set; PP, PK, and Safety Analysis Sets will be 
tabulated only if they are different from ITT Analysis Set for demographics. Extent of exposure, safety, 
biomarker, and anti-drug antibody (ADA) data will be summarized on the Safety Analysis Set. PK 
  
 
 
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parameters will be summarized on the PK Analysis Set. Efficacy analyses will be performed on the ITT 
and (where indicated) PP Analysis Sets. 
6. SPECIFICATION OF ENDPOINTS AND VARIABLES 
Unless specified otherwise, baseline will be the last available measurement taken prior to the first dose of 
study treatment.
Change from baseline will be calculated as the difference between the observed value at a specified visit 
and the corresponding baseline value.
The percentage change from baseline at Week X is defined as: 
100% × {(Observed value at Week X - baseline value) / baseline value} 
6.1 
Demographic and Baseline Characteristics 
6.1.1 
Demography and Physical Characteristics 
Subject demographics will be summarized overall as well as by treatment arm. Additionally, baseline 
values of the efficacy measures for facial IGA, facial inflammatory/noninflammatory lesion counts, 
truncal physician's global assessment (PGA), patient-global impression of severity (PGI-S), dermatology 
life quality index (DLQI) total score, 
 total score, and 
subject satisfaction questionnaire (SSQ) will be summarized overall as well as by treatment arm in the 
baseline disease characteristics output. 
Demographic and baseline characteristic variables summarized will include the following: 
 
Age 
 
Age group ([12, 18) years, [18, 30) years, 30 years) 
 
Age group ([12, 16) years, 16 years) 
 
Age group ([12, 25
25 years) 
 
Sex 
 
Sex and Age group (Male and [12, 25) years, Male and 25 years, Female and [12, 25) years, 
Female and 25 years) 
 
Race 
 
Ethnicity (Hispanic or Non-Hispanic) 
 
Country 
 
Woman of childbearing potential (Yes or No) 
 
Smoking history
 
Weight (kg) 
 
Height (cm) 
 
Body mass index (BMI; kg/m2)
 
Facial IGA at Baseline (Grade 3, Grade 4) 
 
Facial papule lesion counts at Baseline
 
Facial pustule lesion counts at Baseline 
 
Facial nodule lesion counts at Baseline 
 
Facial papule and pustule lesion counts at Baseline 
 
Facial inflammatory lesion counts at Baseline 
 
Facial noninflammatory lesion counts at Baseline 
 
Total facial lesion counts at Baseline 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Truncal PGA (chest, back, neck, and overall) at Baseline (Grade 0 to Grade 4) 
 
PGI-S at Baseline (Grade 1 to Grade 4) 
 
DLQI total score at Baseline 
 
CDLQI total score at Baseline 
 
SSQ at Baseline (Grade 0 to Grade 6) 
6.1.2 
Medical and Surgical History 
Medical and surgical history will be collected at the Screening visit and will be coded using the version of 
the Medical Dictionary for Regulatory Activities (MedDRA) specified in the approved Data Management 
Plan. 
6.1.3 
Prior and Concomitant Medications 
Any medication that the subject is receiving at the time of enrollment and receives during the study will 
be recorded on the Prior and Concomitant Medications CRF page. Prior medication is any medication 
stopped prior to the first dose of study treatment. 
Concomitant medication is any medication continued to be taken at the time of the first dose or started 
after the first dose of study treatment.  
Coding: Verbatim medication or treatment terms will be coded by Everest Clinical Research and will be 
assigned a preferred name and an Anatomical Therapeutic Chemical Class (ATC) Level 2 term (when 
available) using the version of the World Health Organization Drug Dictionary (WHODrug Global) 
specified in the approved Data Management Plan.  
Multiple ATC assignments: If there are multiple ATC codes assigned to the same concomitant 
 
Uncoded Medication: Before the database lock, uncoded medications/treatments may be assigned the 
name, so they 
can be included in the summary tables. In final datasets, all the terms will be coded. 
6.2 
Efficacy 
6.2.1 
Study Day and Visit Window Definitions 
Efficacy data obtained from unscheduled visits will be allocated to the scheduled visit corresponding to 
the visit window they fall in as specified in Table 3. For summary tables and figures, efficacy data will be 
analyzed based on the visit window specified in Table 3. Only if the data from the nominal visit or time 
point is missing will data from unscheduled visits for the same nominal visit or time point be used. If 
more than one unscheduled visit exists in a given window, the earlier (closer to nominal visit) 
measurement will be used. Efficacy from scheduled and unscheduled visits will be listed. 
Table 3
Analysis Visit Windows 
Nominal Visit 
Nominal Day 
Visit Window (day) 
Screening
-30 to -1 
-30 to -1
Day 1 
1 
1 (Pre-dose) 
Week 2 
15 
1 (Post-dose) to 22 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 3
Analysis Visit Windows 
Nominal Visit 
Nominal Day 
Visit Window (day) 
Week 4 
29 
23 to 42 
Week 8 
57 
43 to 71 
Week 12 
85 
72 to 99 
Week 20 
141 
100 
Study Day and Day of Assessment or Event definitions are provided in Appendix 1, Data Handling 
Rules. 
6.2.2 
Primary Efficacy Variable
The primary endpoint for this study is the change from baseline in facial inflammatory lesion counts at 
Week 12. The number of facial inflammatory lesions (pustules, papules, and nodular lesions) will be 
counted at the visits specified in the Schedule of Activities in Table 2, according to the definitions 
presented in Table 4. Facial inflammatory lesion counts will be made at the forehead, left and right 
cheeks, nose, and chin. The number of pustules, papules, and nodular lesions as well as the summed total 
for each visit will be documented in the electronic case report form (eCRF). Change from baseline at 
Week 12 will be calculated as the difference between the observed value at Week 12 and the 
corresponding baseline value. 
Table 4
Definitions of Inflammatory Lesions 
Type of Lesion 
Definition 
Papule 
A small, solid elevation 5 mm or less in diameter 
Pustule 
A small, circumscribed elevation of the skin that contains yellow-white exudate 
Nodule 
A circumscribed, elevated, lesion generally more than 5 mm in diameter. 
6.2.3 
Secondary Efficacy Variables 
The secondary efficacy endpoints are as follows. 
 
Percent change from Baseline in facial inflammatory lesion counts at each visit 
The percentage change from baseline in facial inflammatory lesion counts at each visit (Weeks 2, 
4, 8, 12, and 20) will be calculated. 
 
Change from Baseline in facial inflammatory lesion counts at visits other than Week 12 
Change from baseline in facial inflammatory lesion counts at visits other than Week 12 (Weeks 2, 
4, 8, and 20) will be calculated. 
 
Percent change from Baseline in facial noninflammatory lesion counts at each visit 
The number of facial noninflammatory lesions (open and closed comedones) will be counted at 
the visits specified in the Schedule of Activities in Table 2, according to the definitions presented 
in Table 5. Noninflammatory lesion counts will be made at the forehead, left and right cheeks, 
  
 
 
 
 
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and chin. The percentage change from baseline in facial noninflammatory lesion counts at each 
visit (Weeks 2, 4, 8, 12, and 20) will be calculated. 
Table 5
Definitions of Noninflammatory Lesions 
Type of Lesion 
Definition 
Open comedone
A mass of sebaceous material that is impacted behind an open follicular orifice (blackhead) 
Closed comedone 
A mass of sebaceous material that is impacted behind a closed follicular orifice (whitehead) 
 
 
Change from Baseline in facial noninflammatory lesion counts at each visit 
Change from baseline in facial noninflammatory lesion counts at each visit (Weeks 2, 4, 8, 12, 
and 20) will be calculated. 
 
Percent change from Baseline in total facial lesion (inflammatory and noninflammatory 
lesions) counts at each visit
The percentage change from baseline in total facial lesion (inflammatory and noninflammatory 
lesions) counts at each visit (Weeks 2, 4, 8, 12, and 20) will be calculated. 
 
Change from Baseline in total facial lesion (inflammatory and noninflammatory lesions) 
counts at each visit 
Change from baseline in total facial lesion (inflammatory and noninflammatory lesions) counts at 
each visit (Weeks 2, 4, 8, 12, and 20) will be calculated. 
 
Change from Baseline in facial IGA at each visit 
The facial IGA is a 5-point morphological assessment of facial acneiform rash, ranged from 0 
distance from the subject and must be performed before the facial inflammatory lesion count. 
Change from baseline in facial IGA at each visit (Weeks 2, 4, 8, 12, and 20) will be calculated. 
The number and percentage of subjects who have facial IGA Grade 0, 1, 2, 3, 4 at baseline and 
the shifts from baseline grades to each visit (Weeks 2, 4, 8, 12, and 20) will be calculated based 
on these values.
 
Proportion of subjects achieving a facial IGA of clear (0) or almost clear (1) with at least a 
2-grade decrease from Baseline at each visit 
For each treatment group, the number of subjects achieving a facial IGA of clear (0) or almost 
clear (1) with at least a 2-grade decrease from baseline will be calculated at each visit (Weeks 2, 
4, 8, 12, and 20). The proportion of such subjects will be calculated for each treatment group at 
each visit as: 
 
 
Proportion of subjects in each response category for the PGI-S at each visit
The PGI-S is a single-item question, which asks the subject to rate the current severity of AV 
Moderate
 
  
 
 
 
 
 
 
 
  
 
 
 
   
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
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For each treatment group, the number of subjects in each response category for the PGI-S will be 
calculated at each visit specified in the Schedule of Activities in Table 2. The proportion of such 
subjects will be calculated for each treatment group at each visit (Weeks 0, 2, 4, 8, 12, and 20) as: 
 
 
 
 
 
Proportion of subjects in each response category for the PGI-C at each post-Baseline visit 
The Patient Global Impression of change (PGI-C) is a single item, self-administered 
uch 
 
For each treatment group, the number of subjects in each response category for the PGI-C will be 
calculated at each post-baseline visit specified in the Schedule of Activities in Table 2. The 
proportion of such subjects will be calculated for each treatment group at each post-baseline visit 
(Weeks 2, 4, 8, 12, and 20) as: 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
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Percent change from Baseline in facial nodule lesion counts at each visit 
The percentage change from baseline in facial nodule lesion counts at each visit (Weeks 2, 4, 8, 
12, and 20) will be calculated. 
 
Change from Baseline in facial nodule lesion counts at each visit 
Change from baseline in facial nodule lesion counts at each visit (Weeks 2, 4, 8, 12, and 20) will 
be calculated. 
 
Change from Baseline in Truncal PGA for chest at each visit 
The Truncal PGA is a global assessment that will be used to assess the current state of AV on the 
chest, neck, and back at each visit. Each area will be evaluated and scored separately on a scale 
ranging from 0 (clear) to 4 (severe).
Change from baseline in Truncal PGA for chest at each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated. 
The number and percentage of subjects who have Truncal PGA Grade 0, 1, 2, 3, 4 for chest at 
baseline and the shifts from baseline grades to each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated based on these values. 
 
Change from Baseline in Truncal PGA for neck at each visit 
Change from baseline in Truncal PGA for neck at each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated. 
The number and percentage of subjects who have Truncal PGA Grade 0, 1, 2, 3, 4 for neck at 
baseline and the shifts from baseline grades to each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated based on these values. 
 
Change from Baseline in Truncal PGA for back at each visit 
Change from baseline in Truncal PGA for back at each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated. 
The number and percentage of subjects who have Truncal PGA Grade 0, 1, 2, 3, 4 for back at 
baseline and the shifts from baseline grades to each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated based on these values. 
 
Change from Baseline in overall Truncal PGA at each visit 
The overall Truncal PGA is determined from the average of Truncal PGA scores for 3 body areas 
in the form of a whole number, according to the definitions presented in Table 6. 
Change from baseline in overall Truncal PGA at each visit (Weeks 2, 4, 8, 12, and 20) will be 
calculated. 
Table 6 
Overall Truncal PGA 
Overall Truncal PGA 
Average Score 
0 
0 (all component=0) 
1 
0 to <1.5
2 
 
3 
 
4 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Proportion of subjects with at least 1-point decrease from Baseline in facial IGA at each 
visit 
For each treatment group, the number of subjects with at least 1-point decrease from baseline in 
facial IGA will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The proportion of such 
subjects will be calculated for each treatment group at each visit as: 
 
 
Proportion of subjects with at least 2-point decrease from Baseline in facial IGA at each 
visit 
For each treatment group, the number of subjects with at least 2-point decrease from baseline in 
facial IGA will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The proportion of such 
subjects will be calculated for each treatment group at each visit as: 
 
 
Proportion of subjects with at least 1-point decrease from Baseline in overall Truncal PGA 
at each visit for subjects with Baseline overall Truncal PGA score of at least 1 
For each treatment group, the number of subjects with at least 1-point decrease from baseline in 
overall Truncal PGA will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The proportion 
of such subjects will be calculated for each treatment group at each visit as: 
 
 
Proportion of subjects with at least 2-point decrease from Baseline in overall Truncal PGA 
at each visit for subjects with Baseline overall Truncal PGA score of at least 2 
For each treatment group, the number of subjects with at least 2-point decrease from baseline in 
overall Truncal PGA will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The proportion 
of such subjects will be calculated for each treatment group at each visit as: 
 
 
Proportion of subjects achieving a Truncal PGA for chest of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit 
For each treatment group, the number of subjects achieving a Truncal PGA for chest of clear (0) 
or almost clear (1) with at least a 2-grade decrease from baseline will be calculated at each visit 
(Weeks 2, 4, 8, 12, and 20). The proportion of such subjects will be calculated for each treatment 
group at each visit as: 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
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Proportion of subjects achieving a Truncal PGA for neck of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit 
For each treatment group, the number of subjects achieving a Truncal PGA for neck of clear (0) 
or almost clear (1) with at least a 2-grade decrease from baseline will be calculated at each visit 
(Weeks 2, 4, 8, 12, and 20). The proportion of such subjects will be calculated for each treatment 
group at each visit as: 
 
 
Proportion of subjects achieving a Truncal PGA for back of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit 
For each treatment group, the number of subjects achieving a Truncal PGA for back of clear (0) 
or almost clear (1) with at least a 2-grade decrease from baseline will be calculated at each visit 
(Weeks 2, 4, 8, 12, and 20). The proportion of such subjects will be calculated for each treatment 
group at each visit as: 
 
 
Proportion of subjects achieving an overall Truncal PGA of clear (0) or almost clear (1) 
with at least a 2-grade decrease from Baseline at each visit for subjects with Baseline overall 
Truncal PGA score of at least 2 
For each treatment group, the number of subjects achieving an overall Truncal PGA of clear (0) 
or almost clear (1) with at least a 2-grade decrease from baseline will be calculated at each visit 
(Weeks 2, 4, 8, 12, and 20). The proportion of such subjects will be calculated for each treatment 
group at each visit as: 
 
 
Proportion of subjects achieving improvement 
) 
according to the PGI-C at each post-Baseline visit 
For each treatment group, the number of subjects achieving improvement 
) according to the PGI-C will be calculated at each post-baseline visit 
specified in the Schedule of Activities in Table 2. The proportion of such subjects will be 
calculated for each treatment group at each post-baseline visit (Weeks 2, 4, 8, 12, and 20) as: 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
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Proportion of subjects achieving improvement 
) according to the PGI-C at each post-Baseline visit 
For each treatment group, the number of subjects achieving improvement (
) according to the PGI-C will be calculated at each post-
baseline visit specified in the Schedule of Activities in Table 2. The proportion of such subjects 
will be calculated for each treatment group at each post-baseline visit (Weeks 2, 4, 8, 12, and 20) 
as: 
 
 
Propor
-S at each 
visit 
For each treatment group, the number of subjects achieving 
 according to 
the PGI-S will be calculated at each visit specified in the Schedule of Activities in Table 2. The 
proportion of such subjects will be calculated for each treatment group at each visit (Weeks 0, 2, 
4, 8, 12, and 20) as: 
 
 
Change from Baseline in PGI-S at each visit 
Change from baseline in PGI-S at each visit (Weeks 2, 4, 8, 12, and 20) will be calculated. 
The number and percentage of subjects who have PGI-S Grade 1, 2, 3, 4 at baseline and the shifts 
from baseline grades to each visit (Weeks 2, 4, 8, 12, and 20) will be calculated based on these 
values. 
 
Proportion of subjects in each response category for the SSQ at each visit 
The SSQ asks subjects to rate their satisfaction with their acne condition on a 7-point scale from 
0 (extremely dissatisfied) to 6 (extremely satisfied). It will be assessed at the visits specified in 
the Schedule of Activities in Table 2. 
For each treatment group, the number of subjects in each response category for the SSQ will be 
calculated at each visit (Weeks 0, 2, 4, 8, 12 and 20). The proportion of such subjects will be 
calculated for each treatment group at each visit as: 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
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Proportion of subjects achieving slightly satisfied , somewhat satisfied,  or extremely 
satisfied  according to the SSQ at each visit 
For each treatment group, the number of subjects achieving slightly satisfied , somewhat 
satisfied , or extremely satisfied  according to the SSQ will be calculated at each visit (Weeks 0, 
2, 4, 8, 12 and 20). The proportion of such subjects will be calculated for each treatment group at 
each visit as: 
 
 
Proportion of subjects in each response category for the SSRS at Week 12 and Week 20 
The SSRS asks subjects to rate their satisfaction with their study treatment on a 7-point scale 
from 0 (extremely dissatisfied) to 6 (extremely satisfied). It will be assessed at Weeks 12 and 20. 
For each treatment group, the number of subjects in each response category for the SSRS will be 
calculated at Weeks 12 and 20. The proportion of such subjects will be calculated for each 
treatment group at Weeks 12 and 20 as: 
 
 
 
 
 
 
 
 
Proportion of subjects achieving slightly satisfied , somewhat satisfied , or extremely 
satisfied  according to the SSRS at Week 12 and Week 20 
For each treatment group, the number of subjects achieving slightly satisfied , somewhat 
satisfied , or extremely satisfied  according to the SSRS will be calculated Week 12 and 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
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Week 20. The proportion of such subjects will be calculated for each treatment group at each visit 
as: 
 
 
Proportion of subjects achieving a DLQI of 0 or 1 at each visit for subjects with Baseline 
DLQI of at least 2 
For each treatment group, the number of subjects achieving a DLQI of 0 or 1 with baseline DLQI 
of at least 2 will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The proportion of such 
subjects will be calculated for each treatment group at each visit as:
 
Proportion of subjects with less than 5 facial inflammatory lesion count (papules and 
pustules) at each visit 
For each treatment group, the number of subjects with less than 5 facial inflammatory lesion 
count (papules and pustules) will be calculated at each visit (Weeks 2, 4, 8, 12, and 20). The 
proportion of such subjects will be calculated for each treatment group at each visit as: 
 
6.2.4.1 
Photography 
The exploratory endpoints based on photography of face include the following: 
 
Change from Baseline in lesion counts based on blinded photographic assessment at each 
visit 
The number of facial lesion counts (inflammatory and noninflammatory) will be counted by a 
standardized review of photographs at the visits specified in the Schedule of Activities in 
Table 2. 
The change from baseline in total lesion counts based on blinded photographic assessment at each 
visit (Weeks 2, 4, 8, 12 and 20) will be calculated. 
 
Change from Baseline in inflammatory lesion counts based on blinded photographic 
assessment at each visit 
The change from baseline in inflammatory lesion counts based on blinded photographic 
assessment at each visit (Weeks 2, 4, 8, 12 and 20) will be calculated. 
 
Change from Baseline in noninflammatory lesion counts based on blinded photographic 
assessment at each visit 
The change from baseline in noninflammatory lesion counts based on blinded photographic 
assessment at each visit (Weeks 2, 4, 8, 12 and 20) will be calculated. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
    
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
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Change from Baseline in Parametric Acne Severity (PAS) score based on blinded 
photographic assessment at each visit 
The change from baseline in PAS score based on blinded photographic assessment at each visit 
(Weeks 2, 4, 8, 12 and 20) will be calculated. 
 
Change from Baseline in erythema score based on blinded photographic assessment at each 
visit 
The change from baseline in erythema score based on blinded photographic assessment at each 
visit (Weeks 2, 4, 8, 12 and 20) will be calculated. 
6.3 
Pharmacokinetic Variables 
Concentration time data will be collected following imsidolimab administration to evaluate the PK profile 
of imsidolimab. Samples from subjects having received imsidolimab only will be analyzed for PK; no 
placebo samples will be analyzed. Pharmacokinetic samples will be collected at the time points indicated 
in Table 7 below. 
Table 7
Pharmacokinetic Sample Collection and Time Points 
Study Visit 
Pharmacokinetic Sample Time Point 
Day 1 
Pre-dose 
Day 1 
2 hours ±10 minutes post-dose 
Day 15
Anytime 
Day 29
Pre-dose 
Day 57
Pre-dose 
Day 85
Anytime 
Day 141 
Anytime 
 
Non-compartmental analysis (NCA) will not be conducted due to minimal PK sampling. However, other 
presentations of PK information may be added at the discretion of the PK scientist.
Population PK modelling may be performed by the Sponsor or another designated vendor, and if done, 
will be described in a separate PK analysis plan and report. 
6.4 
Immunogenicity Variables 
 
Presence of ADA to imsidolimab 
Anti-drug antibodies samples will be collected at the time points indicated in Table 8 below: 
Table 8
ADA Sample Collection and Time Points 
Study Visit 
ADA Sample Time Point 
Day 1 
Pre-dose 
Day 15
Anytime 
Day 29
Pre-dose 
  
 
 
 
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Day 57
Pre-dose 
Day 85
Anytime 
Day 141 
Anytime 
Abbreviations: ADA = anti-drug antibody 
 
ADA assessments will be conducted utilizing a tiered approach that includes: 
1. A screening assay that identifies potential binding ADA in serum samples. 
2.
A confirmatory assay that confirms the binding specificity of the drug.
3. A titer assay that measures the titer of confirmed ADA. A sample that has been found 
negative in the screening or confirmatory assay will not have a titer value. 
A subject will be considered to be positive for imsidolimab-induced immunogenicity if the 
subject has one confirmed positive ADA response after dosing. Confirmed positive ADA samples 
may also be tested for neutralizing ADA. 
Antidrug antibody variables include status (positive or negative) and titers as follows: 
 
Total subjects with negative ADA response at all times 
 
Total subjects with confirmed positive ADA response at any time 
 
Pre-existing immune-reactivity, defined as either  
o A positive ADA at baseline with all post-treatment ADA results negative, or 
o A positive ADA at baseline with all post-treatment ADA responses less than 4-fold 
over baseline titer levels. 
 
Treatment-emergent: any post-treatment positive ADA when the baseline ADA result is 
negative 
 
Treatment-boosted: any post-treatment positive ADA that is greater than or equal to 4-fold 
over baseline titer level when baseline is ADA positive 
 
Overall ADA incidence: the proportion (%) of subjects with positive ADA, either treatment-
emergent or treatment-boosted, relative to all imsidolimab treated subjects 
 
Titer values 
6.5 
Biomarker Variables 
 
Assessment of biomarkers in tape strips 
The analysis of tape strips biomarkers will be performed by an additional third party designated 
by the Sponsor. 
6.6 
Safety 
Adverse events, serious adverse events (SAEs), AEs leading to discontinuation of study treatment, and 
AEs leading to withdrawal from study, as well as changes in vital signs, clinical laboratory parameters 
(hematology, biochemistry, and urinalysis), and 12-lead electrocardiograms (ECGs) will be evaluated to 
meet the safety objectives of the study. 
6.6.1 
Study Day and Visit Window Definitions 
Adverse events will be closely monitored on each subject throughout their participation in the study. 
  
 
 
 
 
 
 
 
 
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Safety assessments for other safety variables will occur as detailed in the Schedule of Activities in 
Table 2. 
6.6.2 
Extent of Exposure to Study Medication and Compliance 
The number of doses received by the subject for a study treatment will be calculated.
The number of days of exposure to a study treatment will be defined as (Date of last treatment  Date of 
first dose of treatment) + 1. 
Total dose received will be the total amount (in mg) of study treatment taken during the treatment period.
Dose intensity for a specified period is defined as (total dose received by a subject during that period/total 
expected dose during the same period) x 100%. 
The expected number of doses for imsidolimab treatment arms is as follows: 
 
Imsidolimab 400 mg/200 mg: 400 mg on Day 1, 200 mg on Days 29 and 57. 
 
Imsidolimab 200 mg/100 mg: 200 mg on Day 1, 100 mg on Days 29 and 57. 
6.6.3 
Adverse Events 
Adverse events experienced by the subjects will be collected throughout the entire study and will be 
coded using the version of the MedDRA specified in the approved Data Management Plan. Analysis of 
AEs will be carried out on the Safety Analysis Set. 
An AE is considered treatment-emergent if the date of onset is during or after first dose of study 
treatment, or if the AE present at Baseline that worsens in either intensity or frequency after first dose of 
study treatment. An AE that begins on the same date as the first dose of study treatment is treatment-
emergent if the AE begins on or after the time of first dose or if the time of AE onset is unknown. 
 
Section 8.2.1.3.1 of the study protocol. 
Adverse events will be classified as related, possibly related, unlikely to be related, or unrelated to study 
treatment using the criteria specified in Section 8.2.1.3.2 of the study protocol. If the relationship to study 
t
related
Adverse events will be categorized as serious or non-serious using the definition specified in 
Section 8.2.1 of the study protocol.
Events with Partial Onset Dates 
All treatment-emergent adverse events (TEAEs) will be included in the tabulations regardless of the 
completeness of the onset dates. Partial dates will be imputed in order to determine if an AE is treatment-
emergent using the rules in Appendix 1; however, imputed dates will not be provided in the data listings. 
Uncoded Events: 
the body system, and the verbatim term will be used as the preferred term, so they can be included in the 
summary tables. In the final dataset, all the adverse events will have been coded. 
6.6.3.1 
Deaths 
All deaths (if any) which occur during the study will be listed. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.6.4 
Laboratory Data 
Clinical laboratory tests that will be performed in this study are summarized in Appendix 10 of the study 
Protocol. Local laboratory samples will be collected in the eCRF when the central laboratory results are 
not available immediately, and the Investigator needs to take an immediate decision for any safety 
concerns, however, local laboratory results will be not used in the summary tables. All laboratory data 
will be listed, but only hematology, biochemistry, and urinalysis will be summarized. 
Conversion to the International System of Units
All laboratory data will be stored in the database with the units in which they are originally reported. 
Laboratory data in summary tables and subject data listings will be presented in the International System 
of Units (SI units). Laboratory data not reported in SI units will be converted to SI units before further 
processing or data analysis.
Abnormal Values 
Based upon laboratory normal ranges, laboratory test results will be categorized according to the normal 
range as low, normal, and high. Subjects with laboratory data outside the normal range will be listed with 
abnormal values flagged. 
6.6.5 
Vital Signs 
Vital signs including body temperature (°C), pulse rate (bpm), systolic and diastolic blood pressure 
(mmHg), respiratory rate (breath/min), weight (kg), and height (cm) will be obtained in accordance with 
the Schedule of Activities in Table 2. Changes from baseline in vital signs variables will be evaluated. 
6.6.6 
Electrocardiogram (ECG) 
ECG parameters, including heart rate as well as RR, PR, QRS, QT, and QTcF intervals will be collected 
according to the Schedule of Activities in Table 2. Changes in ECG parameters between baseline and 
each subsequent scheduled assessment will be calculated. 
The outcome of the overall evaluation is to be recorded as normal/abnormal in the eCRF, with any 
abnormalities being recorded as not clinically significant or clinically significant. 
6.6.7 
Other Safety Assessments 
The following assessments will be performed, but will not be used to define additional safety parameters 
for the study: chest X-ray, physical examination, tuberculosis (TB) screening, pregnancy tests (serum or 
urine), viral serology, and follicle-stimulating hormone (FSH). Data from these assessments will be 
available in datasets and will be listed. 
7. STATISTICAL ANALYSIS 
7.1 
Data Handling Rules and Definitions, Including Handling of Missing Data 
Except where specified all continuous variables will be summarized with descriptive statistics (the 
number of non-missing values, mean, SD, median, first and third quartiles, minimum, and maximum). 
Where data have been logarithmically transformed for analysis, the summary statistics on the back-
transformed data will include the geometric mean (calculated as [exp (m)], where m is the mean of the 
data on the log scale) and the coefficient of variation (CV; 
exp (s2)-1], where s is the 
SD of the data on the log scale). All categorical variables will be summarized with frequency counts and 
  
 
  
  
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percentages. Tabulations will be provided based on all subjects combined, as well as separately by 
treatment group. 
Missing data will be maintained as missing in the analysis datasets, unless specified otherwise. For 
variables where missing data are imputed, the analysis dataset will contain a new variable with the 
imputed value and the original variable value will be maintained as missing. 
Data Imputation for Primary and Secondary Efficacy Analyses 
1. Multiple Imputation with Fully Conditional Specification (FCS) Method 
The FCS method will be used as a sensitivity analysis for the analyses of facial IGA and facial 
inflammatory/noninflammatory lesion counts. FCS methods can be used to impute missing values for 
variables with an arbitrary missing data pattern, assuming the existence of a joint distribution for these 
variables. Both intermittent and monotone missing values will be imputed in the same way with 
regression-based predictive mean matching method. The missing values will be imputed sequentially, 
with all previous visits included as additional covariates. 
The steps of performing a sequential regression imputation are as follows: 
a) If there is any missing value at Week 2, it will be imputed using a regression-based predictive 
mean matching method. For facial inflammatory/noninflammatory lesion counts, randomization 
seeds of 20220118 and 20220119 will be used respectively, the regression will include the 
covariates of age, sex, treatment group, facial IGA score at baseline (Grade 3 vs. 4), and the 
baseline measurement of corresponding lesion counts. For facial IGA, a randomization seed of 
20220121 will be used, and the covariates included in the regression will be age, sex, treatment 
group, and baseline facial IGA score as a continuous variable. 
b) All remaining missing visits will be imputed sequentially by the same regression, with covariates 
specified above in Step (a) and the lag values (including the imputed values) from earlier visits. 
c) The imputed values will be rounded to the nearest integer for facial IGA and facial 
inflammatory/noninflammatory lesion counts. 
d) The linear mixed model for repeated measures (MMRM) for continuous endpoints as described in 
Section 7.5.1 and Section 7.5.2, respectively, will be applied to each imputed dataset. For 
categorical endpoints, the binary outcomes will be derived from the imputed data for each patient. 
The Cochran-Mantel-Haenszel (CMH) test as described in Section 7.5.2 will be used for each 
imputed dataset, and the effect will be measured as Prob (concordance) - Prob (discordance) by 
ss the facial IGA 
strata.5 
One hundred independent data replications will be done with SAS PROC MI. Results across the 
replicated datasets will then be combined into the final estimate using SAS PROC MIANALYZE. 
2. Tipping Point Analyses 
As the primary analysis (MMRM) relies on the missing at random assumption, to evaluate the robustness 
of the primary analysis approach, a sensitivity analysis using the tipping-point approach will be 
conducted. 
The following steps will be used to determine the tipping point: 
a) Intermittent missing values will be imputed using the Monte Carlo Markov Chain (MCMC) 
approach to create a monotone missing pattern. The imputation will be implemented separately 
for each treatment and each facial IGA stratum (Grade 3 or 4), under the assumption that different 
treatments and facial IGA strata may have distinct posterior distributions. The imputation will 
  
  
 
 
  
 
 
 
 
 
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include all the post-baseline values, with age, and baseline value of the corresponding endpoint as 
covariates. 
b) If there is any missing value at timepoint 1 (Week 2), it will be imputed using a regression based 
MI method for monotone missingness. Covariates included in the modelling are age, sex, 
treatment group, facial IGA score at baseline (Grade 3 vs. 4), and baseline value of the 
corresponding endpoint. 
c) A delta score will be added to the imputed value at timepoint 1 for subjects missing data at 
timepoint 1 in the imsidolimab treatment groups, thus worsening the imputed value. The delta 
value will start at 0 and will be increased in a repeated process until the comparison of 
imsidolimab to placebo is no longer significant at 0.10 level in Step (f). 
d) All remaining timepoints will be imputed sequentially by repeating Steps (b) and (c) for each 
timepoint, including lag values from earlier timepoints in the imputation model (lag values will 
include imputed values from the previous step), in addition to the covariates specified above in 
Step (b). Data from subjects who have already had their responses increased by delta in the 
previous step(s) will not be further increased by delta again since the regression on the previous 
value carries this increase forward. This principle also extends to the preliminary step of imputing 
intermittently missing visits. Thus, if an intermittent missing value is encountered for a subject in 
the imsidolimab treatment groups, delta adjustment will not apply for the subsequent imputations 
of the monotone part of the missing visits, for that subject. 
e) For each imputed dataset, perform the same primary analysis (MMRM) as described in 
Section 7.5.1 to estimate treatment differences between each dose of imsidolimab and placebo. 
Results across the imputed datasets will then be combined using SAS PROC MIANALYZE. 
f) Step (c) to (e) will be repeated with gradually increased delta values until the tipping point is 
reached. 
One hundred independent dataset replications will be done with SAS PROC MI. The resulting one 
hundred estimates of the treatment differences and standard errors will then be combined into the final 
estimate using SAS PROC MIANALYZE. 
Data Imputation for Adverse Events Summaries by Relationship to Study Drug 
For the AE summaries by relationship to study drug, an AE with a missing relationship to study drug will 
be deemed as definitely related. Imputed values will not be listed in data listings. 
Use of Data from Unscheduled Assessments for Laboratory, ECG, and Vital Sign Summaries 
(Continuous Parameters) 
Data from unscheduled visits will be listed; duplicate unscheduled measurements will not be shown 
twice. If the data from the scheduled visit is missing, data from unscheduled visits that fall in the visit 
window of the same scheduled visit will be used. In cases where there are multiple unscheduled visits, the 
most recent unscheduled visit will be used. 
Data Imputation (All Laboratory, Immunogenicity, and Biomarker Summaries) 
prefixed with 
, the available original value +0.001 will be used for table summaries; if a laboratory 
0.001 will be used in table summaries. 
Study Dates and Day of Assessment or Event 
Study Day and Day of Assessment or Event definitions are provided in Appendix 1, Data Handling 
Rules. 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 
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Incorrect Stratification 
If there is any discrepancy between the IWRS-based and clinical-data-based stratification factor, the 
clinical-data-based value will be used for efficacy analyses. 
7.2 
Subject Disposition 
Disposition for all subjects will be tabulated and listed. The tabulation will include the number of subjects 
screened, randomized, and treated, randomized but not treated, the number of subjects completing the 
treatment period, and the number of subjects who complete the study (including follow-up) as well as 
who discontinue study early will also be presented; for subjects who discontinue, the reason for 
discontinuation will also be included. The number and percentage of randomized subjects included in the 
ITT, PP, Safety, and PK Analysis Sets will also be tabulated. 
The randomization stratification factor and treatment assignment will be listed together. If there are any 
subjects who took study treatment other than what was randomized during the study, both the treatment 
assigned at randomization and actual treatment(s) received during the Treatment Period will be listed. The 
duration of actual treatment will also be listed. 
The reason for exclusion of a subject from the PP, Safety, and PK Analysis Sets will be listed for all 
randomized subjects; the Coronavirus Disease 2019 (COVID-19) related reasons for exclusion from the 
PP Analysis Set may be considered. In addition, randomized subjects who violate the important protocol 
deviations will be listed. 
7.3 
Deviations 
All protocol deviations will be identified and discussed with the Sponsor during the BDRM prior to final 
database lock. Important protocol deviations for exclusion from the PP Analysis Set will be determined 
and appropriately categorized in this meeting. These are defined as potential protocol deviations that may 
significantly affect the reliability of efficacy study data. 
All important protocol deviations will be summarized by treatment group and overall subjects for the ITT 
Analysis Set. All protocol deviations will be listed. 
7.4 
Demographic and Baseline Characteristics 
7.4.1 
Demography and Physical Characteristics 
Demographics and baseline characteristics variables that are listed in Section 6.1 will be summarized by 
treatment and all data will be provided in listings. Continuous baseline parameters (such as age, height, 
weight, BMI, facial inflammatory lesion counts, facial noninflammatory lesion counts, and DLQI/CDLQI 
total score), facial IGA, Truncal PGA, PGI-S, and SSQ will be summarized descriptively using mean, 
median, SD, minimum, maximum, first quartile, and third quartile. For categorical baseline and 
demographic parameters (such as age group, country, reproductive status, sex, ethnicity, race, smoking 
history, facial IGA, Truncal PGA, PGI-S, and SSQ), frequencies and percentages of subjects will be 
provided; baseline facial IGA will be reported by individual Grade 3 or 4. 
7.4.2 
Medical and Surgical History 
Medical and surgical history at screening will be summarized for the Safety Analysis Set and listed for 
the ITT Analysis Set.
  
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7.4.3 
Prior and Concomitant Medications 
Refer to Appendix 1 for definitions of prior and concomitant medications. Prior and concomitant 
medications will be summarized by ATC class, preferred term, and actual treatment received for the 
Safety Analysis Set. In summary tables, subjects will only be reported once for the medication or for the 
class of drug s/he has taken. Prior and concomitant medications will be displayed in separate listings. 
7.5 
Efficacy Analyses 
The ITT Analysis Set will be used as the primary analysis set for all efficacy analyses. Per protocol 
analyses will be performed on the primary as well as the following secondary endpoints: 
Change from Baseline in facial inflammatory lesion counts at visits other than Week 12
 
Change from Baseline in facial noninflammatory lesion counts at each visit 
 
Change from Baseline in total facial lesion (inflammatory and noninflammatory lesions) counts at 
each visit 
 
Change from Baseline in facial IGA at each visit 
 
Proportion of subjects achieving a facial IGA of clear (0) or almost clear (1) with at least a 
2-grade decrease from Baseline at each visit 
No adjustment for multiplicity will be made. 
All statistical tests will be performed at the 10% level of significance unless otherwise stated. All 
confidence intervals (CIs) will be reported as 2-sided 90% CIs unless otherwise stated. Descriptive 
statistics will be provided for the continuous variables as number of subjects, mean, SD, standard error of 
the mean, first and third quartiles, minimum, and maximum. Descriptive summaries of continuous 
variables will be shown for baseline, change from baseline to endpoint, and percent change from baseline 
to endpoint. All data will be listed in data listings. 
7.5.1 
Primary Efficacy Analysis 
The primary estimand, comprising four components, is defined as follows: 
a) The target population consists of patients with acne vulgaris that are eligible to be included in the 
clinical trial based on the inclusion/exclusion criteria in the protocol. The ITT Analysis Set will 
include all randomized subjects. For the analysis, treatment will be assigned based upon the 
treatment arm to which subjects were randomized regardless of which treatment they receive. 
b) The primary variable is the change from baseline in facial inflammatory lesion count of an 
individual subject at Week 12. 
c) To handle intercurrent events such as use of rescue medications, the hypothetical strategy for 
estimand will be used. Data collected following receipt of rescue medication (if any) will be 
considered missing in the analysis. 
d) The population-level summary measures will be the population mean differences in the primary 
variable between each dose of imsidolimab and placebo at Week 12. 
A MMRM model will be used with treatment, visit (Weeks 2, 4, 8, and 12), treatment by visit interaction, 
and facial IGA score at baseline (Grade 3 vs. 4) as categorical covariates and the baseline value of 
response as the only continuous covariate; only the visits up to and including week 12 are used. An 
unstructured correlation (UN) matrix will be used to model correlation within a subject; if convergence is 
an issue, a Toeplitz structure may be considered. Subjects with missing data at Week 12 due to early 
discontinuation will be included in the model. 
  
 
 
 
 
 
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The least squares (LS) mean and the standard error of this mean with the corresponding two-sided 90% 
CI will be provided for each treatment based on the model. The LS mean difference between treatments 
(imsidolimab  placebo), as well as the corresponding two-sided 90% CI will be provided based on the 
model. Summary statistics and the results of statistical testing in facial inflammatory lesion count at Week 
12 will be tabulated. The LS mean change from baseline as well as differences between treatments in 
facial inflammatory lesion count will be plotted across post-baseline visits by treatment in separate plots. 
7.5.2 
Secondary Efficacy Analyses
7.5.2.1 
Percent Change from Baseline in Facial Inflammatory Lesion Counts at Each 
Visit 
Percent change from baseline in facial inflammatory lesion counts will be presented together with the 
primary endpoint. This endpoint will be analyzed using a similar MMRM model as specified for the 
primary endpoint. The percent change from baseline in facial inflammatory lesion counts will be the 
response variable in the model. 
7.5.2.2 
Change from Baseline in Facial Inflammatory Lesion Counts at Visits Other 
Than Week 12 
This secondary endpoint will be presented together with the primary endpoint. Summary statistics and the 
results of statistical testing in facial inflammatory lesion counts at visits other than Week 12 will be 
tabulated. The change from baseline in facial inflammatory lesion counts will be analyzed using the same 
MMRM model as for the primary endpoint. 
7.5.2.3 
Percent Change from Baseline in Facial Noninflammatory Lesion Counts at 
Each Visit 
Percent change from baseline in facial noninflammatory lesion counts at each visit will be analyzed using 
a similar MMRM model as specified for the primary endpoint. The percent change from baseline in facial 
noninflammatory lesion counts will be the response variable in the model. 
7.5.2.4 
Change from Baseline in Facial Noninflammatory Lesion Counts at Each Visit 
Change from baseline in facial noninflammatory lesion counts at each visit will be analyzed using a 
similar MMRM model as specified for the primary endpoint. The change from baseline in facial 
noninflammatory lesion counts will be the response variable in the model. 
7.5.2.5 
Percent Change from Baseline in Total Facial Lesion (Inflammatory and 
Noninflammatory Lesions) Counts at Each Visit 
Percent change from baseline in total facial lesion (inflammatory and noninflammatory lesions) counts at 
each visit will be analyzed using the MMRM approach defined for the primary endpoint. The percent 
change from baseline in total facial lesion (inflammatory and noninflammatory lesions) counts will be the 
response variable in the model. 
7.5.2.6 
Change from Baseline in Total Facial Lesion (Inflammatory and 
Noninflammatory Lesions) Counts at Each Visit 
Change from baseline in total facial lesion (inflammatory and noninflammatory lesions) counts at each 
visit will be analyzed using a similar MMRM model as specified for the primary endpoint. The change 
  
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from baseline in total facial lesion (inflammatory and noninflammatory lesions) counts will be the 
response variable in the model. 
7.5.2.7 
Change from Baseline in Facial IGA at Each Visit 
Change from baseline in facial IGA at each visit will be analyzed using a similar MMRM model as 
specified for the primary endpoint. The MMRM model will include treatment, visit, and treatment by visit 
interaction as categorical covariates and baseline facial IGA score as the only continuous variable. An 
unstructured correlation (UN) matrix will be used to model correlation within a subject; if convergence is 
an issue, a Toeplitz structure may be considered. 
In addition, the following exploratory analyses will be performed: 
 
Change from baseline in facial IGA will be summarized in shift tables. In the shift table, for each 
treatment, the counts and percentages will be shown for baseline values crossed with each 
post-baseline timepoint. Agreement between the baseline score and each post-baseline score will 
be estimated with a weighted Kappa coefficient and corresponding 90% CI7. A test of treatment 
difference for agreement will consist of a CMH test (ANOVA of row means) applied to a 2×3×5 
Table (Baseline IGA facial strata × treatment × agreement score), where the agreement score is 
the Cicchetti-Allison weight8 used for the weighted Kappa coefficient, which is 1-|difference|/4 
for a 5 point score such as the facial IGA, so the value is =1 if there is perfect agreement, ¾ if the 
scores are one category apart (in either direction), ½ if 2 apart, ¼ if 3 apart and 0 if 4 apart. The 
latter score can happen only if baseline score is 4 and post-baseline score is 0. 
 
Change from baseline in facial IGA at Week 12 will be analyzed using an ordinal logistic 
regression model with treatment, facial IGA score at baseline (Grade 3 vs. 4) as categorical 
covariates. Odds ratios resulting from this model along with 90% CI will be reported.
7.5.2.8 
Proportion of Subjects Achieving a Facial IGA of Clear (0) or Almost Clear (1) 
With at Least a 2-Grade Decrease from Baseline at Each Visit 
The frequency and percentage of subjects achieving a facial IGA of clear (0) or almost clear (1) with at 
least a 2-grade decrease from baseline will be summarized at each visit. The difference in percentage 
between each dose of imsidolimab and placebo will be estimated by an unadjusted risk difference in 
proportions with 90% exact unconditional CIs. This will be performed overall and within each facial IGA 
stratum (Grade 3 or 4). The common risk difference will also be tested using a generalized CMH test 
(ANOVA for row means), adjusting for facial IGA at baseline (Grade 3 vs. 4).
An additional exploratory analysis will be performed by visit for the proportion of subjects achieving a 
facial IGA of clear (0) or almost clear (1) with at least a 2-grade decrease from baseline. A repeated 
measures generalized estimating equations (GEE) model with a logit link will be used. The model will 
include treatment, visit, treatment by visit interaction, and baseline facial IGA score as categorical 
covariates. Data from protocol-specified visits up to Week 20 will be included in the analysis. An 
unstructured correlation matrix will be used to model correlation within a subject; if convergence is an 
issue, a Toeplitz structure may be considered. An odds ratio resulting from this model along with 90% CI 
will be reported. 
7.5.2.9 
Proportion of Subjects in Each Response Category for the PGI-S at Each Visit 
The frequency and percentage of subjects in each response category for the PGI-S will be summarized at 
each visit. The difference in distribution between each dose of imsidolimab and placebo will be compared 
using a Wilcoxon rank-sum test and 
 D statistic which may be interpreted as a generalized risk 
  
 
 
 
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difference.5 This will be performed over all subjects and within each stratum for facial IGA (Grade 3 or 
4). The common risk difference will also be tested using a generalized CMH test (ANOVA for row 
means), adjusting for facial IGA at baseline (Grade 3 vs. 4). 
7.5.2.10 
Proportion of Subjects in Each Response Category for the PGI-C at Each Post-
Baseline visit 
Proportion of subjects in each response category for the PGI-C at each post-Baseline visit will be 
summarized and analyzed using the approach defined for the proportion of subjects in each response 
category for the PGI-C, as described in Section 7.5.2.9. 
7.5.2.11 
Change from Baseline in DLQI/CDLQI at each visit 
Change from baseline in DLQI/CDLQI total score at each visit will be analyzed separately as well as 
together using a similar MMRM model as specified for the primary endpoint in Section 7.5.1. 
7.5.3 
Exploratory Efficacy Analyses 
The continuous data endpoints of change and percent change from baseline will be analyzed using the 
MMRM approach as described for the primary efficacy analysis in Section 7.5.1. Summary statistics and 
the results of statistical testing at each visit will be provided for each continuous exploratory variable. In 
addition, the change from baseline in PGI-S and Truncal PGA (by body region as well as the overall and 
the worst score across three regions) will be summarized and analyzed by shift tables and ordinal logistic 
regressions as described in Section 7.5.2.7. Baseline of the response variable will be added to the ordinal 
logistic regression model as a categorical variable. The overall Truncal PGA will be presented separately 
for all subjects, adolescents, and adults. 
The frequency and percentage of subjects for subjects for categorical exploratory endpoints related to 
Truncal PGA (by body region as well as the overall and the worst score across three regions), facial IGA, 
PGI-C, PGI-S, SSQ, and SSRS will be summarized at each protocol-specified visit. For proportion of 
subjects in each response category for the SSQ and SSRS, the difference in distribution between each 
dose of imsidolimab and placebo will be analyzed using the approach described for the proportion of 
subjects in each response category for the PGI-C in Section 7.5.2.9. For other categorical exploratory 
endpoints, an unadjusted risk difference and 90% exact unconditional CIs will be estimated between each 
dose of imsidolimab and placebo for all subjects and within each stratum for facial IGA at baseline 
(Grade 3 vs. 4); the common risk difference will also be tested using a generalized CMH test as described 
in Section 7.5.2.8. 
7.5.4 
Sensitivity Analyses 
A number of sensitivity analyses are planned to evaluate the robustness of the primary and secondary 
efficacy results. 
For the primary efficacy endpoint, the following sensitivity analyses will be performed: 
 
Analysis of primary efficacy endpoint using the PP Analysis Set. 
 
Analysis of primary efficacy endpoint for adolescent subjects (age <16 years). 
 
Analysis of primary efficacy endpoint by age group ([12, 25
25 years). 
 
Analysis of primary efficacy endpoint by age and sex (male and [12, 25) years, male and 25 
years, female and [12, 25) years, female and 25 years) 
 
Sex (male, female) will be added to the MMRM as a categorical variable if this model can 
converge.  
  
 
 
 
 
 
 
 
  
 
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Site will be added to the MMRM as a fixed categorical effect if this model can converge. Small 
sites (enrollment less than 5 subjects) will be pooled together. 
 
Smoking history (current smoker vs non-current smoker) will be added to the MMRM as a fixed 
categorical effect if this model can converge. 
 
The papule and pustule count will be summed and analyzed using a similar MMRM model as 
specified for the primary analysis for ITT Analysis Set. 
 
Multiple imputation with FCS method (Section 7.1). 
 
Tipping point analysis (Section 7.1). 
 
Prior to database lock and unblinding, the assumption of normality in the change from baseline in 
facial inflammatory lesion count will be checked by visually inspecting the distribution of the 
residuals. If the normality assumption is not met, a repeated measures model using a GEE
approach with an alternative distribution or any transformation will be considered. An 
unstructured correlation matrix will be used in the model if GEE is decided to be used; a Toeplitz 
structure may be considered if convergence is an issue. However, the results from the primary 
efficacy analysis will be considered the primary efficacy results. 
For the secondary efficacy endpoints listed in Section 7.5, the following sensitivity analyses will be 
performed:  
 
Analyses of secondary efficacy endpoints using the PP Analysis Set.
 
Multiple imputation with FCS method (Section 7.1). 
7.5.5 
Subgroup Analyses 
Subgroup analyses will be carried out but only for the primary efficacy endpoint. Each subgroup will be 
analyzed separately using descriptive statistics. No hypothesis tests will be performed. Subgroup variables 
that will be examined include: 
 
Baseline Facial Inflammatory Lesion Count: 
o 
value 
o < Median value 
 
Age groups: 
o [12, 18) years 
o [18, 30) years 
o 
30 years
 
Sex groups: 
o Male 
o Female 
 
Baseline facial IGA: 
o Grade 3 
o Grade 4 
 
Race: 
o White 
o Non-white 
 
Prior systemic oral antibiotics: 
o No 
o Yes 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Prior systemic oral retinoid: 
o No 
o Yes 
 
7.6 
Pharmacokinetic Analyses 
The PK analysis will be performed for subjects in the PK Analysis Set. 
Mean trough serum concentration-time data for samples collected on Days 29, 57, and 85 will be 
tabulated as well as graphically presented as scatter plots. Nominal collection times will be used for 
graphs. 
A subject listing of all concentration-time data following SC injections will be presented by subject and 
scheduled sample collection time. All concentration data of imsidolimab will be summarized by day and 
nominal time point using the number of observations, arithmetic mean, SD, CV, minimum, median, 
maximum, geometric mean, and CV of geometric mean. Concentration time data values reported as 
below the limit of quantification (BLQ) that occur at pre-dose or prior to the first observed non-BLQ 
positive concentration will be set to zero or will be set to missing for records that occur after the last 
quantifiable concentration.
7.7 
Immunogenicity Analyses 
ADA status and titer values will be listed by subject and time point. ADA incidences (overall, 
treatment-emergent, and treatment-boosted) will be tabulated as absolute occurrence (n) and proportion 
(%) of subjects by treatment group and visit. Descriptive statistics including number of subjects, mean, 
median, SD, minimum, and maximum of the titer values by treatment group and visit, where possible, 
will be provided. Neutralizing antibodies, if assayed and present, will also be summarized. The 
relationship between changes in PK profile and treatment-emergent positive responses will be evaluated 
to identify a potential impact ADA on imsidolimab exposure. Box plots of ADA status relative to trough 
concentrations will be plotted. Where possible, evaluation of ADA impact on efficacy and safety may be 
performed and summarized separately. 
All immunogenicity results will be listed. 
7.8 
Biomarker Analyses 
Biomarker analyses will be performed by a third party designated by the Sponsor. A separate analysis 
plan will be created for the biomarker analyses. 
7.9 
Safety Analyses 
Safety analyses will be performed using the Safety Analysis Set. Safety parameters include AEs, 
exposure, clinical laboratory parameters (hematology, biochemistry, and urinalysis), vital signs, and 
ECGs. Summaries of safety parameters will be presented overall as well as by treatment group. 
7.9.1 
Extent of Exposure to Study Medication and Compliance 
Descriptive statistics (n, mean, SD, median, minimum, and maximum) will be presented for the number 
of doses received, the number of days of exposure to study treatment, total dose received, total dose 
  
 
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expected, and dose intensity by treatment group. In addition to summary statistics on the dose intensity as 
a continuous variable, this will also be categorized into bins: 0-33%, >33-66%, >66-100%, and >100%. 
Dose intensity and dosing information will be listed. 
7.9.2 
Adverse Events 
Adverse events will be summarized by the number and percentage of subjects experiencing an event. 
Tables will show the overall incidence of AEs and the incidence for each treatment group. All reported 
AEs will be listed, but only TEAEs will be summarized.
Adverse Events Counting Rules: 
1. A subject with more than one different AE in a particular system organ class (SOC) will be 
counted only once in the total of subjects experiencing adverse events in that particular SOC. 
2. A subject having experienced the same event (AE preferred term) more than once during the 
study will be counted only once in the number of subjects with that event for counts of subjects or 
incidence measures. 
3. If an event changes in intensity or in seriousness during the study, it will be counted only once 
with the worst grade and seriousness respectively. 
4. If the causal relationship to the study drug is assessed differently, it will be counted only once by 
 
A TEAE overview summary table will be provided with the incidences of subjects with at least one 
TEAE, at least one serious TEAE, at least one TEAE related to study treatment, at least one serious 
TEAE related to study treatment, at least one TEAE leading to treatment discontinuation, at least one 
serious TEAE leading to treatment discontinuation, at least one TEAE leading to withdrawal from study, 
at least one serious TEAE leading to withdrawal from study, at least one severe TEAE, at least one severe 
study treatment-related TEAE, and number of deaths. 
Summary tabulations of the following will be prepared for all subjects, for each treatment, for each 
primary system organ class, and for each preferred term within a system organ class. These will report 
counts and incidences of these categories: 
 
All TEAEs 
 
Study treatment-related TEAEs 
 
TEAEs leading to discontinuation of study treatment 
 
TEAEs leading to withdrawal from study 
 
Non-serious TEAEs with >5% incidence rate in any treatment group
 
Serious TEAEs 
 
Study treatment-related serious TEAEs 
 
TEAEs by relationship to study treatment 
 
TEAEs by highest severity and treatment 
 
Severe TEAEs 
 
Severe study treatment-related TEAEs 
Supporting data listings will be provided by treatment group, including: 
 
All AEs (including any AEs reported in the study) 
 
SAEs 
 
AEs resulting in study treatment discontinuation 
 
AEs leading to withdrawal from study 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
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7.9.3 
Laboratory Data 
Summary statistics (n, mean, median, SD, minimum, and maximum) for the baseline assessment and for 
the observed value and change from baseline at each nominal post-baseline visit for scheduled laboratory 
assessments of continuous laboratory variables will be tabulated. Shift tables (e.g., tables that show the 
number of subjects who are low, normal, or high at baseline vs. each post-baseline scheduled assessment) 
will be produced. 
If there are multiple laboratory values for the same parameter at a given visit, the last value will be chosen 
for analysis. 
All data will be displayed in subject data listings for Safety Analysis Set. 
7.9.4
Vital Signs
Summary statistics (n, mean, median, SD, minimum, and maximum) of the raw values and change from 
baseline for pulse rate, systolic blood pressure, diastolic blood pressure, body temperature, respiratory 
rate, weight, and height will be tabulated by treatment and visit separately for adolescents and adults, as 
well as together. 
Vital sign measurements (pulse rate, systolic blood pressure, diastolic blood pressure, body temperature, 
respiratory rate, weight, and height) during the study will be displayed in a vital signs listing. 
7.9.5 
Electrocardiogram (ECG) 
ECG data (heart rate, PR interval, RR interval, QRS interval, QT interval, and QTcF interval) will be 
tabulated with summary statistics (n, mean, median, SD, minimum, and maximum) by visit for both the 
raw values as well as the changes from baseline. If there are multiple ECG values for the same parameter 
at a given visit, the last value will be chosen for analysis. 
The overall ECG results 
-by-three contingency tables will be presented to 
summarize the shift from the baseline category to the worst post-baseline value. Summary results will 
include the count and percentage of subjects within each shift category and treatment group. 
All ECG data as well as clinically significant abnormalities will be presented in a by-subject listing. 
7.9.6 
Other Safety Assessments 
Chest X-ray, physical examination, TB test results, pregnancy test, viral serology, and FSH will be 
presented in listings for the Safety Analysis Set. The overall evaluation of physical examination results at 
each visit will be listed for subjects with any abnormal physical examination findings. No AEs of special 
interest will be defined. 
8. CHANGES FROM METHODS PLANNED IN THE PROTOCOL 
The following exploratory analyses have been added:  
 
Change and percent change from Baseline in facial papule lesion counts at each visit  
 
Change and percent change from Baseline in facial pustule lesion counts at each visit  
 
Change and percent change from Baseline in facial nodule lesion counts at each visit  
 
Change from Baseline in overall Truncal PGA at each visit  
 
Proportion of subjects with at least 1-point decrease from Baseline in facial IGA at each visit  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Proportion of subjects with at least 1-point decrease from Baseline in overall Truncal PGA at 
each visit for subjects with Baseline overall Truncal PGA score of at least 1  
 
Proportion of subjects with at least 2-point decrease from Baseline in overall Truncal PGA at 
each visit for subjects with Baseline overall Truncal PGA score of at least 2  
 
Proportion of subjects achieving an overall Truncal PGA of clear (0) or almost clear (1) with at 
least a 2-grade decrease from Baseline at each visit for subjects with Baseline overall Truncal 
PGA score of at least 2  
 
P
to the PGI-C at each visit  
 
Proportion of 
-C at each visit  
 
P
-S at each visit  
 
Change from Baseline in PGI-S at each visit  
 
P
  
 
Proportion of subjects achieving 
according to the SSRS at Week 12 and Week 20  
 
Proportion of subjects achieving a DLQI of 0 or 1 at each visit for subjects with Baseline DLQI 
of at least 2 
 
Change from Baseline in PAS score based on blinded photographic assessment at each visit  
 
Change from Baseline in erythema score based on blinded photographic assessment at each visit 
9. STATISTICAL SOFTWARE 
The statistical software to be used for generation of the tables, listings, and figures is Statistical Analysis 
System® (SAS) version 9.4 or higher. 
10. REFERENCES 
1. 
US, LLC, Bridgewater, NJ. 
2. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure for 
routine clinical use. Clin Exper Dermatol. 1994;19(3):210-216.
3. Cardiff University School of Medicine. Quality of Life Questionnaires. 
https://www.cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires/dermatology-life-quality-
index. Accesssed 15APR2021. 
4. Lewis-
initial 
validation and practical use. British Journal of Dermatology. 1995; 132(6):942-949. 
5. Edwardes MD, M Baltzan. The generalization of the odds ratio, risk ratio and risk difference to r x k 
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Statistical Analysis Plan 
Protocol No. ANB019-209
Last Revision Date: 28 FEB 2022 
 
CONFIDENTIAL 
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13. APPENDIX 3 MOCKUP TABLES, LISTINGS, AND GRAPHS (TLGs) 
Mockup tables, listings, and graphs are presented in a separate document. 
  
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