Clinical trial NCT05194540
Conditions: Atopic Dermatitis
Sponsor: LEO Pharma
Start date: 2022-01-13; Completion date: 2023-06-21
Enrollment: 136 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this trial is to evaluate the efficacy and safety of tralokinumab administered as subcutaneous (SC) injection by an autoinjector in adults and adolescents (age 12 to 17 years) with moderate-to-severe atopic dermatitis (AD).

Detailed description:
This is a single-arm, phase 3 trial designed to evaluate the efficacy and safety of tralokinumab when administered by an autoinjector in adults and adolescent subjects with moderate-to-severe AD. At baseline, the subjects will receive an initial SC dose of 600 mg tralokinumab. For the rest of the treatment period, all subjects will self-administer a dose of 300 mg tralokinumab every other week for 14 weeks.

Arms: arm 1: An initial SC dose of 600 mg tralokinumab at baseline followed by self-administration of a 300 mg dose of tralokinumab every other week for 14 weeks.
Interventions: intervention 1: Tralokinumab
Intervention descriptions: intervention 1: Tralokinumab is a human recombinant monoclonal antibody of immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin-13 (IL-13) and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous administration

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
 
 
 
 
Cover Page 
 
 
Study title: Efficacy and safety of tralokinumab administered by an autoinjector in adults and adolescents 
with moderate-to-severe atopic dermatitis INJECZTRA  
LEO Pharma number: LP0162-1338 
NCT number: NCT05194540 
Date: 24-Aug-2022 
 


CONFIDENTIAL 
THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION AND MUST NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY WITHOUT 
THE PRIOR WRITTEN CONSENT OF THE LEO PHARMA GROUP 
Updated Clinical trial protocol 
LP0162-1338 
Efficacy and safety of tralokinumab administered by an autoinjector in adults and 
adolescents with moderate-to-severe atopic dermatitis  
INJECZTRA 
Phase 3 efficacy and safety of tralokinumab administered by an autoinjector 
An open-label, single-arm, phase 3 trial to evaluate the efficacy and safety of tralokinumab 
administered by an autoinjector in subjects with moderate-to-severe atopic dermatitis 
This clinical trial will be conducted in compliance with the clinical trial protocol, ICH GCP, 
and the applicable regulatory requirement(s). 
LEO Pharma A/S 
Trial ID: 
LP0162-1338 
Date: 
24-Aug-2022
EudraCT no: 
Not applicable 
Version: 
3.0 
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Clinical trial protocol statements 
Approval statement LEO Pharma A/S 
Electronic signatures made within LEO Pharma Clinical Vault are legally binding equivalent 
of traditional handwritten signatures. The following persons have approved this clinical trial 
protocol by using electronic signatures as presented on the last page of this document: 
, MD, PhD, HD(O) 
Vice president, R&D APAC Hub 
, MSc Stat 
Biostatistics lead, Medical Sciences 
, MD 
Medical lead, Medical Sciences 
, MSc Pharm 
Clinical operations lead, Global Clinical Operations 
Approval statement signatory investigator 
The signatory investigator approves the clinical trial protocol by manually signing the 
signatory investigator clinical trial protocol approval form, which is a separate document 
appended to this document. 
The following person has approved this clinical trial protocol: 
, MD 
Signatory investigator 
Acknowledgement statement investigator(s) 
Each participating investigator must agree to the approved clinical trial protocol by signing a 
clinical trial protocol acknowledgement form or similar document. 
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PPD
PPD
PPD
PPD
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Protocol amendment summary of changes table 
Document history 
Document 
Date 
Type of protocol amendment 
Amendment 2 (substantial) 
24-Aug-2022
Global 
Amendment 1 (substantial) 
25-Oct-2021
Global 
Original protocol 
26-Apr-2021
NA 
Amendment 2 (24-Aug-2022) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
or subsequent regulation. 
Overall rationale for the amendment 
The main reason for this amendment is due to a revision in sample size. The revision is to 
ensure that FDA’s request for sample size is met. 
Additional changes are also presented in the table below. Changes have either been 
summarised (written in plain text only) or marked as tracked changes (text added to the 
protocol is written in bold and deleted text has a line through it). 
Section no. and 
title 
Description of change 
Brief rationale 
1 Protocol synopsis, 
7.2 Number of 
subjects needed, 
14.1 Sample size 
Number of subjects (sample size) needed for the trial was 
revised:  
•
Total sample size was increased from
approximately 120 subjects to approximately
130 subjects.
•
Adolescents sample size was decreased from a
minimum of 40 subjects to approximately
30 subjects.
To meet FDA’s request 
for sample size. 
7.2 Number of 
subjects needed 
Number of subjects screened for the trial was increased 
from approximately 160 subjects to approximately 
174 subjects. 
Consequential to 
change in sample size. 
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Section no. and 
title 
Description of change 
Brief rationale 
14.1 Sample size 
Assuming IGA 0/1 and EASI75 response rates of 19% and 
29% at Week 16, respectively, a sample size of 120 
130 subjects will give a standard error of 3.58% 3.44% 
and 4.14% 3.98%, and thus a half-width for the 95% CIs 
of 7.02% 6.74% and 8.12% 7.80% for each of the primary 
endpoints. 
Consequential to 
change in sample size. 
Appendix 9 
Protocol 
amendment history 
New appendix added. 
Information about amendment 1 was moved from Clinical 
trial protocol amendment summary to Appendix 9. 
Administrative change. 
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Table of contents 
Protocol amendment summary of changes table ................................................................... 3 
Table of contents ....................................................................................................................... 5 
List of panels ............................................................................................................................. 9 
List of abbreviations ............................................................................................................... 10 
1 
Protocol synopsis ........................................................................................................... 13 
2 
Trial identification ........................................................................................................ 17 
3 
Schematic of trial design .............................................................................................. 17 
4 
Schedule of trial procedures ........................................................................................ 18 
5 
Introduction and trial rationale .................................................................................. 23 
5.1 
Atopic dermatitis.................................................................................................... 23 
5.2 
Experience with investigational medicinal product ............................................... 23 
5.3 
Trial rationale ......................................................................................................... 25 
5.4 
Ethical considerations ............................................................................................ 25 
5.5 
Benefit/risk assessment .......................................................................................... 26 
6 
Trial objectives and endpoints ..................................................................................... 28 
7 
Trial design .................................................................................................................... 30 
7.1 
Overall trial design................................................................................................. 30 
7.2 
Number of subjects needed .................................................................................... 31 
7.3 
End-of-trial definition ............................................................................................ 31 
8 
Trial population ............................................................................................................ 32 
8.1 
Subject eligibility ................................................................................................... 32 
8.2 
Inclusion criteria .................................................................................................... 32 
8.3 
Exclusion criteria ................................................................................................... 34 
8.4 
Screening and screening failures ........................................................................... 37 
9 
Treatments ..................................................................................................................... 39 
9.1 
Trial product description ........................................................................................ 39 
9.2 
Administration of investigational medicinal product ............................................ 39 
9.3 
Treatment assignment ............................................................................................ 41 
9.4 
Background treatment ............................................................................................ 41 
9.5 
Rescue treatment .................................................................................................... 41 
9.6 
Concomitant medication and concurrent procedures............................................. 42 
9.7 
Prohibited medications and procedures ................................................................. 43 
9.8 
Treatment logistics and accountability .................................................................. 44 
9.8.1 
Labelling and packaging of trial products ................................................... 44 
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9.8.2 
Storage of trial products ............................................................................... 44 
9.8.3 
Investigational medicinal product accountability ........................................ 45 
9.8.4 
Treatment compliance .................................................................................. 46 
9.8.5 
Trial product destruction .............................................................................. 46 
9.9 
Provision for subject care following trial completion ........................................... 46 
9.10 
Reporting product complaints ................................................................................ 47 
10 
Discontinuation and withdrawal ................................................................................. 48 
10.1 
General principles .................................................................................................. 48 
10.2 
Reasons for discontinuation of IMP ...................................................................... 48 
10.2.1 
Reasons for permanent discontinuation of IMP .......................................... 48 
10.2.2 
Reasons for temporary discontinuation of IMP ........................................... 49 
10.3 
Early termination assessments ............................................................................... 50 
10.4 
Lost to follow-up ................................................................................................... 50 
11 
Trial assessments and procedures ............................................................................... 51 
11.1 
Overview ................................................................................................................ 51 
11.2 
Assessments performed only at screening and/or baseline .................................... 51 
11.2.1 
Demographics .............................................................................................. 51 
11.2.2 
Medical history ............................................................................................ 51 
11.2.3 
Physical examination ................................................................................... 52 
11.2.4 
Columbia-Suicide Severity Rating Scale ..................................................... 53 
11.2.5 
Body surface area involvement .................................................................... 53 
11.3 
Rating of subject’s ability to self-administer ......................................................... 53 
11.4 
Efficacy assessments .............................................................................................. 54 
11.4.1 
Investigator’s Global Assessment ................................................................ 54 
11.4.2 
Eczema Area and Severity Index ................................................................. 55 
11.4.3 
Patient-reported outcomes ........................................................................... 56 
11.5 
Safety assessments ................................................................................................. 58 
11.5.1 
Height and weight ........................................................................................ 58 
11.5.2 
Vital signs .................................................................................................... 58 
11.5.3 
Laboratory testing ........................................................................................ 59 
11.5.4 
Anti-drug antibody measurements ............................................................... 62 
11.6 
Pharmacokinetic assessments ................................................................................ 62 
11.7 
Photography ........................................................................................................... 63 
11.8 
End-of-trial............................................................................................................. 64 
11.9 
Estimate of total blood volume collected .............................................................. 64 
11.10 Storage of biological samples ................................................................................ 65 
12 
Scientific rationale for trial design and appropriateness of assessments ................ 66 
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12.1 
Scientific rationale for trial design......................................................................... 66 
12.2 
Appropriateness of assessments............................................................................. 67 
13 
Adverse events .............................................................................................................. 68 
13.1 
Definition and classification of adverse events ..................................................... 68 
13.2 
Collection of adverse event reports ....................................................................... 68 
13.3 
Reporting of adverse events ................................................................................... 68 
13.4 
Reporting of serious adverse events ...................................................................... 69 
13.4.1 
Investigator reporting responsibilities ......................................................... 69 
13.4.2 
LEO Pharma reporting responsibilities ........................................................ 70 
13.5 
Other events that require expedited reporting ........................................................ 70 
13.5.1 
Pregnancy ..................................................................................................... 70 
13.6 
Reporting of other events ....................................................................................... 71 
13.6.1 
Adverse events of special interest ................................................................ 71 
13.6.2 
Medication error .......................................................................................... 74 
13.6.3 
Misuse or abuse ........................................................................................... 74 
13.6.4 
Aggravation of condition ............................................................................. 75 
13.7 
Follow-up for final outcome of adverse events ..................................................... 75 
13.8 
Handling of an urgent safety measure ................................................................... 75 
14 
Statistical methods ........................................................................................................ 77 
14.1 
Sample size ............................................................................................................ 77 
14.2 
Trial analysis sets ................................................................................................... 77 
14.3 
Statistical analysis .................................................................................................. 77 
14.3.1 
Disposition of subjects ................................................................................. 77 
14.3.2 
Demographics and other baseline characteristics ........................................ 78 
14.3.3 
Exposure and treatment compliance ............................................................ 78 
14.3.4 
Rescue treatment .......................................................................................... 78 
14.3.5 
Testing strategy ............................................................................................ 79 
14.3.6 
Estimand strategy ......................................................................................... 79 
14.3.7 
Analysis of primary endpoints ..................................................................... 80 
14.3.8 
Analysis of secondary endpoints ................................................................. 80 
14.3.9 
Analysis of other endpoints related to subject self-administration .............. 80 
14.3.10 
Analysis of other binary endpoints .............................................................. 80 
14.3.11 
Analysis of other continuous endpoints and patient-reported outcomes ..... 81 
14.3.12 
Analysis of safety ......................................................................................... 81 
14.3.13 
Pharmacokinetic analysis ............................................................................. 82 
14.3.14 
Anti-drug antibodies .................................................................................... 82 
14.3.15 
Interim analysis ............................................................................................ 83 
14.3.16 
General principles ........................................................................................ 83 
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14.3.17 
Handling of missing values .......................................................................... 84 
15 
References ...................................................................................................................... 85 
Appendix 1: Definitions of adverse events and serious adverse events ............................. 90 
Appendix 2: Classification of adverse events ....................................................................... 92 
Appendix 3: Trial governance considerations ..................................................................... 95 
Appendix 3A: Regulatory and ethical considerations .................................................. 95 
Appendix 3B: Informed consent process ..................................................................... 96 
Appendix 3C: Subject and data confidentiality ............................................................ 97 
Appendix 3D: Record keeping, quality control, and data handling ............................. 98 
Appendix 3E: Registration, reporting, and publication policy ................................... 101 
Appendix 3F: Insurance ............................................................................................. 102 
Appendix 3G: Financial disclosure ............................................................................ 103 
Appendix 3H: Trial and trial site closure ................................................................... 103 
Appendix 3I: Responsibilities .................................................................................... 104 
Appendix 4: Hanifin and Rajka (1980) diagnostic criteria for AD (18) .......................... 105 
Appendix 5: Guidance for anaphylaxis diagnosis (21) ..................................................... 106 
Appendix 6: Short version of eligibility criteria ................................................................ 107 
Appendix 7: Contact list ...................................................................................................... 110 
Appendix 8: COVID-19 pandemic contingency plan......................................................... 111 
Appendix 9: Protocol amendment history ......................................................................... 113 
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List of panels 
Panel 1: Trial design ................................................................................................................. 17 
Panel 2: Schedule of trial procedures ....................................................................................... 18 
Panel 3: Objectives and endpoints ........................................................................................... 28 
Panel 4: Identification of investigational medicinal product ................................................... 39 
Panel 5: Investigator’s Global Assessment .............................................................................. 55 
Panel 6: Calculation of the EASI score .................................................................................... 56 
Panel 7: EASI severity score scale and area score scale .......................................................... 56 
Panel 8: Clinical laboratory tests .............................................................................................. 60 
Panel 9: Adverse events of special interest .............................................................................. 72 
Panel 10: Adverse events of special interest – injection site reaction ...................................... 73 
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List of abbreviations 
AD 
atopic dermatitis 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BP 
blood pressure 
BSA 
body surface area 
CDISC 
Clinical Data Interchange Standards Consortium 
CDLQI 
Children’s Dermatology Life Quality Index 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CMO 
contract manufacturing organisation 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CRA 
clinical research associate 
C-SSRS
CTR
Columbia-Suicide Severity Rating Scale 
clinical trial report 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
EASI90 
at least 90% reduction in EASI score 
EASI75 
at least 75% reduction in EASI score 
EASI50 
at least 50% reduction in EASI score 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ePRO 
electronic patient-reported outcome 
FAS 
full analysis set 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
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HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification number 
IGA 
Investigator’s Global Assessment 
IGA 0/1 
IGA score of 0 (clear) or 1 (almost clear) 
IgE 
immunoglobulin E 
IL-13 
interleukin-13 
IMP 
investigational medicinal product 
IRB 
institutional review board 
IRT 
interactive response technology 
JAK 
Janus Kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
nAb 
neutralising antibodies 
NBUVB 
narrow band ultraviolet B 
NRS 
numeric rating scale 
PD 
pharmacodynamic 
PDE-4 
phosphodiesterase-4 
PK 
pharmacokinetics 
POEM 
Patient-Oriented Eczema Measure 
PRO 
patient-reported outcome 
PUVA 
psoralen + ultraviolet A 
Q2W 
every other week 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous(ly) 
SCORAD 
Scoring Atopic Dermatitis  
SD 
standard deviation 
SDTM 
Standard Data Tabulation Model 
SOC 
(MedDRA) system organ class 
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TCI 
topical calcineurin inhibitor(s) 
TCS 
topical corticosteroid(s) 
Th2 
T-helper-2
ULN 
upper level of normal 
UVA1 
ultraviolet A1 
UVB 
ultraviolet B 
WHO 
World Health Organization 
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1 
Protocol synopsis 
Trial ID 
IND no. 
FDA center 
LP0162-1338 
123797 
CDER 
Title of trial 
An open-label, single-arm, phase 3 trial to evaluate the efficacy and safety of 
tralokinumab administered by an autoinjector in subjects with moderate-to-
severe atopic dermatitis. 
Short title of trial 
Efficacy and safety of tralokinumab administered by an autoinjector in adults 
and adolescents with moderate-to-severe atopic dermatitis. 
Main objectives 
and endpoints 
Primary Objective 
Primary endpoints 
To evaluate the efficacy of 
tralokinumab administered by an 
autoinjector when used to treat 
subjects with moderate-to-severe AD. 
•
IGA score of 0 (clear) or 1
(almost clear) at Week 16.
•
EASI75 at Week 16.
Secondary objective 
Secondary endpoint 
To evaluate the safety and tolerability 
of tralokinumab administered by an 
autoinjector when used to treat 
moderate-to-severe atopic dermatitis 
(AD). 
•
Number of treatment-emergent
adverse events (AEs) from
baseline to Week 16.
•
Presence of treatment-emergent
ADA from baseline to Week 16.
Final collection 
of data for the 
primary endpoint 
Week 16. 
Trial design 
This is an open-label, single-arm, phase 3 trial, in adult and adolescent (age 12 
to 17 years) subjects with moderate-to-severe AD. The trial is designed to 
evaluate the efficacy and safety of tralokinumab when administered by an 
autoinjector. A scheme of the trial design is provided below. 
Abbreviations: IMP = investigational medicinal product; Q2W = every other week; 
w = weeks. 
The trial consists of a 2-to-4-week screening period, a 16-week treatment 
period, and a 4-week safety follow-up period. 
The screening period has a minimum duration of 2 weeks and a maximum 
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duration of 4 weeks depending on the need for wash-out. 
At the baseline visit (Week 0, Visit 2), eligible subjects will receive an initial 
loading dose of SC tralokinumab 600 mg. This dose will be administered with 
the use of 2 autoinjectors containing 300 mg/2mL each. During the 
administration of the initial loading dose, subjects will be trained on the usage 
of autoinjector by the investigator or delegated trial staff. Subjects will have a 
choice to either self-administer the second injection under observation by 
qualified trial staff or receive both injections by the investigator/trial delegate. 
For the rest of the treatment period, all subjects will self-administer a dose of 
300 mg tralokinumab Q2W (2 mL). The IMP will be administered every other 
week during the treatment period, and the last IMP administration (relating to 
this protocol) will occur at Week 14. 
All subjects will use an emollient twice daily (or more, as needed) for at least 
14 days before baseline and will continue this treatment throughout the trial 
(including safety follow-up). 
Subjects who during the treatment period or safety follow-up experience 
intolerable AD symptoms may be treated with rescue treatment at the 
investigator’s discretion. 
All subjects completing the treatment period will have safety follow-up 
assessments 6 weeks after the last IMP administration. Note that for subjects 
who permanently discontinue IMP, the 6-week follow-up period will start at 
the time of last IMP injection. 
Main assessments 
Assessment related to primary endpoints: 
•
IGA score.
•
EASI.
Assessment related to secondary endpoints: 
AEs, vital signs, laboratory tests and ADA. 
Main criteria for 
inclusion 
•
Age 12 years and above at baseline (Week 0).
•
Subject able and willing to self-administer tralokinumab using an
autoinjector.
•
Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria
for AD.
•
History of AD for ≥1 year.
•
A recent history (within 1 year before the screening visit) of
inadequate response to treatment with topical medication or for whom
topical treatments are otherwise medically inadvisable.
•
AD involvement of ≥10% body surface area at screening and
baseline.
•
An Eczema Area and Severity Index score of ≥12 at screening
and ≥16 at baseline.
•
An Investigator’s Global Assessment score of ≥3 at screening and at
baseline.
•
Applied a stable dose of emollient twice daily (or more, as needed)
for at least 14 days before baseline.
Main criteria for 
exclusion 
•
Active dermatologic conditions that may confound the diagnosis of
AD or would interfere with assessment of treatment.
•
Use of tanning beds or phototherapy within 4 weeks prior to baseline.
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•
Treatment with systemic immunosuppressive/immunomodulating
drugs and/or systemic corticosteroids within 4 weeks prior to
baseline.
•
Treatment with topical corticosteroids, topical calcineurin inhibitors,
topical phosphodiesterase-4 inhibitors, or topical Janus kinase
inhibitors within 2 weeks prior to baseline.
•
Receipt of any marketed biological therapy (i.e. immunoglobulin,
anti-immunoglobulin E) including dupilumab or investigational
biologic agents 3-6 months prior to baseline.
•
Active skin infections within 1 week prior to baseline.
•
Clinically significant infection within 4 weeks prior to baseline.
•
A helminth parasitic infection within 6 months prior to the date
informed consent is obtained.
•
Tuberculosis requiring treatment within the 12 months prior to
screening.
•
Known primary immunodeficiency disorder.
Investigational 
medicinal product 
•
Active substance: tralokinumab.
•
Dosage form: 150 mg/mL solution for injection in 2 mL autoinjector
(total of 300 mg of tralokinumab per injection).
•
Concentration: 150 mg/mL.
•
Dose: 600 mg initial loading dose, then 300 mg every other week.
•
Method of administration: SC injection.
Duration of trial 
participation 
The trial duration for an individual subject is up to 24 weeks: 
•
Screening period: 2 to 4 weeks.
•
Treatment period: 16 weeks.
•
Safety follow-up period: 4 weeks.
Number of 
subjects 
Approximately 130 subjects, of which approximately 30 subjects will be 
adolescents, will be assigned to treatment. 
Number and 
distribution of 
trial sites 
Approximately 30 sites in the US. 
Statistical 
methods 
Primary endpoints: 
The primary endpoints (IGA 0/1 at Week 16 and EASI75 at Week 16) will be 
analysed using the composite estimand strategy to handle the occurrence of 
intercurrent events. Subjects with missing data will be imputed as 
non-responders.   
Number and percentage of subjects achieving response will be presented 
together with the corresponding 95% CI. 
Secondary endpoints: 
AEs will be summarised for all treated subjects (safety analysis set) and will 
be presented by Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term and primary system organ class (SOC) as number and 
percentage of AEs, the rate of AEs (number of AEs per 100 patient-years of 
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observation time), and number and percentage of subjects with AEs. 
Presence of treatment-emergent ADA from baseline to Week 16 will be 
summarised descriptively. 
Signatory 
investigator 
Dr.
, MD, 
Clinical Professor, Dermatology, 
, 
Director, Clinical Research, 
Sponsor 
LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark. 
PPD
PPD
PPD
PPD
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2 
Trial identification 
IND number: 123797 
The clinical trial protocol will be registered in local registries if required by local legislation. 
3 
Schematic of trial design 
The overall trial design is illustrated in Panel 1. The trial consists of a 2-to-4-week screening 
period, a 16-week treatment period, and a 4-week safety follow-up period. 
Panel 1: Trial design 
Abbreviations: IMP = investigational medicinal product; Q2W = every other week; w = weeks. 
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4 
Schedule of trial procedures 
Panel 2: Schedule of trial procedures 
Screening 
Treatment period 
Follow-
up2 
Unscheduled 
visit, if 
applicable3 
Early 
termination, 
if applicable4 
References 
(protocol 
section) 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Week 
-4/-2
0 
2 
4 
6 
8 
10 
12 
14 
16 
20 
Visit type 
Site 
Site 
Site 
Site 
Phone 
Phone 
Phone 
Site 
Phone 
Site 
Site 
Visit window (days)1 
±3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Population and eligibility 
Informed consent5 
X 
Appendix 3B 
Subject eligibility 
X 
X 
8.2 and 8.3 
Investigator assessments at screening/baseline only 
Demographics 
X 
11.2.1 
Medical history 
X 
11.2.2 
Physical examination 
X 
11.2.3 
C-SSRS
X 
11.2.4 
BSA 
X 
X 
11.2.5 
Treatments 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.6 
Concomitant procedure 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.6 
Background treatment - 
initiation and continuation 
of emollients6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.4 
Dispensing of IMP7 
X 
X 
X 
X 
9.2 and 9.8.3 
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Screening 
Treatment period 
Follow-
up2 
Unscheduled 
visit, if 
applicable3 
Early 
termination, 
if applicable4 
References 
(protocol 
section) 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Week 
-4/-2
0 
2 
4 
6 
8 
10 
12 
14 
16 
20 
Visit type 
Site 
Site 
Site 
Site 
Phone 
Phone 
Phone 
Site 
Phone 
Site 
Site 
Visit window (days)1 
±3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
IMP administration and 
Investigator-led training in 
the use of autoinjector 
X8 
9.2 
Subject 
self-administration of IMP 
at site 
X8 
X8 
X 
9.2 
Subject 
self-administration of IMP 
at home 
X 
X 
X 
X 
9.2 
Treatment compliance 
X 
X 
X 
X 
X 
X 
X 
X 
9.8.4 
Return of autoinjector and 
accountability 
X 
X 
9.8.3 
Observer assessment of 
subject IMP 
self-administration 
X 
X 
X 
11.3 
Subject assessment of 
IMP self-administration 
X 
X 
X 
X 
11.3 
Investigator assessments of efficacy 
IGA 
X 
X 
X 
X 
X 
X 
11.4.1 
EASI 
X 
X 
X 
X 
X 
X 
11.4.2 
Patient-reported outcomes 
POEM 
X 
X 
X 
X 
X 
11.4.3.1 
DLQI/CDLQI9 
X 
X 
X 
X 
X 
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Screening 
Treatment period 
Follow-
up2 
Unscheduled 
visit, if 
applicable3 
Early 
termination, 
if applicable4 
References 
(protocol 
section) 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Week 
-4/-2
0 
2 
4 
6 
8 
10 
12 
14 
16 
20 
Visit type 
Site 
Site 
Site 
Site 
Phone 
Phone 
Phone 
Site 
Phone 
Site 
Site 
Visit window (days)1 
±3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Eczema-related Sleep 
NRS 
X 
X 
X 
X 
X 
11.4.3.3 
Worst Weekly Pruritus 
NRS/Adolescent’s 
Pruritus NRS10 
X 
X 
X 
X 
X 
11.4.3.4 
Investigator assessments of safety 
Height11 and weight 
X 
X 
11.5.1 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
11.5.2 
Serum pregnancy test 
(central laboratory)  
X 
11.5.3 
Hepatitis B and C, HIV 
(central laboratory) 
X 
11.5.3 
Chemistry, haematology, 
(central laboratory) 
X 
X 
X 
X 
X 
X 
11.5.3 
PK blood sample 
X 
X 
X 
X 
11.6 
ADA blood sample 
X 
X 
X 
X 
11.5.4 
Urine dipstick (urinalysis, 
central laboratory)12 
X 
X 
X 
X 
X 
X 
11.5.3 
Urine pregnancy test 
X 
X 
X 
X 
11.5.3 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
13 
Other assessment 
Photography13 
X 
X 
X 
11.7 
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Screening 
Treatment period 
Follow-
up2 
Unscheduled 
visit, if 
applicable3 
Early 
termination, 
if applicable4 
References 
(protocol 
section) 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Week 
-4/-2
0 
2 
4 
6 
8 
10 
12 
14 
16 
20 
Visit type 
Site 
Site 
Site 
Site 
Phone 
Phone 
Phone 
Site 
Phone 
Site 
Site 
Visit window (days)1 
±3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
End of treatment/trial 
End-of-treatment 
X 
X 
11.8 
End-of-trial 
X 
X 
11.8 
1.
If the date of a trial visit does not conform to the clinical trial protocol, subsequent visits should be planned to maintain the visit schedule relative to baseline
(Week 0, Visit 2).
2.
An end-of-treatment form and/or end-of-trial form must be completed in the eCRF for all subjects assigned to treatment. See Section 11.8 for further details.
3.
Assessments to be performed at unscheduled visits will be at the discretion of the investigator. If the unscheduled visit involves administration of rescue
treatment, the investigator should make every attempt to conduct efficacy and safety assessments (at least disease severity scores [IGA and EASI], concomitant
medications/procedures, and AEs) immediately before administering any rescue treatment (see Section 9.5).
4.
Subjects who permanently discontinue IMP or withdraw from the trial will be followed up as described in Section 11.8. All subjects will have a final safety
follow-up visit 6 weeks after last dose of IMP.
5.
The informed consent form must be signed prior to performing any protocol-related procedures, including but not limited to screening evaluations and
wash-out of disallowed medications. Screening evaluations may start at a later date than the informed consent form was signed.
6.
All subjects will use an emollient, as background treatment, twice daily (or more, as needed) for at least 14 days before baseline and will continue this
treatment throughout the trial (including safety follow-up).
7.
At Week 4 and Week 12 (Visit 4 and Visit 8), subjects will be provided with tralokinumab to be administered at home until the next site visit.
8.
For the first 3 IMP administrations, all subjects will be monitored for a minimum of 30 minutes with vital signs taken at 30 minutes or until stable, whichever is
later.
9.
Subjects <18 years of age at the baseline visit will perform the CDLQI throughout the trial, independent of the subject’s age during the remainder of the trial.
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10. Subjects <18 years of age at the baseline visit will perform Worst Weekly Pruritus NRS with phrasings tailored to adolescent subjects, independent of the
subject’s age during the remainder of the trial.
11. Measurement of height at Week 16 (Visit 10) will be applicable only to subjects <18 years of age at the baseline visit.
12. Urine samples will be tested with a dipstick at the trial site. A urine sample will be sent to the central laboratory for further analysis only if considered required
by the investigator based on the dipstick results.
13. Applicable only for adult subjects (age 18 years and above at the baseline visit).
Abbreviations: ADA= anti-drug antibodies; BSA = body surface area; CDLQI = Children’s Dermatology Life Quality Index; C-SSRS = Columbia-Suicide 
Severity Rating Scale; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; ECG = electrocardiogram; eCRF = electronic case 
report form; HIV = human immune deficiency virus; IGA= Investigator’s Global Assessment; IMP = investigational medicinal product; NRS = numeric rating 
scale; PK= pharmacokinetics; POEM = Patient-Oriented Eczema Measure.
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5 
Introduction and trial rationale 
5.1 
Atopic dermatitis  
Atopic dermatitis (AD) is a chronic inflammatory skin disease that may affect up to 20% of 
children and up to 10% of adults (1, 2). In its moderate and severe form, AD is characterised 
by widespread skin lesions, intractable itch, as well as enhanced susceptibility to bacterial, 
viral, and fungal skin infections. AD is associated with a substantial patient burden that 
typically includes poor quality of life and sleep disturbance (3). 
AD is characterised by an activated T-helper-2 (Th2) pathway with interleukin-13 (IL-13) as 
the dominant cytokine in the skin (4-6). The expression of IL-13 is increased in lesional skin 
compared to non-lesional skin,  the proportion of CD4+ and CD8+ cells expressing IL-13 is 
upregulated in AD patients compared to individuals without AD, and there is a correlation 
between IL-13 expressing skin-homing T-cells and disease severity (7, 8).  
IL-13 acts on keratinocytes to release chemokines that recruit more IL-13 expressing Th2 
cells, decrease differentiation, and contribute to decreased barrier function (9). IL-13 also 
drives immunoglobulin E (IgE) production and contributes to mast cell activation status and, 
once allergen cross-links IgE on the cell surface, drives histamine release, induces itch, alters 
the skin microbiome, and stimulates skin fibrosis (10-12). These effects together drive and 
exacerbate the disease phenotype. Data from the phase 2B trial (D2213C00001) have 
confirmed IL-13 as a valid target in AD (13). 
5.2 
Experience with investigational medicinal product 
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 
(IgG4) subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 
receptors (14-16). A compilation of clinical and nonclinical data on tralokinumab including 
pharmacokinetics (PK) is given in the current version of the investigator’s brochure. 
LEO Pharma is currently conducting a clinical development program with tralokinumab in 
AD comprising of 7 completed and 4 ongoing trials.  
The completed trials have been conducted with the accessorised pre-filled syringe and 
include: a phase 2b dose-finding trial (trial D2213C00001), 2 phase 3 trials with tralokinumab 
as monotherapy (LP0162-1325 and LP0162-1326), 2 phase 3 trials with tralokinumab in 
combination with topical corticosteroids (TCS) (LP0162-1339 and LP0162-1346), a phase 2 
vaccine response trial (LP0162-1341), and a phase 1 drug-drug interaction trial 
(LP0162-1342).  
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The tralokinumab dosing regimen of 300 mg every other week (Q2W) selected for this trial is 
based on the dosing regimen used in the tralokinumab phase 3 development program in adult 
subjects.  
The 300 mg Q2W dose is considered safe in the adolescent population and is currently being 
investigated as part of the ongoing adolescent trial (LP0162-1334) where an independent Data 
Monitoring Committee regularly reviews unblinded safety data. Adolescent subjects with 
asthma have been investigated in a single-dose phase 1 trial (20 adolescent subjects exposed 
to tralokinumab) as well as in 2 completed phase 3 trials (58 adolescent subjects exposed to 
tralokinumab). In these trials, the tralokinumab PK and safety profile (based on reporting of 
AEs, SAEs, and AEs leading to discontinuation of IMP) was largely similar in the adult and 
adolescent trial populations with asthma. 
In the phase 3 completed trials, IGA, EASI, Worst Daily Pruritus NRS, SCORAD, and DLQI 
were included as the main assessments supporting the multiplicity-adjusted primary and 
secondary efficacy endpoints. The efficacy of tralokinumab as monotherapy in subjects with 
moderate-to-severe AD was demonstrated in the replicate confirmatory phase 3 trials 
(LP0162-1325 and LP0162-1326) with statistically significant results for all primary and 
multiplicity-adjusted secondary endpoints at Week 16. Noninferiority of tralokinumab vs 
placebo with respect to immune responses to concomitantly administered non-live vaccines 
was demonstrated in the LP0162-1341 trial. 
A total of 4,465 subjects across indications (healthy subjects, and subjects with AD, asthma, 
ulcerative colitis, and idiopathic pulmonary fibrosis) have been exposed to tralokinumab in 
24 completed clinical trials, including 2,276 subjects with AD in 7 completed clinical trials. A 
total of 2175 subjects with AD received tralokinumab 300 mg, and 807 of these were exposed 
to tralokinumab for 52 weeks.  
The safety data supports that tralokinumab was well-tolerated with a favourable safety profile 
when used as a monotherapy or in combination with TCS in subjects with moderate-to-severe 
AD who are candidates for systemic therapy. The overall frequency of SAEs was lower for 
tralokinumab compared with placebo, and the frequencies of AEs leading to permanent 
discontinuation of treatment were low and similar for the 2 treatment groups. Overall, AEs 
were mild or moderate in severity, and transient in nature. Furthermore, tralokinumab was 
well-tolerated across all evaluated subgroups, and the safety profile with self-administration 
of tralokinumab at home was similar to that observed after administration of tralokinumab at 
the site by trial site staff. 
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Data from the phase 3 clinical trials in adults and adolescents, evaluating tralokinumab in AD, 
showed that the incidence rate of ADA and nAb after 16 weeks of treatment was low and 
similar for tralokinumab and placebo, confirming the low immunogenicity of tralokinumab. 
All doses studied so far have had an acceptable benefit/risk profile, and no major safety 
concerns have been identified. 
5.3 
Trial rationale 
In the phase 3 clinical development program, tralokinumab was presented as a 1 mL 
accessorised pre-filled syringe (containing tralokinumab 150 mg/mL) for SC injection, with 
dosing consisting of a 600 mg initial loading dose (4 x 1 mL) followed by 300 mg (2 x 1 mL) 
of tralokinumab Q2W. To improve convenience for patients, an autoinjector containing 2 mL 
tralokinumab 150 mg/mL has been developed to allow a single injection of 300 mg of 
tralokinumab (and 2 injections at Week 0 for 600 mg initial loading dose of tralokinumab).  
To support the new presentation, a PK comparability trial intended to bridge between the 
accessorised pre-filled syringe and the newly developed autoinjector device is currently 
ongoing. In addition to the PK comparability and Human Factors data, this clinical trial will 
assess the efficacy and safety of the autoinjector in real-world situations in the AD population 
per FDA request. 
The primary objective of this trial is to evaluate the efficacy of tralokinumab administered by 
an autoinjector when used to treat subjects with moderate-to-severe AD. 
5.4 
Ethical considerations 
Participation in this trial is voluntary and subjects can withdraw at any time. The subjects or 
their legally authorised representative(s) will give informed consent, and adolescent subjects 
will give informed assent (as appropriate and according to national laws and regulations). No 
vulnerable subject incapable of giving informed consent will be included in this clinical trial. 
Furthermore, female subjects who are pregnant, breastfeeding, or trying to become pregnant 
will not be included. Female subjects of childbearing potential who are sexually active must 
agree to use a highly effective method of contraception to prevent pregnancy during the 
clinical trial and until 16 weeks after discontinuation of treatment with the IMP. In addition, 
all female subjects of childbearing potential will have a pregnancy test performed before, 
during, and at end-of-treatment to ensure that no foetuses are exposed to the IMP. 
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In this trial, all subjects will be treated with open-label tralokinumab. Subjects may receive 
rescue therapy at the discretion of the investigator if medically necessary through treatment 
and safety follow-up.  
In accordance with the current version of the ICH GCP guidelines, qualified medical 
personnel employed by LEO Pharma A/S (hereafter LEO Pharma) will be readily available to 
advise on trial-related medical questions (17). Medical monitoring will be performed 
throughout the trial. Safety data will be reviewed regularly by medically qualified staff at 
LEO Pharma to ensure that prompt action is taken, if needed, to maximise patient safety. 
In conclusion, the trial design chosen is regarded as ethically justified and adherent with 
ethical requirements. 
5.5 
Benefit/risk assessment 
This trial is part of the clinical development program of a new autoinjector containing 300 mg 
tralokinumab as a single injection with the aim of improving patient convenience.  
With more than 4,400 subjects exposed to tralokinumab in the completed trials in AD and 
other diseases, the benefit/risk ratio is considered favorable and supports the administration of 
tralokinumab in subjects with moderate-to-severe AD for the purposes of achieving the 
objectives of this trial. 
Based on the extensive clinical experience, a reassuring safety profile of tralokinumab has 
been observed in AD, asthma, ulcerative colitis, idiopathic pulmonary fibrosis, and in trials 
with healthy subjects. No safety concerns have been identified with the use of tralokinumab, 
and tralokinumab was well-tolerated. Generally, the overall incidence of AEs for 
tralokinumab has been similar to that for placebo in controlled clinical trials and the adverse 
drug reactions observed were mainly non-serious and mild or moderate in severity, and ADA 
were detected in only few subjects exposed to tralokinumab for up to 1 year. 
Appropriate measures have been instituted in this trial to protect subjects from potential risks, 
such as: 
•
Exclusion of subjects with untreated systemic helminth infestations or subjects who
have failed to respond to standard of care therapy; neutralisation of IL-13 might
theoretically cause a worsening of parasitic infestation, in particular, prevention of
expulsion of gastrointestinal worms (helminths).
•
Exclusion of subjects with a history of a clinically significant infection (defined as a
systemic or serious skin infection requiring parenteral antibiotics, antiviral, or
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antifungal medication) within 4 weeks prior to baseline, which, in the opinion of the 
investigator or sponsor’s medical expert, may compromise the safety of the subject in 
the trial. 
Participation in clinical trials may currently be associated with increased risks and challenges 
due to the COVID-19 pandemic caused by SARS-CoV-2. A risk of exposure to infected 
people cannot be excluded as the trial subjects may enter public areas (e.g. commute to the 
trial site) and have additional human contact (e.g. with trial site staff). Appropriate risk 
assessments and mitigation measures must be considered to protect the subjects and trial site 
staff and to ensure the integrity of the trial data. 
The FDA has issued new guidelines that aim to provide recommendations for conduct of 
clinical trials during the COVID-19 pandemic. Given the circumstances of the potentially 
relapsing pandemic situation with regard to the spread of COVID-19 in the future, special 
attention will be paid to protecting subjects participating in the trial and site staff involved in 
the investigations against infection with SARS-CoV-2. 
During the trial, the investigators will be trusted to take appropriate actions to ensure the 
safety of the individual subjects according to local authority issued preventive measures. As 
these can differ across regions, no general instruction from the sponsor can be provided 
concerning subject safety and the need for postponing trial visits. In case of local authority 
issued preventive measures, the investigator can convert the Week 12 visit (Visit 8) into phone 
or video consultation. At the phone/video visit, no investigator assessments of efficacy will be 
done. Safety monitoring remains an obligation to LEO Pharma, and it is considered feasible to 
collect safety data remotely (via electronic communication) where on-site visits are not 
possible. Other mitigating measures include collecting PRO data via a web-based solution and 
ensuring supply of IMP to the subjects to overcome local authority-issued preventive 
measures due to the COVID-19 pandemic (see Appendix 8 for details). 
Altogether, the risks associated with participating in this trial are considered very low and 
outweighed by the benefit of a potential more user-friendly future treatment option for 
patients with moderate-to-severe AD. 
No clinically significant safety issues are expected to be identified following 300 mg 
tralokinumab administered by a 1 × 2 mL autoinjector. 
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6 
Trial objectives and endpoints 
Panel 3: Objectives and endpoints 
Objectives 
Endpoints 
Primary objective 
To evaluate the efficacy of tralokinumab 
administered by an autoinjector when 
used to treat subjects with moderate-to-
severe AD. 
Primary endpoints 
•
IGA score of 0 (clear) or 1 (almost clear) at Week 16.
•
EASI75 at Week 16.
Secondary objective 
To evaluate the safety and tolerability of 
tralokinumab administered by an 
autoinjector when used to treat 
moderate-to-severe AD. 
Secondary endpoints 
•
Number of treatment-emergent AEs from baseline to
Week 16.
•
Presence of treatment-emergent ADA from baseline to
Week 16.
Other objectives 
To assess the real-life patient handling 
experience with the use of tralokinumab 
administered by an autoinjector in 
patients with moderate-to-severe AD. 
Other endpoints 
•
Successful IMP self-administration when observed at the
clinic at Week 4.
•
Successful IMP self-administration when administered at
home at Week 8.
To evaluate the efficacy of tralokinumab 
administered by an autoinjector on 
severity and extent of AD, itch, and 
HRQoL in treating moderate-to-severe 
AD. 
Other endpoints 
•
EASI90 at Week 16.
•
EASI50 at Week 16.
•
Percentage change in EASI score from baseline to
Week 16.
•
Change in POEM from baseline to Week 16.
•
Reduction in POEM of at least 4 from baseline to
Week 161,2/Reduction in POEM of at least 6 from
baseline to Week 161,2.
•
Change in DLQI/CDLQI from baseline to Week 16.
•
Reduction in DLQI of at least 4 from baseline to
Week 161,2/Reduction in CDLQI of at least 6 from
baseline to Week 161,2.
•
Change in Eczema-related Weekly Sleep NRS from
baseline to Week 16.
•
Change in Worst Weekly Pruritus NRS/Adolescent’s
Pruritus NRS from baseline to Week 16.
•
Reduction of Worst Weekly Pruritus NRS/Adolescent’s
Pruritus NRS of at least 4 from baseline to Week 163.
1. Only adult subjects with a score of 4 and above and adolescent subjects with a score of 6 and above at
baseline will be included in the analysis.
2. For adult subjects, a response is defined as a reduction of at least 4 from baseline. For adolescent subjects, a
response is defined as a reduction of at least 6 from baseline.
3. Only subjects with Worst Weekly Pruritus NRS/Adolescent’s Pruritus NRS score of 4 or above at baseline
will be included in the analyses.
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Abbreviations: AD = atopic dermatitis; ADA = anti-drug antibodies; AEs = adverse events; CDLQI =Children’s 
Dermatology Life Quality Index; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity 
Index; EASI90/EASI75/EASI50 = at least 90% / 75% / 50% reduction in EASI score; HRQoL =  health-related 
qualify of life; IGA = Investigator’s Global Assessment; IMP = investigational medicinal product; 
NRS = numeric rating scale; POEM = Patient-Oriented Eczema Measure. 
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7 
Trial design 
7.1 
Overall trial design 
This is an open-label, single-arm, phase 3 trial, in adult and adolescent (age 12 to 17 years) 
subjects with moderate-to-severe AD. The trial is designed to evaluate the efficacy and safety 
of tralokinumab administered by an autoinjector. The trial design is illustrated in Section 3. 
Screening period (Week -4/-2 to Week 0) 
The screening period has a minimum duration of 2 weeks and a maximum duration of 
4 weeks depending on the need for wash-out (i.e. screening visit should take place between 
Week -4 and Week -2). Eligibility will be assessed at the screening visit and at baseline prior 
to start of treatment. Trial-specific measurements will be performed as outlined in the 
schedule of trial procedures (Section 4). 
All subjects will use an emollient twice daily (or more, as needed) for at least 14 days before 
baseline and will continue this treatment throughout the trial (including safety follow-up). 
Subjects will initiate emollient treatment no later than the Week -2 visit. 
Treatment period (Week 0 to Week 16) 
At the baseline visit (Week 0, Visit 2), eligible subjects will receive an initial loading dose of 
SC tralokinumab 600 mg. This dose will be administered with the use of 2 autoinjectors 
containing 300 mg/2mL each. During the administration of the initial loading dose, subjects 
will be trained on the usage of the autoinjector by the investigator or a delegated trial staff. 
Subjects will have a choice to either self-administer the second injection under observation by 
qualified trial staff or receive both injections by the investigator/trial delegate. For the rest of 
the treatment period, all subjects will self-administer a dose of 300 mg tralokinumab Q2W 
(2 mL). 
At Weeks 2, 4, and 12, subjects will self-administer tralokinumab at the trial site under 
observation by a qualified trial staff. The observer (investigator or delegated trial staff) will 
assess the subject’s ability to self-administer the injection based on the defined sequence of 
use steps in Section 11.3. 
At Weeks 6, 8, 10, and 14, subjects will self-administer tralokinumab at home. Subjects will 
be asked to assess their ability to self-administer the injection based on the defined sequence 
of use steps in Section 11.3. In addition, the trial staff will contact the subjects via telephone 
at Weeks 6, 8, 10, and 14. At each telephone visit, concomitant medication and procedures, 
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treatment compliance, and AEs information will be collected. Delegation of the telephone 
visit to qualified personnel is allowed at the discretion of the investigator. 
For the first 3 IMP administration visits (i.e. at Weeks 0, 2, and 4), the subjects will be 
monitored after each IMP administration for immediate drug reactions for a minimum of 
30 minutes with vital signs taken at 30 minutes or until stable, whichever is later. 
Safety follow-up period (Week 16 to Week 20) 
All subjects completing the treatment period will have safety follow-up assessments 6 weeks 
after the last IMP administration at Week 14. Note that for subjects who permanently 
discontinue IMP, the 6-week follow-up period will start at the time of last IMP injection. 
7.2 
Number of subjects needed 
Assuming a screening failure rate of 25%, approximately 174 subjects will be screened. 
Approximately 130 subjects, of which approximately 30 subjects will be adolescents, are 
planned to be assigned to treatment. No formal sample size has been calculated. 
This trial will be conducted at approximately 30 sites in the US. The anticipated average 
number of subjects assigned to treatment per trial site is 4. 
7.3 
End-of-trial definition 
A subject is considered to have completed the trial if they have completed all periods of the 
trial including the safety follow-up visit (Week 20). 
The end of the trial is defined as the date of the last visit of the last subject in the trial. 
The final collection of data for the primary endpoint is at Week 16. 
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8 
Trial population 
8.1 
Subject eligibility 
The investigator should only include subjects who meet all eligibility criteria, are not put at 
undue risk by participating in the trial, and can be expected to comply with the protocol. 
The subject’s eligibility for the clinical trial must be verified according to the inclusion and 
exclusion criteria at visits specified in the schedule of trial procedures, Section 4. It will be 
recorded in the electronic case report form (eCRF) if the subject has met all the inclusion 
criteria and none of the exclusion criteria. 
Any implementation of national requirements/law for the subject’s participation in the clinical 
trial will be ensured and described in submission documentation to regulatory authorities and 
IRBs, as applicable. 
8.2 
Inclusion criteria 
The subjects must fulfil all of the following criteria to be eligible for the trial: 
1. Signed and dated informed consent has been obtained prior to any protocol-related
procedures. Signed and dated informed consent for adolescent subjects must be
provided by the subject’s legal representative(s) and by the subject in the form of a
signed and dated informed assent.
2. Age 12 and above at baseline (Week 0).
3. Body weight at screening ≥30 kg.
4. Subjects must be able and willing to self-administer tralokinumab using an
autoinjector. This criterion should be assessed at both screening and baseline visits, as
one of the ‘other objectives’ of the trial is to assess whether subjects can successfully
self-administer the IMP.
5. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (18)
(Appendix 4).
6. History of AD for ≥1 year.
7. Subjects who have a recent history (within 1 year before the screening visit) of
inadequate response to treatment with topical medication or for whom topical
treatments are otherwise medically inadvisable (e.g. due to important side effects or
safety risks).
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•
Inadequate response is defined as failure to achieve and maintain remission or
a low disease activity state (comparable to IGA 0 to 2) despite treatment with a
daily regimen of TCS of medium to higher potency [± topical calcineurin
inhibitors (TCI) as appropriate], applied for at least 28 days or for the
maximum duration recommended by the product prescribing information (e.g.
14 days for strongest TCS), whichever is shorter.
•
Subjects with documented systemic treatment for AD in the past year are also
considered as inadequate responders to topical treatments and are potentially
eligible for treatment with tralokinumab after appropriate washout.
•
Important side effects or safety risks are those that outweigh the potential
treatment benefits and include intolerance to treatment, hypersensitivity
reactions, significant skin atrophy, and systemic effects, as assessed by the
investigator or by the subject’s treating physician.
8. AD involvement of ≥10% body surface area (BSA) at screening and baseline.
9. An EASI score of ≥12 at screening and ≥16 at baseline.
10. An IGA score of ≥3 at screening and at baseline.
11. Subjects must have applied a stable dose of emollient twice daily (or more, as needed)
for at least 14 days before baseline.
12. A woman of childbearing potential* must use a highly effective** form of birth
control throughout the trial and at least for 16 weeks (5 half-lives) after last
administration of IMP.
*A woman of childbearing potential is defined as a female subject, who at the
discretion of the investigator, is deemed to be of reproductive potential. A woman is 
defined as not being of childbearing potential if she is postmenopausal (at least 
12 months with no menses without an alternative medical cause prior to screening), or 
surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 
**A highly effective method of birth control is defined as one which results in a low 
failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine 
device (IUD), intrauterine hormone-releasing system (IUS), combined (oestrogen- and 
progestogen-containing) hormonal contraception associated with inhibition of 
ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception 
associated with inhibition of ovulation (oral, injectable, implantable), sexual 
abstinence (when this is in line with the preferred and usual life style of the subject 
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and not just being without a current partner), same-sex partner, or vasectomised 
partner (given that the subject is monogamous). 
8.3 
Exclusion criteria 
Subjects are not eligible for the trial if they violate any of the following criteria: 
1. Concurrent enrolment in another interventional clinical trial.
2. Previous randomisation in a tralokinumab clinical trial.
3. Active dermatologic conditions that may confound the diagnosis of AD or would
interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or
psoriasis.
4. Known active allergic or irritant contact dermatitis that is likely to interfere with the
assessment of severity of AD.
5. Use of tanning beds or phototherapy (narrow band ultraviolet B [NBUVB],
ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen+ultraviolet A [PUVA]) within
4 weeks prior to baseline.
6. Treatment with the following medications within 4 weeks prior to baseline:
•
Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate,
cyclosporin A, azathioprine, mycophenolate mofetil, Janus kinase (JAK)
inhibitors).
•
Systemic corticosteroid use (excludes topical, inhaled, or intranasal delivery).
•
Three or more bleach baths during any week within the 4 weeks.
7. Treatment with the following medications within 2 weeks prior to baseline:
•
TCS.
•
TCI.
•
Topical PDE 4 inhibitors.
•
Topical JAK inhibitors.
8. Receipt of live attenuated vaccines within 30 days prior to the date of baseline and
during the trial including the safety follow-up period.
•
Receipt of inactive/killed vaccinations (e.g. inactive influenza) is allowed but it
should not be administered in the same location as tralokinumab.
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9. Receipt of any marketed biological therapy (i.e. immunoglobulin, anti-IgE) including
dupilumab or investigational biologic agents:
•
Any cell-depleting agents including but not limited to rituximab: within
6 months prior to baseline, or until lymphocyte count returns to normal,
whichever is longer.
•
Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to
baseline.
10. Receipt of any investigational non-biologic agent within 5 half-lives prior to baseline.
11. Receipt of blood products within 4 weeks prior to screening.
12. Major surgery within 8 weeks prior to screening or planned in-patient surgery or
hospitalisation during the trial period.
13. Known or suspected allergy or reaction to any component of the IMP formulation.
14. History of any active skin infection within 1 week prior to baseline.
15. History of a clinically significant infection within 4 weeks prior to baseline which, in
the opinion of the investigator or sponsor’s medical expert, may compromise the
safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the
subject’s ability to participate in the trial. Clinically significant infections are defined
as:
•
a systemic infection.
•
a serious skin infection requiring parenteral (intravenous or intramuscular)
antibiotics, antiviral, or antifungal medication.
16. A helminth parasitic infection within 6 months prior to the date informed consent is
obtained that has not been treated with, or has failed to respond to, standard of care
therapy.
17. History of anaphylaxis following any biological therapy.
18. History of immune complex disease.
19. History of cancer:
•
Subjects who have had basal cell carcinoma, localised squamous cell
carcinoma of the skin or in situ carcinoma of the cervix are eligible provided
that the subject is in remission and curative therapy was completed at least
12 months prior to the date informed consent was obtained.
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•
Subjects who have had other malignancies are eligible provided that the
subject is in remission and curative therapy was completed at least 5 years
prior to the date informed consent was obtained.
20. Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation
will be according to local guidelines as per local standard of care.
21. History of any known primary immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral
medications as determined by medical history and/or subject’s verbal report.
22. History of subject or subject’s legal representative(s) of chronic alcohol or drug abuse
within 12 months prior to screening, or any condition (e.g. psychotic state, language
barrier, or other) associated with poor compliance, as judged by the investigator.
23. History of attempted suicide or at significant risk of suicide (either in the opinion of
the investigator or defined as a “yes” to suicidal ideation questions no. 4 or 5 or
answering “yes” to suicidal behaviour on the Columbia-Suicide Severity Rating Scale
[C-SSRS] screening version).
24. Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic,
renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological,
immunological, psychiatric, or major physical impairment that is not stable, in the
opinion of the investigator, and could:
•
Affect the safety of the subject throughout the trial.
•
Influence the findings of the trial or their interpretations.
•
Impede the subject’s ability to complete the entire duration of trial.
25. Any clinically significant abnormal findings in physical examination, vital signs,
haematology, clinical chemistry, or urinalysis during the screening period, which in the
opinion of the investigator, may put the subject at risk because of his/her participation
in the trial, or may influence the results of the trial, or the subject’s ability to complete
entire duration of the trial.
26. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times
the upper limit of normal (ULN) at screening.
27. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb),
hepatitis B core antibody (HBcAb) at screening. Subjects with positive HBsAb are
eligible in the trial provided they have negative HBsAg and HBcAb.
28. Positive hepatitis C virus antibody (anti-HCV) serology at screening.
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29. Subjects who are not willing to abstain from donating blood and/or plasma from the
time of informed consent and for 16 weeks (5 half-lives) after last dose of IMP.
30. Subjects who are legally institutionalised.
31. Pregnant, breastfeeding, or lactating women.
32. Employees of the trial site or any other individuals directly involved with the planning
or conduct of the trial, or immediate family members of such individuals.
8.4 
Screening and screening failures
Subject identification number 
Trial participation begins once written informed consent or informed assent, as appropriate, is 
obtained. Refer to Appendix 3B for details on the informed consent process. Once informed 
consent is obtained, a subject identification number (subject ID) will be assigned by a central 
interactive response technology (IRT) system and the screening evaluations to assess 
eligibility criteria may begin. The date of first screening activity could be on the same day or 
a later date than the informed consent form was signed. The subject ID will be used to 
identify the subject during the screening process and throughout trial participation, if 
applicable. Subjects who have given written informed consent and subjects for whom the 
subject’s legally authorised representative(s) have given written informed consent (the subject 
must have given written informed assent) to participate in the trial and who have been 
assigned a subject ID are considered ‘screened’ subjects. 
The investigator will maintain a log of all subjects considered for screening, whether they 
have provided written informed consent (and informed assent as appropriate and according to 
national laws and regulation) or not (screening log). In addition, the investigator will maintain 
a log of all consented subjects at the trial site (subject identification list). This log will include 
each subject’s identity, date of consent, and corresponding subject ID, so that any subject may 
be identified if required for any reason. The log must not be copied or retained by LEO 
Pharma. 
Screening failures  
Screening failures are defined as subjects who consent to participate in the trial but are not 
subsequently assigned to trial treatment. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure subjects to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements (19) and to respond to 
queries from regulatory authorities.  
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As a minimum, the following data will be collected in the eCRF for screening failures: 
•
Date of informed consent(s).
•
Demographics (age, sex, ethnicity, race).
•
Reason for screen failure.
o
Failure to meet eligibility criteria (specify criteria).
o
Lost to follow-up.
o
Withdrawal by subject.
o
Withdrawal by parent/guardian.
o
Other (specify reason).
•
Date of screen failure.
•
Any AEs and SAEs.
In case of any SAEs, these must be followed up as described in Section 13.7. 
Re-screening of screening failures is not allowed. However, if the reason for screening failure 
is administrative and not due to the subject failing to meet the eligibility criteria, re-screening 
may be permitted (this will require approval by the sponsor’s medical expert). Individuals 
who are re-screened will get a new subject ID. 
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9 
Treatments 
9.1 
Trial product description 
Panel 4: Identification of investigational medicinal product 
IMP 
Dosage form 
Active ingredients and 
concentration 
Pack size 
Manufacturer 
responsible for 
batch release 
Tralokinumab 
150 mg/mL solution 
for injection in 2 mL 
autoinjector1 (total of 
300 mg of 
tralokinumab per 
injection) 
Nominal concentration of 
tralokinumab 150 mg/mL in 
 mM sodium 
acetate/acetic acid buffer, 
 mM sodium chloride, 
% (w/v) PS-80, pH 5.5 
solution 
2.0 mL 
autoinjector1 
LEO Pharma 
1.
The autoinjector is a single-use, disposable system that is designed to administer the labelled dose of the
system to the SC space during 1 injection and automatically provide a safety mechanism to reduce the
occurrence of accidental needle sticks during disposal of the system.
Abbreviations: IMP = investigational medicinal product; SC = subcutaneous. 
9.2 
Administration of investigational medicinal product 
The IRT system will assign the required kit number(s) for each subject at each dispensing 
visit. 
The first day of dosing is considered baseline (Week 0, Visit 2). 
At baseline (Week 0, Visit 2), each subject will receive an initial loading dose of SC 
tralokinumab 600 mg. This dose will be administered with the use of 2 autoinjectors 
containing 300 mg/2mL each. During the administration of the initial loading dose, subjects 
will be trained on the usage of autoinjector by the investigator or delegated trial staff. Subjects 
will have a choice to either self-administer the second injection under observation by 
qualified trial staff or receive both injections by the investigator/trial delegate. For the rest of 
the treatment period, all subjects will self-administer a dose of 300 mg tralokinumab Q2W 
(2 mL). A minimum interval of 7 days is required between 2 dosing’s. Dosing visits are 
shown in the schedule of trial procedures, Section 4. 
The subject should be trained on how to handle the IMP and on the correct use of autoinjector 
according to the instructions for use. Furthermore, the subject will be trained on procedures to 
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be followed in the event of an emergency during or following home use of tralokinumab. 
Training provided to the subject will be documented in the eCRF. 
For the initial 600 mg loading dose, each 2 mL injection will be administered at different 
injection sites separated by at least 3 cm within the same body area. Tralokinumab will be 
injected into the SC tissue of anterior thigh or abdomen. It is advised that the site of injection 
of IMP is rotated such that the subject receives IMP at a different anatomical part at each 
treatment. The injection site must be recorded in the source documents at each treatment visit 
and recorded in the eCRF.  
In case the autoinjector is not working properly or damaged (see Section 9.10) or in situations 
where the subject did an error resulting in the subject not receiving any of the intended dose, a 
new autoinjector can be assigned at a scheduled or unscheduled visit at the investigator’s 
discretion, and the site can re-train the subject as needed.  
Further details on IMP administration are provided in a trial product handling manual. 
Subjects will receive the instructions for use and IMP must be administered according to it. 
Monitoring after IMP administration 
For the first 3 IMP administration visits (i.e. at Weeks 0, 2, and 4), the subjects will be 
monitored after each IMP administration for immediate drug reactions for a minimum of 
30 minutes with vital signs taken at 30 minutes or until stable, whichever is later. Vital signs 
will be documented in the eCRF (Section 11.5.2).  
As with any antibody, allergic reactions to dose administration are possible. The World 
Allergy Organization has categorised anaphylaxis into 2 subgroups: allergic anaphylaxis 
(mediated by an immunologic mechanism) and nonallergic anaphylaxis (which has a 
nonimmunologic cause) (20). The clinical criteria for defining anaphylaxis for this trial are 
listed in Appendix 5 (21). 
Appropriate drugs, such as epinephrine, antihistamines, corticosteroids, etc., and medical 
equipment to treat acute anaphylactic reactions must be immediately available at the trial 
sites, and trial personnel should be trained to recognise and respond to anaphylaxis according 
to local guidelines. 
If an anaphylactic reaction occurs, a blood sample will be drawn from the subject as soon as 
possible after the event, at 60 minutes ± 30 minutes after the event, and at discharge, for 
analysis of serum tryptase at the central laboratory (Section 11.5.3). 
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Conditions requiring rescheduling of tralokinumab administration 
If any of the following should occur, the investigator should reschedule the visit and 
tralokinumab should not be administered until the rescheduled visit: 
•
The subject has an intercurrent illness that, in the opinion of the investigator, may
compromise the safety of the subject during the trial (e.g. viral illness).
•
The subject is febrile (defined as ≥38°C) within 72 hours prior to administration of
tralokinumab.
If the trial visit cannot be rescheduled to maintain a minimum of 7 days before the next dose, 
the sponsor’s medical expert should be contacted. 
9.3 
Treatment assignment 
Subjects who have been found to comply with all the inclusion criteria and not to fulfil any of 
the exclusion criteria will be assigned to treatment at baseline. The IRT system will be used to 
control the IMP supply chain and expiry tracking. 
9.4 
Background treatment 
All subjects will use an emollient twice daily (or more, as needed) for at least 14 days before 
baseline. The background treatment should preferably be an additive-free, basic, bland 
emollient. Subjects will continue their background emollient treatment throughout the trial 
(including the safety follow-up). 
It will be recorded in the eCRF if background treatment (emollient) has been used as 
described since last visit; if not, a reason should be provided. 
9.5 
Rescue treatment 
If medically necessary (i.e. to control intolerable AD symptoms), rescue treatment for AD 
may be provided to trial subjects at the discretion of the investigator. If possible, investigators 
should attempt to limit the first step of rescue therapy to topical medications (i.e. TCS/TCI) 
and escalate to systemic medications only for subjects who do not respond adequately after at 
least 14 days of topical treatment.  
Subjects who receive topical rescue treatment will continue IMP treatment. 
If a subject receives rescue treatment with systemic corticosteroids or non-steroidal systemic 
immunosuppressive drugs (methotrexate, mycophenolate mofetil, azathioprine, etc.), IMP will 
be immediately discontinued. After the treatment with these medications is completed, IMP 
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may be resumed if deemed appropriate by the investigator, but not sooner than 5 half-lives 
after the last dose of systemic rescue treatment. The use of biological rescue treatment will be 
disallowed for the entire trial duration. 
Investigators should make every attempt to conduct efficacy and safety assessments (at least 
disease severity scores [IGA and EASI], concomitant medications/procedures, and AEs) 
immediately before administering any rescue treatment. An unscheduled visit may be used for 
this purpose, if necessary. 
Use of rescue medication will be recorded in the eCRF. 
9.6 
Concomitant medication and concurrent procedures 
Any medication or vaccine that the subject receives from 3 months prior to screening through 
safety follow-up must be recorded in the subject’s medical record and the eCRF along with 
details such as: 
•
Medication name.
•
Indication.
•
Start and stop date of administration (it will also be recorded if the medication is
ongoing).
•
Dosage information, including dose per administration, unit, and frequency.
•
Route of administration.
Similarly, any concurrent procedure must also be recorded in the subject’s medical record and 
the eCRF. Note that in this trial, only surgical procedures and procedures related to AD 
treatment (e.g. phototherapy or bleach baths) should be recorded. The following details will 
be recorded: procedure, body location, indication, and start and stop date (it will also be 
recorded if the procedure is ongoing). 
Investigators may prescribe concomitant medications or treatments to provide adequate 
supportive care as deemed necessary, except for medications listed in Section 9.7. The 
sponsor’s medical expert should be contacted if there are any questions regarding concomitant 
or prior therapy. 
The following concomitant medications related to AD treatment are permitted from screening 
through the safety follow-up period (Week 20): 
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•
Oral antibiotics, antiviral, or antifungal therapy for skin infections as appropriate.
•
Stable doses of an emollient (see Section 9.4; subjects must apply emollient twice
daily [or more, as needed] for at least 14 days before baseline and throughout trial
participation).
•
Oral antihistamines.
9.7 
Prohibited medications and procedures 
The medications and procedures listed below are prohibited during the trial from 
baseline (Week 0). Details regarding prohibited medications and procedures prior to baseline 
are described in Section 8.3. 
From baseline through end of treatment (Week 16): 
•
TCS of any potency (unless for rescue treatment, see Section 9.5).
•
Other topical medications used for the treatment of AD, such as TCI and topical
PDE-4 inhibitors.
•
Use of UVA or UVB, psoralen + UVA (PUVA), other phototherapy, or tanning beds.
•
3 or more bleach baths per week.
From baseline through safety follow-up (Week 20): 
•
Investigational agents other than tralokinumab.
•
Systemic corticosteroids (nasal, ophthalmic, and inhaled corticosteroids are allowed).
•
Systemic treatment for AD with an immunosuppressive/immunomodulating agent
(e.g. cyclosporine A, mycophenolate mofetil, azathioprine, methotrexate,
JAK inhibitors, interferon-gamma, dupilumab, or other biologics).
•
Allergen immunotherapy.
•
Live (attenuated) vaccine*.
•
Immunoglobulins.
•
Blood products.
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*Receipt of inactive/killed vaccines (e.g. inactive influenza) is allowed, provided it is not
administered in the same location as tralokinumab. 
Some of the above mentioned prohibited medications can be used provided the indication is 
rescue treatment for AD. Please refer to Section 9.5 for details regarding rescue treatment. 
In case any prohibited treatments are used during the trial, they must be recorded as 
concomitant medication in the eCRF. 
9.8 
Treatment logistics and accountability 
9.8.1 
Labelling and packaging of trial products 
The IMP will be packaged in individually numbered kits. 
Primary and secondary packaging materials (autoinjector and outer carton, respectively) will 
be individually labelled. 
The labelling of IMP will be in accordance with the EU guidelines for Good Manufacturing 
Practices for Medicinal Products for Human and Veterinary use, Annex 13 (22), local 
regulations, and trial requirements. 
9.8.2 
Storage of trial products 
All LEO Pharma supplied IMPs must be stored in a secure and restricted area under the 
conditions specified on the label and remain in the original container until dispensed. 
The IMP must be stored at 2-8°C at the trial site. The temperature during storage should be 
monitored by a calibrated, stationary, and continuously monitoring system. Minimum 
requirement is a calibrated min/max thermometer.  
A temperature log must be kept to document the storage within the right temperature interval. 
Storage facilities should be checked at least every working day. 
Storage of IMP may be delegated, e.g. to a hospital pharmacy, as locally applicable and must 
be documented in the site signature and designation of responsibility log. 
Note that in the cases listed below, site staff should not use the affected IMP and should 
immediately contact their CRA for further guidance: 
•
Temperature excursion upon receipt or during storage at the trial site.
•
Damaged kit upon receipt.
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•
Damaged autoinjector.
Damaged IMP should be documented in the IRT system and reported as product complaint 
(see Section 9.10). Damaged IMP may not be used. 
Further details on IMP storage (including handling of cases listed above) and home use are 
provided in a trial product handling manual. The instructions for use given to subjects also 
provides instruction on IMP storage during home use. 
9.8.3 
Investigational medicinal product accountability 
The investigator is fully responsible for the IMP at the trial site and for maintaining adequate 
control of the IMPs and for documenting all transactions with them. 
Dispensing of IMPs may be delegated, e.g. to a hospital pharmacy, as locally applicable and 
must be documented in the site signature and designation of responsibility log. 
Documentation of IMP accountability must be kept for the IMPs administered to each 
individual subject in the trial. This documentation must be available during monitoring visits 
and will be checked by the CRA to verify correct dispensing of the IMPs. IMP accountability 
information will be recorded in IRT system. The IRT system will also maintain the inventory 
status of all IMPs at the trial site. 
Subjects will attend site visits on a regular basis (see Section 4). At these site visits, subjects 
will be provided with IMP to be administered at home until the next site visit. If needed, 
additional IMP kit may be dispensed to the subject at a scheduled or unscheduled visit at the 
investigator’s discretion. Subjects will be provided with sharps bins to dispose used 
autoinjectors and will return filled sharps bins to the trial site. Subjects will return trial kit 
cartons and any unused IMP at the next site visit. Unused IMP returned by subjects to the trial 
site can be stored at room temperature and must be stored separately from non-allocated IMP. 
All unused IMP (including packaging material) supplied by the contract manufacturing 
organisation (CMO) on behalf of LEO Pharma will be returned to the CMO. Prior to their 
return, the IMPs must be fully accounted for by the CRA with the help of site staff responsible 
for dispensing the IMP. Accountability must be documented on drug accountability forms and 
in the IRT system. 
Refer to the trial product handling manual for information on returning trial products. 
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Reporting in eCRF 
IMP kit numbers and the date of IMP administration will be recorded in the eCRF. In addition, 
the site of IMP injection should be given. Subjects will be asked to record these details in a 
log (paper form) of drug administration for each IMP administration at home, and site staff 
will record the details in the eCRF. 
9.8.4 
Treatment compliance 
At site visits, site staff will keep the accountability records up to date. Any non-compliance 
and the reason for it must be recorded in the eCRF. 
Where IMP is injected by the subject at the trial site, the site staff will record compliance data 
in the eCRF. 
Where IMP is injected by the subject at home, the subject or subject’s caregiver will record 
the date and injection site for each administration in a log of drug administration; these data 
will be transcribed into the eCRF by site staff at the next site or telephone visit. If a subject is 
found to be non-compliant, the investigator should remind the subject of the importance of 
following the treatment instructions including taking the IMP as prescribed. Any 
non-compliance and the reason for it must be recorded in the eCRF.  
9.8.5 
Trial product destruction 
Before autoinjector destruction, refer to Section 9.10 for instructions to follow in case of a 
damaged or defective device. Damaged autoinjector may be returned to the IMP supplier per 
the instructions in the trial product handling manual. 
Used autoinjectors will be destroyed at the trial site provided the trial site has procedures in 
place for such IMP destruction. Trial sites which do not have such IMP destruction procedures 
in place will dispose used IMP in sharps bins which will be shipped to the CMO. 
Unused autoinjector returned to the CMO will be destroyed by the CMO according to 
approved procedures and any local requirements. 
9.9 
Provision for subject care following trial completion 
To ensure appropriate treatment of the subjects after they have completed the trial, the 
subjects will be treated at the investigator’s discretion or referred to other physician(s) 
according to standard practice. 
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9.10 Reporting product complaints 
Any defects or issues with the IMP as well as any device deficiency (including malfunctions, 
use errors, and inadequate labelling) must be reported to the Quality department via Global 
Safety at LEO Pharma on the trial-specific (paper) complaint form within 3 working days of 
first knowledge.  
Critical complaints (defined as any defect, issue, or device deficiency that has or potentially 
could have a serious impact on the subject [e.g. SAE or large particles in the autoinjector]) 
must be reported to the Quality department via Global Safety within 24 hours of knowledge. 
Complaint forms should contain a detailed description of the defect, issue, or device 
deficiency, including whether it led to an AE. (S)AEs which occur due to a defect or issue 
with the autoinjector will be reported by the investigator as described in Sections 13.3 and 
13.4.  
During the investigation of the product complaint, the autoinjector must be quarantined and 
stored at labelled conditions unless otherwise instructed; the trial site will be notified whether 
the autoinjector needs to be returned for further investigation or may be destroyed. 
Global Safety, LEO Pharma contact information for reporting product complaints: 
Fax number: +45 7226 3287  
E-mail address: drug.safety@leo-pharma.com
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10  Discontinuation and withdrawal 
10.1 General principles 
A subject may withdraw from the trial (prior to first dose or during the treatment/safety 
follow-up period) or permanently discontinue trial treatment at any time if the subject, the 
investigator, or LEO Pharma considers that it is not in the subject’s best interest to continue. 
Subjects who withdraw from the trial and subjects who permanently discontinue IMP will not 
be replaced. 
If a subject withdraws from the trial, they or their parent/guardian may request destruction of 
any samples taken and not tested, and the investigator must document this in the subject’s 
medical record. 
10.2 Reasons for discontinuation of IMP 
10.2.1 
Reasons for permanent discontinuation of IMP 
Subjects will permanently discontinue IMP in the event of: 
•
Anaphylactic reaction or other severe systemic reaction to IMP injection.
•
An AE that, in the opinion of the investigator or sponsor’s medical expert,
contraindicates further dosing.
•
Diagnosis of a malignancy during the trial, excluding carcinoma in situ of the
cervix, or localised squamous or basal cell carcinoma of the skin.
•
Evidence of pregnancy (e.g. a positive pregnancy test).
•
Any infection that is opportunistic, such as active tuberculosis and other infections
whose nature or course may suggest an immuno-compromised status.
•
Severe laboratory abnormalities:
o
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values
>3×ULN with total bilirubin >2×ULN (unless elevated bilirubin is related to
Gilbert-Meulengracht Syndrome). 
o
Confirmed AST or ALT >5×ULN for >2 weeks.
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Data to be recorded in the eCRF 
The primary reason for permanent discontinuation of IMP must be recorded in the medical 
records and on the end-of-treatment form in the eCRF where the following options are 
available: 
•
Adverse event (a specification must be provided).
•
Death.
•
Lost to follow-up.
•
Withdrawal by subject.
•
Withdrawal by parent/guardian (applicable for adolescent subjects).
•
Lack of efficacy.
•
Pregnancy.
•
Other (a specification must be provided).
It will also be recorded whether the discontinuation of IMP was related to the COVID-19 
pandemic. 
10.2.2 
Reasons for temporary discontinuation of IMP 
IMP dosing may be temporarily suspended in the event of: 
•
Other intercurrent illness or major surgery.
•
An infection that requires parenteral treatment with antibiotic, antifungal, antiviral,
anti-parasitic, or anti-protozoal agents.
IMP dosing should be temporarily suspended in the event of: 
•
Treatment with systemic corticosteroids or non-steroidal
immunosuppressive/immunomodulating medications (e.g. cyclosporine,
methotrexate, azathioprine, mycophenolate mofetil, JAK inhibitors, dupilumab, or
other biologics).
After the treatment with these medications is completed, IMP may be resumed if deemed 
appropriate by the investigator, but not sooner than 5 half-lives after the last dose of systemic 
rescue treatment. 
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10.3 Early termination assessments 
Permanent discontinuation of IMP 
Subjects who permanently discontinue IMP for any reason will be asked to attend: 
•
Early termination visit as soon as possible after last administration of IMP.
•
Safety follow-up visit (6 weeks after the last IMP administration).
See the schedule of trial procedures (Section 4) for data to be collected at these visits. The 
investigator will review any AEs which will be followed up according to Section 13.7, if the 
subject agrees. 
Withdrawal from trial 
Subjects who withdraw from the trial for any reason will be asked to attend an early 
termination visit as soon as possible after last administration of IMP (see the schedule of trial 
procedures [Section 4] for data to be collected at an early termination visit). The investigator 
will review any AEs which will be followed up according to Section 13.7, if the subject 
agrees. 
Details on data to be recorded in the eCRF for subjects who withdraw from the trial can be 
found in Section 11.8. 
10.4 Lost to follow-up 
A subject will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and if the trial site is not able to get in contact with the subject. 
The following actions must be taken if a subject fails to return to the trial site for a required 
visit: 
•
The trial site must attempt to contact the subject or subject’s parent/guardian and
reschedule the missed visit as soon as possible and counsel the subject on the
importance of maintaining the assigned visit schedule and ascertain whether the
subject wishes to continue in the trial.
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•
Before a subject is deemed lost to follow-up, the investigator or designee must
make every effort to regain contact with the subject or the subject’s parent/guardian
(where possible, 3 telephone calls and, if necessary, a certified letter to the subject’s
last known mailing address or local equivalent methods). These contact attempts
should be documented in the subject’s medical record. Should the subject continue
to be unreachable, they will be considered to have withdrawn from the trial with a
primary reason of lost to follow-up.
11  Trial assessments and procedures 
11.1 Overview 
Evaluations to be done at each visit are shown in the schedule of trial procedures in Section 4 
and the trial design is described in Section 7.1. 
Subjects participating in the trial will be under careful supervision of a dermatologist or 
allergist. Investigators must be experienced in treating AD and have documented experience 
or training in use of the assessments required by the protocol and must be a physician, or MD 
with at least 1 year of dermatology training, or an advanced registered nurse practitioner. 
AEs must be assessed by a physician (Section 13.2). 
11.2 Assessments performed only at screening and/or baseline 
11.2.1 
Demographics 
The following demographic data will be recorded: 
•
Age (in years).
•
Sex: female, male.
•
Ethnic origin (self-reported by the subject): Hispanic or Latino, not Hispanic or
Latino.
•
Race: American Indian or Alaska native, Asian, Black or African American, native
Hawaiian or other Pacific islander, White, other (requires a specification to be
provided).
11.2.2 
Medical history 
Relevant past and concurrent medical/surgical history must be recorded and includes: 
•
All past and current skin disease history, including but not limited to:
o
Alopecia.
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o
Vitiligo.
o
Herpes simplex infection.
•
Atopy history:
o
Duration of AD in years.
o
Previous AD treatments.
o
Asthma.
o
Food allergy.
o
Hay fever.
o
Allergic conjunctivitis.
o
Atopic keratoconjunctivitis.
o
Eczema herpeticum.
•
Other medical and surgical history, including concurrent diagnoses.
For each condition, diagnosis, or surgical procedure, the start date and stop date will be 
recorded; it will also be recorded if the condition, diagnosis, or surgical procedure is ongoing. 
Relevant medical history also includes diseases that are specifically listed as exclusion criteria 
and diseases for which specific treatments are listed as exclusion criteria. 
11.2.3 
Physical examination 
A thorough physical examination of the subject including whole body inspection of the skin, 
auscultation of the heart, lungs, and abdomen, palpation of the abdominal organs, and 
assessment of basic neurological status must be performed at screening (Section 4). 
If a clinically significant abnormality is identified during the physical examination at the 
screening visit, the subject must not be included in the trial. A clinically significant 
abnormality does not include findings of the skin related to the AD. 
Reporting in eCRF 
It will be recorded in the eCRF if a physical examination was performed and, if applicable, 
the investigator’s evaluation (‘normal’, ‘abnormal, not clinically significant’, ‘abnormal, 
clinically significant’). If a physical examination was not performed, a reason should be 
given. 
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Clinically significant abnormal findings at the screening visit will be documented as medical 
history in the eCRF.  
11.2.4 
Columbia-Suicide Severity Rating Scale 
The C-SSRS Screening version is a rater-administered instrument used to assess severity of 
suicidal ideation and suicidal behaviour through a series of simple, plain-language 
questions (23). The C-SSRS must be completed at the screening visit to check that exclusion 
criterion no. 23 does not apply. Further details on the assessment according to the C-SSRS are 
included in the efficacy assessment & C-SSRS manual. 
11.2.5 
Body surface area involvement 
The total BSA affected by AD will be assessed by the investigator for each section of the body 
and will be reported as a percentage of all major body sections combined. The following body 
regions will be assessed (brackets show the highest possible score for each region): head and 
neck (9%), anterior trunk (18%), back (18%), upper limbs (18%), lower limbs (36%), and 
genitals (1%).  
11.3 Rating of subject’s ability to self-administer 
The subject’s ability to self-administer tralokinumab using the autoinjector will be assessed 
following each administration after baseline (Week 0). The assessment is based on the defined 
sequence of use steps: 
1) Choose the correct injection area.
2) Remove the cap.
3) Press device down to begin injection.
4) Hold until the injection is complete.
o
Was the dose completed?
i. Did the yellow plunger cover the viewing window completely when
removing the autoinjector from the injection area?
ii. Was liquid dripping from the tip of the autoinjector when removing it
from the injection area?
For the self-administrations performed at the trial site (Weeks 2, 4, and 12), the observer 
(investigator or delegated trial staff) will assess the subject’s ability to self-administer.  
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For the self-administration performed at home (Weeks 6, 8, 10, and 14), the subjects will 
assess their ability to self-administer based on the defined sequence of use steps.  
Successful subject self-administration for administration at trial site or following dosing at 
home is defined as completion of each of the above defined sequence of use steps without 
errors. 
It will be recorded in the eCRF whether or not the subject could perform each of the defined 
sequence of use steps. 
If a new autoinjector is assigned due to errors resulting in the subject not receiving any of the 
intended dose, the assessment of subject ability to self-administer should not be made for the 
new injection.  
11.4 Efficacy assessments 
11.4.1 
Investigator’s Global Assessment 
The IGA is an instrument used in clinical trials to rate the severity of the subject’s global AD 
and is based on a 5-point scale ranging from 0 (clear) to 4 (severe) (Panel 5). The IGA score 
will be assessed according to the schedule of trial procedures (Section 4). The assessment will 
be based on the condition of the disease at the time of evaluation and not in relation to the 
condition at a previous visit. The disease severity assessment score will be recorded in the 
eCRF. 
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Panel 5: Investigator’s Global Assessment 
Score 
Disease severity 
Standard Investigator’s Global 
Assessment scale 
Investigator’s Global Assessment 
morphological descriptors 
0 
Clear 
No inflammatory signs of atopic 
dermatitis. 
No erythema and no elevation 
(papulation/infiltration). 
1 
Almost clear 
Just perceptible erythema and just 
perceptible papulation/infiltration. 
Barely perceptible erythema and/or 
minimal lesion elevation 
(papulation/infiltration) that is not 
widespread. 
2 
Mild disease 
Mild erythema and mild 
papulation/infiltration. 
Visibly detectable, light pink 
erythema and very slight elevation 
(papulation/infiltration). 
3 
Moderate disease 
Moderate erythema and moderate 
papulation/infiltration. 
Dull red, clearly distinguishable 
erythema and clearly perceptible but 
not extensive elevation 
(papulation/infiltration). 
4 
Severe disease 
Severe erythema and severe 
papulation/infiltration. 
Deep/dark red erythema, marked and 
extensive elevation 
(papulation/infiltration). 
11.4.2 
Eczema Area and Severity Index 
The EASI is a validated measure used in clinical practice and clinical trials to assess the 
severity and extent of AD (24). The EASI score will be assessed according to the schedule of 
trial procedures (Section 4). The assessment will be based on the condition of the disease at 
the time of evaluation and not in relation to the condition at a previous visit. 
The EASI is a composite index with scores ranging from 0 to 72, with higher values 
indicating more severe or more extensive condition. The index will be calculated as shown in 
Panel 6. Briefly, the investigator will assess the severity of 4 AD disease characteristics 
(erythema, induration/papulation, excoriation, and lichenification) on the 4 body regions 
(head/neck, trunk, upper extremities, lower extremities); severity will be assessed according 
to the scale shown in Panel 7. For each body region, a severity sum score will be calculated 
which will be multiplied by an area score (Panel 7) and by a weighting factor. The EASI score 
equals the sum of the scores obtained for each body region (Panel 6). 
The body region, severity of the disease characteristics (erythema, induration/papulation, 
excoriation, and lichenification), and the area score will be recorded in the eCRF.  
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Panel 6: Calculation of the EASI score 
Body region 
Erythema 
Induration/ 
papulation 
Excoriation 
Lichenification 
Area score 
Weighting factor 
Score 
Head/neck 
(SS   + 
   SS   + 
   SS   + 
   SS) 
×  AS 
× 0.1 
Trunk 
(SS   + 
   SS   + 
   SS   + 
   SS) 
×  AS 
× 0.3 
Upper extremities 
(SS   + 
   SS   + 
   SS   + 
   SS) 
×  AS 
× 0.2 
Lower extremities 
(SS   + 
   SS   + 
   SS   + 
   SS) 
×  AS 
× 0.4 
The EASI score is the sum of the 4 body region scores 
(range 0-72) 
Abbreviations: AS = area score; EASI = Eczema Area and Severity Index; SS = severity score. 
Modified from (25). 
Panel 7: EASI severity score scale and area score scale 
Severity score scale 
Area score scale 
0 
None/absent 
0 
0% affected area 
1 
Mild 
1 
1% to 9% affected area 
2 
Moderate 
2 
10% to 29% affected area 
3 
Severe 
3 
30% to 49% affected area 
Note: half-steps (0.5, 1.5, 2.5) are 
allowed. 
4 
50% to 69% affected area 
5 
70% to 89% affected area 
6 
90% to 100% affected area 
Abbreviations: EASI = Eczema Area and Severity Index. 
11.4.3 
Patient-reported outcomes 
The following patient-reported outcomes will be completed by the subjects at the trial site 
according to the schedule of trial procedures (Section 4): 
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•
POEM.
•
DLQI/CDLQI.
•
Eczema-related Weekly Sleep NRS.
•
Worst Weekly Pruritus NRS/Adolescent’s Pruritus NRS.
An electronic device will be supplied to each trial site in which subjects can complete the 
PROs.  
Each subject must make individual assessments relating to their perception of their disease 
and independently of the investigator and trial site staff. 
11.4.3.1 
Patient-Oriented Eczema Measure 
The POEM is a validated questionnaire used to assess disease signs, symptoms, and impact on 
sleep in atopic eczema patients in both clinical practice and clinical trials (26). The tool 
consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, 
cracking, flaking, and dryness). Subject will score how often they have experienced each 
symptom over the previous week on a 5-point categorical response scale (0 = ‘no days’; 
1 = ‘1 to 2 days’; 2 = ‘3 to 4 days’; 3 = ‘5 to 6 days’; 4 = ‘every day’). The total score is the 
sum of the 7 items (range 0 to 28) and reflects disease-related morbidity; a high score is 
indicative of a worse disease severity.  
11.4.3.2 
Dermatology Life Quality Index/Children’s Dermatology Life Quality Index 
All adult subjects will perform DLQI. The DLQI is a validated questionnaire with content 
specific to those with dermatologic conditions. It consists of 10 items addressing the subject’s 
perception of the impact of their skin disease on different aspects of their quality of life over 
the last week such as dermatology-related symptoms and feelings, daily activities, leisure, 
work or school, personal relationships, and the treatment (27). Each item is scored on a 
4-point Likert scale (0 = ‘not at all ⁄not relevant’; 1 = ‘a little’; 2 = ‘a lot’; 3 = ‘very much’).
The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality 
of life.  
All adolescent subjects (<18 years at baseline) will perform the CDLQI. The CDLQI 
questionnaire is designed and validated in subjects with dermatological conditions from 5 to 
16 years (28, 29). The CDLQI is available in text and cartoon versions (30-32). The text 
version will be used in this trial. It consists of 10 items addressing the subject’s perception of 
the impact of their skin disease on various aspects of their QoL over the last week such as 
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dermatology-related symptoms and feelings, leisure, school or holidays, personal 
relationships, sleep, and the treatment. Each item is scored on a 4-point Likert scale (0 = ‘not 
at all’; 1 = ‘only a little’; 2 = ‘quite a lot’; 3 = ‘very much’). The item on school time (item 7) 
has one additional response category ‘prevented school’, which is also scored ‘3’. The total 
score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL. 
11.4.3.3 
Eczema-related Weekly Sleep numeric rating scale 
Subjects will rate how much their eczema interfered with their sleep during the past week 
(based on a recall of sleep interference) using an 11-point NRS (Eczema-related Sleep NRS), 
using whole numbers only, with 0 indicating that it ‘did not interfere’ and 10 indicating that it 
‘completely interfered’. 
11.4.3.4 
Worst Weekly Pruritus numeric rating scale/Adolescent’s Pruritus numeric 
rating scale. 
Subjects will assess their worst itch severity over the past week (based on a recall of itch 
severity) using an 11-point NRS (Worst Weekly Pruritus NRS) with 0 indicating ‘no itch’ and 
10 indicating ‘worst itch imaginable’.  
Subjects <18 years of age at baseline will perform NRS with phrasings tailored to the 
adolescent subjects, independent of the subject’s age during the trial. 
11.5 Safety assessments 
11.5.1 
Height and weight 
The subject’s height (without shoes) and weight (in indoor clothing and without shoes) will be 
measured at the visits specified in the schedule of trial procedures (Section 4). 
Measurement of height at Week 16 (Visit 10) will be applicable only to subjects <18 years of 
age at the baseline visit. 
11.5.2 
Vital signs 
Vital signs (resting blood pressure, pulse, and body temperature) must be assessed according 
to the schedule of trial procedures (Section 4). Vital signs will be measured in a sitting or 
supine position following at least 5 minutes of rest. 
For the first 3 IMP administration visits (i.e. at Weeks 0, 2, and 4), the subjects will be 
monitored after each IMP administration for immediate drug reactions for a minimum of 
30 minutes with vital signs taken at 30 minutes or until stable, whichever is later (see 
Section 9.2). 
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If an abnormal vital sign at screening is considered to be clinically significant by the 
investigator, it will be at the discretion of the investigator if the subject should be included in 
the trial (in accordance with exclusion criterion no. 25). 
In case of abnormal findings, the vital sign measurement can be repeated approximately 
15 minutes later with subjects in a supine or sitting position to verify the first measurement. 
Should the repeated measurement result in a normal value, the measurement must be repeated 
once more. If the third measurement verifies the second (normal) value, the first measurement 
should be considered false and the second measurement should be recorded in the eCRF. If 
the third measurement confirms the first measurement (abnormal), the second measurement 
will be considered false and the first measurement should be recorded in the eCRF. 
Reporting in eCRF 
The vital signs and the date and time they were measured will be recorded in the eCRF. If 
vital signs were not assessed, a reason should be provided. Clinically significant abnormal 
vital signs at the screening visit will be documented as medical history in the eCRF. At 
subsequent visits, any clinically significant deterioration of a pre-existing condition as well as 
any new clinically significant sign, symptom, or illness will be reported as an AE in 
accordance with Section 13.3. 
11.5.3 
Laboratory testing 
11.5.3.1 
Overview 
Blood and urine samples will be collected according to the schedule of trial procedures 
(Section 4).  
The evaluations shown in Panel 8 will be performed by the central laboratory. 
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Panel 8: Clinical laboratory tests 
Chemistry 
Haematology P3
Sodium 
Potassium 
Creatinine 
Urea nitrogen 
Calcium  
Alkaline phosphatase  
Aspartate aminotransferase  
Alanine aminotransferase  
Gamma glutamyl transferase 
BilirubinP1 
Cholesterol 
LDL cholesterol 
HDL cholesterol 
Triglycerides 
Glucose (non-fasting) 
Albumin 
Protein 
Tryptase2 
Erythrocytes 
Haematocrit 
Haemoglobin 
Erythrocyte mean corpuscular volume  
Erythrocyte mean corpuscular haemoglobin 
concentration  
Leukocytes  
Neutrophils   
Neutrophils/leukocytes 
Lymphocytes  
Lymphocytes/leukocytes 
Monocytes  
Monocytes/leukocytes 
Eosinophils  
Eosinophils/leukocytes 
Basophils  
Basophils/leukocytes 
Thrombocytes  
Serology4,5 
Hepatitis B virus surface antigen 
Hepatitis B virus surface antibody 
Hepatitis B virus core antibody 
Hepatitis C virus antibody 
HIV-1 antibody 
HIV-2 antibody 
Urinalysis6
P5 
Serum pregnancy test5,7 
Protein 
Glucose 
Ketones 
Leukocytes 
Erythrocytes 
Nitrite 
Choriogonadotropin beta 
1)
If bilirubin is above upper limit of normal, direct and indirect bilirubin will also be measured.
2)
Only measured in case of suspected anaphylaxis (Section 9.2).
3)
The symbol ‘/’ included in the table represents ‘a ratio’.
4)
In case additional analysis are needed to support the interpretation of the initial test results for hepatitis B,
hepatitis C, or HIV, these will be performed by the central laboratory as applicable.
5)
Measured at screening only.
6)
Urinalysis will only be performed if considered required by the investigator based on dipstick results.
7)
Only women of childbearing potential.
Abbreviations: HDL = high density lipoprotein; HIV = human immunodeficiency virus; LDL = low density
lipoprotein. 
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11.5.3.2 
Investigator evaluation of laboratory samples 
Central laboratory 
Chemistry, haematology, serology, pregnancy tests (serum), and urinalysis (if applicable) will 
be analysed by a central laboratory which will provide results to the trial sites. The 
investigator must evaluate all results outside the reference range (‘clinically significant’ or 
‘not clinically significant’) and sign and date the evaluation. The signed and dated version 
will be filed with the investigator’s trial documentation. In case of clinically significant 
abnormal results, appropriate action, as judged by the investigator, must be taken. 
In case of an increase of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 
≥5×ULN re-sampling for alkaline phosphatase (ALP), ALT, AST, and bilirubin (BILI) should 
be done immediately, without undue delay and no later than within 72 hours from initial 
sampling time to confirm abnormalities. Re-sampling may be relevant at lower levels at the 
discretion of the investigator. In case of re-sampling, analysis should be done at central 
laboratory. 
Abnormal liver function tests of concurrent measurements of alanine aminotransferase (ALT) 
or aspartate aminotransferase (AST) ≥3×ULN and bilirubin (BILI) ≥2× ULN should be 
reported as an SAE (see Section 13.4 for reporting of SAEs). 
If a screening laboratory result is abnormal and clinically significant, it will be at the 
investigator’s discretion to decide if the subject should be included in the trial. 
A laboratory manual will be provided to the trial sites specifying the procedures for 
collection, processing, storage, and shipment of samples, as well as laboratory contact 
information specific to this trial. 
Tests performed at the trial site 
Urine samples will be tested with a dipstick according to the schedule of trial procedures 
(Section 4). It will be at the investigators discretion to decide whether a urine sample should 
be sent to the central laboratory for further analysis.  
Women of childbearing potential will have a urine pregnancy test performed at the trial site as 
shown in the schedule of trial procedures in Section 4. 
Reporting in eCRF 
It will be recorded in the eCRF if a blood sample was taken. If not, a reason should be 
provided. The investigator’s assessment of the results (‘normal’, ‘abnormal, not clinically 
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significant’, ‘abnormal, clinically significant’) will be recorded in the eCRF. 
Site staff will record in the eCRF if a urine dipstick was performed and whether urinalysis is 
required for further assessment, as judged by the investigator. If so, a urine sample should be 
sent to the central laboratory. If the urine sample was not tested with a dipstick, a reason will 
be provided. In case urinalysis is performed, the investigator’s assessment of the results 
(‘normal’, ‘abnormal, not clinically significant’, ‘abnormal, clinically significant’) will be 
recorded in the eCRF. 
It will be recorded in the eCRF if the subject is a woman of childbearing potential and if a 
urine pregnancy test was performed. If not, a reason should be provided. Also, the date and 
the outcome of the urine pregnancy test will be recorded in the eCRF (‘positive’, ‘negative’). 
Clinically significant abnormal laboratory results at the screening visit will be documented as 
medical history in the eCRF. At subsequent visits, any clinically significant deterioration of a 
pre-existing condition will be reported as an AE. Any new clinically significant sign, 
symptom, or illness occurring after screening will be reported as an AE in accordance with 
Section 13.3. 
11.5.4 
Anti-drug antibody measurements 
Blood samples will be collected to determine levels of ADA at pre-determined time points 
according to the schedule of trial procedures (Section 4). It will be recorded in the eCRF if an 
ADA blood sample was taken; if not, a reason will be provided. 
Collection, handling, and shipment instructions for ADA blood samples are provided in a 
laboratory manual. 
Serum samples for determination of presence or absence of ADA will be analysed by a 
laboratory using a validated bioanalytical method. A tiered testing scheme will be employed, 
with the first step being screening. Samples found positive in the screening step will be tested 
in the confirmatory step. Samples confirmed positive for ADA in the confirmatory step will 
undergo endpoint titre determination and will be analysed for the presence of nAb. Details of 
the analytical method used will be described in a bioanalytical report. 
11.6 Pharmacokinetic assessments 
Blood samples for PK assessments will be collected at the time points specified in the 
schedule of trial procedures (Section 4). It will be recorded in the eCRF if the PK sample was 
taken; if not, a reason will be provided. 
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Collection, handling, and shipment instructions for PK blood samples are provided in a 
laboratory manual. 
Serum samples for determination of tralokinumab concentrations will be analysed by a 
laboratory using a validated bioanalytical method. Details of the analytical method used will 
be described in a bioanalytical report. 
11.7 Photography 
Adult subjects (age 18 years and above at the baseline visit) will be asked to participate in a 
photography component of the trial which involves digital photography assessments to 
investigate disease progression over time.  
Participation in this photography component requires that the subject provides additional 
informed consent. 
Digital colour photographs will be taken of the disease area and a representative lesion 
according to the schedule of trial procedures (Section 4). It will be recorded in the eCRF if the 
photograph(s) was taken; if not, a reason should be provided. 
All sites participating in photography will receive all photo equipment from a central 
photography vendor. Instructions for photography will be provided to the sites in a 
photography manual. Photography standards and procedures are provided to the trial sites by 
the central photography vendor.  
The trial sites must ensure that the photographs contain no other subject identifier than the 
specific subject ID number. The photographs will be transmitted electronically to the 
photography vendor using a secure file transfer protocol. 
The photographs must be included as part of the individual subject source documentation. 
LEO Pharma may at its discretion use the anonymised photographs in publications, posters, 
and similar types of information material or media targeting patients and healthcare 
professionals. The photographs may also be part of training material used for training and 
educational purposes. Steps will be taken to ensure that the identity of the subject is protected 
to the extent possible. 
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11.8 End-of-trial 
End-of-treatment form 
An end-of-treatment form will be completed in the eCRF for all subjects when they have had 
their last administration of IMP. This form will also be completed for subjects who 
permanently discontinue IMP and subjects who withdraw from trial (see Section 10.3 for 
early termination assessments). 
The following data will be collected on the end-of-treatment form: 
•
Date of last IMP administration.
•
Did the subject permanently discontinue IMP before Week 14? If yes, the primary
reason for permanent discontinuation of IMP must be recorded (see Section 10.2.1).
End-of-trial form 
An end-of-trial form must be completed in the eCRF for all assigned subjects. The end-of-trial 
form will be completed when the subject has had their last visit (that is, the safety follow-up 
visit, or early termination visit.) 
The following data will be collected: 
•
Date of last contact.
•
Did the subject attend the safety follow-up visit? If not, primary reason for not
attending safety follow-up visit must be recorded (AE, death, lost to follow-up,
withdrawal by subject, withdrawal by parent/guardian, lack of efficacy, pregnancy, or
other). If ‘AE’ or ‘other’ is selected, a specification must be provided.
11.9 Estimate of total blood volume collected 
Blood samples will be drawn for chemistry, haematology, serology, PK, ADA and pregnancy 
test (if applicable). For adult subjects, the total volume of blood to be drawn is approximately 
78 mL. If additional blood samples are required, the amount of blood drawn may be more 
than this stated value; however, the total volume of blood drawn will be less than that taken 
during a blood donation (approximately 500 mL).  
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For adolescents, the total amount of blood drawn during the trial will be approximately 
57 mL. The largest volume of blood drawn at any visit during the trial will be 22 mL, drawn 
at the screening visit. The maximum possible blood volume drawn at one visit is less than 1% 
of the total blood volume, and the maximum possible blood volume drawn within 4 weeks is 
less than 3% of the total blood volume, as recommended for the age group 0–18 years (33). 
11.10 Storage of biological samples 
The blood and urine samples for laboratory testing (chemistry, haematology, serology, PK, 
ADA and urinalysis) are only taken to ensure and monitor subject safety during this trial and 
will only be stored until the analysis is completed by the central laboratory. 
PK samples will be retained for as long as the quality of the material permits evaluation, but 
for no longer than 6 months after completion of the CTR. 
Samples for ADA and nAb evaluation will be retained for as long as the quality of the 
material permits evaluation but for no longer than 10 years after completion of the CTR. 
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12 Scientific rationale for trial design and appropriateness of 
assessments 
12.1 Scientific rationale for trial design 
This is an open-label trial to evaluate efficacy and safety of tralokinumab administered by an 
autoinjector for the treatment of moderate-to-severe AD. Adolescent subjects (age 
12-17 years) are included in the trial per FDA request. The trial also facilitates improved
convenience for patients and to reflect the intended use of tralokinumab in a real-world 
setting. The autoinjector allows a single injection of 300 mg of tralokinumab. 
The selected dose of 300 mg Q2W administered SC is based on the dosing regimen used in 
the tralokinumab phase 3 development program to demonstrate its efficacy and safety in adult 
subjects with moderate-to-severe AD. All subjects will receive an initial loading dose of 
600 mg tralokinumab. The administration of the loading dose will allow systemic 
concentrations to reach steady state faster and potentially reduce the time to onset of clinical 
effect. The serum concentrations of tralokinumab after the 600 mg loading dose have 
demonstrated not to exceed the serum tralokinumab concentrations at steady state for the 
300 mg Q2W. 
The 300 mg Q2W dose is considered safe in the adolescent population and is currently being 
investigated as part of the ongoing adolescent trial (LP0162-1334). Adolescent subjects with 
asthma have been evaluated as part of a phase 1 trial in 20 adolescents 
(trial CD-RI-CAT-354-1054) and 2 phase 3 trials (trials D2210C00007 and D2210C00008) 
including 58 adolescents. Overall, the PK parameters including maximum serum 
concentration (Cmax), time of maximum serum concentration (Tmax), and absolute clearance 
(CL/F) were largely similar to those observed in the adult population. Tralokinumab was 
well-tolerated, no SAEs were reported, and no ADA were detected after dosing. Further, the 
data from this phase 1 trial in adolescents with asthma, along with all available adult PK and 
pharmacodynamic (PD) data, were combined in a population PKPD model. This model 
supported the finding that tralokinumab PK is dose-linear and stationary with time, and that 
overall exposure and variability are similar between weight-based and non-weight-based 
dosing at the dose level of 300 mg Q2W.  
Based on interaction with FDA, the main objectives of this trial are to assess the efficacy and 
safety of tralokinumab administered by an autoinjector when used to treat subjects with 
moderate-to-severe AD. As defined in ‘other objectives’, this trial also assesses whether 
subjects can successfully self-administer the IMP.  
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It is crucial that the investigator/site staff thoroughly explains to the subject that 
self-administration is mandatory in this trial (after Visit 2) and that both investigator/site staff 
and subject feel confident that the subject can live up to the expectation in inclusion criterion 
number 4 (‘Subjects must be able and willing to self-administer tralokinumab using an 
autoinjector’) throughout the trial. Another important inclusion criterion for entry into the trial 
is a diagnosis of AD (as defined by the Hanifin and Rajka 1980 criteria for AD) (18) at 
screening and a history of AD for at least one year, to ensure correct diagnosis and rule out 
differential diagnosis. A prerequisite for inclusion into the trial is a documented history of 
topical AD treatment failure (due to inadequate response), to ensure that the subject is 
candidate for systemic treatment. 
12.2 Appropriateness of assessments 
The clinical efficacy of tralokinumab treatment will be assessed using IGA and EASI. The 
efficacy assessments are similar to the 3 pivotal trials with tralokinumab (ECZTRA 1, 2 and 
3). IGA is a key instrument used in clinical trials to rate the severity of the subject’s global 
AD. EASI is a validated measure used in clinical practice and clinical trials to assess the 
severity and extent of AD (24). The clinical efficacy of tralokinumab treatment will also be 
assessed using PROs related to disease symptoms, quality of life, general health status, and 
itch. POEM is a validated questionnaire used to assess disease symptoms in atopic eczema 
patients in both clinical practice and clinical trials (26), and is recommended by the 
Harmonising Outcome Measures for Eczema for measuring patient-reported symptoms in 
eczema trials (25). DLQI/CDLQI is a validated and widely used questionnaire designed to 
measure the quality of life of dermatological patients (27). 
Safety will be assessed using standard clinical methods of subject evaluations, such as AE 
monitoring, vital signs, and clinical laboratory measurements. Data on ADA will be collected 
and the potential for immunogenicity will be evaluated. The blood samples for determination 
of presence or absence of ADA will be analysed using a validated bioanalytical method. 
Blood concentrations of tralokinumab will be analysed using a validated bioanalytical method 
and standard PK parameters will be derived to evaluate tralokinumab exposure. 
At the baseline visit (Week 0, Visit 2) during the administration of the initial loading dose, 
subjects will be trained on the usage of the autoinjector by investigator or delegated trial staff. 
On the same day, subjects will have a choice to either self-administer the second injection 
under observation by qualified trial staff or subjects will receive both the injections by the 
investigator/trial delegate. For the rest of the treatment period, all subjects will self-administer 
a dose of 300 mg tralokinumab Q2W (2 mL). The subject’s ability to self-administer the 
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injection tralokinumab at the trial site (at Week 4 under observation by a qualified trial staff) 
and at home (at Week 8) will be assessed based on the defined sequence of use steps in 
Section 11.3. 
13 Adverse events 
13.1 Definition and classification of adverse events 
Adverse events (AEs) and serious adverse events (SAEs) are defined in Appendix 1. 
Classification of AEs in terms of severity, causality, and outcome is defined in Appendix 2. 
13.2 Collection of adverse event reports 
AE data must be collected from time of first trial-related activity after the subject has signed 
the informed consent form until subject’s completion of the trial (Sections 7.3 and 10.3). 
AEs must be assessed by a physician. 
At all visits, the subject will be asked a non-leading question by the investigator about AEs, 
e.g.: “How have you felt since I saw you last?” No specific symptoms should be asked for. It
is important that the investigator also observes the subject for any changes not reported by the 
subject and records these changes. 
Refer to Sections 11.5.1 and 11.5.3 for principles for data entry in the eCRF. 
13.3 Reporting of adverse events 
AEs reported by the subject or observed by the investigator must be recorded on the AE form 
of the eCRF and should be described in the following manner: 
The AE term must be in precise English medical terminology (that is, not necessarily the 
exact words used by the subject). Whenever possible, a specific diagnosis should be stated 
(e.g. ‘allergic contact dermatitis’). 
The duration of the AE must be reported by the start date and stop date of the event (it will be 
recorded if the event is ongoing). In addition, it will be recorded if the AE started prior to first 
administration of IMP. 
AEs must be classified in terms of severity, causality, and outcome according to the 
definitions in Appendix 2. 
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Action taken with IMP: any action taken with IMP as a consequence of the AE must be 
recorded (dose not changed, dose reduced, dose increased, drug interrupted, drug withdrawn, 
not applicable, unknown). 
Other action taken: any other action taken as a result of the AE must be recorded (none, 
concomitant medication, concurrent procedure). 
Withdrawn from trial due to this AE: it must be recorded whether the AE led to withdrawal 
from the trial.  
13.4 Reporting of serious adverse events 
The criteria that define an AE as serious (that is, an SAE) are defined in Appendix 1. SAE 
criteria are also listed on the SAE form. 
13.4.1 
Investigator reporting responsibilities 
Any SAE must be reported to LEO Pharma on the (paper) SAE form immediately, without 
undue delay and no later than 24 hoursU of obtaining knowledge. This report should contain 
amongst others an assessment of available information on seriousness, severity, causal 
relationship to the IMP, device, or trial procedure, the action taken, the outcome to date, and a 
narrative description of the course of the event. For more details regarding reporting of any 
SAE, please see the guidance text on the SAE form. 
By signing and dating the SAE form, the investigator acknowledges that he/she is aware of 
the SAE and has assessed the causal relationship of the IMP and any of the other medications 
to the SAE. 
The actual reporter, if not the investigator, should also sign and date the SAE form. 
The completed SAE form must be faxed or scanned and e-mailed to Global Safety at LEO 
Pharma using the e-mail address or fax number below: 
UGlobal Safety at LEO Pharma 
E-mail address: drug.safety@leo-pharma.com
Fax number: +45 7226 3287 
If relevant, the investigator will enclose other information with the SAE form, such as 
anonymised reports of diagnostic procedures, hospital records, autopsy reports, etc. 
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Additionally, Global Safety at LEO Pharma may request further information in order to fully 
assess the SAE. The investigator must forward such information to LEO Pharma upon request 
by fax or e-mail (see contact details above). 
The investigator must notify the local IRB(s) of SAEs, as required by current applicable 
legislation for the concerned country. 
SAEs occurring after the completion of the clinical trial (as defined in Section 7.3) should not 
be routinely sought or recorded. However, such events should be reported immediately 
without undue delay and no later than 24 hours of obtaining knowledge to Global Safety at 
LEO Pharma (see contact details above) if the investigator becomes aware of them. 
13.4.2 
LEO Pharma reporting responsibilities 
Global Safety at LEO Pharma is responsible for assessing whether an SAE is expected. The 
relevant reference safety information document for this clinical trial is: 
•
The tralokinumab investigator’s brochure, Section 7.2 edition 19 and subsequent
updates must be used.
Global Safety at LEO Pharma will notify the regulatory authorities and concerned 
investigators of SAEs according to the current applicable legislation for the concerned 
country. 
The IRB(s) will be notified of SAEs according to the current applicable legislation for the 
concerned country.  
All SAEs which are assessed as causally related to the IMP(s) by LEO Pharma (34, 35) and 
which are unexpected (serious and unexpected suspected adverse reactions [IND safety 
report]) are subject to expedited reporting to regulatory authorities and IRB(s). Investigators 
will be notified of the evolving safety profile of the IMP on an ongoing basis. 
13.5 Other events that require expedited reporting 
13.5.1 
Pregnancy 
Any pregnancy occurring after first exposure to IMP and until the subject has completed the 
trial must be reported to LEO Pharma within 24 hours of first knowledge using the (paper) 
pregnancy form (part I). All pregnancies must be followed up until delivery or termination, 
and outcome must be reported on the (paper) pregnancy form (part II) within 24 hours of first 
knowledge.  
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The completed pregnancy forms must be faxed or scanned and e-mailed to Global Safety at 
LEO Pharma. Contact details are given in Section 13.4.1. 
Pregnant subjects must immediately discontinue IMP permanently (Sections 10.2.1 and 10.3). 
13.6 Reporting of other events 
13.6.1 
Adverse events of special interest 
The AEs listed in Panel 9 are considered adverse events of special interest (AESIs) in this trial 
and will require additional details to be recorded in the eCRF. An AESI may be serious 
(requiring expedited reporting, Section 13.4) or non-serious.  
Injection site reactions could be reported at any time after dosing. If one or more signs or 
symptoms of an injection site reaction are spontaneously reported by the subject, a single AE 
will be recorded as part of the general AE reporting, with reported term either ‘injection site 
reaction’ or reflecting the most dominant sign/symptom. Additional information on all 
objective and subjective symptoms listed in Panel 10 should be provided on the AESI form 
associated with the AE. Severity and start and stop date for each sign/symptom should be 
recorded on the AESI form. If the severity of a sign/symptom changes, multiple start/stop 
dates and associated severities can be recorded on the AESI form to reflect the development 
over time. 
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Panel 9: Adverse events of special interest 
Adverse event of 
special interest 
Additional data to be included in the eCRF (if available) 
Injection site reactions 
See Panel 10 for details. 
Eczema herpeticum 
Skin findings: 
•
Lesion type (papules, vesicles, crusts, eroded pits, other).
•
Disseminated/localised.
•
Location (face, scalp, back, chest, upper limb, lower limb, genitals).
•
Present in an area with visible eczema / no visible eczema / present in
areas with and without eczema.
•
Monomorphic/polymorphic.
Confirmation of herpes simplex virus (not confirmed, PCR, viral culture, Tzanck, 
other). 
Malignancy diagnosed 
after treatment 
assignment, excluding 
basal cell carcinoma, 
localised squamous 
cell carcinoma of the 
skin, and carcinoma in 
situ of the cervix 
•
Histology report available.
•
Oncology assessment available.
•
Treatments (surgery, radiation, chemotherapy, other).
Skin infection 
requiring systemic 
treatment 
•
Location (face, scalp, back, chest, upper limb, lower limb, genitals).
•
Outcome of pathogenic swab (positive, negative, not performed).
Conjunctivitis 
•
Aetiology (viral, bacterial, allergic, unknown).
•
Bacterial culture outcome (for events with bacterial aetiology).
•
Diagnosis confirmed by ophthalmologist.
Keratoconjunctivitis 
•
Aetiology (infectious, non-infectious, other, unknown).
•
Bacterial culture outcome (for events with bacterial aetiology).
•
Diagnosis confirmed by ophthalmologist.
Keratitis 
•
Aetiology (infectious, non-infectious, other, unknown).
•
Bacterial culture outcome (for events with bacterial aetiology).
•
Diagnosis of herpes simplex keratitis (for events with viral aetiology).
•
Diagnosis confirmed by ophthalmologist.
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Panel 10: Adverse events of special interest – injection site reaction 
Adverse event of 
special interest 
Additional data to be collected 
Injection site reactions 
Objective signs 
Erythema 
•
Largest diameter (mm)
Swelling/Oedema 
•
Largest diameter (mm)
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Bruising/Haematoma 
•
Largest diameter (mm)
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Induration 
•
Largest diameter (mm)
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Other 
•
Description
•
Largest diameter (mm)
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Subjective symptoms 
Itch 
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Pain/Burning/Stinging 
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
Other 
•
Description
•
Effect on activity
o
Does not interfere with activity
o
Interferes with activity
o
Prevents daily activity
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13.6.2 
Medication error 
Medication error refers to any unintentional error in the dispensing or administration of an 
IMP.  
Medication errors include accidental overdose or underdose, inappropriate schedule of 
product administration, incorrect route of product administration, and expired product 
administered.  
Accidental overdose or underdose where a clinical consequence occurred or could have 
occurred should be recorded based on investigator judgement. An overdose is defined as a 
subject receiving a quantity of IMP which is in excess of that specified in this protocol.  
Medication errors where a clinical consequence occurred or could have occurred should be 
recorded based on investigator judgement. For recording of treatment non-compliance where 
no clinical consequence occurred or could have occurred, see Section 9.8.4. 
Medication error must be recorded on the AE form in the eCRF. In addition, any clinical 
consequences of the medication error must be recorded as separate AEs on the AE form. If the 
AE originating from the medication error qualifies as an SAE, expedited reporting is required 
(Section 13.4). 
If the medication error is due to a device deficiency, the device deficiency must be reported as 
a product complaint as described in Section 9.10. 
13.6.3 
Misuse or abuse 
The terms misuse and abuse are similar in that they both represent the intentional use of a 
drug in a way other than defined in the protocol. 
Misuse refers to situations where the IMP is intentionally and inappropriately used for 
therapeutic purposes not in accordance with the protocol. 
Abuse refers to intentional use of an IMP for what could be considered desirable 
non-therapeutic effects (e.g. sedative, stimulant, euphoric effects). 
Misuse and abuse must be recorded on the AE form in the eCRF. In addition, any clinical 
consequence of misuse or abuse must be recorded as separate AE on the AE form. If the AE 
originating from the misuse or abuse qualifies as an SAE, expedited reporting is required 
(Section 13.4). 
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13.6.4 
Aggravation of condition 
Any clinically significant aggravation/exacerbation/worsening of any medical condition(s), 
compared with screening, must be reported as an (S)AE in accordance with Sections 13.3 and 
13.4. AD is a fluctuating disease with possible periods of remission. In case of 
relapses/recurrences, only aggravations/exacerbations exceeding normal disease fluctuation or 
lesions appearing in a body area normally not affected by AD should be reported as an AE. 
13.7 Follow-up for final outcome of adverse events 
During the trial, the investigator should follow up for final outcome on all AEs (including 
SAEs). Once a subject leaves the clinical trial, the investigator should follow up on the 
outcome of all non-serious AEs classified as possibly or probably related to the IMP for 
2 weeks or until the final outcome is determined, whichever comes first. Non-serious AEs 
classified as not related to the IMP do not need to be followed up for the final outcome.  
All SAEs must be followed up until a final outcome has been established, that is, the 
follow-up may continue beyond the end of the clinical trial. For SAEs which have stabilised 
and from which the subject cannot be expected to recover during the trial or the safety 
follow-up periods, e.g. chronic or stabilised conditions, the final outcome at the investigator’s 
discretion should be reported as ‘recovering/resolving’ or ‘not recovered/not resolved’. In 
addition, a statement detailing why the subject cannot be expected to recover during the trial, 
e.g. that the SAE has stabilised or is chronic, should be added to the narrative description of
the SAE on the SAE form. 
13.8 Handling of an urgent safety measure 
An urgent safety measure is a measure taken to implement an action/protocol deviation under 
an emergency. This is defined as “…the occurrence of any new event relating to the conduct 
of the trial or the development of the investigational medicinal product where that new event 
is likely to affect the safety of the subjects, the sponsor and the investigator shall take 
appropriate urgent safety measures to protect the subjects against any immediate 
hazard.” (36) . 
If the investigator becomes aware of information that requires an immediate change in a 
clinical trial procedure or a temporary halt of the clinical trial to protect clinical trial subjects 
from any immediate hazard to their health and safety, the investigator can do so without prior 
approval from LEO Pharma, regulatory authorities, or IRBs. 
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The investigator must immediately inform LEO Pharma – by contacting the clinical project 
manager or medical expert via the CRA – of this change in a clinical trial procedure or of the 
temporary halt; the investigator will provide full details of the information and the 
decision-making process leading to the implementation of the urgent safety measure. 
LEO Pharma must act immediately upon receipt of the urgent safety measure notification in 
accordance with internal procedures and local legislation.
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14  Statistical methods 
14.1 Sample size 
Approximately 130 subjects, of which approximately 30 subjects will be adolescents, will be 
assigned to treatment. This is considered sufficient to allow an evaluation of the efficacy of 
tralokinumab. 
Assuming IGA 0/1 and EASI75 response rates of 19% and 29% at Week 16, respectively, a 
sample size of 130 subjects will give a standard error of 3.44% and 3.98%, and thus a 
half-width for the 95% CIs of 6.74% and 7.80% for each of the primary endpoints. 
14.2 Trial analysis sets 
All screened subjects will be accounted for in the CTR. 
All subjects who receive IMP will be included in the full analysis set (FAS) and the safety 
analysis set. Exclusions from the FAS can be considered in special cases as described in 
ICH E9, Section 5.2.1., Full Analysis Set. If it is decided to exclude a subject who has 
received IMP from the FAS, a justification addressing ICH E9 will be given. 
The decisions regarding inclusion/exclusion of subjects or subject data from the trial analysis 
sets will be documented in the analysis set definition document. 
14.3 Statistical analysis 
All results will be presented for the total cohort of subjects as well as for adults and 
adolescents, separately. 
14.3.1 
Disposition of subjects 
The reasons for permanent discontinuation of IMP and for withdrawal from trial will be 
presented for all subjects assigned to treatment. Furthermore, the number of subjects not 
trained in self-injection at baseline and the reasons for this will be presented for all subjects 
assigned to treatment. 
In addition, plots of the cumulative proportions of subjects who discontinue IMP or withdraw 
from trial over time will be presented overall and by reason.  
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14.3.2 
Demographics and other baseline characteristics 
Descriptive statistics of demographics, baseline disease characteristics, and other baseline 
characteristics will be presented for all subjects assigned to treatment. 
Demographics include age, sex, race, and ethnicity. Baseline disease severity characteristics 
include IGA and EASI scores, BSA, Eczema-related Weekly Sleep NRS, and Worst Weekly 
Pruritus NRS/Adolescent’s Pruritus NRS. Other baseline characteristics include vital signs 
(including weight, body mass index), duration of AD, concurrent diagnoses (from medical 
history and indications for concomitant medication), concomitant medication, and previous 
AD treatments. 
14.3.3 
Exposure and treatment compliance 
Exposure to treatment will be presented for the safety analysis set as days of exposure in total. 
Days of exposure will be calculated as the number of days from the date of the first IMP dose 
to the date of the end of treatment visit, or – if the end of treatment visit is missing – to the 
date of permanent discontinuation of IMP. 
Treatment compliance will be presented for the safety analysis set. Adherence to treatment 
regimen will be recorded in the eCRF. The log of drug administration may be used as source. 
14.3.4 
Rescue treatment 
Rescue treatment will be defined by the following algorithm: Concomitant medications with 
‘Dermatitis atopic’ or ‘Dermatitis infected’ as the preferred term for the indication and either 
of the following: 
•
ATC2 code H02 or D07.
•
ATC4 code D11AH
•
Preferred name delgocitinib, crisaborole, methotrexate, ciclosporin, azathioprine,
mycophenolate-mofetil, mycophenolate-sodium, mycophenolate-acid, ruxolitinib or
dupilumab.
As described in Section 9.5, investigators should make every attempt to conduct efficacy and 
safety assessments immediately before administering any rescue treatment. Therefore, if 
rescue medication has start date the same day as an efficacy assessment, then it is assumed 
that the assessment is not influenced by rescue treatment. 
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Rescue treatment will be summarised for the treatment period. In addition, a summary table of 
rescue treatment by type (topical and systemic) and by overall group (corticosteroids, 
immunosuppressants, and other) will be made for the treatment period. 
14.3.5 
Testing strategy  
There will be no formal testing. All CIs will be presented with a two-sided 95 % degree of 
confidence.  
CIs for binary endpoints will be based on a normal approximation. 
14.3.6 
Estimand strategy 
The primary endpoints will be analysed using a composite estimand strategy to handle the 
occurrence of two intercurrent events considered to affect the interpretation of the estimates of 
the endpoints: 
•
Initiation of rescue treatment: This event occurs when a subject initiates rescue
treatment. This event can occur at the discretion of the investigator as described in Section
5.4. The timing of the event is defined as the date of initiation of the rescue treatment
recorded in the eCRF.
•
Permanent discontinuation of IMP: This event occurs when a subject is permanently
withdrawn from treatment or the trial as described in Section 10.2.1. This event can occur
at the subject's own initiative, at the discretion of the investigator or the sponsor as
described in Section 10.2.1 or if the subject is lost to follow-up. The timing of the event is
defined as the date of last IMP administration recorded in the eCRF.
The composite estimand evaluates the response rate without initiation of rescue treatment or 
permanent discontinuation of IMP. For subjects who received rescue treatment prior to Week 
16 or who have permanently discontinued IMP prior to Week 16, observed data after the 
intercurrent events will be considered non-response, reflecting an assumption that initiation of 
rescue treatment or permanent discontinuation of IMP indicates either failure of the treatment 
to achieve response or that a possible positive response is not attributable to the treatment 
alone. Missing data for subjects who do not attend the Week 16 visit and where rescue 
medication has not been used, nor the subject has permanently discontinued IMP, will be 
imputed as non-response.  
Binary efficacy endpoints will be analysed using the same estimand strategy as for the 
primary endpoints. The endpoints on successful self-injection will be analysed using the 
principles of estimands in ICH E9(R1) targeting the estimand attributes (population, variable, 
intercurrent event, and population-level summary) (37), while continuous efficacy endpoints 
will be presented as observed. 
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14.3.7 
Analysis of primary endpoints 
The primary endpoints (IGA 0/1 at Week 16 and EASI75 at Week 16) will be analysed using 
the composite estimand strategy (see Section 14.3.6) to handle the occurrence of intercurrent 
events (initiation of rescue medication or permanent discontinuation of IMP). Subjects with 
missing data will be imputed as non-responders.   
Number and percentage of subjects achieving response will be presented together with the 
corresponding 95% CI. 
The analyses will be based on the FAS. 
14.3.8 
Analysis of secondary endpoints 
The secondary endpoint, number of treatment-emergent AEs from baseline up to Week 16, 
and the analysis of this is covered in Section 14.3.12. 
The secondary endpoint, presence of treatment-emergent ADA from baseline to Week 16, and 
the analysis of this is covered in Section 14.3.14. 
14.3.9 
Analysis of other endpoints related to subject self-administration 
The number and percentage of subjects with successful IMP self-administration when 
observed in clinic at Week 4 will be presented together with the corresponding 95% CI. The 
analysis will be based on the population of subjects who have been trained on the usage of the 
autoinjector by the investigator or delegated trial staff, have tried self-injection at least once, 
and have not permanently discontinued IMP prior to Week 4. Subjects with missing data at 
Week 4 will be excluded from the analysis.  
The successful IMP self-administration when administered at home at Week 8, will be 
analysed in the same way as for the endpoint at Week 4 with the modification that subjects 
must not have permanently discontinued IMP prior to Week 8. 
All data captured to assess subject’s ability to self-administer tralokinumab using the 
autoinjector will be presented descriptively as observed by week. 
14.3.10 
Analysis of other binary endpoints 
Other binary efficacy endpoints (EASI50 and EASI90 at Week 16, reduction in Worst Weekly 
Pruritus NRS/Adolescent’s Pruritus NRS of at least 4 from baseline to Week 16, and 
reduction in POEM, and DLQI/CDLQI of at least 4 from baseline to Week 16 in adults and at 
least 6 from baseline to Week 16 in adolescents) will be analysed using the composite 
estimand strategy in the same way as for the primary endpoints. 
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14.3.11 
Analysis of other continuous endpoints and patient-reported outcomes 
Other continuous efficacy endpoints (change in Eczema-related Weekly Sleep NRS, Worst 
Weekly Pruritus NRS/Adolescent’s Pruritis NRS, DLQI/CDLQI and POEM from baseline to 
Week 16 and percentage change in EASI from baseline to Week 16) will be presented as 
observed, thus irrespectively of intercurrent events, while all PROs will be summarised by 
visit using descriptive statistics. 
The DLQI will be analysed and presented for adult subjects only, and the CDLQI score will 
be analysed and presented for adolescent subjects only.  
Analysis and data presentation will be based on the FAS. 
14.3.12 
Analysis of safety 
The analysis of safety will be based on the safety analysis set. 
14.3.12.1 
Adverse events 
AEs will be coded during the course of the trial according to Medical Dictionary for 
Regulatory Activities (MedDRA). AEs will be presented by preferred terms and primary 
system organ class (SOC). 
Treatment-emergent AEs will be summarised; however, all AEs recorded during the course of 
the trial will be included in subject data listings. An event will be considered 
treatment-emergent if started after the first use of IMP. The tabulations described in the 
following will only include the treatment-emergent events. In each of the tabulations, AEs are 
defined by MedDRA preferred terms within their primary SOC. 
An overall summary of the number (percentage) of AEs, the rate of AEs (number of AEs per 
100 patient-years of observation time), and the number (percentage) of subjects with any 
treatment-emergent AEs, deaths, SAEs, premature discontinuations from IMP and/or 
withdrawals from the trial due to AEs, treatment-related AEs, and severe AEs will be 
presented. 
The number (percentage) of AEs, rate of AEs, and number of subjects with each type of AEs 
will be tabulated. 
The severity and causal relationship to IMP or device for each type of AE will be tabulated. In 
addition, for the AESI injection site reactions, a separate severity grading derived from the 
data collected according to Panel 10 will be tabulated. 
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Related AEs are defined as AEs for which the investigator has not described the causal 
relationship to IMP as ‘not related’. The number of related AEs and the number of subjects 
with each type of related AE will be tabulated.  
SAEs and AESIs will be evaluated separately. A narrative for each SAE will be given. 
AEs leading to withdrawal from trial or permanent discontinuation of IMP and AESIs will be 
tabulated and listed. 
No narratives will be given unless the events are considered as SAEs. 
14.3.12.2 
Vital signs  
The change in vital signs (resting blood pressure, pulse, and body temperature) from baseline 
to each site visit will be summarised as mean, standard deviation (SD), median, minimum, 
and maximum values. 
14.3.12.3 
Clinical laboratory evaluation 
The change in each of the laboratory parameters from baseline to Week 16 will be 
summarised as mean, SD, median, minimum, and maximum values. 
Laboratory parameters will be classified as ‘low’, ‘normal’, or ‘high’, depending on whether 
the value is below, within, or above the reference range, respectively. A shift table will be 
produced showing the categories at baseline against those at end of treatment. Subjects with 
laboratory parameters outside the reference range will be listed. 
14.3.13 
Pharmacokinetic analysis 
All the PK samples in the trial are trough samples. The trough concentration (Ctrough) will be 
listed and descriptive statistics will be applied. 
14.3.14 
Anti-drug antibodies 
The presence of treatment-emergent ADA from baseline to Week 16 is a secondary endpoint 
included to assess the safety and tolerability (immunogenicity) of tralokinumab. 
ADA status (positive versus negative) at each site visit will be summarised. If considered 
relevant, descriptive statistics including number of subjects, mean, SD, median, 1st quartile, 
3rd quartile, and range of the actual ADA titres and visit will be provided. The ADA status 
across the trial for each subject (positive versus negative) will also be classified and 
summarised. 
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The association of ADA status across the trial (positive versus negative) with AEs/SAEs may 
be evaluated. In addition, the association of ADA titres (≥ median titre in positive subjects 
versus < median titre) with AE/SAEs may be evaluated for ADA positive treated subjects 
only. 
The ADA status will be categorised as follows: 
•
Positive
1. Pre-existing: ADA positive at baseline, no post-baseline ADA response ≥4-fold over
baseline titre level, and at least 1 non-missing post-baseline ADA assessment.
2. Treatment-boosted: ADA positive at baseline and at least 1 post-baseline ADA response
≥4-fold over baseline titre level.
3. Treatment-emergent: ADA negative or missing at baseline and at least 1 positive post-
baseline ADA response.
•
Perishing
4. ADA positive at baseline, all post-baseline ADA assessments negative
•
Negative
5. ADA negative or missing at baseline, all post-baseline ADA assessments negative
•
No post-baseline ADA assessment
For subjects who develop ADA and are considered treatment boosted or treatment emergent, 
the IGA score, change in EASI at end of treatment, and titre information will be listed. 
Evaluations of nAb will be conducted on those serum samples that test positive for ADA. The 
test sample is deemed positive or negative for the presence of nAb to tralokinumab relative to 
a pre-determined (in assay validation), statistically derived cut point. 
14.3.15 
Interim analysis 
An interim CTR including only adult subjects will be considered to support submission for 
marketing approval of tralokinumab. 
14.3.16 
General principles 
All CIs will be presented with 95% degree of confidence, unless otherwise specified. 
An observed-cases approach will be used for tabulations of data by visit (that is, involving 
only those subjects who attended each specific visit). 
Categorical data will be summarised using the number and percentage of subjects in each 
category. Continuous data will be summarised using the mean, median, SD, minimum, and 
maximum values. 
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Any changes from the statistical analyses planned in this clinical trial protocol will be 
described and justified in a protocol amendment, the statistical analysis plan, and/or in the 
CTR, dependent on the type of change. 
14.3.17 
Handling of missing values 
Procedures for handling of missing values are included under the sections describing the 
individual analyses. 
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15 References 
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Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122.
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May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH, Dodd AJ, Corkill
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neutralizing antibody, for the treatment of severe uncontrolled asthma. Br J
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Thom G, Minter R. Optimization of CAT-354, a therapeutic antibody directed against
interleukin-13, using ribosome display. Methods Mol Biol. 2012;805:393-401.
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Blanchard C, Mishra A, Saito-Akei H, Monk P, Anderson I, Rothenberg ME.
Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation
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2005;35(8):1096-1103.
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ICH. International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use: Integrated Addendum to ICH E6(R1): Guideline for
Good Clinical Practice. (E6)(R2), Step 4; 09-Nov. 2016.
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Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol.
1980;60(92):44-47.
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Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for
reporting parallel group randomised trials. BMC Med. 2010;8:18.
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Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, Motala C,
Ortega Martell JA, Platts-Mills TA, Ring J, et al. Revised nomenclature for allergy for
global use: Report of the Nomenclature Review Committee of the World Allergy
Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832-836.
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Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A,
Brown SG, Camargo CA, Cydulka R, Galli SJ, et al. Second symposium on the
definition and management of anaphylaxis: summary report--Second National Institute
of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.
J Allergy Clin Immunol. 2006;117(2):391-397.
22.
European Commission. EudraLex: The Rules Governing Medicinal Products in the
European Union. Guidelines for good manufacturing practices for medicinal products
for human and veterinary use. 2010;Volume 4.
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Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification
Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the
FDA's pediatric suicidal risk analysis of antidepressants. Am J Psychiatry.
2007;164(7):1035-1043.
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Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area
and severity index (EASI): assessment of reliability in atopic dermatitis. EASI
Evaluator Group. Exp Dermatol. 2001;10(1):11-18.
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HOME. Harmonising Outcome Measures for Eczema. Eczema Area and Severity
Index (EASI) case report form. Aged 8 and over. 2017.
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Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure:
development and initial validation of a new tool for measuring atopic eczema severity
from the patients' perspective. Arch Dermatol. 2004;140(12):1513-1519.
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Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical
measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210-216.
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Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index
(CDLQI): initial validation and practical use. Br J Dermatol. 1995;132(6):942-949.
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29.
Salek MS, Jung S, Brincat-Ruffini LA, MacFarlane L, Lewis-Jones MS, Basra MK,
Finlay AY. Clinical experience and psychometric properties of the Children's
Dermatology Life Quality Index (CDLQI), 1995-2012. Br J Dermatol.
2013;169(4):734-759.
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Holme S, Man I, Sharpe J, Dykes P, Lewis‐Jones M, Finlay A. The Children's
Dermatology Life Quality Index: validation of the cartoon version. Br J Dermatol.
2003;148(2):285-290.
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Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in
children with skin disease and children with other chronic childhood diseases. Br J
Dermatol. 2006;155(1):145-151.
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Clayton TH, Clark SM, Britton J, Pavlov S, Radev S. A comparative study of the
Children's Dermatology Life Quality Index (CDLQI) in paediatric dermatology clinics
in the UK and Bulgaria. J Eur Acad Dermatol Venereol. 2007;21(10):1436-1437.
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Ethical considerations for clinical trials on medicinal products conducted with minors.
Recommendations of the expert group on clinical trials for the implementation of
Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use.
2017.
34.
FDA. The Food and Drug Administration. Guidance for Industry and Investigators.
Safety Reporting Requirements for INDs and BA/BE Studies. 2012.
35.
FDA. The Food and Drug Administration. Guidance for Clinical Investigators,
Sponsors, and IRBs. Adverse Event Reporting to IRBs - Improving Human Subject
Protection. 2009.
36.
European Parliament Union, European CoT. Directive 2001/20/EC of the European
Parliament and of the Council of 4 April 2001 on the approximation of the laws,
regulations and administrative provisions of the Member States relating to the
implementation of good clinical practice in the conduct of clinical trials on medicinal
products for human use. 2001.
37.
ICH. International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use: Estimands and Sensitivity Analysis in Clinical Trials
Addendum. (E9)(R1), Step 2; 16-Jun. 2017.
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38.
ICH. International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use: Clinical Safety Data Management. Definitions and
Standards for Expected Reporting (E2A), Step 4; 27-Oct. 1994.
39.
WMA. World Medical Association. Declaration of Helsinki – ethical principles for
medical research involving human subjects. Amended by the 64th WMA General
Assembly, Fortaleza, Brazil. 2013.
40.
CIOMS. International Ethical Guidelines for Health-related Research Involving
Humans. Council for International Organizations of Medical Sciences. 4th. Geneva.
2016.
41.
ICH. International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use. Integrated addendum to ICH E6(R1): Guideline for
good clinical practice E6(R2). 2016.
42.
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Principles for Responsible Clinical Trial Data Sharing. 2013.
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Appendix 1: Definitions of adverse events and serious adverse events 
Adverse event definition 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavourable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product (38). 
This definition includes: 
•
Accidental injuries.
•
Events related to trial procedures.
•
Reasons for any unfavourable and unplanned change in medication (drug and/or dose).
•
Clinically significant worsening of pre-existing conditions.
•
Reasons for admission to hospital or surgical procedures*.
•
AEs commonly observed and AEs anticipated based on the pharmacological effect of
the IMP.
•
Any laboratory abnormality assessed as clinically significant by the investigator (see
Section 11.5.3.2).
Serious adverse event definition 
An SAE is any untoward medical occurrence that: 
•
Results in death.
•
Is life-threatening – at risk of death at the time of the SAE (not an event that
hypothetically might have caused death if more severe).
•
Requires in-patient hospitalisation or prolongation of existing hospitalisation*.
•
Results in persistent or significant disability or incapacity.
•
Is a congenital anomaly or birth defect.
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•
Is a medically important condition. Events that may not be immediately
life-threatening or result in death or hospitalisation but may jeopardise the subject or
may require intervention to prevent one of the other outcomes listed in the definition
above. Examples are intensive treatment in an emergency room or at home for allergic
bronchospasm, blood dyscrasias, and convulsions that do not result in hospitalisation,
development of drug dependency, or drug abuse.
Additionally, all malignancies, including skin malignancies, should be reported as SAEs. 
*Hospitalisation for procedures or treatments planned prior to the subject consented to trial
participation do not constitute an AE and should therefore not be reported as AE or SAE. 
*Hospitalisation for elective treatment of a pre-existing condition which did not worsen from
the subject consented to trial participation is not considered an AE and should therefore not be 
reported as AE or SAE, even if not planned before consent to trial participation. 
*Hospitalisation for routine scheduled treatment or monitoring of the studied indication not
associated with any aggravation of the condition do not constitute an AE and should therefore 
not be reported as AE or SAE. 
*Hospitalisation for administrative, trial-related or social purpose do not constitute an AE and
should therefore not be reported as AE or SAE. 
*Complications that occur during hospitalisation are (S)AEs. If a complication prolongs
hospitalisation, the event is an SAE. 
*When in doubt as to whether hospitalisation occurred or was necessary, the AE should be
considered serious. 
Definition of adverse events of special interest 
An AESI (serious or non-serious) is an event type of scientific and medical concerns specific 
to the product or development program, for which additional monitoring may be appropriate. 
Such an event might warrant further investigation in order to characterize and understand it. 
AESIs are described in Section 13.6.1. 
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Appendix 2: Classification of adverse events 
Severity 
The severity of the AE should be described in terms of mild, moderate, or severe according to 
the investigator’s clinical judgement.  
Mild 
An AE that is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
Moderate 
An AE that is usually alleviated with additional specific therapeutic intervention. The event 
interferes with usual activities of daily living, causing discomfort, but poses no significant 
or permanent risk of harm to the subject. 
Severe 
An AE that interrupts usual activities of daily living, or significantly affects clinical status, 
or may require intensive therapeutic intervention. 
If the severity of an AE worsens, a new AE should be recorded. 
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Causality 
The causal relation of the AE to the use of the IMP should be described in terms of probably, 
possibly, or not related according to the investigator’s clinical judgement.  
Probably 
related 
Follows a reasonable temporal sequence from administration of the IMP. 
Could not be reasonably explained by the subject’s clinical state, environmental or toxic 
factors, or other therapies administered to the subject. 
Follows a known pattern of response to the IMP. 
Disappears or decreases on cessation or reduction in dose of the IMP. 
Reappears or worsens upon re-challenge. 
Possibly 
related 
Follows a reasonable temporal sequence from the administration of the IMP. 
Could also be reasonably explained by the subject’s clinical state, environmental or toxic 
factors, or other therapies administered to the subject. 
Follows a known pattern of response to the IMP. 
Not related 
Does not follow a reasonable temporal sequence from administration of the IMP. 
Is better explained by other factors like the subject’s clinical state, environmental or toxic 
factors, or other therapies administered to the subject. 
Does not reappear or worsen upon re-challenge. 
Does not follow a known pattern of response to the IMP. 
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Outcome 
The outcome of the event according to the investigator’s clinical judgement should be 
classified using the categories below. 
Recovered/ 
resolved 
The event has stopped. The stop date of the event must be recorded. 
Recovering/ 
resolving 
The subject is clearly recovering from an event. The event is not yet completely resolved. 
Not recovered/ 
not resolved 
Event is still ongoing. 
Recovered/ 
resolved with 
sequelae 
The event has reached a state where no further changes are expected and the residual 
symptoms are assumed to persist. An example is hemiparesis after stroke. 
The stop date of the event must be recorded. In case of an SAE, the sequelae should be 
specified. 
Fatal 
The subject has died as a consequence of the event. Date of death is recorded as stop date for 
the AE. 
Unknown 
Unknown to investigator, e.g. subject lost to follow-up. 
LEO Pharma definitions versus CDISC definitions 
Note that as per the above definition, LEO Pharma uses ‘recovered/resolved’ only if an event 
has actually stopped. According to the CDISC definition, the category ‘recovered/resolved’ 
also includes events which have improved. However, following the LEO Pharma definitions 
above, such an improved event will instead be classified as ‘not recovered/not resolved’ or 
‘recovering/resolving’. 
Similarly, it should be noted that as per the above definition, LEO Pharma uses 
‘recovered/resolved with sequelae’ only if an event has reached a state where the residual 
symptoms are assumed to persist. According to CDISC, an event is considered ‘with 
sequelae’, if it has ‘retained pathological conditions’. Consequently, it is likely that some of 
the events classified by LEO Pharma with the outcome ‘recovered/resolved with sequelae’ 
could have been classified with the outcome ‘recovered/resolved’ according to the CDISC 
definition. 
In summary, the definitions used by LEO Pharma are more conservative than those used by 
CDISC.  
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Appendix 3: Trial governance considerations 
Appendix 3A: Regulatory and ethical considerations 
This trial will be conducted in accordance with the protocol and with the following: 
•
Consensus ethical principles derived from international guidelines including the
current version of the Declaration of Helsinki (39) and Council for International
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines (40).
•
Current version of applicable International Council for Harmonisation Good Clinical
Practice (ICH GCP) Guidelines (41).
•
EU General Data Protection Regulation 2016/679 of 27 April 2016.
•
Applicable laws and regulations.
The appropriate regulatory authority (FDA) must be notified of/approve the clinical trial as 
required. 
Any documents that the IRB may need to fulfil its responsibilities (such as the trial protocol, 
protocol amendments, investigator’s brochure [as applicable], subject information sheet, and 
informed consent form(s), or advertisements) will be submitted to the IRB. These documents 
must be reviewed and approved by the IRB before the trial is initiated. 
Any amendments to the protocol must be approved by/receive favourable opinion from 
relevant regulatory authorities and IRBs, as required, prior to implementation. 
The principal investigator will be responsible for the following, if required by local 
legislation: 
•
Providing written summaries of the status of the trial to the IRB annually or more
frequently in accordance with the requirements, policies, and procedures established
by the IRB.
•
Notifying the local IRB of SAEs or other significant safety findings as required by
IRB procedures.
•
Providing oversight of the conduct of the trial at the trial site and ensuring adherence
to applicable national and international legislation.
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Appendix 3B: Informed consent process 
Subjects and the subject’s legally authorised representative, if applicable, will receive written 
and verbal information concerning the clinical trial. This information will emphasise that 
participation in the clinical trial is voluntary and that the subject may withdraw from the 
clinical trial at any time and for any reason. All subjects and subjects’ legally authorised 
representative(s) will be given an opportunity to ask questions and will be given sufficient 
time to consider before consenting. 
The subject’s signed and dated informed consent to participate in the clinical trial (or their 
legally authorised representative’s signed and dated informed consent, if applicable) will be 
obtained prior to any clinical trial-related procedure being carried out in accordance with 
ICH GCP and all applicable laws and regulations. The authorised person obtaining the 
informed consent must also sign the informed consent form (ICF). The subject’s decision not 
to participate or to withdraw will be respected, even if consent is given by the subject’s 
legally authorised representative(s). 
Subjects and their legally authorised representative(s) (if applicable) will be re-consented to 
the most current version of the ICF(s) during their participation in the trial, if applicable. A 
copy of the ICF(s) must be provided to the subject or the subject’s legally authorised 
representative (if applicable). 
Adolescent subjects must give their written assent as appropriate and according to national 
laws and regulation. The subject’s signed and dated informed assent to participate in the 
clinical trial must be obtained prior to any clinical trial-related procedure being carried out in 
accordance with ICH GCP (Section 4.8) and all applicable laws and regulations. The 
adolescent subject will be re-consented to the most current version of the ICF(s) during the 
trial, if applicable and in accordance with national laws or regulations. A copy of the ICF(s) 
must be provided to the adolescent subject in accordance with national laws or regulations. 
Subjects who become of legal age during the trial will be consented to the most current 
version of the ICF for adult subjects, if required by national laws or regulations. 
Subsequently, these subjects will be re-consented to the most current version of the ICF(s) for 
adult subjects during the trial, if applicable. 
Subject card 
At screening, subjects will be provided with a card stating that they are participating in a 
clinical trial and which contains contact address(es) and telephone number(s) of relevant trial 
site staff including the number for the investigator in case of emergency situations. 
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Appendix 3C: Subject and data confidentiality 
This clinical trial protocol as well as all other information, data, and results relating to this 
clinical trial and/or to the IMP is confidential information of LEO Pharma and shall not be 
used by the investigator for purposes other than this clinical trial. 
The investigator agrees that LEO Pharma may use any and all information, data, and results 
from this clinical trial in connection with the development of the IMPs and, therefore, may 
disclose and/or transfer information, data, and/or results to other investigators, regulatory 
authorities, and/or commercial partners. 
Trial subjects will be assigned a unique identifier (subject ID) by LEO Pharma. Any subject’s 
records or datasets that are transferred to LEO Pharma will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be transferred. 
Trial subjects must be informed that their personal trial-related data will be used by LEO 
Pharma in accordance with local data protection law.   
Trial subjects must be informed and consent to that their medical records may be examined by 
clinical quality assurance auditors or other authorised personnel appointed by LEO Pharma, 
by appropriate IRB members, and by inspectors from regulatory authorities. 
Trial subjects must be informed that LEO Pharma might keep their trial-related data for as 
long as they are useful for developing treatments for the disease or other diseases and future 
research. 
Processing of personal data 
This protocol specifies the personal data on trial subjects (e.g. race, ethnicity, age, sex, health 
condition, medical history, test results, etc.) which shall be collected as part of the clinical trial 
and processed during and after trial completion.  
Personal data collected as part of the clinical trial will be transferred to/from the 
institution/investigator, LEO Pharma, and third parties acting on behalf of LEO Pharma. 
Processing of personal data on behalf of LEO Pharma requires a written agreement between 
LEO Pharma and the relevant party which covers collection, processing, and transfer of 
personal data in the clinical trial. In certain cases, an agreement on transfer of personal data 
may also be required. 
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Investigators and LEO Pharma must ensure that collection, processing, and transfer of 
personal data are in compliance with applicable legislation on data protection and privacy, 
including but not limited to the EU General Data Privacy Regulation. 
Subjects (or their legally acceptable representative) must be asked to consent to the collection, 
processing, and transfer of their personal data to EU and non-EU countries for the purpose of 
conducting the clinical trial, research and development of new or existing products/services, 
improving existing products/services, applying for marketing authorisations for 
products/services, marketing of products/services, and other related activities. 
LEO Pharma has obtained the necessary authorisations for the processing of personal data 
collected in the trial. 
Appendix 3D: Record keeping, quality control, and data handling 
Source data at trial sites 
For all data recorded, the source document must be defined in a source document agreement 
or similar document at each trial site. There must only be 1 source defined at any time for any 
data elements. 
Source data should as a general rule be recorded in the subject’s medical record or other 
defined document normally used at the trial site. Source data not normally collected as a 
routine part of the clinical practice at the site may be entered on a worksheet. Safety 
evaluations must be signed and dated by a physician. While certain AE assessments can be 
delegated to investigators with other qualifications, the diagnosis, seriousness, and causality 
of the AEs must be assessed by a physician. Clinical assessments must be signed and dated by 
the investigators. 
If the worksheet does not become part of the subject’s medical record, the following should as 
a minimum be added to the subject’s medical record: 
•
Date(s) of conducting the informed consent process, including date of
provision of subject information.
•
Subject ID.
•
The fact that the subject is participating in a clinical trial in AD involving
open-label treatment with tralokinumab for 16 weeks.
•
Other relevant medical information.
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Trial monitoring 
The trial will be monitored on an ongoing basis to verify that (i) the rights and well-being of 
the trial subjects is protected; (ii) the reported trial data are accurate, complete, and verifiable 
from source documents; and (iii) the conduct of the trial is in compliance with the currently 
approved protocol/amendment(s), ICH GCP, and all applicable regulatory requirement(s). 
The monitoring will be performed in a systematic, prioritised, risk-based approach, and as a 
combination of on-site, remote, and centralised monitoring. For more details, please refer to 
the trial-specific monitoring guideline and data review plan.  
In order to perform their role effectively, CRAs and persons involved in quality assurance and 
inspections will need direct access to source data, e.g. medical records, laboratory reports, 
appointment books, etc. If the electronic medical record does not have a visible audit trail, the 
investigator must provide the CRA with signed and dated printouts. In addition, relevant site 
staff should be available for discussions at monitoring visits and between monitoring visits 
(e.g. by telephone). 
Protocol compliance 
Protocol deviations will be documented and notified to the investigator. Protocol deviations 
will be assessed by LEO Pharma and important deviations described in the CTR. 
Sponsor audits, IRB review, and regulatory agency inspections 
The clinical trial will be subject to audits conducted by LEO Pharma or inspections from 
domestic or foreign regulatory authorities or from IRBs. Audits and inspections may take 
place during or after the trial. The investigator and the site staff as well as LEO Pharma staff 
have an obligation to cooperate and assist in audits and inspections. This includes giving 
auditors and inspectors direct access to all source documents and other documents at the trial 
site relevant to the clinical trial. This includes permission to examine, verify, and reproduce 
any records and reports that are important to the evaluation of the trial. 
If the trial site is contacted for an inspection by competent authorities, LEO Pharma must be 
notified immediately. 
Risk assessment  
In this trial, the risks to critical trial processes and data have been evaluated. 
To ensure consistent data capture with respect to investigator assessment of efficacy (IGA and 
EASI), all investigators will receive training. 
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Data quality review meetings will be held during the trial to ensure that improvements in data 
collection can be made and that mistakes are prevented on an ongoing basis. During 
monitoring, the CRA will verify that investigators work according to the protocol. 
Data handling 
Data will be collected by means of electronic data capture unless transmitted electronically to 
LEO Pharma or designee (e.g. laboratory data). The investigator or staff authorised by the 
investigator will enter subject data into an electronic CRF (eCRF). Data recorded in the eCRF 
will be accessible to the trial site and LEO Pharma personnel immediately after entry. The 
eCRF must be maintained in an up-to-date state by the trial site at all times. 
The investigator must verify the correctness of the data entered by the site by electronically 
dating and signing the eCRF. This signature information will be kept in the audit trail and 
cannot be altered. Any correction(s) made by the investigator or authorised site staff to the 
eCRF after original entry will be documented in the audit trail. Changes to data already 
approved will require re-signature by the investigator. The person making the change to the 
data, and the date, time, and reason for the change will be identified in the audit trail. 
Subject data should be entered into the eCRF no later than 5 working days after each visit, 
unless a different deadline is stated in the clinical trial agreement. Queries for discrepant data 
will be generated automatically by the system upon entry or manually by the CRA, sponsor’s 
medical expert, or the data manager. All queries will be raised electronically within the 
electronic data capture system. This systematic validation will ensure that a clean and 
consistent database is provided for the statistical analysis. 
An electronic PRO (ePRO) solution will be used to capture patient-reported data from 
questionnaires completed at the trial site. By the use of an ePRO, data will be available 
immediately after data entry and available for CRAs and site personnel, including the 
investigator, with reader access only. The ePRO system is a separate application from the 
eCRF and data captured from the eCRF and the ePRO will be stored on different servers 
during data capture. Data from both systems will be included in the final trial database. 
Recalled PROs (Eczema-related Weekly Sleep NRS, Worst Weekly Pruritus 
NRS/Adolescent’s Pruritus NRS) will be recorded for the period of 7 days before each site 
visit. 
External data transfers from vendors to LEO Pharma will be transmitted and handled via a 
secure file transfer protocol site.  
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Transmissions of data are documented in more detail in a data flow plan which is part of the 
trial master file. 
Statistical programming standards 
CDISC controlled terminology version 18-Dec-2020 was used for definition of controlled 
terminology throughout this protocol and will be used for statistical programming and output. 
Standard data tabulation model (SDTM) version 1.7 and SDTM implementation guide 
version 3.3 will be used for data tabulations.  
Archiving of trial documentation 
The investigator at each trial site must make arrangements to store the essential trial 
documents, including the investigator trial file (41). Essential trial documents must be stored 
until LEO Pharma informs the investigator that the documents are no longer to be retained, or 
longer if required by local regulations. 
In addition, the investigator is responsible for the archiving of all relevant source documents 
so that the trial data can be compared against source data after the completion of the trial (e.g. 
in case of an inspection from regulatory authorities). 
The investigator is required to ensure the continued storage of the documents even if the 
investigator leaves the trial site or retires before the end of the required storage period. 
No documents may be destroyed during the retention period without the written approval of 
LEO Pharma. No documents may be transferred to another location or party without written 
acceptance from LEO Pharma. 
The destruction process must ensure confidentiality of data and must be done in accordance 
with local regulatory requirements. 
For archiving purposes, each investigator will be supplied with an electronic copy of the 
eCRFs and ePRO data for all screened subjects at the trial site. This is done after completion 
of the trial and before access to the eCRF/ePRO is revoked. Audit trail information will be 
included. eCRFs and ePRO data must be available for inspection by authorised 
representatives from LEO Pharma, from regulatory authorities and/or IRBs. 
Appendix 3E: Registration, reporting, and publication policy 
Trial disclosure 
LEO Pharma is committed to be transparent with respect to its clinical trials. 
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Basic information of this clinical trial will be registered in the global data registry, 
www.ClinicalTrials.gov. before the first subject enters into the trial. The trial may also 
become registered in other online data registries, according to applicable law and regulations. 
Results of this clinical trial will be posted at leopharmatrials.com in accordance with LEO 
Pharma’s Position on Public Access to Clinical Trial Information no later than 6 months after 
trial completion. Trial results may also become reported in www.ClinicalTrials.gov, 
www.clinicaltrialsregister.eu, and national data registries in accordance with applicable law 
and regulations after clinical trial completion or premature termination. 
Publications 
The investigator shall be entitled to make publications of the results generated by the 
investigator in accordance with the process described here. 
A primary publication including the primary results of the trial (i.e. the results of the primary 
endpoint) may be submitted for publication within 12 months of database lock. In such case, 
LEO Pharma would be responsible for this publication. All authors (trial responsible 
employees and/or applicable investigators and advisors) must fulfil the criteria for authorship 
from the International Committee of Medical Journal Editors (ICMJE). 
The investigators may reach out to LEO Pharma to publish results that are not included in the 
primary publication. The investigator and LEO Pharma should agree on terms for data sharing 
and collaboration on such publications, as well as timing for release of the publication(s). In 
all cases, LEO Pharma retains the right to review and comment on the draft publication in due 
time before submission, but the investigator is not required to revise the draft accordingly, 
unless it discloses company confidential information or protected personal information, or 
may compromise intellectual property rights of LEO Pharma. 
LEO Pharma may give researchers outside LEO Pharma access to anonymised data from this 
trial for further research according to the principles outlined by the European Federation of 
Pharmaceutical Industries and Associations (EFPIA) (42). In that case, the researchers are 
obliged to attempt publication of the results obtained from their analyses. 
Any publication must comply with Good Publication Practice (GPP3) standards. 
Appendix 3F: Insurance 
LEO Pharma has taken out relevant insurances covering the subjects in the present clinical 
trial in accordance with applicable laws and regulations. 
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Appendix 3G: Financial disclosure 
Investigators will provide LEO Pharma with sufficient, accurate financial information as 
requested to allow LEO Pharma to submit complete and accurate financial certification or 
disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests and update this information, should any 
relevant change occur, during the course of the clinical trial and for 1 year after completion of 
the clinical trial, or for a longer period of time if required by local legislation. 
Appendix 3H: Trial and trial site closure  
Premature termination of trial or trial site 
LEO Pharma, the investigator, the IRBs, or competent authorities may decide to stop the 
clinical trial, part of the trial, or a trial site at any time, but agreement on procedures to be 
followed must be obtained. 
If a clinical trial is suspended or prematurely terminated, the investigator must inform the 
subjects promptly and ensure appropriate therapy and follow-up. As specified by applicable 
regulatory requirements, the investigator or LEO Pharma must promptly inform IRBs and 
provide a detailed written explanation. Relevant competent authorities must be informed. 
The trial must be terminated if the perception of the benefit/risk ratio (judged from clinical 
signs and symptoms, [S]AEs, and/or remarkable safety laboratory changes) becomes 
unfavourable for the continuation of the trial. 
Reasons for the premature closure of a trial site by LEO Pharma or investigator may include 
but are not limited to: 
•
Failure of the investigator to comply with the protocol, the requirements of the
IRB or local health authorities, LEO Pharma procedures, or GCP guidelines.
•
Inadequate recruitment of subjects by the investigator.
Completion of trial 
Investigators will be informed when subject recruitment is to cease. Screening activities will 
be stopped at a trial site when the total requested number of subjects for the clinical trial has 
been obtained, irrespective of the specific site’s planned inclusion number. 
Trial sites will be closed upon trial completion. LEO Pharma will undertake arrangements for 
the collection and disposal of any unused trial material that the investigator is not required to 
keep in his/her files. A trial site is considered closed when all required documents and trial 
supplies have been collected and a trial site closure visit has been performed. 
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Appendix 3I: Responsibilities 
The signatory investigator is responsible for the approval of the clinical trial protocol and 
the CTR on behalf of all clinical trial investigators and as agreed to in a signatory investigator 
agreement. 
Each participating investigator is responsible for all aspects of the clinical trial conduct at 
his/her trial site as agreed to in a clinical trial agreement.  
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Appendix 4: Hanifin and Rajka (1980) diagnostic criteria for AD (18) 
Major Features: must have 3 or more of the following: 
•
Pruritus
•
Typical morphology and distribution:
o
Flexural lichenification or linearity in adults
o
Facial and extensor involvement in infants and children
•
Chronic or chronically-relapsing dermatitis
•
Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis)
Minor Features: should have 3 or more of the following: 
•
Xerosis
•
Ichthyosis, palmar hyperlinearity, or keratosis pilaris
•
Immediate (type 1) skin-test reactivity
•
Raised serum IgE
•
Early age of onset
•
Tendency toward cutaneous infections (especially S. aureus and herpes
simplex) or impaired cell-mediated immunity
•
Tendency toward non-specific hand or foot dermatitis
•
Nipple eczema
•
Cheilitis
•
Recurrent conjunctivitis
•
Dennie-Morgan infraorbital fold
•
Keratoconus
•
Anterior subcapsular cataracts
•
Orbital darkening
•
Facial pallor or facial erythema
•
Pityriasis alba
•
Anterior neck folds
•
Itch when sweating
•
Intolerance to wool and lipid solvents
•
Perifollicular accentuation
•
Food intolerance
•
Course influenced by environmental or emotional factors
•
White dermographism or delayed blanch
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Appendix 5: Guidance for anaphylaxis diagnosis (21) 
The National Institute of Allergy and Infectious Diseases (NIAID) and Food Allergy and 
Anaphylaxis Network Guidance for Anaphylaxis Diagnosis (FAAN) define anaphylaxis as a 
serious allergic reaction that is rapid in onset and may cause death. They recognise 
3 categories of anaphylaxis, with criteria designated to capture from 80% of cases 
(category 1) to >95% of all cases of anaphylaxis (for all 3 categories). 
Clinical criteria for diagnosing anaphylaxis 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1) Acute onset of an illness (minutes to several hours) with involvement of the skin,
mucosal tissue, or both (e.g. generalized hives, pruritus or flushing, swollen
lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING: 
•
Respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced
peak expiratory flow [PEF], hypoxemia)
•
Reduced blood pressure (BP) or associated symptoms of end-organ
dysfunction (e.g. hypotonia [collapse], syncope, incontinence)
2) Two or more of the following that occur rapidly after exposure to a likely allergen for
that patient (minutes to several hours):
•
Involvement of the skin-mucosal tissue (e.g. generalized hives, itch-flush,
swollen lips-tongue-uvula)
•
Respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced
PEF, hypoxemia)
•
Reduced BP or associated symptoms (e.g. hypotonia [collapse], syncope,
incontinence)
•
Persistent gastrointestinal symptoms (e.g. crampy abdominal pain, vomiting)
3) Reduced BP after exposure to known allergen for that patient (minutes to several
hours):
•
Infants and children: low systolic BP (age specific) or greater than 30%
decrease in systolic BP
•
Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from
that person’s baseline
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Appendix 6: Short version of eligibility criteria 
Inclusion criteria 
No. 
Short version 
1 
Signed and dated informed consent has been obtained prior to any protocol-related procedures. 
2 
Age 12 years and above. 
3 
Body weight at screening of 30.0 kg or more. 
4 
Subject able and willing to self-administer tralokinumab in an autoinjector. 
5 
Diagnosis of AD (as defined by Hanifin and Rajka (1980) criteria for AD). 
6 
History of AD for 1 year or more. 
7 
History of TCS and/or TCI treatment failure (due to inadequate response or intolerance) or subjects for whom these topical AD treatments 
are medically inadvisable. 
8 
AD involvement of 10% (or more) body surface area at screening and baseline (Visit 3). 
9 
An EASI score of 12 (or more) at screening and 16 (or more) at baseline. 
10 
An IGA score of 3 or more at screening and at baseline, equivalent to moderate-to-severe AD. 
11 
Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline. 
12 
Female subjects of childbearing potential must use a highly effective form of birth control throughout the trial and for at least 16 weeks after 
last administration of IMP. 
Exclusion criteria 
No. 
Short version 
1 
Current participation in any other interventional clinical trial. 
2 
Previous randomisation in tralokinumab trials. 
3 
Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, 
cutaneous lymphoma, or psoriasis. 
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4 
Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD. 
5 
Use of tanning beds or phototherapy (NBUVB, UVB, UVA1, PUVA), within 4 weeks prior to baseline. 
6 
Treatment with immunomodulatory medications, systemic corticosteroids, or bleach baths within 4 weeks prior to baseline. 
7 
Treatment with the topical medications TCS, TCI, PDE-4 or JAK inhibitor within 2 weeks prior to baseline. 
8 
Receipt of live attenuated vaccines within 30 days prior to the date of baseline and during the trial including the safety follow-up period. 
9 
Receipt of any marketed or investigational biologic agent (e.g. cell-depleting agents or dupilumab) within 6 months prior to baseline or until 
cell counts return to normal, whichever is longer. 
10 
Subjects who have received treatment with any non-marketed drug substance within 5 half-lives prior to baseline. 
11 
Receipt of blood products within 4 weeks prior to screening. 
12 
Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period. 
13 
Known or suspected allergy or reaction to any component of the IMP. 
14 
History of any active skin infection within 1 week prior to baseline. 
15 
History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior 
to baseline. 
16 
A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to 
respond to, standard of care therapy. 
17 
History of anaphylaxis following any biological therapy. 
18 
History of immune complex disease. 
19 
History of cancer. 
20 
Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local 
standard of care. 
21 
History of any known primary immunodeficiency disorder including a positive HIV test at screening, or the subject taking antiretroviral 
medications. 
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22 
History of subject or subject’s legally authorised representative(s) of chronic alcohol/drug abuse or any condition associated with poor 
compliance, as judged by the investigator. 
23 
History of attempted suicide or at significant risk of suicide (either in the opinion of the investigator or on the C-SSRS). 
24 
Any disorder which is not stable and in the investigator’s opinion could affect the safety of the subject, influence the findings of the trial, or 
impede the subject’s ability to complete the trial. 
25 
Any abnormal finding which in the investigator’s opinion may put the subject at risk, influence the results of the trial, or influence the 
subject’s ability to complete the trial. 
26 
ALT or AST level 2.0 times the upper limit of normal or more at screening. 
27 
Positive HBsAg, HBsAb, HBcAb serology at screening. Subjects with positive HBsAb may be eligible provided they have negative HBsAg 
and HBcAb. 
28 
Positive hepatitis C virus antibody (anti-HCV) serology at screening. 
29 
Subjects who are not willing to abstain from donating blood and/or plasma from the time of informed consent and for 16 weeks (5 half-lives) 
after last dose of IMP. 
30 
Subjects who are legally institutionalised. 
31 
Female subjects who are pregnant or lactating. 
32 
Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members 
of such individuals. 
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Appendix 7: Contact list 
Contact details for the clinical project manager, CRA, and sponsor’s medical expert are 
provided to the trial sites as a separate contact list. 
Sponsor 
ULEO Pharma A/SU (referred to as ‘LEO Pharma’ or ‘the sponsor’ in this clinical trial protocol) 
is the sponsor of the clinical trial: 
LEO Pharma A/S  
Industriparken 55 
DK-2750 Ballerup 
Denmark 
Coordinating investigator 
Dr.
, MD, 
Clinical Professor, Dermatology, 
Director, Clinical Research,
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Appendix 8: COVID-19 pandemic contingency plan 
Without compromising the safety of subjects and trial integrity, it is expected that efforts are 
made to secure attendance at sites for all visits, ensuring important efficacy and safety 
assessments for the trial. 
If on-site visits are not possible due to local authority-issued preventive measures or subjects 
are unwilling to come to the trial site or are quarantined at home, the affected site will 
postpone screening and baseline visits of subjects until on-site visits can be conducted. 
Furthermore, it is a requirement that all subjects attend the first 3 dosing visits (Weeks 0, 2, 
and 4, i.e. Visits 2, 3, and 4) at the clinic according to protocol to ensure the 30 min. post-dose 
observation time for the 3 dosing visits. The primary endpoint of the trial, efficacy of 
tralokinumab administered by an autoinjector, will be assessed at the clinic at Week 16.  If 
attending the first 3 dosing visits is not possible, then the subject cannot self-administer IMP 
at home during the remainder of the trial. 
For subjects already assigned to treatment, Week 12 (Visit 8) can be done remotely via phone 
or video. At phone/video visits, no investigator assessments of efficacy will be done, but the 
following data will be collected remotely (according to the schedule of trial procedures in 
Section 4): 
•
Use of emollients
•
AE reporting.
•
Concomitant medication and concurrent procedures.
•
PROs (DLQI/CDLQI, POEM, Eczema-related Sleep NRS, Worst Weekly
Pruritus NRS/Adolescents Pruritus NRS). The subjects will receive a link to
complete the PROs in a web browser.
•
Urine pregnancy test. Women of childbearing potential will receive 1 extra
urine pregnancy test at the baseline visit to keep at home in case on-site visit
becomes impossible during the trial. The subject will perform the test at home
and inform the investigator about the result via phone before self-administering
the IMP.
In the eCRF, it will be recorded whether a visit or a given assessment was done remotely or 
not done. If not done, it will be recorded in the comments log if this was due to the 
COVID-19 pandemic. 
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It will be at the discretion of the investigator to decide whether clinical laboratory samples are 
considered necessary to ensure subject safety in periods when on-site visits are not possible. 
To ensure availability of IMP, the trial sites will dispense additional IMP if considered 
relevant (i.e. if local authority issued preventive measures are to be expected at the given trial 
site). This will allow subjects to continue treatment with IMP although they are not able to go 
to the trial site. If a subject will not be able to attend on-site visits due to the pandemic before 
running out of IMP, the trial site will ensure shipping of IMP to the subject’s home.  
If a subject is tested positive for COVID-19, the investigator will evaluate whether this is an 
AE that contraindicates further dosing, in which case the subject will permanently discontinue 
IMP as described in Section 10.2. 
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Appendix 9: Protocol amendment history 
Amendment 1 (25-Oct-2021) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
or subsequent regulation. 
Overall rationale for the amendment 
The main reason for this amendment is to change the primary objective to evaluate the 
efficacy of tralokinumab administered by an autoinjector, when used to treat subjects with 
moderate-to-severe AD. Consequently, endpoints have been rearranged. In addition, 
assessment of PK and ADA levels have been included in this trial. 
Additional changes included are also presented in the table below. Changes have either been 
summarised (written in plain text only) or marked as tracked changes (text added to the 
protocol is written in bold and deleted text has a line through it). 
Section no. and title 
Description of change 
Brief rationale 
1 Protocol synopsis 
Title of trial  
An open-label, single-arm, phase 3 trial to evaluate 
the efficacy and safety safe and effective use of an 
autoinjector for administration of tralokinumab 
administered by an autoinjector in subjects with 
moderate-to-severe atopic dermatitis. 
To align with the primary 
and secondary objectives of 
the trial. 
1 Protocol synopsis 
Short title of trial 
Efficacy and safety Safe and effective use of 
tralokinumab administered by an autoinjector in 
adults and adolescents with moderate-to-severe 
atopic dermatitis. 
To align with the primary 
and secondary objectives of 
the trial. 
1 Protocol synopsis, 6 
Trial objectives and 
endpoints 
Primary objective  
To evaluate the efficacy of tralokinumab 
administered by an autoinjector when used to 
treat subjects with moderate-to-severe AD. 
To evaluate the safe and effective use of the 
autoinjector for administration of tralokinumab. 
Primary endpoints 
•
IGA score of 0 (clear) or 1 (almost clear) at
Week 16.
•
EASI75 at Week 16.
To reflect the change in the 
primary objective of the 
trial.  
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Section no. and title 
Description of change 
Brief rationale 
Successful investigational medicinal product (IMP) 
self-administration when observed at the clinic at 
Week 4. 
Key secondary endpoint 
Successful IMP self-administration when 
administered at home at Week 8. 
1 Protocol synopsis, 6 
Trial objectives and 
endpoints 
Secondary objective 
To evaluate the safety and tolerability of 
tralokinumab administered by in an autoinjector 
when used to treat moderate-to-severe atopic 
dermatitis (AD). and administered with the 
autoinjector. 
Secondary endpoint 
•
Number of treatment-emergent adverse events
(AEs) from baseline up to Week 16.
•
Presence of treatment-emergent ADA from
baseline to Week 16.
To reflect that ADA has 
been added as a safety 
endpoint. 
1 Protocol synopsis, 
7.3 end-of-trial 
definition 
Final collection of data for the primary endpoint 
Week 16. Week 4  
To reflect the change in 
primary endpoints. 
1 Protocol synopsis, 
7.1 Overall trial 
design 
Trial design has been updated for clarification. 
To reflect the change in 
primary and secondary 
objectives of the trial. 
To clarify the subject’s 
option to self-administer the 
second injection under 
observation by qualified trial 
staff. 
To clarify that subjects will 
not transfer to the long-term 
extension trial ‘ECZTEND’, 
due to updated timelines of 
the trial. 
1 Protocol synopsis 
Main assessments 
To reflect the change in 
primary endpoints and 
addition of ADA as a safety 
endpoint. 
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Section no. and title 
Description of change 
Brief rationale 
Assessment related to primary and key secondary 
endpoints: 
•
IGA score.
•
EASI.
•
Rating of subject’s ability to self-
administer at trial site. 
•
Rating of subject’s ability to self-
administer following dosing at home. 
Assessment related to secondary endpoint: 
AEs, vital signs, laboratory tests and ADA. 
1 Protocol synopsis 
Statistical methods 
Primary endpoint: 
The primary endpoints (IGA 0/1 at Week 16 and 
EASI75 at Week 16) will be analysed using the 
composite estimand strategy to handle the 
occurrence of intercurrent events. Subjects with 
missing data will be imputed as non-responders.  
Number and percentage of subjects achieving 
response will be presented together with the 
corresponding 95% CI. 
Details on autoinjector self-administration and key 
secondary endpoints have been deleted from this 
section. 
To reflect the change in 
primary endpoints. 
4 Schedule of trial 
procedures 
Panel 2 Schedule of trial procedures 
Background treatment – initiation and 
continuation of emollients (X has been added in 
this row from week 0 to Early termination [if 
applicable] visit). 
To clarify that subjects 
should continue emollient 
use throughout the trial 
period. 
4 Schedule of trial 
procedures 
Investigator assessments of safety 
Added PK blood sampling on Weeks 4, 12, 16, and 
20. 
Added ADA blood sampling on Weeks 0, 4, 16, 
and 20. 
To align with the newly 
added assessments in the 
trial. 
6 Trial objectives and 
endpoints 
Other objective 
To assess the real-life patient handling 
experience with the use of tralokinumab 
administered with an autoinjector in patients 
with moderate-to-severe AD. 
Other endpoints 
To reflect the rearrangement 
of trial objectives. 
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Section no. and title 
Description of change 
Brief rationale 
•
Successful IMP self-administration
when observed at the clinic at Week 4
•
Successful IMP self-administration
when administered at home at Week 8.
•
IGA score of 0 (clear) or 1 (almost clear)
at Week 16. 
•
EASI75 at Week 16.
7.3 End-of-trial 
definition 
Subjects entering the long-term extension trial 
(ECZTEND) will also be considered as trial 
completers 
This is no longer applicable 
as subjects will not transfer 
to the ECZTEND trial. 
9.2 Administration of 
investigational 
medicinal product 
Text updated regarding the administration of initial 
loading dose at baseline. 
To clarify that, at baseline, 
subjects can self-administer 
the second injection under 
observation by qualified trial 
staff. 
9.8.3 Investigational 
medicinal product 
accountability 
Subjects will return trial kit cartons and any unused 
IMP at the each next site visit. 
Clarification. 
11.1 Overview, 13.2 
Collection of adverse 
event reports 
AEs must be assessed by a physician. medically 
qualified personnel 
To align with latest protocol 
template. 
11.5.4 Anti-drug 
antibody 
measurements 
This section is added for ADA blood sampling and 
assessment. 
Addition of ADA blood 
sampling in trial procedure. 
11.6 Pharmacokinetic 
assessments 
This section is added for PK blood sampling and 
assessment. 
Addition of PK blood 
sampling in trial procedure. 
11.9 Estimate of total 
blood volume 
collected 
For adult subjects, the total volume of blood to be 
drawn is approximately 78 68 mL. 
For adolescents, the total amount of blood drawn 
during the trial will be approximately 57 47 mL. 
The largest volume of blood drawn at any visit 
during the trial will be 22 12 mL, drawn at the 
screening visit. 
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Section no. and title 
Description of change 
Brief rationale 
11.10 Storage of 
biological samples 
PK samples will be retained for as long as the 
quality of the material permits evaluation, but 
for no longer than 6 months after completion of 
the CTR. 
Samples for ADA and nAb evaluation will be 
retained for as long as the quality of the material 
permits evaluation but for no longer than 10 
years after completion of the CTR. 
For information on storage 
of PK and ADA samples. 
12.2 Appropriateness 
of assessments 
This section has been updated with information on 
PK and ADA blood sampling analyses. 
To include relevant 
information on PK and ADA 
analyses. 
14 Statistical methods 
Sample size calculation has been updated. 
Statistical analyses and estimand strategy for 
primary endpoint has been updated. 
Key secondary endpoint section has been removed. 
Details regarding analyses of PK and ADA have 
been added.  
Possibility of interim analysis has been added. 
To align with rearrangement 
of endpoints. 
Appendix 8 
COVID-19 pandemic 
contingency plan 
For subjects already assigned to treatment, Week 
12 (Visit 8) Week 8 (Visit 12) can be done 
remotely via phone or video. 
Correction. 
Throughout 
Minor editorial and template related revisions. 
Minor, therefore not 
summarised. 
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Statistical Analysis Plan 
LP0162-1338 
Efficacy and safety of tralokinumab administered by an autoinjector in 
adults and adolescents with moderate-to-severe atopic dermatitis  
INJECZTRA 
Design of trial: 
Phase 3 efficacy and safety of tralokinumab administered by an autoinjector  
An open-label, single-arm, phase 3 trial to evaluate the efficacy and safety of tralokinumab 
administered by an autoinjector in subjects with moderate-to-severe atopic dermatitis 
LEO Pharma A/S 
Trial ID: 
LP0162-1338 
Date: 
26-Apr-2023
Version: 
2.0 
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Statistical analysis plan statement 
Approval statement, LEO Pharma A/S 
Electronic signatures made within LEO Pharma Clinical Vault are legally binding equivalent 
of traditional handwritten signatures. The following persons have approved this statistical 
analysis plan by using electronic signatures as presented on the last page of this document: 
, MSc Stat 
Biostatistics lead, Global Clinical Development 
, MD 
Medical lead, Global Clinical Development 
, Msc, PhD 
QC Biostatistician, Biostatistics 
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Guidance documents 
This statistical analysis plan is designed to comply with the standards issued by the 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) E3 Structure and Content of Clinical Study Reports, E6 Good Clinical 
Practice, E9 Statistical Principles for Clinical Trials, and E9(R1) Addendum on Estimands and 
Sensitivity Analysis in Clinical Trials. 
 
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Table of contents 
Statistical analysis plan statement .......................................................................................... 2 
Guidance documents ................................................................................................................ 3 
Table of contents ....................................................................................................................... 4 
List of panels ............................................................................................................................. 6 
List of abbreviations ................................................................................................................. 7 
Version history .......................................................................................................................... 9 
1 
Introduction .................................................................................................................. 10 
1.1 
Trial objectives, estimands, and endpoints ............................................................ 11 
1.2 
Trial design ............................................................................................................ 12 
2 
Testing strategy ............................................................................................................. 13 
3 
Sample size .................................................................................................................... 13 
4 
Trial analysis sets .......................................................................................................... 14 
5 
Statistical analysis ......................................................................................................... 15 
5.1 
General principles .................................................................................................. 15 
5.1.1 
Missing values ............................................................................................. 15 
5.1.2 
Trial periods and date of permanent discontinuation of IMP ...................... 15 
5.1.3 
Treatment and trial completers .................................................................... 16 
5.1.4 
Early termination and unscheduled visits .................................................... 16 
5.2 
Extent of exposure ................................................................................................. 17 
5.3 
Intercurrent events ................................................................................................. 17 
5.4 
Primary endpoints analyses ................................................................................... 18 
5.4.1 
Definition of endpoints ................................................................................ 18 
5.4.2 
Primary analyses .......................................................................................... 18 
5.5 
Secondary and other endpoints analyses ............................................................... 19 
5.5.1 
Successful subject self-administration ......................................................... 19 
5.5.2 
Other binary efficacy endpoints ................................................................... 20 
5.5.3 
Other continuous endpoints and patient reported outcomes ........................ 20 
5.6 
Pharmacokinetics analysis and antidrug antibodies............................................... 21 
5.6.1 
Pharmacokinetic analysis ............................................................................. 21 
5.6.2 
Anti-drug antibodies analysis ...................................................................... 21 
5.7 
Safety analysis ....................................................................................................... 21 
5.7.1 
Adverse events ............................................................................................. 22 
5.7.2 
Adverse events of special interest ................................................................ 22 
5.7.3 
Vital signs .................................................................................................... 25 
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5.7.4 
Clinical laboratory evaluation ...................................................................... 25 
5.8 
Subgroup analyses ................................................................................................. 26 
5.9 
Interim analysis ...................................................................................................... 26 
6 
Changes to analyses described in the protocol ........................................................... 26 
7 
Supporting documentation .......................................................................................... 29 
7.1 
Appendix 1: PRO scoring algorithms .................................................................... 29 
 
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List of panels 
Panel 1: Trial design ................................................................................................................. 13 
Panel 2: Trial analysis sets ....................................................................................................... 14 
Panel 3: Date of permanent discontinuation of IMP, exposure start and end ........................... 16 
Panel 4: Visit windows ............................................................................................................. 17 
Panel 5: Successful subject self-administration ....................................................................... 19 
Panel 6: Other binary efficacy endpoints ................................................................................. 20 
Panel 7: Other continuous efficacy endpoints .......................................................................... 21 
Panel 8: Adverse events of special interest .............................................................................. 23 
Panel 9: Adverse events of special interest - injection site reaction ......................................... 24 
Panel 10: Injection site reaction severity grading scale ........................................................... 25 
Panel 11: Changes to the analyses described in the protocol ................................................... 27 
Panel 12: PRO scoring algorithms ........................................................................................... 29 
 
 
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List of abbreviations 
AE 
adverse event 
AESI 
adverse event of special interest 
AD 
atopic dermatitis 
ADA           
anti-drug antibodies 
ADaM 
Analysis Data Model 
ADRG 
analysis data reviewer’s guide 
ASDD 
analysis set definition document 
ATC 
Anatomic Therapeutic Chemical Classification 
BSA 
body surface area 
CDISC 
Clinical Data Interchange Standards Consortium 
CDLQI 
Children’s Dermatology Life Quality Index 
CI 
confidence interval 
COVID-19 
coronavirus disease 2019 
CTP 
clinical trial protocol 
CTR 
clinical trial report 
DBL 
database lock 
Define.xml 
data definition document 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
EASI75 
at least 75% reduction in EASI score from baseline 
EASI50 
at least 50% reduction in EASI score from baseline 
EASI90 
at least 90% reduction in EASI score from baseline 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
ePRO 
electronic patient-reported outcome 
FAS 
full analysis set 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IGA 
investigator’s Global Assessment 
IMP 
investigational medicinal product 
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ISR 
injection site reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
nAb 
neutralising antibodies 
PCR 
polymerase chain reaction 
PK 
pharmacokinetic(s) 
POEM 
Patient-Oriented Eczema Measure 
PRO 
patient-reported outcome 
PT 
preferred term 
PYE 
patient years of exposure 
Q2W 
every other week 
SAE 
serious adverse event 
SAF 
safety analysis set 
SAS 
Statistical Analysis Software 
SC 
subcutaneous(ly) 
SD 
standard deviation 
SFU 
safety follow-up 
SOC 
system organ class 
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Version history 
The statistical analysis plan (SAP) for trial LP0162-1338 is based on the clinical trial protocol 
(CTP) version 3.0 dated 24-Aug-2022.  
SAP version 
Date 
Change 
Rationale 
1.0 
13-Feb-2023 
Not applicable 
Original version 
2.0 
26-Apr-2023 
Include entire trial 
period for all adult 
subjects in the interim 
analysis 
Scope of interim 
analysis changed 
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1 
Introduction 
The statistical analysis will be performed as outlined in the CTP version 3.0. This SAP, 
prepared before database lock, supplements the CTP, and contains a more technical and 
detailed elaboration of topics related to the specification and implementation of the statistical 
analysis described in the CTP. The level of detail should enable the reader to reproduce all 
statistical analyses described in the SAP and the CTP.  
Changes to the protocol-planned analyses are described/summarised in Section 6, while 
supplementary analysis specifications are elaborated in the individual sections. 
Data handling decisions and derivation rules used in the analysis datasets are specified in the 
analysis data reviewer’s guide (ADRG) and Data Definition document (define.xml). 
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1.1 
Trial objectives, estimands, and endpoints  
Objectives 
Endpoints 
Primary objective 
 
To evaluate the efficacy of tralokinumab 
administered by an autoinjector when 
used to treat subjects with moderate-to-
severe AD. 
Primary endpoints 
• 
IGA score of 0 (clear) or 1 (almost clear) at Week 16. 
• 
EASI75 at Week 16. 
Secondary objective 
 
To evaluate the safety and tolerability of 
tralokinumab administered by an 
autoinjector when used to treat 
moderate-to-severe AD. 
Secondary endpoints 
• 
Number of treatment-emergent AEs from baseline to 
Week 16. 
• 
Presence of treatment-emergent ADA from baseline to 
Week 16. 
Other objectives 
 
To assess the real-life patient handling 
experience with the use of tralokinumab 
administered by an autoinjector in 
patients with moderate-to-severe AD. 
Other endpoints 
• 
Successful IMP self-administration when observed at the 
clinic at Week 4. 
• 
Successful IMP self-administration when administered at 
home at Week 8. 
To evaluate the efficacy of tralokinumab 
administered by an autoinjector on 
severity and extent of AD, itch, and 
HRQoL in treating moderate-to-severe 
AD. 
Other endpoints 
• 
EASI90 at Week 16. 
• 
EASI50 at Week 16. 
• 
Percentage change in EASI score from baseline to 
Week 16. 
• 
Change in POEM from baseline to Week 16. 
• 
Reduction in POEM of at least 4 from baseline to 
Week 161,2/Reduction in POEM of at least 6 from 
baseline to Week 161,2. 
• 
Change in DLQI/CDLQI from baseline to Week 16. 
• 
Reduction in DLQI of at least 4 from baseline to 
Week 161,2/Reduction in CDLQI of at least 6 from 
baseline to Week 161,2. 
• 
Change in Eczema-related Weekly Sleep NRS from 
baseline to Week 16. 
• 
Change in Worst Weekly Pruritus NRS/Adolescent’s 
Pruritus NRS from baseline to Week 16. 
• 
Reduction of Worst Weekly Pruritus NRS/Adolescent’s 
Pruritus NRS of at least 4 from baseline to Week 163. 
1. Only adult subjects with a score of 4 and above and adolescent subjects with a score of 6 and above at 
baseline will be included in the analysis. 
2. For adult subjects, a response is defined as a reduction of at least 4 from baseline. For adolescent subjects, a 
response is defined as a reduction of at least 6 from baseline.  
3. Only subjects with Worst Weekly Pruritus NRS/Adolescent’s Pruritus NRS score of 4 or above at baseline 
will be included in the analyses. 
Abbreviations: AD = atopic dermatitis; ADA = anti-drug antibodies; AEs = adverse events; CDLQI =Children’s 
Dermatology Life Quality Index; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity 
Index; EASI90/EASI75/EASI50 = at least 90% / 75% / 50% reduction in EASI score; HRQoL =  health-related 
qualify of life; IGA = Investigator’s Global Assessment; IMP = investigational medicinal product; 
NRS = numeric rating scale; POEM = Patient-Oriented Eczema Measure. 
 
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The primary endpoints will be analysed using a composite estimand strategy to handle the 
occurrence of two intercurrent events considered to affect the interpretation of the estimates of 
the endpoints (initiation of rescue medication and permanent discontinuation of IMP). 
The composite estimand evaluates the response rate without initiation of rescue treatment or 
permanent discontinuation of IMP. For subjects who received rescue treatment prior to Week 
16 or who have permanently discontinued IMP prior to Week 16, observed data after the 
intercurrent events will be considered non-response, reflecting an assumption that initiation of 
rescue treatment or permanent discontinuation of IMP indicates either failure of the treatment 
to achieve response or that a possible positive response is not attributable to the treatment 
alone. Missing data for subjects who do not attend the Week 16 visit and where rescue 
medication has not been used, nor the subject has permanently discontinued IMP, will be 
imputed as non-response. 
1.2 
Trial design 
This is an open-label, single-arm, phase 3 trial, in adult and adolescent (age 12 to 17 years) 
subjects with moderate-to-severe AD. The trial is designed to evaluate the efficacy and safety 
of tralokinumab administered by an autoinjector. The trial design is illustrated in Panel 1. 
The trial will consist of a 2- to 4-week screening period, a 16-week treatment period, and a 4-
week safety follow-up period. 
Approximately 130 subjects, of which approximately 30 subjects will be adolescents are 
planned to be assigned to the treatment. The trial will be conducted at approximately 30 sites 
in US. The anticipated average number of subjects assigned to treatment per trial site is 4. 
For details on trial design, see Section 7 of the CTP. 
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Panel 1: Trial design 
 
Approximately 130 subjects, of which approximately 30 subjects will be adolescents are planned to be assigned 
to the treatment. 
Abbreviations: IMP = investigational medicinal product; Q2W = every other week; w = weeks. 
An interim CTR including only adult subjects will be made to support submission for 
marketing approval of tralokinumab. The interim analysis will be based on data collected for 
adult subjects during the trial period and performed after interim database lock (DBL). 
The primary analysis based on 100% data availability and all subjects (adults and adolescents) 
will be performed after DBL.   
2 
Testing strategy 
There will be no formal testing. 
3 
Sample size  
Sample size documentation is provided in the CTP Section 14.1.  
Approximately 130 subjects of whom approximately 30 are adolescents, will be assigned to 
treatment. 
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4 
Trial analysis sets 
All screened subjects will be accounted for in the CTR. 
All subjects assigned to treatment and who received at least 1 dose of IMP will be included in 
the full analysis set (FAS) and the safety analysis set (SAF). Exclusions from the FAS can be 
considered in special cases as described in ICH E9, Section 5.2.1., Full Analysis Set. If it is 
decided to exclude a subject who has received IMP from the FAS, a justification addressing 
ICH E9 will be given. 
The decisions regarding inclusion/exclusion of subjects or subject data from the trial analysis 
sets will be documented in the analysis set definition document ASDD (TMF-000811745).  
For the purposes of analysis, the definition of the analysis sets are listed in Panel 2. 
Panel 2: Trial analysis sets 
Trial analysis set 
Description and purpose  
Full analysis set (FAS) 
• All subjects assigned to treatment and who received at 
least 1 dose of IMP.  
• The FAS is used to analyse endpoints related to the 
efficacy objectives 
Safety analysis set (SAF) 
• All subjects assigned to treatment and who received at 
least 1 dose of IMP.  
• The SAF is used to analyse the endpoints and assessments 
related to safety, PK and ADA during the treatment period. 
Usability analysis set 
• All subjects assigned to treatment, who received at least 1 
dose of IMP and have been trained in the usage of the 
autoinjector by investigator or delegated staff at the 
baseline visit.  
• Usability analysis set will be used to analyse objectives 
related to subject self-administration. 
Safety follow-up (SFU) 
analysis set 
• All subjects for whom date of last contact is after the date 
of exposure end, where exposure end is defined as the date 
of week 16 visit for subjects completing the treatment 
period, and otherwise the date of permanent 
discontinuation of IMP for subjects not completing the 
treatment period. 
• SFU analysis set is used to analyse endpoints and 
assessments related to safety during the SFU period. 
Abbreviations: IMP = investigational medicinal product 
 
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5 
Statistical analysis 
5.1 
General principles 
The first day of dosing is considered baseline (Week 0, Visit 2). 
All CIs will be presented with 95% degree of confidence, unless otherwise specified. The 
Wilson method is used to calculate the CI for the binary endpoints, and the statistically 
method Student's t-CI is used to calculate the CI for the continuous endpoints.  
An observed-cases approach will be used for tabulations of data by visit (that is, involving 
only those subjects who attended each specific visit). 
Categorical data will be summarised using the number and percentage of subjects in each 
category. Continuous data will be summarised using the mean, standard deviation (SD), 
median, 1st quartile, 3rd quartile, minimum, and maximum values. 
5.1.1 
Missing values 
Missing baseline values will not be imputed, meaning that such subjects will be excluded 
from analyses concerning change from baseline as this cannot be derived. Unless otherwise 
specified, the baseline value is defined as the latest pre-dose assessment. 
Procedures for handling missing values that are not baseline values are included in the 
sections describing the individual analyses. 
Analysis of PK parameters will only include samples that are available, i.e. missing values 
will not be imputed. 
5.1.2 
Trial periods and date of permanent discontinuation of IMP 
The treatment period will be defined as the time from exposure start to exposure end and the 
remaining time after exposure end will be defined as the safety follow-up period. SFU period 
is only applicable for subjects where last date of contact does not equal the date of exposure 
end. 
Definition of date of permanent discontinuation of IMP, exposure start, and exposure end are 
given in Panel 3.  
 
 
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Panel 3: Date of permanent discontinuation of IMP, exposure start and end 
Time point 
Definition 
Date of permanent 
discontinuation of IMP* 
• Defined as the latest date of early termination visit (if 
existing) or date of onset of latest AE leading to 
withdrawal of IMP, otherwise date of the last visit, 
excluding SFU visit. 
Exposure start 
• Date and time of first dose. 
Exposure end 
• Date of Week 16 visit (if existing) at time 23:59:00, 
otherwise date of permanent discontinuation of IMP (if 
existing) at time 23:59:00, otherwise date of last IMP 
administration at time 23:59:00.  
*) Only defined for subjects who have a reason for permanent discontinuation of IMP recorded. 
Abbreviations: AE = adverse event, IMP = investigational medicinal product, SFU=safety follow-up 
5.1.3 
Treatment and trial completers 
A subject who has not permanently discontinued IMP before Week 16 will be defined as a 
treatment completer.  
A subject is considered to have completed the trial if they have completed all periods of the 
trial including the safety follow-up visit (Week 20). 
5.1.4 
Early termination and unscheduled visits 
When no data are available from a certain scheduled post-baseline visit for a subject, data 
from early termination visits and unscheduled visits may replace data from that scheduled 
visit in data summaries, provided the data are collected between 6 days before and 7 days 
after the planned time point for the scheduled visits, as given in Panel 4. 
When both unscheduled and early termination visits exist within the given visit window, the 
early termination visit will be selected for analysis. When no early termination visits and 
several unscheduled visits exist, the unscheduled visit closest to the target day will be selected 
for analysis. If the difference is a tie, the latest unscheduled visit will be selected. 
 
 
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Panel 4: Visit windows 
Visit (target day) 
Visit window (day is date of assessment 
minus date of first dose)   
Week 2 (Day 14) 
Day 8 to 21 
Week  (Day 7  x, where x = 4, 6, 8, …, 16) 
Day 7x-6 to 7x+7 
SFU 
36-49 days after last dose 
5.2 
Extent of exposure 
Exposure time will be presented as patient years of exposure (PYE) and will be calculated as 
the difference between the exposure start date and time and the exposure end date and time 
and divided by   60  60  24  365.25. Exposure start date and time and exposure end date and 
time are defined in Panel 3, Section 5.1.2. 
Exposure time will be summarized and listed for the safety analysis set. The summaries will 
be using descriptive statistics for continuous data as well as number and percentage of 
subjects with less than 6 weeks of exposure time, 6-11 weeks of exposure time, 12-15 weeks 
of exposure time, and >= 16 weeks of exposure time. 
5.3 
Intercurrent events 
Two intercurrent events are considered to affect the interpretation of the estimates of the 
endpoints: 
• Initiation of rescue treatment: This event occurs when a subject initiates rescue 
treatment. This event can occur at the discretion of the investigator. The timing of the 
event is defined as the date of initiation of the rescue treatment recorded in the eCRF. 
Rescue treatment will be defined by the following algorithm: Concomitant 
medications with ‘Dermatitis atopic’ or ‘Dermatitis infected’ as the preferred term for 
the indication and either of the following: 
1.  
ATC2 code H02 or D07. 
2.  
ATC4 code D11AH. 
3.  
Preferred name:  
• 
delgocitinib,  
• 
crisaborole, 
• 
methotrexate,  
• 
ciclosporin,  
• 
azathioprine,  
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• 
mycophenolate-mofetil, 
• 
mycophenolate-sodium, 
• 
mycophenolate-acid, 
• 
ruxolitinib,  
• 
dupilumab,  
• 
upadacitinib or  
• 
abrocitinib 
• Permanent discontinuation of IMP: This event occurs when a subject is 
permanently withdrawn from treatment or the trial. This event can occur at the 
subject's own initiative, at the discretion of the investigator or the sponsor, or if the 
subject is lost to follow-up.  
5.4 
Primary endpoints analyses 
5.4.1 
Definition of endpoints 
Two primary endpoints are considered:  
• IGA 0/1 at Week 16: obtaining an IGA score of 0 (clear) or 1 (almost clear) at Week 
16. 
• EASI75 at Week 16: obtaining at least 75% reduction in EASI score at Week 16 
relative to baseline.  
Both endpoints are binary and take the values ‘1’ (response) and ‘0’ (non-response) depending 
on whether the condition is met.  
5.4.2 
Primary analyses 
The primary endpoints (IGA 0/1 at Week 16 and EASI75 at Week 16) will be analysed using 
the composite estimand strategy to handle the occurrence of intercurrent events (initiation of 
rescue medication or permanent discontinuation of IMP).  
Missing data for subjects who do not attend the Week 16 visit and where rescue medication 
has not been used, nor the subject has permanently discontinued IMP, will be imputed as non-
response. 
The number and percentage of subjects achieving response will be presented together with the 
corresponding 95% CI.  
The analysis will be based on the FAS. 
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5.5 
Secondary and other endpoints analyses 
The secondary endpoint, number of treatment-emergent AEs from baseline up to Week 16, 
and the analysis of this is covered in Section 5.7.1. 
The secondary endpoint, presence of treatment-emergent ADA from baseline to Week 16, and 
the analysis of this is covered in Section 5.6. 
5.5.1 
Successful subject self-administration 
The subject’s ability to self-administer tralokinumab using the autoinjector will be assessed 
following each administration after baseline (Week 0). The assessment is based on the defined 
sequence of use steps described in CTP section 11.3 and as outlined in Panel 5.  
Successful subject self-administration for administration at trial site or following dosing at 
home is defined as completion of each defined sequence of use steps without errors. Each step 
is recorded in the eCRF. 
Panel 5 shows the combination of answers that constitutes a successful self-injection. For all 
other combinations of answers, the self-administration is defined as unsuccessful.   
Panel 5: Successful subject self-administration 
Question in eCRF  
Answer corresponding to errorless 
completion 
Did the subject choose the correct injection area? 
Yes* 
Did the subject remove the cap? 
Yes 
Did the subject press device down to begin 
injection? 
Yes 
Did the subject hold until the injection is 
complete? 
Yes 
Did the yellow plunger cover the viewing window 
completely when removing the autoinjector from 
the injection area? 
Yes 
Was liquid dripping from the tip of the 
autoinjector when removing it from the injection 
area? 
No 
*) The injection area is considered correct if the subject chose left or right anterior thigh, or abdomen. 
Abbreviations: eCRF = electronic case report form. 
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The number and percentage of subjects with successful IMP self-administration when 
observed in clinic at Week 4 will be presented together with the corresponding 95% CI (based 
on the Wilson method). Subjects who permanently discontinue IMP before Week 4 and 
subjects with missing values will be excluded from the analysis. 
The analysis will be based on the usability analysis set.  
The successful IMP self-administration when administered at home at Week 8, will be 
analysed in the same way as for the endpoint at Week 4 with the modification that subjects 
must not have permanently discontinued IMP prior to Week 8. 
5.5.2 
Other binary efficacy endpoints 
Other binary efficacy endpoints are listed in Panel 6. All binary endpoints take the values ‘1’ 
(response) or ‘0’ (non-response) depending on whether the condition is met.  
The binary efficacy endpoints listed in Panel 6, IGA 0/1 and EASI75 will be tabulated from 
baseline to Week 16 by visit using the same strategy as for the primary endpoints. Missing 
values where no intercurrent events have occurred, will be imputed as non-response. 
Panel 6: Other binary efficacy endpoints 
Description of endpoint 
EASI90: obtaining at least 90% reduction in EASI score  
EASI50: obtaining at least 50% reduction in EASI score 
Reduction in Worst Weekly Pruritus NRS/Adolescent’s Pruritus NRS of at least 4 
Reduction in POEM of at least 4 in adults/ Reduction in POEM of at least 6 in adolescents. 
Subjects with POEM < 4 for adults / <6 for adolescents at baseline will not be included in 
the analysis 
Reduction in DLQI of at least 4 in adults/Reduction in CDLQI of at least 6 in adolescents. 
Subjects with DLQI < 4 for adults / CDLQI <6 for adolescents at baseline will not be 
included in the analysis 
 
5.5.3 
Other continuous endpoints and patient reported outcomes 
The mean, 95% CI and SD will be calculated for the change and percentage change for other 
continuous efficacy endpoints listed in Panel 7. 
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The DLQI will be analysed and presented for adult subjects only, and the CDLQI score will 
be analysed and presented for adolescent subjects only.  
Analysis and data presentation will be based on the FAS. 
Panel 7: Other continuous efficacy endpoints 
Description of endpoint 
Change in Eczema-related Weekly Sleep NRS will be tabulated from baseline to Week 16 
by visit. 
Change in Worst Weekly Pruritus NRS/Adolescent’s Pruritis NRS will be tabulated from 
baseline to Week 16 by visit 
Change in DLQI/CDLQI will be tabulated from baseline to Week 16 by visit. 
Change in POEM will be tabulated from baseline to Week 16 by visit. 
Percentage change in EASI will be tabulated from baseline to Week 16 by visit. 
 
5.6 
Pharmacokinetics analysis and antidrug antibodies 
5.6.1 
Pharmacokinetic analysis 
All the PK samples in the trial are trough samples. The trough concentration (Ctrough) will be 
listed and descriptive statistics will be applied. 
Missing data will not be imputed. 
5.6.2 
Anti-drug antibodies analysis 
Anti-drug antibodies are tabulated as described in the CTP section 14.3.14. 
For subjects who develop ADA and are considered treatment boosted or treatment emergent, 
the IGA score, change in EASI at end of treatment, and titre information will be listed. 
Neutralising antibodies (nAb) will be conducted on those serum samples that test positive for 
ADA. The nAb status will be listed for subjects who develop ADA.  
5.7 
Safety analysis 
The analysis of safety will be presented separately for the treatment period and SFU period.  
Details on incomplete dates, duplicate measurements, unscheduled visits can be found in the 
ADRG or Define.xml. 
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5.7.1 
Adverse events 
AEs will be coded during the course of the trial according to Medical Dictionary for 
Regulatory Activities (MedDRA) version 24.0 and presented as described in the CTP section 
14.3.12.1. 
An AE will be considered treatment emergent if started after the first use of IMP. Only 
treatment emergent AEs will be summarized and tabulated. 
AEs will be presented by preferred terms (PT) and primary system organ class (SOC). 
An overall summary of the number (percentage) of AEs, the rate of AEs (number of AEs per 
100 patient years of observation time), and the number (percentage) of subjects with any 
treatment-emergent AEs, death, SAEs, AEs leading to premature discontinuation from IMP 
and/or withdrawals from the trial, treatment-related AEs, and severe AEs will be presented. In 
addition, AEs will be presented by severity and causal relationship to IMP. 
A summary of all AESIs will be tabulated, and for the AESI injection site reactions, a separate 
severity grading derived from the data collected according to Panel 9 will be tabulated as 
described in Section 5.7.2 
The number (percentage) of AEs, rate of AEs, and number of subjects with each type of AEs 
will be tabulated. 
SAEs and AESIs will be evaluated separately. A narrative for each SAE will be given. 
All AEs recorded during the course of the trial will be included in subject data listings. 
5.7.2 
Adverse events of special interest 
The AEs listed in Panel 8 are considered adverse events of special interest (AESIs) in this trial 
and will have additional details recorded in the eCRF. 
Injection site reactions 
Injection site reactions (ISR)s are considered AEs of special interest (AESIs). Additional 
information on objective signs and subjective symptoms for ISRs, given in Panel 9, will be 
provided on the AESI form. The information will be used to derive the severity of each 
sign/symptom according to the severity grading scale given in Panel 10. 
Injection site reactions will be summarised descriptively in terms of number of subjects and 
percentage of subjects reporting an injection site reaction within each category of the injection 
site reaction severity grading scale given in Panel 10. 
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Furthermore, all ISRs will be listed in the subject data listings.  
Panel 8: Adverse events of special interest 
Adverse event of 
special interest 
Additional data to be included in the eCRF (if available) 
Injection site reactions 
See Panel 9 for details. 
Eczema herpeticum 
Skin findings: 
• 
Lesion type (papules, vesicles, crusts, eroded pits, other). 
• 
Disseminated/localised. 
• 
Location (face, scalp, back, chest, upper limb, lower limb, genitals). 
• 
Present in an area with visible eczema / no visible eczema / present in 
areas with and without eczema. 
• 
Monomorphic/polymorphic. 
Confirmation of herpes simplex virus (not confirmed, PCR, viral culture, Tzanck, 
other). 
Malignancy diagnosed 
after treatment 
assignment, excluding 
basal cell carcinoma, 
localised squamous 
cell carcinoma of the 
skin, and carcinoma in 
situ of the cervix 
• 
Histology report available. 
• 
Oncology assessment available. 
• 
Treatments (surgery, radiation, chemotherapy, other). 
Skin infection 
requiring systemic 
treatment 
• 
Location (face, scalp, back, chest, upper limb, lower limb, genitals). 
• 
Outcome of pathogenic swab (positive, negative, not performed). 
Conjunctivitis 
• 
Aetiology (viral, bacterial, allergic, unknown). 
• 
Bacterial culture outcome (for events with bacterial aetiology). 
• 
Diagnosis confirmed by ophthalmologist. 
Keratoconjunctivitis 
• 
Aetiology (infectious, non-infectious, other, unknown). 
• 
Bacterial culture outcome (for events with bacterial aetiology). 
• 
Diagnosis confirmed by ophthalmologist. 
Keratitis 
• 
Aetiology (infectious, non-infectious, other, unknown). 
• 
Bacterial culture outcome (for events with bacterial aetiology). 
• 
Diagnosis of herpes simplex keratitis (for events with viral aetiology). 
• 
Diagnosis confirmed by ophthalmologist. 
  Abbreviations: eCRF = electronic case report form, PCR=polymerase chain reaction 
 
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Panel 9: Adverse events of special interest - injection site reaction 
Adverse event of 
special interest 
Additional data to be collected 
Injection site reactions 
Objective signs 
Erythema 
• 
Largest diameter (mm) 
 
Swelling/Oedema 
• 
Largest diameter (mm) 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Bruising/Haematoma 
• 
Largest diameter (mm) 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Induration 
• 
Largest diameter (mm) 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Other 
• 
Description 
• 
Largest diameter (mm) 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Subjective symptoms 
Itch 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Pain/Burning/Stinging 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
Other 
• 
Description 
• 
Effect on activity 
o 
Does not interfere with activity 
o 
Interferes with activity 
o 
Prevents daily activity 
 
 
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Panel 10: Injection site reaction severity grading scale 
Injection site reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain 
Does not interfere with 
activity 
Interferes with activity 
Prevents daily activity 
Itching 
Does not interfere with 
activity 
Interferes with activity 
Prevents daily activity 
Erythema 
2.5 to 5 cm 
5.1 to 10 cm 
> 10 cm 
Swelling/Oedema 
2.5 to 5 cm and does not 
interfere with activity 
5.1 to 10 cm or interferes 
with activity 
> 10 cm or prevents 
daily activity 
Bruising/Hematoma 
2.5 to 5 cm and does not 
interfere with activity 
5.1 to 10 cm or interferes 
with activity 
> 10 cm or prevents 
daily activity 
Induration 
2.5 to 5 cm and does not 
interfere with activity 
5.1 to 10 cm or interferes 
with activity 
> 10 cm or prevents 
daily activity 
Symptoms assessed and found not present will be graded 0.  
5.7.3 
Vital signs 
Vital signs, observed values and change from baseline, will be summarised at each site visit 
using mean, standard deviation (SD), median, 1st quartile, 3rd quartile, minimum, and 
maximum values. 
5.7.4 
Clinical laboratory evaluation 
Laboratory parameters (chemistry and haematology) – observed values and change from 
baseline – will be summarised at each site visit using mean, SD, median, 1st quartile, 3rd 
quartile, minimum, and maximum values.  
Urinalysis dipstick results and urinalysis investigator interpretation will be listed. 
Laboratory parameters (chemistry and haematology), except eosinophils, will be classified as 
‘low’, ‘normal’, or ‘high’, depending on whether the value is below, within, or above the 
reference range, respectively. Eosinophils will be classified at ‘≤ 0.5’, ‘>0.5 and ≤1.5’, or 
‘>1.5’.  Three shift tables will be produced; one showing the categories at baseline against 
those at end of treatment (Week 16), one showing the categories at baseline against the 
highest post-baseline value, and one showing the categories at baseline against the lowest 
post-baseline value.  
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Mean plots with standard deviation (SD) by visit and boxplots of actual values will be 
presented for the selected laboratory parameters listed below: 
• chemistry (alkaline phosphatase, alanine aminotransferase, aspartate 
aminotransferase, total bilirubin, gamma glutamyl transferase)  
• haematology (basophils, eosinophils, leukocytes, lymphocytes, monocytes, 
neutrophils) 
Furthermore, the mean plots with SD by visit will be presented for the change from baseline 
for the aforementioned selected chemistry and haematology parameters.  
5.8 
Subgroup analyses 
To assess the consistency of the number of responders for the composite estimand across 
subgroups, the primary endpoints (EASI75 at Week 16 and IGA 0/1 at Week 16) will be 
analysed by baseline IGA. 
Subjects will be divided into two groups depending on their IGA score at baseline; subjects 
with an IGA score of 3 (Moderate disease) and subjects with an IGA score of 4 (Severe 
disease), respectively. The subgroup definition will not be changed if group sizes are skewed. 
The subgroup analyses will be based on the FAS. 
5.9 
Interim analysis 
An interim analysis including only adult subjects will be made to support submission for 
marketing approval of tralokinumab. The interim analysis will be based on data collected for 
adult subjects during the trial period and performed after interim DBL. The interim DBL will 
be performed when all adult subjects have ended trial participation (i.e., completed the end of 
trial form). The analyses will be in accordance with those specified in the CTP and in this 
SAP . 
There is no blinding to maintain as this trial is an open label trial, and so there will be no 
impact on data integrity or trial results from proceeding trial conduct. 
6 
Changes to analyses described in the protocol 
All changes to the specified analyses and derivations planned in the CTP are summarized in 
Panel 11.  
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Panel 11: Changes to the analyses described in the protocol 
Section in CTP 
Description of change 
Brief rational 
14.2 Trial 
analysis sets 
The description of the full analysis set, and the safety 
analysis set has been updated such that subjects 
should both be assigned to treatment and dosed. 
The definition in the CTP did 
not specify subjects to be 
assigned to treatment, but only 
dosed. 
14.2 Trial 
analysis sets 
In addition to the analysis sets defined in the CTP, an 
analysis set, called "usability analysis set ", for 
analysing endpoints related to IMP self-injection has 
been defined. Furthermore 
The analysis set is described in 
the CTP, but not named. To 
ease readability and 
communication it has been 
defined and named usability 
analysis set 
14.2 Trial 
analysis sets 
A SFU analysis set is added to the list of the analyses 
sets 
To analyse endpoints and 
assessments related to safety 
during the SFU period 
14.3.16 General 
principles 
In addition to what is stated in the CTP, the lower and 
upper quartiles will be used to summarise continuous 
data. 
To align outputs with previous 
trials in the Tralokinumab 
project. 
14.3.16 General 
principles 
Baseline definition is added. 
To define the baseline data. 
14.3.16 General 
principles 
It has been specified that the Wilson method is used 
to calculate the confidence interval for the responder 
analyses, and the statistically method Student's t-CI is 
used to calculate the CI for the continuous endpoints. 
To specify what method is used. 
14.3.6 Estimand 
strategy 
Definition of date of permanent discontinuation of 
IMP has been changed to latest date of early 
termination visit (if existing) or date of onset of latest 
AE leading to withdrawal of IMP, otherwise date of 
the last visit, excluding safety follow-up visit rather 
than date of last IMP administration. 
Definition in the CTP was 
erroneous. 
14.3.3 Exposure 
and treatment 
compliance 
From exposure start to end, not date of disc. of IMP. 
Presented both as continuous data and categorical. 
End of exposure definition in 
CTP was erroneous. 
14.3.7 Analysis of 
primary endpoints 
Added a subgroup analysis for the primary endpoints 
(EASI75 at Week 16 and IGA 0/1 at Week 16). Each 
endpoint will be analysed by baseline IGA. 
To look into subgroups. 
14.3.4 Rescue 
medication 
Definition of rescue medication has been updated to 
include upadacitinib and abrocitinib as preferred 
name. 
The two treatments have been 
approved in the meantime. 
14.3.10 
Other binary efficacy endpoints will be tabulated 
from baseline to Week 16 by visit and not only from 
baseline to week 16 as stated in the protocol.  
To assess the efficacy at each 
visit.   
14.3.11 
Other continuous efficacy endpoints will be tabulated 
from baseline to Week 16 by visit and not only from 
baseline to week 16 as stated in the protocol. 
To assess the efficacy at each 
visit.   
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14.3.12.1 Adverse 
events 
The percentage of treatment-emergent AEs will not 
be presented. Rate of AEs (per 100 patient-years of 
observation time), and percentage of subjects with 
treatment-emergent AEs will be presented. 
Percentage of treatment-
emergent AEs was included by 
mistake in the CTP. 
14.3.12.2 Vital 
Signs 
Added reporting of observed values of vital signs. 
To align output with previous 
trial in the Tralokinumab project 
and the way of data 
presentation. 
14.3.12.3 Clinical 
laboratory 
evaluation 
Added reporting of observed values of laboratory 
parameters (chemistry and haematology). 
To align output with previous 
trial in the Tralokinumab project 
and the way of data 
presentation. 
14.3.12.3 Clinical 
laboratory 
evaluation 
Added two shift tables for laboratory parameters; one 
against highest post-baseline value, and one against 
lowest post-baseline value. 
To align output with previous 
trial in the Tralokinumab project 
and the way of data 
presentation. 
Abbreviations: AE = adverse event, CTP = clinical trial protocol, EASI = Eczema Area and Severity Index, 
EASI75 = at least 75% reduction in EASI score from baseline, IGA = Investigator’s Global Assessment, IGA 
0/1 = IGA score of clear (0) or almost clear (1), IMP = investigational medicinal product.  
 
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7 
Supporting documentation 
7.1 
Appendix 1: PRO scoring algorithms 
References to the scoring algorithms of the PROs are specified in Panel 12. 
Panel 12: PRO scoring algorithms 
DLQI 
Scored according to: 
https://www.cardiff.ac.uk/medicine/resources/quality-of-life-
questionnaires/dermatology-life-quality-index 
CDLQI 
Scored according to: 
https://www.cardiff.ac.uk/medicine/resources/quality-of-life-
questionnaires/childrens-dermatology-life-quality-index 
POEM 
Scored according to: 
https://www.nottingham.ac.uk/research/groups/cebd/documents/methodological-
resources/poem-for-self-completion.pdf 
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8 
Change log 
Version 
Section of SAP 
Description of change 
Brief rational 
2.0 
Statistical analysis 
plan statement 
Department names updated for 
statistical lead and medical lead 
Correction of error 
Version history 
Date for version 1.0 changed to 
match date of version 1.0 on front 
page 
Correction of error 
1.2 Trial design 
Update of description of DBL for 
interim analysis and data in scope 
To include safety follow up data 
for all adults in the interim 
analysis 
5.1 General 
principles 
Removal of description of DBL for 
interim analysis and data in scope 
To include safety follow up data 
for all adults in the interim 
analysis 
5.9 Interim 
analysis 
Update of description of DBL for 
interim analysis and data in scope 
To include safety follow up data 
for all adults in the interim 
analysis 
6 Changes to 
analysis described 
in the protocol 
Removal of description for section 
14.3.6 about data for interim analysis 
This text was removed from 
section 5.1 General principles as 
described above 
1.0 
NA 
NA 
Original version 
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