Clinical trial NCT04809623
Conditions: Cutaneous Lupus Erythematosus
Sponsor: Gilead Sciences
Start date: 2021-09-01; Completion date: 2022-10-18
Enrollment: 3 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the safety and tolerability of edecesertib (formerly GS-5718) in participants with cutaneous lupus erythematosus (CLE) with or without systemic lupus erythematosus (SLE).

Detailed description:

Arms: arm 1: Participants continuing their standard of care therapy will receive edecesertib at a dose of 115 mg orally once daily for up to 4 weeks. arm 2: Participants continuing their standard of care therapy will receive placebo to match edecesertib orally once daily for up to 4 weeks.
Interventions: intervention 1: Edecesertib intervention 2: Placebo intervention 3: Standard of Care
Intervention descriptions: intervention 1: Tablets administered orally intervention 2: Placebo to match edecesertib tablets administered orally intervention 3: Immunosuppressive/immunomodulatory agents including but not limited to antimalarials (i.e. hydroxychloroquine), methotrexate, azathioprine and corticosteroids (i.e. prednisone)

Protocol documents:
Prot_000.pdf: 



















































































































































































SAP_001.pdf: 


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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 3 
LIST OF ABBREVIATIONS ........................................................................................................................................ 4 
1. 
INTRODUCTION ................................................................................................................................................ 6 
1.1. 
Study Objectives ...................................................................................................................................... 6 
1.2. 
Study Design ............................................................................................................................................ 7 
1.3. 
Sample Size and Power ............................................................................................................................ 7 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 8 
2.1. 
Interim Analyses ...................................................................................................................................... 8 
2.2. 
Final Analysis .......................................................................................................................................... 8 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES .............................................................................. 9 
3.1. 
Analysis Sets ............................................................................................................................................ 9 
3.1.1. 
All Randomized Analysis Set ................................................................................................. 9 
3.1.2. 
Full Analysis Set .................................................................................................................... 9 
3.1.3. 
Safety Analysis Set ................................................................................................................. 9 
3.2. 
Participant Grouping ................................................................................................................................ 9 
3.3. 
Strata and Covariates .............................................................................................................................. 10 
3.4. 
Examination of Participant Subgroups ................................................................................................... 10 
3.5. 
Multiple Comparisons ............................................................................................................................ 10 
3.6. 
Missing Data and Outliers ...................................................................................................................... 10 
3.6.1. 
Missing Data ........................................................................................................................ 10 
3.6.2. 
Outliers ................................................................................................................................. 10 
3.7. 
Data Handling Conventions and Transformations ................................................................................. 10 
3.8. 
Analysis Visit Windows ......................................................................................................................... 11 
3.8.1. 
Definition of Study Day ....................................................................................................... 11 
3.8.2. 
Definition of Baseline .......................................................................................................... 12 
3.8.3. 
Analysis Visit Windows ....................................................................................................... 12 
4. 
PARTICIPANT DISPOSITION ......................................................................................................................... 13 
4.1. 
Participant Enrollment and Disposition ................................................................................................. 13 
4.2. 
Extent of Study Drug Exposure and Adherence ..................................................................................... 14 
4.2.1. 
Duration of Exposure to Study Drug .................................................................................... 14 
4.2.2. 
Prescribed Adherence to Study Drug ................................................................................... 14 
4.3. 
Protocol Deviations ................................................................................................................................ 15 
4.4. 
Assessment of COVID-19 Impact .......................................................................................................... 15 
5. 
BASELINE CHARACTERISTICS .................................................................................................................... 16 
5.1. 
Demographics and Baseline Characteristics .......................................................................................... 16 
5.2. 
Other Baseline Characteristics ............................................................................................................... 16 
5.3. 
Medical History ...................................................................................................................................... 17 
6. 
EFFICACY ANALYSES ................................................................................................................................... 18 
6.1. 
Exploratory Efficacy Endpoint ............................................................................................................... 18 
6.1.1. 
Definition of Exploratory Efficacy Endpoints ...................................................................... 18 
6.1.2. 
Analysis Methods for Exploratory Efficacy Endpoints ........................................................ 18 
7. 
SAFETY ANALYSES ........................................................................................................................................ 19 


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7.1. 
Adverse Events and Deaths .................................................................................................................... 19 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 19 
7.1.2. 
Adverse Event Severity ........................................................................................................ 19 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 19 
7.1.4. 
Serious Adverse Events ........................................................................................................ 19 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 19 
7.1.5.1. 
Definition of Treatment-Emergent Adverse Events ....................................... 19 
7.1.5.2. 
Incomplete Dates ............................................................................................ 20 
7.1.6. 
Summaries of Adverse Events and Deaths ........................................................................... 20 
7.2. 
Laboratory Evaluations .......................................................................................................................... 21 
7.2.1. 
Summaries of Numeric Laboratory Results ......................................................................... 21 
7.2.2. 
Graded Laboratory Values ................................................................................................... 21 
7.2.2.1. 
Treatment-Emergent Laboratory Abnormalities ............................................. 21 
7.2.2.2. 
Summaries of Laboratory Abnormalities ........................................................ 21 
7.2.3. 
Liver-related Laboratory Evaluations ................................................................................... 22 
7.3. 
Body Weight , Height, and Vital Signs .................................................................................................. 22 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 22 
7.4.1. 
Prior Medications ................................................................................................................. 22 
7.4.2. 
Concomitant Medications ..................................................................................................... 23 
7.5. 
Electrocardiogram Results ..................................................................................................................... 23 
7.5.1. 
Corrected QT Intervals ......................................................................................................... 23 
7.6. 
Other Safety Measures ........................................................................................................................... 23 
7.7. 
Changes From Protocol-Specified Safety Analyses ............................................................................... 24 
8. 
PHARMACOKINETIC (PK) ANALYSES ........................................................................................................ 25 
9. 
REFERENCES ................................................................................................................................................... 26 
10. SOFTWARE ....................................................................................................................................................... 27 
11. SAP REVISION .................................................................................................................................................. 28 
12. APPENDICES .................................................................................................................................................... 29 
 
 
LIST OF IN-TEXT FIGURES 
 
Figure 1-1. Study Design Schema ......................................................................................................................... 7 
 


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LIST OF ABBREVIATIONS 
ACLE 
acute cutaneous lupus erythematosus 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BLQ 
below the limit of quantitation 
BMI 
body mass index 
CI 
confidence interval 
CLASI 
cutaneous lupus erythematosus disease area and severity index 
CLASI-A 
CLASI-Activity 
CLASI-D 
CLASI-Damage 
CLE 
cutaneous lupus erythematosus 
CRF 
case report form 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ET 
early termination 
FAS 
Full Analysis Set 
HLGT 
high-level group term  
HLT 
high-level term 
HLT 
high-level term 
LOQ 
limit of quantitation 
LTT 
lower-level term 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetics 
PT 
preferred term 
PTM 
Placebo-to-match 
Q1, Q3 
first quartile, third quartile 
QD 
Once a day 
SAE 
Serious adverse events  
SAP 
statistical analysis plan 
SCLE 
subacute cutaneous lupus erythematosus 
SD 
standard deviation 
SE 
standard error  
SGA 
subject’s global assessment  
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
systemic lupus erythematosus disease activity index - 2000 
SOC 
system organ class 


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TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
ULN 
upper limit of normal 
VAS 
Visual Analog Scale 
WHO 
World Health Organization 
 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-497-5888. This SAP is based on the study protocol amendment 1 dated 
01 July 2021 and the electronic case report forms (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR. 
The decision to discontinue the study has been made on 18 October 2022. The screening has 
been stopped on 20 December 2021, with total 3 participants enrolled in the study. Of the 
3 enrolled participants, 2 participants completed the study and 1 participant was prematurely 
terminated by sponsor. 
This SAP describes the analyses to support the abbreviated CSR. 
1.1. 
Study Objectives 
The primary objective of this study is as follows: 
• To evaluate the safety and tolerability of GS-5718 in participants with CLE with or without 
systemic lupus erythematosus (SLE) 
The secondary objectives of this study are as follows: 
• To characterize the PK of GS-5718 in participants with CLE with or without SLE 
The exploratory objectives of this study are as follows: 
CCI


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1.2. 
Study Design 
This is a Phase 1b, multicenter, randomized, sponsor-unblinded, placebo-controlled, 4-week 
study evaluating the safety and tolerability of GS-5718 in participants with CLE. Adult male or 
female participants at ≥ 18 and ≤ 75 years of age who either fulfill EULAR/ACR 2019 
classification criteria for SLE or have biopsy-proven CLE and have acute CLE (ACLE)/subacute 
CLE (SCLE) with cutaneous lupus erythematosus disease area and severity index {Klein 2010} 
(CLASI) activity score of  ≥ 6 during screening and Day 1 may be eligible for entry (refer to the 
protocol for complete inclusion and exclusion criteria). Eligible participants are randomly 
assigned to 1 of the following 2 treatment groups in a 2:1 ratio: 
• GS-5718 115 mg once a day in addition to standard of care for 4 weeks (n = 8) 
• Placebo-to-match (PTM) once a day in addition to standard of care for 4 weeks (n = 4) 
A schematic of this study is provided in Figure 1-1. 
Figure 1-1. Study Design Schema 
 
 
1.3. 
Sample Size and Power 
Sample size was determined based on practical considerations and no sample size calculation 
was performed. A sample size of 12 participants (8 participants randomized to GS-5718 and 
4 participants randomized to placebo) would provide a suitable assessment of the descriptive 
safety and pharmacokinetics (PK) profile. 
The enrollment was stopped after 3 participants were randomized.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2. 
TYPE OF PLANNED ANALYSIS 
2.1. 
Interim Analyses 
No interim analysis is planned. 
2.2. 
Final Analysis 
The unblinded final analysis will be performed after all participants have completed the study, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
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3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented. 
By-participant listings will be presented for all participants in the All Randomized Analysis Set 
and sorted by participant ID number, visit date, and time (if applicable). Data collected on log 
forms, such as AEs, will be presented in chronological order within the participant. The 
treatment group to which participants were randomized will be used in the listings. Age, sex at 
birth, race, and ethnicity will be included in the listings, as space permits. 
3.1. 
Analysis Sets 
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before the study blind is broken for analysis. The analysis set will be identified and 
included as a subtitle of each table, figure, and listing. 
A listing of reasons for exclusion from analysis sets will be provided by participant. 
3.1.1. 
All Randomized Analysis Set 
All Randomized Analysis Set includes all participants who were randomized in the study. 
3.1.2. 
Full Analysis Set 
The Full Analysis Set (FAS) includes all randomized participants who took at least 1 dose of 
study drug. This is the primary analysis set for efficacy analyses. 
3.1.3. 
Safety Analysis Set 
The Safety Analysis Set includes all participants who took at least 1 dose of study drug. This is 
the primary analysis set for safety analyses. 
3.2. 
Participant Grouping 
For analyses based on the FAS, participants will be grouped according to the treatment to which 
they were randomized. For analyses based on the Safety Analysis Set, participants will be 
grouped according to the actual treatment received. The actual treatment received will differ 
from the randomized treatment only when their actual treatment differs from randomized 
treatment for the entire treatment duration. 


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3.3. 
Strata and Covariates 
This study does not use a stratified randomization schedule when enrolling participants. 
No covariates will be included in efficacy and safety analyses. 
3.4. 
Examination of Participant Subgroups 
There are no prespecified participant subgroups for efficacy and safety analyses. 
3.5. 
Multiple Comparisons 
Adjustments for multiplicity will not be made. 
3.6. 
Missing Data and Outliers 
3.6.1. 
Missing Data 
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document. 
For missing last dosing date of study drug, imputation rules are described in Section 4.2. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
prior and concomitant medications in Section 7.4. 
3.6.2. 
Outliers 
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis. 
3.7. 
Data Handling Conventions and Transformations 
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected: 
• If only month and year of birth is collected, then “15” will be imputed as the day of birth. 
• If only year of birth is collected, then “01 July” will be imputed as the day and month of 
birth. 
• If year of birth is missing, then date of birth will not be imputed. 
Partial CLE/SLE diagnosis dates will be imputed using same rules as for the partial dates of 
birth.  
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, then age derived based on date of birth and the 
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drug, the randomization date will be used instead of the Day 1 visit date. For screen failures, the 
date the first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (e.g., estimates of creatinine clearance, age 
at date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified. 
The data that are continuous in nature but are less than the lower limit of quantitation (LOQ) or 
above the upper LOQ will be imputed as follows: 
• A value that is 1 unit less than the lower LOQ at the same precision level of the originally 
reported value will be used to calculate descriptive statistics if the datum is reported in the 
form of “< x” (where x is considered the lower LOQ). For example, if the values are reported 
as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to calculate summary 
statistics. An exception to this rule is any value reported as < 1 or < 0.1, etc. For values 
reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to calculate 
summary statistics. 
• A value that is 1 unit above the upper LOQ will be used to calculate descriptive statistics if 
the datum is reported in the form of “> x” (where x is considered the upper LOQ). Values 
with decimal points will follow the same logic as above. 
• The lower or upper LOQ will be used to calculate descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the lower or upper LOQ, 
respectively). 
3.8. 
Analysis Visit Windows 
3.8.1. 
Definition of Study Day 
Study day will be calculated from the first dosing date of study drug and derived as follows: 
• For postdose study days: Assessment Date – First Dosing Date  + 1 
• For days prior to the first dose: Assessment Date – First Dosing Date  
Therefore, study day 1 is the day of first dose of study drug administration. 


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3.8.2. 
Definition of Baseline  
Baseline will be defined as the last nonmissing value on or prior to the first dosing date of study 
drug. All visits, including unscheduled visits, prior to the first dosing date of study drug, will be 
used for baseline derivation. If there are multiple records with the same time or no time recorded 
on the same day, the baseline value will be the average of the measurements for continuous data, 
or the measurement with the lowest severity (e.g., normal will be selected over abnormal for 
safety electrocardiogram [ECG] findings) for categorical data. 
3.8.3. 
Analysis Visit Windows 
No analysis visit windows will be derived for this study. The baseline and relevant nominal visits 
as recorded on the CRF will be used when data are summarized by visit. Any data relating to 
unscheduled visits will not be assigned to a particular visit or time point. However, the following 
exceptions will be made: 
• An unscheduled visit prior to the first dosing of study drug may be included in the calculation 
of the baseline value, if applicable. 
• Unscheduled visits after the first dose of study drug will be included in determining the 
maximum postbaseline toxicity grade. 
• For participants who prematurely discontinue from the study, early termination (ET) data 
will be summarized as a separate visit, labeled as “Early Termination Visit”. 
• Data collected on a follow-up visit will be summarized as a separate visit and labeled 
“Follow-up Visit”. 
• Data obtained after the follow-up visit or last dose date plus 28 days (whichever is later) will 
be excluded from the summaries but will be included in the listings. 
All records will be listed by collection date. 


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4. 
PARTICIPANT DISPOSITION 
4.1. 
Participant Enrollment and Disposition 
Key study dates (i.e., first participant screened, first participant randomized, last participant 
randomized, last participant last visit for the primary endpoint, and last participant last visit for 
the clinical study report) will be provided. 
No summary of participant enrollment will be provided. Relevant patient enrollment information 
will be presented in a by-participant listing.  
The randomization schedule used for the study will be provided as an appendix to the CSR. 
Randomization scheme will be presented in a by-participant listing.  
A summary of participant disposition will be provided by treatment group. This summary will 
present the number of participants in each of the categories listed below: 
• Screened  
• All Randomized Analysis Set 
• Safety Analysis Set 
• Full Analysis Set  
• Completed study drug 
• Did not complete study drug with reasons for premature discontinuation of study drug 
• Completed study  
• Did not complete the study with reasons for premature discontinuation of study 
For the status of study drug and study completion, and reasons for premature discontinuation, the 
number and percentage of participants in each category will be provided. The denominator for 
the percentage calculation will be the total number of participants in the Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition. 


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The following by-participant listings will be provided by participant identification (ID) number 
in ascending order to support the above summary tables: 
• Reasons for premature study drug or study discontinuation 
• Reasons for exclusion from analysis sets 
• Lot number and bottle ID of assigned study drugs 
4.2. 
Extent of Study Drug Exposure and Adherence 
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of adherence relative to the study drug regimen specified in the protocol. 
4.2.1. 
Duration of Exposure to Study Drug 
Total duration of exposure to study drug will be defined as last dosing date minus first dosing 
date plus 1, regardless of any temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (e.g., 4.5 weeks). If the last study drug dosing 
date is missing, the latest date among the study drug end date, clinical visit date, laboratory 
sample collection date, and vital signs assessment date that occurred during the on-treatment 
period will be used for participants included in the final analyses. If month and year of the last 
dose are known, and the last study drug dosing date imputed above is different from the month 
collected, the last date of that month will be used. If only year of the last dose is known, and the 
last study drug dosing date imputed above is after the year collected, the last date of that year 
will be used; if the last study drug dosing date imputed above is before the year collected, the 
first date of that year will be used. 
The total duration of exposure to study drug will be summarized using descriptive statistics and 
using the number (i.e., cumulative counts) and percentage of participants exposed through the 
following time periods: Baseline (Day 1), Week 1 (Day 8), Week 2 (Day 15) and Week 4 (Day 29). 
Summaries will be provided by treatment group for the Safety Analysis Set.  
No formal statistical testing is planned. 
4.2.2. 
Prescribed Adherence to Study Drug 
The presumed total number of doses administered to a participant will be determined by the data 
collected on the drug accountability CRF using the following formula: 
Total Number of Doses Administered =
No. of Doses Dispensed
No. of Doses Returned




−








∑
∑
 


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The level of prescribed adherence to the study drug regimen will be determined by the total 
amount of study drug administered relative to the total amount of study drug specified by the 
protocol for a participant who completes treatment in the study. 
The level of prescribed adherence will be expressed as a percentage using the following formula: 
Total Amount of Study Drug Administered
Prescribed Adherence (%) =
 x 100
Total Amount of Study Drug Specified by Protocol






 
If a bottle was dispensed and returned empty, then the number of tablets returned will be entered 
as zero. If a bottle is dispensed but not returned (missing) then the number of tablets from that 
bottle will be counted as zero. 
If calculated adherence is greater than 100%, the result will be set to 100%. 
The prescribed adherence to study drug will not be summarized but listed. 
A by-participant listing of study drug administration and drug accountability will be provided 
separately by participant ID number (in ascending order) and visit (in chronological order). 
4.3. 
Protocol Deviations  
A by-participant listing will be provided for those participants who did not meet at least 1 
eligibility (inclusion or exclusion) criterion, but enrolled in the study. The listing will present the 
eligibility criterion (or criteria if more than 1 deviation) that participants did not meet and related 
comments, if collected. 
Important protocol deviations occurring after participants entered the study are documented 
during routine monitoring. A by-participant listing will be provided for those participants with 
important protocol deviation.  
4.4. 
Assessment of COVID-19 Impact 
Study conduct was not impacted by the novel coronavirus (COVID-19) pandemic. No analyses 
will be provided for the assessment of COVID-19 impact. 


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5. 
BASELINE CHARACTERISTICS 
5.1. 
Demographics and Baseline Characteristics 
Participant demographic variables (i.e., age, sex, race, and ethnicity) and baseline characteristics 
(body weight [in kg], height [in cm], body mass index [BMI; in kg/m2]) will be summarized by 
treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of participants for categorical variables. The summary of demographic 
data will be provided for the Safety Analysis Set. 
A by-participant demographic listing, including the informed consent date, will be provided by 
participant ID number in ascending order. 
5.2. 
Other Baseline Characteristics 
Other baseline characteristics include: 
• Time from CLE diagnosis to enrollment (years) 
• CLE disease subtype 
• SLE diagnosis (yes/ no) 
• Time from SLE diagnosis to enrollment (years) 
• CLASI-Activity (CLASI-A) score at baseline 
• CLASI-Damage (CLASI-D) score at baseline 
• Subject’s global assessment (SGA) of CLE activity (mm) at baseline 
• Physician’s global assessment (PGA) of CLE activity (mm) at baseline 
These baseline characteristics will be summarized by treatment group and overall using 
descriptive statistics for continuous variables and using number and percentage of participants 
for categorical variables. The summary of these baseline characteristics will be provided for the 
Safety Analysis Set. No formal statistical testing is planned. 
The time from CLE/SLE diagnosis to enrollment will be calculated in years between the date of 
enrollment and the date of diagnosis, as (the date of enrollment – the date of diagnosis 
+1)/365.25. 
A by-participant listing of other baseline characteristics will be provided by participant ID 
number in ascending order. 


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5.3. 
Medical History 
Medical history will be collected at screening for disease-specific and general conditions 
(i.e., conditions not specific to the disease being studied). Both medical history data will not be 
coded and will be listed only.  




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7. 
SAFETY ANALYSES 
7.1. 
Adverse Events and Deaths 
7.1.1. 
Adverse Event Dictionary 
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset. 
7.1.2. 
Adverse Event Severity 
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria using CTCAE v5.0. The severity grade of events for which the investigator did not record 
severity will be categorized as “missing” for tabular summaries and data listings. The missing 
category will be listed last in summary presentation. 
7.1.3. 
Relationship of Adverse Events to Study Drug 
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-participant data listings will show the relationship as missing. 
7.1.4. 
Serious Adverse Events 
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAEs in the Patient Safety database before data 
finalization. 
7.1.5. 
Treatment-Emergent Adverse Events  
7.1.5.1. 
Definition of Treatment-Emergent Adverse Events 
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following: 
• Any AEs with an onset date on or after the study drug start date and no later than 28 days 
after permanent discontinuation of study drug 
• Any AEs leading to premature discontinuation of study drug. 


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7.1.5.2. 
Incomplete Dates 
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met: 
• The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and 
• The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 28 days after the date of the last dose of study drug  
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent. 
7.1.6. 
Summaries of Adverse Events and Deaths 
Treatment-emergent AEs will be summarized based on the Safety Analysis Set. 
A brief, high-level summary of the number and percentage of participants who experienced at 
least 1 TEAE in the categories described below will be provided by treatment group. All deaths 
observed in the study will also be included in this summary. 
The number and percentage of participants who experienced at least 1 TEAE will be provided 
and summarized by treatment group for the following:  
• TEAEs 
• TEAEs with Grade 3 or higher 
• TEAEs with Grade 2 or higher 
• TEAE Related to Study Drug 
• TEAE Related to Study Drug with Grade 3 or Higher 
• TEAE Related to Study Drug with Grade 2 or Higher 
• TE Serious AE 
• TE Serious AE Related to Study Drug  
• TEAE leading to discontinuation of study drug 
• TEAE leading to discontinuation of study 
• TE AE leading to death (i.e., outcome of death) 


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Multiple events will be counted only once per participant in each summary.  
In addition, data listings will be provided for all AEs and all SAEs indicating whether the event 
is treatment emergent, and all deaths. 
7.2. 
Laboratory Evaluations 
A by-participant listings for laboratory test results will be provided by participant ID number and 
visit in chronological order for hematology, serum chemistry, and urinalysis separately. Values 
falling outside of the relevant reference range and/or having a severity grade of 1 or higher on 
the Common Terminology Criteria for Adverse Events (CTCAE severity grade) will be flagged 
in the data listings, as appropriate. 
No formal statistical testing is planned. 
7.2.1. 
Summaries of Numeric Laboratory Results 
Descriptive statistics for laboratory tests will not be provided. Hematology, chemistry and 
urinalysis results will be listed. 
7.2.2. 
Graded Laboratory Values 
The CTCAE v5.0 will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (i.e., increased, decreased) will be presented separately.  
7.2.2.1. 
Treatment-Emergent Laboratory Abnormalities 
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 28 days for participants who permanently discontinued study drug. If the 
relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent.  
7.2.2.2. 
Summaries of Laboratory Abnormalities 
The graded laboratory abnormalities summaries (number and percentage of participants) for 
treatment-emergent laboratory abnormalities will be provided by lab test and treatment group; 
participants will be categorized according to the most severe postbaseline abnormality grade for 
a given lab test. Treatment-emergent laboratory abnormalities summary will be presented 
regardless of fasting status.  
For all summaries of laboratory abnormalities, the denominator is the number of participants 
with nonmissing postbaseline values up to 28 days after last dosing date. 


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A by-participant listing of treatment-emergent laboratory abnormalities will be provided by 
participant ID number and visit in chronological order. This listing will include all test results 
that were collected throughout the study for the lab test of interest, with all applicable severity 
grades displayed. 
7.2.3. 
Liver-related Laboratory Evaluations 
Liver-related abnormalities after initial study drug dosing will be examined using following 
criteria based on the laboratory test values for postbaseline measurements: 
• Aspartate aminotransferase (AST): (a) > 3 times of the upper limit of reference range (ULN); 
(b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN 
• Alanine aminotransferase (ALT): (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; 
(d) > 20 x ULN 
• AST or ALT: (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN 
• Total bilirubin: > 2 x ULN 
• Alkaline phosphatase (ALP) > 1.5 x ULN 
• AST or ALT > 3 x ULN and total bilirubin: (a) > 1.5 x ULN; (b) > 2 x ULN 
A listing of liver test results by visit for participants who met at least 1 of the above criteria will 
be provided. 
7.3. 
Body Weight , Height, and Vital Signs 
A by-participant listing of vital signs will be provided by participant ID number and visit in 
chronological order. In the same manner, a by-participant listing of body weight, height, and 
BMI will be provided separately. 
7.4. 
Prior and Concomitant Medications 
Medications collected at screening and during the study will be coded using the March 2022 
version of the World Health Organization (WHO) Drug dictionary version. 
7.4.1. 
Prior Medications 
Prior medications are defined as any medications taken before a participant took the first study 
drug. 
Any medication with a start date prior to the first dosing date of study drug will be considered 
prior regardless of when the stop date is. If a partial start date is entered the medication will be 
considered prior unless the month and year (if day is missing) or year (if day and month are 
missing) of the start date are after the first dosing date. Medications with a completely missing 
start date will be considered prior, unless otherwise specified. 


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7.4.2. 
Concomitant Medications 
Concomitant medications are defined as medications taken while a participant took study drug.  
Any medications with a start date prior to or on the first dosing date of study drug and continued 
to be taken after the first dosing date, or started after the first dosing date but prior to or on the 
last dosing date of study drug will be considered concomitant medications. Medications started 
and stopped on the same day as the first dosing date or the last dosing date of study drug will 
also be considered concomitant. Medications with a stop date prior to the date of first dosing date 
of study drug or a start date after the last dosing date of study drug will not be considered 
concomitant. If a partial stop date is entered, any medication with the month and year (if day is 
missing) or year (if day and month are missing) prior to the date of first study drug 
administration will not be considered concomitant. If a partial start date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
after the study drug stop date not be considered concomitant. Medications with completely 
missing start and stop dates will be cosidered concomitant, unless otherwise specified.  
Prior and concomitant medications will not be summarized in the study. 
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-participant listing sorted by participant ID number and administration date in chronological 
order. The general prior and concomitant medication and CLE/SLE-specific prior and 
concomitant medications will be presented separately. 
7.5. 
Electrocardiogram Results 
By-participant listings for overall assessment of electrocardiogram (ECG) and 12-lead ECG 
results will be provided by participant ID number and visit in chronological order. 
7.5.1. 
Corrected QT Intervals 
The QT interval (measured in millisecond [msec]) is a measure of the time between the start of 
the Q wave and the end of the T wave in the heart’s electrical cycle. The QT interval represents 
electrical depolarization and repolarization of the ventricles. The QT interval is affected by heart 
rate, and a number of methods have been proposed to correct QT for heart rate.  
Corrected QT (QTc) intervals will be derived using Fridericia’s correction (QTcF) as follows:  
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄= 𝑄𝑄𝑄𝑄
√𝑅𝑅𝑅𝑅
3
 
where QT is measured in msec; RR = 60/Heart Rate (beats per min [bpm]) and RR is measured 
in seconds. 
7.6. 
Other Safety Measures 
No additional safety measures are specified in the protocol. 


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7.7. 
Changes From Protocol-Specified Safety Analyses 
Only limited safety summaries are provided due to small number of participants enrolled in the 
study prior to study termination. 


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8. 
PHARMACOKINETIC (PK) ANALYSES 
Pharmacokinetic analyses will not be performed. 


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9. 
REFERENCES 
Klein RS, Morganroth PA, Werth VP. Cutaneous Lupus and the Cutaneous Lupus 
Erythematosus Disease Area and Severity Index (CLASI) Instrument. Rheumatic 
diseases clinics of North America 2010;36 (1):33-51, vii. 
 
 


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10. 
SOFTWARE 
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA. 
 


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11. 
SAP REVISION 
Revision Date 
(DD MMM YYYY) 
Section 
Summary of Revision 
Reason for Revision 
 
 
 
 
 
 
 
 


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12. 
APPENDICES 
Appendix 1. 
Schedule of Assessments 
Procedure 
Screening 
V0 
Study Treatment Period 
Early 
Terminationb 
Follow 
Up 
Instructions 
Day 
1 
Week 
1 
Week 
2 
Week 
4 
−28a 
0a 
+7 
Daysa 
(±2 
Days) 
+14 
Daysa 
(±2 
Days) 
+28 
Daysa 
(±2 
Days) 
Any 
+28 
Daysa 
(±5 
Days) 
Informed Consent  
X 
 
 
 
 
 
 
Written, signed, and dated 
informed consent must be 
obtained prior to screening 
Inclusion/Exclusion 
Criteria 
X 
X 
 
 
 
 
 
Documentation of select 
criteria must be submitted to 
the study sponsor for review 
and confirmation of 
participant eligibility 
Medical History, 
Demographics, Substance 
Use  
X 
 
 
 
 
 
 
Medical history will include 
demographics, a review of 
surgical history, and 
CLE/SLE history 
Prior and Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
 
 
 
 
 
 
Participants should be 
instructed to remove shoes 
prior to baseline height 
measurement 
Weight 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signs  
X 
X 
X 
X 
X 
X 
X 
Blood pressure, Pulse, 
Respiratory Rate, 
Temperature 
12-Lead ECG 
X 
 
 
X 
X 
X 
X 
Resting ECG, performed and 
assessed locally; for 
participants with chest lesions, 
study assessments should 
precede ECG, as applicable 
Complete Physical 
Examination  
X 
 
 
 
 
 
 
 
Symptom-Driven 
Physical Examination 
 
X 
X 
X 
X 
X 
X 
Performed, as needed, based 
on signs and symptoms 
CLASI Assessment  
X 
X 
X 
X 
X 
X 
X 
Participants must have a 
CLASI activity (CLASI-A) 
score of ≥ 6 (excluding the 
alopecia component) during 
screening and Day 1 


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Procedure 
Screening 
V0 
Study Treatment Period 
Early 
Terminationb 
Follow 
Up 
Instructions 
Day 
1 
Week 
1 
Week 
2 
Week 
4 
−28a 
0a 
+7 
Daysa 
(±2 
Days) 
+14 
Daysa 
(±2 
Days) 
+28 
Daysa 
(±2 
Days) 
Any 
+28 
Daysa 
(±5 
Days) 
Photography of Skin 
Lesion(s) 
X 
X 
X 
X 
X 
X 
X 
Participant identifying 
features should be obscured, 
as much as possible. 
Follow-up photographs must 
target the same area of 
clinically active disease 
evaluated and photographed at 
baseline. 
SLEDAI-2K Assessment  
 
X 
 
X 
X 
X 
X 
To be completed for 
participants with concurrent 
SLE 
Subject’s Global 
Assessment 
X 
X 
X 
X 
X 
X 
X 
Subject’s global assessment of 
CLE disease activity (visual 
analogue scale) 
Physician’s Global 
Assessment 
X 
X 
X 
X 
X 
X 
X 
Physician’s global assessment 
of CLE disease activity 
(visual analogue scale) 
Chemistry  
X 
X 
X 
X 
X 
X 
X 
See protocol 
Hematology  
X 
X 
X 
X 
X 
X 
X 
See protocol 
Fasting Lipids 
 
X 
 
 
X 
 
 
No food or drinks, except 
water for at least 8 hours prior 
to blood sample collection 
Serum Pregnancy Test 
X 
 
 
 
 
 
 
Females of childbearing 
potential only (see protocol) 
Urine Pregnancy Test 
 
X 
X 
X 
X 
X 
X 
Females of childbearing 
potential only (see protocol) 
FSH Test 
X 
 
 
 
 
 
 
Females of nonchildbearing 
potential only (see protocol) 
Urine drug and Alcohol 
screen 
X 
 
 
 
 
 
 
 
Urinalysis  
X 
X 
X 
X 
X 
X 
X 
 
Urine Biomarkers 
 
X 
 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
Urine Spot 
Protein/Creatinine Ratio  
 
X 
 
X 
X 
X 
X 
 
QuantiFERON®-TB Gold 
In-Tube test 
X 
 
 
 
 
 
 
Not required for participants 
with prior latent TB who have 
been treated with a full course 
of prophylaxis 
HIV, HBV, and HCV 
Serology 
X 
 
 
 
 
 
 
 


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Procedure 
Screening 
V0 
Study Treatment Period 
Early 
Terminationb 
Follow 
Up 
Instructions 
Day 
1 
Week 
1 
Week 
2 
Week 
4 
−28a 
0a 
+7 
Daysa 
(±2 
Days) 
+14 
Daysa 
(±2 
Days) 
+28 
Daysa 
(±2 
Days) 
Any 
+28 
Daysa 
(±5 
Days) 
HCV Serology  
 
 
 
 
X 
 
 
Only applicable for 
participants with baseline 
positive HCV antibody and 
negative HCV RNA VL 
Skin Biopsy FFPE 
(4 mm) 
 
X 
 
 
X 
 
 
A separate manual will be 
provided for skin biopsy 
instructions. Skin biopsies 
should be performed at the 
end of the respective visit 
after all other study 
procedures have been 
completed, as much as 
possible. Day 1 biopsies are to 
be taken predose. 
Skin Biopsy RNA later 
(2-4 mm) 
 
X 
 
 
X 
 
 
PaxGene RNA Sample 
X 
X 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
Immunophenotyping 
Whole Blood  
 
X 
 
X 
X 
X 
X 
 
TBNK Whole Blood 
 
X 
 
X 
X 
X 
X 
 
Antinuclear Antibody by 
IFA 
X 
 
 
 
 
 
 
 
ENA panel 
(anti-Sm, -RNP, -Ro, -La) 
and antiphospholipid 
antibodies 
X 
 
 
 
 
Anti-dsDNA antibody 
 
X 
 
X 
X 
X 
X 
Day 1 sample to be taken for 
all participants. 
Samples thereafter only 
applicable for participants 
with concurrent SLE. 
Complement Panel (C3, 
C4, CH50) 
X 
 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
Quantitative Serum 
Immunoglobulin Test 
 
X 
 
 
X 
X 
X 
 
Serum Biomarker  
 
X 
X 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
Plasma Biomarker  
 
X 
X 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
Viably Frozen PBMC 
 
X 
 
X 
X 
X 
X 
Day 1 sample to be taken 
predose 
CCI