Clinical trial NCT04753034
Conditions: Atopic Dermatitis
Sponsor: Teres Bio, Inc.
Start date: 2021-01-18; Completion date: 2021-05-03
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This Phase 2 study will assess efficacy, safety, and tolerability of TER-101 ointment and vehicle twice daily for 28 days in adult and adolescent subjects with mild to moderate atopic dermatitis.

Detailed description:

Arms: arm 1: BID (twice daily) application arm 2: Vehicle ointment, BID (twice daily) application
Interventions: intervention 1: TER-101 intervention 2: Vehicle
Intervention descriptions: intervention 1: Active Comparator intervention 2: Placebo Comparator

Protocol documents:
Prot_000.pdf: 









































































































































SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
Protocol Number: TER101-AD-201 
A Multicenter, Randomized, Double-blind, Vehicle-Controlled, Phase 2a Study of TER-
101 2.75% Topical Ointment to Assess Efficacy and Safety in Subjects with Mild to  
Moderate Atopic Dermatitis 
The information contained in this analysis plan and all other information relevant to TER-101  
2.75% Topical Ointment are the confidential and proprietary information of Teres Bio, Inc. and,  
except as may be required by federal, state, or local laws or regulation, may not be disclosed to  
others without the prior written permission of Teres Bio, Inc.
Compound: TER-101
Teres Bio
Protocol TER101-AD-201
CSR Date and Version: 22Sep2021, V1.0
16.1.9 Documentation of Statistical Methods




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Table of Contents 
1 
STUDY OBJECTIVES AND SAMPLE SIZE RATIONALE ................................... 7 
1.1 
STUDY OBJECTIVES ................................................................................................ 7 
1.2 
SAMPLE SIZE ............................................................................................................. 8 
1.3 
UNBLINDING ............................................................................................................. 8 
2 
STUDY DESIGN SUMMARY ..................................................................................... 8 
2.1 
VISITS .......................................................................................................................... 8 
2.2 
SUBJECTS ................................................................................................................. 13 
2.2.1 
Number of Subjects ................................................................................................ 13 
2.2.2 
Diagnosis and Main Criteria for Inclusion ............................................................. 13 
2.2.3 
Study Population Characteristics ............................................................................ 13 
2.2.4 
Replacement Subjects ............................................................................................. 13 
2.3 
TREATMENT AND RANDOMIZATION ............................................................... 13 
2.3.1 
Study Medications, Treatment, and Mode of Administration ................................ 13 
2.3.2 
Randomization ........................................................................................................ 14 
2.3.3 
Administration of Treatment .................................................................................. 14 
2.3.4 
Duration of Treatment ............................................................................................ 14 
2.4 
ASSESSMENTS ........................................................................................................ 14 
2.4.1 
Evaluators ............................................................................................................... 14 
2.4.2 
Evaluations – Efficacy ............................................................................................ 14 
2.4.2.1 
Eczema Area Severity Index ............................................................................... 14 
2.4.2.2 
Investigator Global Assessment .......................................................................... 15 
2.4.2.3 
Worst Itch Numeric Rating Scale ........................................................................ 16 
2.4.2.4 
Total Body Surface Area ..................................................................................... 16 
2.4.3 
Evaluations – Safety ............................................................................................... 16 
2.4.3.1 
Local Tolerability ................................................................................................ 16 
2.4.3.2 
Adverse Events .................................................................................................... 17 
2.4.3.3 
Laboratory Sampling ........................................................................................... 17 
2.4.3.4 
Physical Examination, Height, and Body Weight ............................................... 18 


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2.4.3.5 
Vital Signs ......................................................................................................... 18 
2.4.3.6 
Electrocardiogram ............................................................................................. 18 
2.4.4 
Evaluations – PK ................................................................................................... 18 
3 
STATISTICAL METHODOLOGY ........................................................................ 19 
3.1 
GENERAL STATISTICAL CONSIDERATIONS .................................................. 19 
3.2 
ANALYSIS POPULATION AND DISPOSITION OF SUBJECTS ....................... 20 
3.2.1 
Data Sets Analyzed ............................................................................................... 20 
3.2.2 
Protocol Deviations ............................................................................................... 20 
3.2.3 
Disposition of Subjects ......................................................................................... 20 
3.3 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ................... 20 
3.4 
MEDICAL HISTORY .............................................................................................. 21 
3.5 
PRIOR/CONCOMITANT MEDICATIONS ........................................................... 21 
3.6 
EFFICACY ANALYSIS .......................................................................................... 21 
3.6.1 
EASI Analyses ...................................................................................................... 21 
3.6.2 
IGA Analyses ........................................................................................................ 23 
3.6.3 
WI-NRS Analyses ................................................................................................. 23 
3.6.4 
TBSA Analyses ..................................................................................................... 24 
3.7 
SAFETY ANALYSIS .............................................................................................. 24 
3.7.1 
Study Drug Exposure And Compliance ................................................................ 24 
3.7.2 
Local Tolerability .................................................................................................. 24 
3.7.3 
Adverse Events ..................................................................................................... 25 
3.7.4 
Laboratory Tests ................................................................................................... 26 
3.7.5 
Physical Examinations .......................................................................................... 26 
3.7.6 
Vital Signs ............................................................................................................. 26 
3.7.7 
Electrocardiogram ................................................................................................. 26 
3.8 
PK ANALYSES ....................................................................................................... 26 
3.9 
INTERIM ANALYSES ............................................................................................ 26 
4 
CHANGES TO PLANNED ANALYSES ............................................................... 27 


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List of Abbreviations 
Abbreviations/Acronyms 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BID 
twice daily 
BMI 
body mass index 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CRF 
case report form 
CV 
coefficient of variation 
EASI 
eczema area and severity index 
ECG 
electrocardiogram 
ES 
efficacy analysis set 
GLMM 
generalized linear mixed model 
IGA 
investigator global assessment 
KM 
Kaplan-Meier 
LE 
lower extremities 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetics 


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Abbreviations/Acronyms 
PKS 
pharmacokinetics analysis set 
PPES 
per protocol efficacy analysis set 
PT 
preferred term 
SAE 
serious adverse event 
Std Dev 
standard deviation 
SOC 
system organ class 
SS 
safety analysis set 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TBSA 
total body surface area 
UE 
upper extremities 
VS 
vital signs 
WI-NRS 
worst itch numeric rating scale 
w/w 
weight for weight 


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1 
STUDY OBJECTIVES AND SAMPLE SIZE RATIONALE 
1.1 
STUDY OBJECTIVES 
TER-101 is a cytosolic phospholipase A2 alpha (cPLA2α) inhibitor currently in development 
for the treatment of inflammatory skin diseases, including atopic dermatitis (AD). This Phase 
2a study is to assess efficacy, safety, and tolerability of TER-101 (2.75% weight for weight 
[w/w]) ointment (TER-101 Ointment) with its vehicle (TER-101 Placebo Ointment) twice 
daily for 28 days in adult and adolescent subjects with mild to moderate AD. Primary and 
Secondary Objectives are summarized below. 
OBJECTIVES 
ENDPOINTS 
Primary 
To assess the efficacy of TER-
101 (2.75% w/w) ointment vs. 
vehicle in subjects aged 12 – 65 
with mild to moderate AD 
Primary Efficacy Endpoints 
Percent change in EASI from baseline at Day 29 
Secondary Efficacy Endpoints 
Percent change in EASI from baseline over time 

Percent change in EASI by region (head, trunk, 
UE, LE) from baseline over time 
EASI-75, EASI-50 responder analysis over time 
Absolute change in EASI from baseline over time 
Change in IGA from baseline over time 

Change from baseline WI-NRS at Days 15, 29 
(WI-NRS captured on e-diary daily) 

Responder analysis: Reduction of ≥ 3 in 
subjects with baseline WI-NRS ≥ 4 
Change in TBSA affected from baseline over time 
Secondary 
To assess the safety and tolerability 
of TER-101 (2.75% w/w) ointment vs. 
vehicle in subjects with AD 
Safety: TEAEs, SAEs, VS, ECGs, laboratories 

Tolerability: Scored by investigator at 
baseline and post-baseline visits on 4-point scale 
(0 = none; 3 = severe) to include subscores for 
erythema, burning/stinging, pruritus. 
To assess systemic exposure to TER-101 
(2.75% w/w) ointment after BID treatment 
for 28 days 
PK: systemic plasma trough levels of TER-101 
on Days 15, 29 
BID = twice daily; EASI = Eczema Area and Severity Index; EASI-50/75 = 50 or 75% reduction in EASI score 
from baseline; ECG = electrocardiogram; IGA = Investigator Global Assessment; LE = lower extremities; PK = 


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pharmacokinetics; SAE = serious adverse event; TBSA = Total Body Surface Area; TEAE = treatment emergent 
adverse event; UE = upper extremities; VS = vital signs; WI-NRS = Worst Itch Numeric Rating Scale; w/w =. 
weight for weight. 
1.2 SAMPLE SIZE 
The sample size is based on a clinical rather than statistical rationale. Approximately 60 
subjects are planned to be enrolled and randomized, considering a potential 15% drop-out rate, 
to yield approximately 50 subjects completing the study. 
1.3 UNBLINDING 
After all subjects complete the end of treatment visit, the database will be locked and 
unblinded for statistical analysis of topline results while awaiting completion of 30-day post-
treatment period for all subjects. Topline summaries will be provided to the sponsor’s Chief 
Medical Officer for planning future drug development strategies, with no impact on this 
study’s conduct. Subject level unblinded results will not be disclosed to study subjects, 
investigators, or TrialSpark project team members until 30 days after the last visit of the last 
subjects to collect reported adverse events (AEs). 
2 
STUDY DESIGN SUMMARY 
This is a Phase 2a, randomized, double-blind, vehicle-controlled study assessing efficacy, 
safety, and local tolerability of TER-101 (2.75% w/w) ointment vs. its ointment vehicle 
topically twice daily in adolescent and adult subjects (age 12 - 65) subjects with mild to 
moderate AD. 
Subjects will be randomized 1:1 to receive either TER-101 (2.75% w/w) ointment or vehicle. 
Both the subject and the investigator will be blinded to the treatment assignments. 
The study will include up to a 35-day screening period prior to enrollment/baseline visit and a 
28-day active treatment period. Subjects will apply assigned treatment to all areas affected by 
AD at baseline twice daily throughout the treatment period. If the subject develops new areas 
of AD, those areas will also be treated. Treatment areas will exclude the scalp, nose, mouth 
and eyes. Subjects may use bland emollients on non-affected body sites once daily. Rescue 
medications are not permitted. 
2.1 VISITS 
Study schema is as below: 


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Teres Bio, Inc. 


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SAP for Protocol Number: TER101 -AD-201 
Treatment Period 
TER lot 2.'5 . Ointment  
((nice daily opical apphcaton)
Ointment Vehicle 
(Twice daily topical applicaton) 
Bac.line 
D
y .
v. 
0 
a 


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Table 1: 
Schedule of Activities 
Period 
Screening 
Baseline 
Treatment Period 
Visit 
1 
2 
3 
4 
5 
Notes 
Visit Day and Window 
D-35 to D-1 
Day 1 
D8 (phone) 
±3 days 
D15 
±3 days 
D29/ETVa
±3 days 
Informed consent 
X 
Informed consent will be obtained from adult subjects 
and parent/guardian of subjects age 12 – 17; assent will 
be obtained from any subject age 12 – 17. 
Demographics 
X 
Medical history, including 
AD history 
X 
X 
Complete medical and AD history will be collected at 
screening and interval medical history (or any change 
from Screening Visit) collected at baseline.
Physical examination 
X 
X 
X 
Clinically significant abnormal findings from the physical 
examinations after baseline will be reported as AEs. 
Vital signs 
X 
X 
X 
X 
Blood pressure, pulse rate, and temperature strongly 
recommended to be measured after the subject has rested for 
> 5 minutes seated. 
Body weight, height 
X 
Clinical laboratory testsb  
X 
X 
X 
ECGc
X 
X 
ECG strongly recommended to be performed after the 
subject has rested in a supine position for > 10 minutes.
Blood for PKd
X 
X 
Date/time of last dose should be recorded for PK 
blood draws.
Urine pregnancy test 
(WOCBP) 
X 
X 
X 
Urine pregnancy tests may be performed more frequently as 
required by local regulations. The use of contraception will 
be discussed at each visit. 
AD assessment 
X 
X 
X 
X 
Includes IGA, EASI, and TBSA (in this order). 
Inclusion/exclusion  
criteria 
X 
X 
Confirm subject meets all inclusion/exclusion criteria before 
randomization. 
Emollient and cleanser 
review 
X 
X 
X 
X 
X 
Site should confirm the emollient and cleanser the 
subject plans to use during the study are acceptable. 
Concomitant medications 
X 
X 
X 
X 
X 


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Period 
Screening 
Baseline 
Treatment Period 
Visit
1
2
3
4
5
Notes
Visit Day and Window 
D-35 to D-1 
Day 1 
D8 (phone)  
±3 days 
D15 
±3 days 
D29/ETVa
±3 days 
AE recording 
X 
X 
X 
X 
X 
AEs will be monitored and recorded throughout the 
study, beginning at the time that informed consent has 
been obtained. 
Photography 
X 
X 
X 
Baseline photographs will be obtained prior to study drug 
application. The same regions will be photographed 
through the study under same conditions.
Randomization 
X 
Local tolerability 
X 
X 
X 
At baseline, tolerability will be assessed pre-dose and 15 
minutes after the first dose and also at Days 15 and 29. 
Study drug application 
X 
1st dose of study drug will be applied by site staff and 
the subjects instructed on application. All subsequent 
application will be at home through evening dose on 
Day 28.
Dispense study 
medication, Instructions 
for Use, e-diary 
X 
[X] 
Study drug will be weighed at the Baseline Visit, prior to 
first dose. Additional study drug may be dispensed on 
Day 15 if needed. 
Instruct on WI-NRS tool 
X 
X 
X 
Review e-diary, WI-
NRS for compliance 
X 
X 
X 
The e-diary will be reviewed at each visit. 
Collect and weigh study 
drug. 
X 
X 
Study drug (used and unused tubes) will be collected and 
weighed at in person visits on Day 15 and Day 29. Study 
drug will be returned to subject at Day 15 and not 
returned to subject at Day 29. 
AE=adverse event; BID = twice daily; D = Day; e-diary = electronic diary; EASI = Eczema Area and Severity Index; ECG= electrocardiogram; IGA = 
Investigator Global Assessment; PK = pharmacokinetics; TBSA = Total Body Surface Area; WI-NRS = Worst Itch Numeric Rating Scale. 
aETV: Early Termination Visit. All assessments scheduled for Day 29 will be conducted in event subject early terminates from study.
bClinical labs: Complete blood count with differential, chemistry will be conducted at screening, baseline, Day 29. Urinalysis will be conducted at screening
only. If the clinical laboratories were obtained within 14 days of baseline (Day 1), the screening labs will be used as the baseline labs and do not need to be 
repeated. 
cThe screening ECG will be used as the baseline ECG.


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dPK blood draws should be done at least 4 hours after last study drug application. The date, time of last application will be recorded on electronic case report form page. 
Avoid drawing PK samples through study drug application site.


2.2 SUBJECTS 
2.2.1 
Number of Subjects 
Approximately 60 adolescent and adult subjects (age 12 – 65) with mild to moderate AD will 
be enrolled across approximately 12 clinical research sites in the United States. 
2.2.2 
Diagnosis and Main Criteria for Inclusion 
Adolescent or adult subjects aged 12 – 65 years are eligible for the study if they have a 
diagnosis of AD with disease duration of at least 6 months and no change in treatment or 
severity for at least 4 weeks prior to screening. 
At baseline, subjects must have an overall IGA score of 2 (mild) or 3 (moderate) on a 5-point 
Investigator Global Assessment (IGA) scale, Eczema Area and Severity Index (EASI) score ≥ 
5, and total body surface area (TBSA) affected of between 2 and 30%. 
2.2.3 
Study Population Characteristics 
Subjects with a clinical diagnosis of AD who meet all the inclusion criteria and none of 
the exclusion criteria will be eligible to enroll in the study. Detailed inclusion and 
exclusion criteria are provided in the protocol (see protocol sections 5.1 and 5.2). 
2.2.4 
Replacement Subjects 
No replacement of subjects is allowed for the study. 
2.3 
TREATMENT AND RANDOMIZATION 
2.3.1 
Study Medications, Treatment, and Mode of Administration 
TER-101 (2.75% w/w) ointment and ointment vehicle will be applied topically twice a day 
for 28 days, with at least 8 hours between applications. Subjects will apply sufficient study 
drug to provide a thin covering. A pea-sized amount (approximately 250 mg) should cover 
approximately 2% body surface area (BSA). Additional instructions on application will be 
provide in the ‘Instructions for Use’ provided to each subject at randomization. 


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2.3.2 
Randomization 
Qualified subjects will be randomly assigned (1:1) to two treatment groups: TER-101 2.75% 
ointment or vehicle ointment. Blinded study drug will be dispensed on Day 1 (Baseline Visit).
2.3.3 
Administration of Treatment 
The study medications are for external, topical use on the AD areas twice daily for 28 days. 
2.3.4 
Duration of Treatment
The duration of the study participation is anticipated to be up to 64 days, including up to 35 
days for screening/prior treatment washout and 28 days of study drug treatment. Subjects 
may be followed for up to an additional 30 days for resolution of AEs after end of treatment. 
2.4 ASSESSMENTS 
2.4.1 
Evaluators 
The investigator, a designated and appropriately trained staff member (e.g., sub investigator) 
or the subject will perform the study assessments according to the defined schedules. 
2.4.2 
Evaluations – Efficacy 
2.4.2.1 
Eczema Area Severity Index 
The EASI is a scoring system that measures 4 clinical signs, the extent of BSA involved, over 
4 separate areas (head/neck, trunk, upper extremities, and lower extremities). Total EASI 
scores range from 0 to 72. 
The 4 clinical signs are: 

Erythema 

Induration/papulation 

Excoriation 

Lichenification 
And each feature is graded for each region on a 4-point severity scale of 0 to 3, as below, with: 

0 = absent 

1 = mild 


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
2 = moderate 

3 = severe 
Half-point scores of 1.5 and 2.5 can also be reported. The investigator or qualified assessor will 
enter the value for erythema, induration/papulation, excoriation and lichenification and extent of 
BSA for each region on the electronic case report form (eCRF) page. The EASI score will be 
calculated by the sponsor/designee. The formulation of the score is as shown below: 
2.4.2.2 
Investigator Global Assessment 
The IGA is a 5-point scale that provides a global clinical assessment of overall AD severity 
based on an ordinal scale. The assessment is static, meaning that the evaluation is done 
without reference to any other time point. 

0 = Clear: minor residual hypo/hyperpigmentation; no erythema or 
induration/papulation; no oozing/crusting. 


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
1 = Almost clear: trace faint pink erythema, with barely 
perceptible induration/papulation and no oozing/crusting. 

2 = Mild: faint pink erythema with mild induration/papulation and no oozing/crusting. 

3= Moderate: pink-red erythema with moderate induration/papulation with or without 
oozing/crusting. 

4= Severe: deep or bright red erythema with severe induration/papulation and with 
oozing/crusting. 
2.4.2.3 
Worst Itch Numeric Rating Scale 
The WI-NRS asks subjects to report their worst itch (maximal intensity) during the last 24 
hours on an 11-point NRS, ranging from 0 = “no itch at all” to 10 = “worst itch you can 
imagine”. This will be recorded by the subjects daily in the e-diary. 
2.4.2.4 
Total Body Surface Area 
The TBSA involved with AD will be determined. The subject’s palm and fingers with fingers 
together represent approximately 1% of the TBSA. 
2.4.3 
Evaluations – Safety 
2.4.3.1 
Local Tolerability 
The investigator will assess local tolerability by inspecting the application sites for application 
site erythema and query the subject as to symptoms of burning/stinging or pruritus associated 
with study drug application. The local tolerability assessment will be conducted at baseline 
pre-dose and approximately 15 minutes after the first dose, Day 15, and Day 29. The 
investigator should score the individual components of burning/stinging, pruritus, and 
erythema based on the average for scores of all application sites. 
Grade 
Burning/Stinging 
Pruritus 
Erythema 
0 (none) 
No stinging/burning 
No pruritus 
No detectable erythema, 
skin of normal color 
1 (mild) 
Slight warm, tingling 
sensation, not really 
bothersome
Occasional, slight 
itching/scratching 
Skin pinkness present 
2 (moderate) 
Definite warm, tingling 
sensation that is 
somewhat bothersome
Constant or intermittent 
itching/scratching which 
is not disturbing sleep
Definite redness, easily 
recognized 
3 (severe) 
Hot, tingling/stinging 
sensation 
Bothersome 
Intense redness 


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2.4.3.2 Adverse Events 
AEs or serious AEs (SAEs) occurring in the 30-day period following the last dose of 
investigational product will be reported, regardless of causality. SAEs occurring after this 30-
day period will be reported only if considered related to investigational product or a study-
related procedure. 
 
2.4.3.3 Laboratory Sampling 

All study-required laboratory assessments as detailed in the following table and the 
laboratory manual will be performed by a local laboratory, and confirmation of review 
of the results must be entered into the electronic case report form (eCRF). 

Additional tests may be performed at any time during the study as 
determined necessary by the investigator or required by local regulations. 

Tests listed below will be those analyzed descriptively and/or listed. 
Hematology 
Chemistry 
Urinalysis 
Platelet Count 
Red blood cell (RBC) Count 
Hematocrit 
Hemoglobin 
RBC Indices: 
MCV 
MCH 
White blood cell (WBC) count 
with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Blood urea nitrogen (BUN) 
Bicarbonate 
Calcium 
Chloride 
Creatinine 
Glucose (random) 
Potassium 
Sodium 
Alanine aminotransferase 
(ALT) 
Aspartate aminotransferase 
(AST) 
Alkaline phosphatase 
Total bilirubin 
Total protein 
Albumin 
Specific gravity 
pH, glucose, protein, blood, 
ketones, (bilirubin, urobilinogen, 
nitrite, leukocyte esterase) by 
dipstick 
Microscopic examination (if 
blood or protein is abnormal) 
Other Screening Tests 
Follicle stimulating hormone (as needed to confirm menopausal status for 
women of nonchildbearing potential only). 
Highly sensitive urine human chorionic gonadotropin (hCG) urine 
pregnancy test (as needed for women of childbearing potential).a
All study-required laboratory assessments will be performed by a local laboratory. 
MCH = mean corpuscular hemoglobin, MCV = mean corpuscular volume. 
aLocal urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB.


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2.4.3.4 
Physical Examination, Height, and Body Weight 
A physical examination including a thorough skin examination will be conducted by 
the investigator at the Screening and Baseline Visits to ensure that the subject does not 
have conditions that would interfere with participation in the study. 
A complete physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal systems. Height and body weight will also be 
measured and recorded at baseline. Physical examinations will only be performed at the 
indicated visits per study schedule of activities. For all other visits during the study, physical 
examinations will only be performed when there is a complaint from the subject. Clinically 
significant abnormal findings from the physical examinations after baseline will be reported as 
AEs; prior to baseline, they will be reported as medical history. 
2.4.3.5 
Vital Signs 
At in person visits at screening, baseline, Day 15, and Day 29, vital signs will be collected. 
Blood pressure and pulse measurements will be assessed in a sitting position with a 
completely automated device. Manual techniques will be used only if an automated device 
is not available. 
Blood pressure, pulse measurements, and temperature (to be taken before blood collection for 
laboratory tests) are strongly recommended to be preceded by at least 5 minutes of rest with 
the subject in a quiet setting without distractions (eg, television, cell phones). 
2.4.3.6 
Electrocardiogram 
At screening and Day 29/end of treatment (EOT), a single 12-lead electrocardiogram (ECG) 
with the subject in a supine position will be performed. The ECG is strongly recommended to 
be preceded by at least 10 minutes of rest with the subject in a quiet setting without 
distractions (eg, television, cell phones) and before any blood sampling procedures. 
2.4.4 
Evaluations – PK 
Plasma levels of TER-101 on Days 15, 29 will be analyzed and reported in a separate PK 
report, if topline results indicate a signal for clinical activity or before the samples exceed their 
stability, whichever comes first. 


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3 
STATISTICAL METHODOLOGY 
This plan describes methods planned for the analysis and display of efficacy and safety 
endpoints. 
3.1 
GENERAL STATISTICAL CONSIDERATIONS 
Descriptive statistics (mean, standard deviation [Std Dev], median, minimum, and maximum) 
will be used for continuous variables; number and percentage of subjects will be used for 
discrete variables. In general, the last measurement prior to the first dose of study treatment 
will be used as the baseline value with exception of WI-NRS, where the score recorded on 
Day 1 describing the worst itch score 24 hours prior will be used as the baseline. Nominal 
visits will be used for by-visit summaries and analyses for safety evaluations (i.e., laboratory 
sampling, physical examinations, vital signs, and electrocardiogram). For efficacy evaluations 
of EASI, IGA, and TBSA, analysis visits will be used for by-visit summaries. Analysis visits 
are defined as below: 
Analysis Visit* 
Target Day 
Range 
Day 8 
Day 8 
Day 2 – Day 11 
Day 15 
Day 15 
Day 12 – Day 21 
Day 29 
Day 29 
≥Day 22 
* If there are multiple observations in the range, then the record collected closest to the target day will be 
selected; if there are multiple observations that have equal distance from the target day, the latter one will 
be used.
All treatment group comparisons will be made at the 0.05 level using a two-sided hypothesis 
test, unless otherwise specified. Given the exploratory nature of this study, p-values from all 
significance tests will be reported without adjustment for multiplicity. 
Summaries will be presented by each treatment group, ie, TER-101 2.75% ointment, Vehicle 
ointment. 
All tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed using SAS® Version 9.4 or higher. 


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3.2 ANALYSIS POPULATION AND DISPOSITION OF SUBJECTS 
3.2.1 
Data Sets Analyzed 
For purposes of analysis, the following populations are defined 
Population 
Description 
Efficacy analysis set (ES) 
All randomized subjects who receive at least 
1 application of the study treatment and have 
at least 1 post-baseline efficacy assessment. 
The treatment group as assigned (randomized 
to) will be used for analyses. 
Per protocol efficacy analysis set (PPES) 
All subjects in ES without major protocol 
deviations that impact the interpretation of 
the results. The treatment group for the first 
application will be used for analyses. 
Safety analysis set (SS) 
All randomized subjects who receive at least 1 
application of the study treatment. If any 
TER-101 was applied, then the subject will be 
summarized under TER-101 treatment group.
PK analysis set (PKS) 
All subjects in SS with at least 1 blood draw to 
measure TER-101. 
 3.2.2 Protocol Deviations 
Protocol deviations (eg, due to violations of inclusion or exclusion criteria, lack of study 
treatment compliance, or use of nonpermitted medication) will be identified and documented 
before database lock and unblinding. Number and percentage of subjects with deviations will 
be summarized by deviation categories. Major protocol deviations leading to exclusion of 
efficacy data from the analysis set PPES as described above will be listed. 
 3.2.3 Disposition of Subjects 
The numbers of subjects screened (ie, signed informed consent), randomized, treated, and 
discontinued from treatment (by reason) or completed treatment, discontinued from study (by 
reason) or completed study will be summarized for each treatment group separately. Any 
mis-randomization or mis-treatment will also be described. 
3.3 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and baseline characteristics will be summarized for the SS. Gender, race, and 
ethnicity will be summarized with number and percentage presented for each category. Age, 


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height, weight, body mass index (BMI) will be described with summary statistics (n, mean, 
Std Dev, median, minimum, and maximum). 
3.4 MEDICAL HISTORY 
All medical history and current ongoing medical history will be summarized separately by 
system organ class using the SS. 
3.5 PRIOR/CONCOMITANT MEDICATIONS 
The number and percentage of prior medications, and concomitant medications will be 
summarized by Anatomical Therapeutic Chemical (ATC) and preferred term (PT) separately 
using SS. 
Medications taken any time prior to the first study treatment and stopped prior to the first 
study treatment are counted as prior medications. Those taken any time on or after the first 
application of study treatment or ongoing medication started prior to the first application of 
study treatment are counted as concomitant. 
Subject will be counted only once within each classification. The same subject may contribute 
to two or more PTs within the same ATC classification. 
3.6 
EFFICACY ANALYSIS 
All efficacy analyses and summaries will be performed on the ES by randomized treatment 
group. Additional analyses based on PPES will be specifically mentioned. 
3.6.1 
EASI Analyses 
For each visit (baseline, Day 15, Day 29), the following analyses will be performed. All 
analyses will be based on the ES. 

Descriptive statistics (n, mean, Std Dev, median, minimum, and maximum) will be 
provided for the per-subject EASI total score (continuous), change from baseline, and 
percent change from baseline in EASI total score. 

Descriptive statistics (n, %) will be provided for the number and percentage of subjects 
who achieve EASI-50 (i.e., ?50% reduction from baseline) and EAST-75 (i.e., ?75%). 
Descriptive statistics (n, mean, Std Dev, median, minimum, and maximum) will be provided 
for the per-subject EASI by region (head, trunk, upper extremity [UE], lower extremity [LE]), 
change from baseline, and percent change from baseline values. Treatment group comparisons 


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in percent change from baseline in EASI total score will be analyzed using a mixed model for 
repeated measures (MMRM). The model will include fixed effect for study treatment (TER-
101 2.75%, vehicle), visit day (Day 15, Day 29), and treatment-by-visit interaction, with visit 
as the repeating factor, subject nested within the investigational site as a random effect, and 
baseline score as a covariate. The variance-covariance matrix will be assumed to be 
unstructured. If the procedure does not converge then the replacement of variance-covariance 
matrix will be explored in the order of Toeplitz, first-order autoregressive, compound 
symmetric. The treatment p-value (TER-101 2.75% vs. vehicle), treatment difference, and 
95% confidence limits from the model will be presented for the percent change from baseline 
in EASI at Day 29. Similarly, the treatment difference (TER-101 2.75% vs. vehicle) and 95% 
confidence limits will be presented for Day 15 as well. Line graphs of least squares mean in 
percent change from baseline of EASI scores will be presented for Day 15 and Day 29. These 
treatment group comparisons will be repeated for the PPES. 
The following sensitivity analyses will be conducted for the percent change from baseline in 
EASI total score at Day 29 to explore the impact of dropouts and missing data at Day 29. 

Last value carried forward (LOCF): for timepoint Day 29, if missing, the last 
available post baseline EASI total score will be carried forward to the timepoint. After 
this imputation, an analysis of covariance (ANCOVA) will be used for analyzing the 
treatment effect at Day 29. The treatment group will be the fixed effect and baseline 
score will be the covariate. The treatment difference, 95% confidence limits, and p-
value will be presented. 

Return to baseline: missing Day 29 value will be imputed based on the baseline value 
for the patient, with variance adjustment of the Day 29 EASI total score. That is, the 
missing data will be imputed with values from Normal distribution N (baselinel,, _,2); i 
= ith subject, where ó, 2 is the variance estimate of treatment k at Day 29. Five hundred 
(500) imputation will be implemented. ANCOVA model will be used for each 
imputation. The results from all imputed datasets will be combined using Rubin’s 
combination rule (PROC MIANALYZE). 
In addition, the percent change from baseline in EASI scores and the absolute change from 
baseline in EASI total score by each region will be analyzed using the MMRM model, as 
described above. In each case, the treatment p-value (TER-101 2.75% vs. vehicle), treatment 
difference, and 95% confidence limits from the model, will be presented. 


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The effect of treatment on response rates (EASI-75, EASI-50) at each visit will be evaluated 
using a logistic generalized linear mixed model (GLMM) for binary data. The model will 
include fixed effect for treatment, visit and treatment-by-visit interaction, with subject nested 
within the investigational site as a random effect. The treatment p-value (TER-101 2.75% vs. 
vehicle), treatment odds ratio, and 95% confidence limits from the model, will be presented. 
[Note: In the event of model non-convergence, the response proportions will be analyzed 
using the Cochran-Mantel-Haenszel test, stratified by baseline IGA.] Bar charts of the 
response rates at Day 15 and Day 29 will be presented by treatment groups for each response 
rate (EASI-75, EASI-50). 
 3.6.2 IGA Analyses 
Descriptive statistics (n, mean, Std Dev, median, minimum, and maximum) will be provided 
for the IGA scale, and its change from baseline at Day 15 and Day 29. Number and percentage 
of subjects for each scale value (0-4) will also be provided for each visit. 
The change from baseline IGA values will be analyzed using generalized linear model for 
repeated ordinal data method. The multinomial distribution will be used with link function of 
cumulative logit. The model will include fixed effect for study treatment (TER-101 2.75%, 
vehicle), visit day (Day 15, Day 29), and treatment-by-visit interaction, with subject nested 
within the investigational site as a random effect, and baseline IGA scale as a covariate. The 
treatment p-value (TER-101 2.75% vs. vehicle), treatment difference, and 95% confidence 
limits from the model, will be presented. All analyses will be based on ES. 
 3.6.3 WI-NRS Analyses 
Descriptive statistics (n, mean, Std Dev, median, minimum, and maximum) will be provided 
for the 11-point WI-NRS scale at baseline, Day 15 and Day 28 visits, and its change from 
baseline at Day 15 and Day 28. A line plot over time of the change from baseline (daily, and 
weekly average [see intervals specified below]) will be generated. Mean (±Std Dev) will be 
displayed at each time point. Change from baseline WI-NRS scale will also be analyzed 
using the MMRM model for Day 15 and Day 28 assessments. The model will include fixed 
effect for study treatment (TER-101 2.75%, vehicle), visit day (Day 15, Day 28), and 
treatment-by-visit interaction, with visit as the repeating factor, subject within the 
investigational site as a random effect, and baseline WI-NRS scale as a covariate. The 
treatment p-value (TER-101 2.75% vs. vehicle), treatment difference, and 95% confidence 
limits from the model, will be presented. 


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The proportion of WI-NRS responders (defined by a reduction of ? 3 in subjects with baseline 
WI-NRS ? 4) will be analyzed using a logistic regression. The odds ratio, and 95% confidence 
limits from the model, will be presented. The chi-square test p-value will also be provided. In 
addition, the number and percentage of subjects who respond during each weekly interval 
(defined by the maximum reduction between Day 2-Day 8, Day 9-Day 15, Day 16-Day 22, 
Day 23-Day 28) will be summarized and presented in a bar chart. 
All analyses will be based on ES. 
3.6.4 
TBSA Analyses 
The TBSA involved with AD at baseline, Day 15, and Day 29 will be summarized 
descriptively (n, mean, Std Dev, median, minimum, and maximum). The change from baseline 
values will also be analyzed using MMRM method. The model will include fixed effect for 
study treatment (TER-101 2.75%, vehicle), visit day (Day 15, Day 29), and treatment-by-visit 
interaction, with visit as the repeating factor, subject as a random effect, and baseline TBSA as 
a covariate. The treatment p-value (TER-101 2.75% vs. vehicle), treatment difference, and 95% 
confidence limits from the model, will be presented. All analyses will be based on ES. 
3.7 
SAFETY ANALYSIS 
The safety and tolerability of the investigational product will be determined by local 
tolerability assessment, reported AEs, laboratory tests, physical examinations, vital signs, and 
ECGs. The Safety analysis set with actual treatment received (as opposed to randomized 
treatment) will be used for all safety summaries, unless otherwise specified. 
3.7.1 
Study Drug Exposure And Compliance 
Duration of treatment (Last study treatment application date – First study treatment 
application date + 1) will be summarized descriptively for the SS. Study drug compliance 
will be assessed based on subject reports in the e-diary. The number of actual treatment 
applications as a percentage of the number of expected applications will be summarized. 
The usage of ointment (dispensed kit weight – returned kit weight) and average daily use (g) 
will also be summarized by treatment group. 
3.7.2 
Local Tolerability 
For each visit (baseline [pre-dose, post-dose], Day 15, Day 29), the number and percentage of 
subjects with grades 0, 1, 2, 3 will be tabulated at timepoints specified for erythema and 


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symptoms of burning/stinging or pruritus associated with study drug application. In addition, 
severity grades will be summarized using a shift table based on the baseline pre-dose value at 
each visit. Severity grade shift from pre-medication at baseline to post-medication will be 
analyzed. The shift from pre-dose severity grade at baseline to the last post-dose severity grade 
will also be summarized by treatment groups for erythema, burning/stinging, and pruritus. 
3.7.3 
Adverse Events 
All AEs will be coded and summarized using the Medical Dictionary for Regulatory Activities 
(MedDRA) (version 23.1). Treatment-emergent AEs (TEAEs) are defined as any new or 
worsening events reported at any time from the date of first dose of study medication until the 
end of study participation. All AEs will be presented in by-subject data listings, including the 
verbatim and coded terms, onset day (relative to start of treatment), severity, relationship to 
study medication, action taken, and outcome. 
An overview of AEs for the SS will be provided, summarizing the frequency/incidence of the 
following: 

Incidence of all AEs; 

Count of TEAEs; 

Incidence of TEAEs; 

Count of Treatment-emergent SAEs (TESAEs); 

Incidence of TESAEs; 

Incidence of TEAE by maximum severity; 

Incidence of TESAE by maximum severity; 

Incidence of TEAEs that lead to discontinuation of study treatment; 

Incidence of TESAEs that lead to discontinuation of study treatment; 

Incidence of TEAEs that lead to interruption of study treatment; 

Incidence of TESAEs that lead to interruption of study treatment; 

Incidence of Treatment-related TEAEs; 

Incidence of Treatment-related TESAEs. 
The number and percentage of subjects with AEs will also be summarized by System Organ 
Class (SOC) and Preferred Term (PT) for the following categories: 

Incidence of TEAEs; 

Incidence of TESAEs; 

Incidence of TEAEs by maximum severity; 


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
Incidence of TEAEs that lead to discontinuation from study treatment; 

Incidence of TEAEs that lead to interruption from study treatment; 

Incidence of Treatment-related TEAEs. 
3.7.4 
Laboratory Tests 
For each laboratory test, summaries will be provided for baseline and Day 29. The absolute 
value and its change from baseline will be descriptively presented. Abnormal laboratory 
observations and urinalysis microscopic exams, if performed, will be listed. 
3.7.5 
Physical Examinations  
Physical examination results will listed.
3.7.6 
Vital Signs 
Vital signs measurements include pulse rate, temperature, systolic blood pressure, and 
diastolic blood pressure. Measures at baseline and changes from baseline to post baseline 
visit (Day 15, Day 29) will be summarized using descriptive statistics. 
3.7.7 
Electrocardiogram 
Electrocardiogram results will be descriptively summarized (n, mean, Std Dev, ..., etc.) for 
heart rate, PR, RR, QRS, QT interval, QTcB, and QTcF by visit. In addition, number and 
percentage of subjects with abnormal QTcB/QTcF (ie, >450 msec, >480 msec, >500 msec) or 
increase of QTcB/QTcF (>30 msec, >60 msec) from screening will be provided for each visit. 
3.8 
PK ANALYSES 
Plasma concentration of the study drug will be summarized using descriptive statistics 
including number of subjects with plasma samples, number of assays with concentrations 
above lower limit of quantification (LLOQ), arithmetic mean, geometric mean, Std Dev, 
coefficient of variation (CV), minimum and maximum at each nominal visit (Day 15, Day 29). 
A concentration that falls below the LLOQ will be treated as zero in the summary. Analysis 
will be conducted on PKS. 
3.9 INTERIM ANALYSES 
There is no interim analysis planned for the study. 


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4 
CHANGES TO PLANNED ANALYSES 
Due to the small sample size of the study and the infrequent assessment of response over time, 
the Kaplan-Meier (KM) analysis of time to onset of response (EASI-75, EASI-50) will not be 
conducted. 
Because the change from baseline in the IGA is expected to take on a limited set of values, it 
will be considered as ordinal data rather than a continuous variable, and thus will be analyzed 
using a generalized linear model for repeated ordinal data. 
The change in individual components of EASI (erythema, edema/papulation, excoriation, 
lichenification) by visit will not be analyzed, only EASI by region will be analyzed due to 
limitation in defining EASI score for each sign/symptom.