Conditions: Atopic Dermatitis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 1672
Healthy volunteers: no

Brief summary:
The purpose of this extension trial is to evaluate the long-term safety of tralokinumab.

Detailed description:

Arms:
arm 1: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. From Week 2 up to Week 266: SC injection of tralokinumab maintenance dose. The length of treatment for each subject will depend on when they enter the trial, and on which parent trial and country they come from.

Interventions: intervention 1: Tralokinumab
Intervention descriptions: intervention 1: Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection.

Protocol document:
Prot_000.pdf: 
Cover Page 
Study title: Long-term Extension Trial in Subjects With Atopic Dermatitis Who Participated in Previous 
Tralokinumab Trials - ECZTEND   
LEO Pharma number: LP0162-1337 
NCT number: NCT03587805
Date: 21-Feb-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 
 
LP0162-1337 
 
 
Long-term extension trial in subjects with atopic dermatitis who 
participated in previous tralokinumab trials – ECZTEND 
 
Phase 3 – long-term extension trial 
An open-label, single-arm, multi-centre, long-term extension trial to evaluate the safety and 
efficacy of tralokinumab in subjects with atopic dermatitis who participated in previous 
tralokinumab clinical trials 
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: 
LP0162-1337 
 
Date: 
 
21-Feb-2022 
 
EudraCT no: 
2018-000746-19 
 
Version: 
14.0 
 
 
 
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Clinical trial protocol statements 
Approval statement LEO Pharma A/S 
The following persons have approved this clinical trial protocol by using electronic signatures 
as presented on the last page of this document: 
 MSc Stat 
 
 Medical Sciences 
 
 
 
 MD 
 
 Medical Sciences 
 
 
 
 MD, PhD 
 
 Medical Sciences 
 
 
 MSc Pharm 
 
 Global Clinical Operations 
 
 
 
, BN, RN, MIND 
 
 Qualified Person for Pharmacovigilance  
 
 
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, MBA 
 
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
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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Protocol amendment summary of changes table 
Document history: 
Document 
Date 
Type of protocol 
amendment 
Amendment 10 (non-substantial) 
(protocol version 14.0) 
21-Feb-2022 
Global 
Amendment 9 (substantial) 
(protocol version 13.0) 
08-Feb-2022 
Global 
Amendment 2 DE (substantial) 
(protocol version 12.0 DE) 
22-Mar-2021 
Local (DE, applicable for 
subjects from the 1 site of 
the parent trial TRA-WEI-
0015-I ) 
Amendment 2 JP (substantial) 
(protocol version 12.0 JP) 
22-Mar-2021 
Local (JP) 
Amendment 8 (non-substantial) 
(protocol version 11.0) 
12-Feb-2021 
Global 
Amendment 7 (substantial) 
(protocol version 10.0) 
25-Nov-2020 
Global 
Amendment 1 DE (substantial) 
(protocol version 9.0 DE) 
03-Nov-2020 
Local (DE, to add parent 
trial TRA-WEI-0015-I) 
Amendment 1 JP (substantial) 
(protocol version 9.0 JP) 
22-Oct-2020 
Local (JP, to add parent 
trial LP0162-1343) 
Amendment 6 (substantial) 
(protocol version 8) 
(protocol version 7.0 was made obsolete) 
17-Feb-2020 
Global 
Amendment 5 (non-substantial) 
(protocol version 6.0) 
24-Jun-2019 
Global 
Amendment 4 (substantial) 
(protocol version 5.0) 
28-May-2019 
Global 
Amendment 3 (substantial) 
(protocol version 4.0) 
13-Dec-2018 
Global 
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Amendment 2 (substantial) 
(protocol version 3.0) 
31-Aug-2018 
Global 
Amendment 1 (substantial) 
(protocol version 2.0) 
27-Jun-2018 
Global 
Original protocol (protocol version 1.0) 
01-Jun-2018 
NA 
 
Amendment 10 (21-Feb-2022) 
This amendment is considered to be non-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 because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the trial.  
Overall rationale for amendment 10: 
The main reason for amendment 10 is to correct the visit window back to ±3 days in Panel 5. 
This was by mistake changed to ±7 days in amendment 9. Changes introduced with 
amendment 9 are presented below. 
Amendment 9 (08-Feb-2022) 
Amendment 9 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 amendment 9: 
The main reason for amendment 9 is to shorten the safety follow-up period from 16 weeks to 
4 weeks for subjects transferred from the adolescent parent trial LP0162-1334. Furthermore, 
changes that were made for the local protocol versions for Japan and Germany have been 
implemented in the protocol, and the definition of treatment completers has been updated.  
In addition, the amendment includes other changes, as presented in the table below. 
The table below describes the changes in each section, summarised as plain text, and/or as 
tracked changes (text added to the protocol is written in bold and deleted text has a line 
through it). 
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Section no. and name 
Description of change 
Brief rationale 
Whole document 
Protocol versions in-text have either been 
deleted or reworded to avoid stating the 
protocol version, or updated to e.g. ‘prior to 
protocol version 10’ or ‘protocol versions 10 
to 13’.  
Update to 
correspond to the 
applicable versions 
of the protocol. 
1 Protocol synopsis 
3 Schedule of trial design 
4 Schedule of trial procedures 
7.1 Overall trial design 
 
 
For subjects transferred from the adolescent 
parent trial LP0162-1334, the safety follow-
up period has been shortened from 16 weeks 
to 4 weeks. 
To offer a shorter 
safety follow-up 
period for the 
adolescent subjects 
to allow subjects the 
possibility of 
treatment prior to 
complete wash-out 
of tralokinumab. 
This is possible as 
no safety concerns 
were identified in the 
parent trial. 
4.2 ECZTEND - schedule of trial 
procedures after May 2021 
Panel 5 ECZTEND -schedule of 
trial procedures for subjects who 
re-consent/consent to participate 
in the trial after May 2021 
In alignment with the schedule of trial 
procedures until end of May 2021, the 
timings of the electrocardiogram, chemistry, 
haematology, immunoglobulin E, and urine 
dipstick assessments during the first 8 weeks 
in the schedule of trial procedures after May 
2021 have been corrected as follows: 
• Electrocardiogram: addition of 
assessments at Week 0. 
• Chemistry, haematology, immunoglobulin 
E: addition of assessments at Weeks 0 
and 8. 
• Urine dipstick: addition of assessments at 
Weeks 0 and 8. 
The 
electrocardiogram, 
chemistry, 
haematology, 
immunoglobulin E, 
and urine dipstick 
assessments during 
the first 8 weeks in 
the trial must be the 
same for all included 
subjects to be able to 
sufficiently monitor 
the safety of 
subjects. 
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Section no. and name 
Description of change 
Brief rationale 
 
5.2 Experience with 
investigational medicinal product 
The AD development programme investigates 
tralokinumab in subjects with 
moderate-to-severe AD. To date, 9 clinical 
trials have been completed: a phase 2b 
dose-finding trial (trial D2213C00001), 
2 phase 3 trials with tralokinumab as 
monotherapy (LP0162-1325 and 
LP0162-1326), a phase 3 trial with 
tralokinumab in combination with TCS 
(LP0162-1339), a phase 2 vaccine response 
trial (LP0162-1341), a phase 3 trial in 
adolescent subjects (LP0162-1334), a phase 
1 drug-drug interaction trial 
(LP0162-1342), a phase 3 trial in adult 
subjects with severe AD ineligible to 
treatment with cyclosporin A 
(LP0162-1346), and a phase 3 trial with 
tralokinumab in combination with TCS 
(LP062-1343) in Japanese subjects with 
moderate-to-severe AD who are candidates 
for systemic therapy.  
To provide 
information on the 
current status of the 
AD development 
programme for 
tralokinumab. 
7.3 End of trial definition 
The duration of the treatment period for 
each subject will depend on when the 
To update the 
definition of 
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Section no. and name 
Description of change 
Brief rationale 
subject enters the trial after completing the 
parent trial, and by which treatment stop 
date they have consented to (end of May 
2021, end of May 2022, or a country-
specific end of treatment day according to 
Appendix 3J). Hence, a subject is 
considered to have completed the treatment 
period for either of the following scenarios: 
if the subject has completed the EOT visit 
with no ‘primary reason for withdrawal from 
trial’. This will be: 
• 
Approximately end of May 
2021 for subjects 
completing according to 
earlier versions than 
protocol version 10 or 
earlier versions. 
• 
Approximately end of May 
2022 for subjects from the 
parent trial LP0162-1334 
who consented to continue 
in the trial after May 2021 
completing according to 
protocol version 11. 
• 
At a country-specific end of 
treatment date (Appendix 
3J) for subjects from the 
parent trials LP0162-1325, 
-1326, -1339, -1341, -1342, 
-1343, -1346, and TRA-
WEI-0015-I who 
consented to continue in 
the trial after May 2021 
completing according to 
protocol version 11.  
treatment 
completers.  
8.3 Exclusion criteria 
Receipt of inactive/killed vaccines (for 
example, inactive influenza and inactive 
COVID-19 vaccines) is allowed, provided 
they are not administered within 5 days 
before/after any IMP injection. 
 
To specify that for 
COVID-19 vaccines, 
only inactive 
vaccines are 
allowed. 
9.10 Reporting product 
complaints 
The fax number for Global Safety, LEO 
Pharma has been changed: 
To provide 
information on 
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Section no. and name 
Description of change 
Brief rationale 
13.4.1 Investigator reporting 
responsibilities 
Fax number: +45 6910 2468 
updated contact 
information for 
Global Safety, LEO 
Pharma 
11.4.5.3 Investigator evaluation 
of laboratory samples 
Urine samples will be tested at the trial site 
with a dipstick. If the dipstick shows any 
Until end of May 2021, in case of abnormal 
dipstick results reading, a urine sample was 
must always be collected and sent to the 
central laboratory for microscopic 
examination (leucocytes, erythrocytes, and 
casts). further analysis, regardless of 
causality or local assessment of significance 
After May 2021, a urine sample will only 
be sent to the central laboratory to 
perform urinalysis if considered required 
by the investigator based on the urine 
dipstick results.  
To correct the 
discrepancy between 
Section 4.2 footnote 
no. 11 and text in 
Section 11.4.5.3 
regarding testing of 
urine samples.  
11.8 End of trial 
An end of treatment form must be completed 
in the eCRF for all subjects assigned to 
completing treatment. The following data 
will be collected: 
• 
Date of last administration of IMP. 
To correct error. 
13.6.6 Aggravation of condition 
Any clinically significant 
aggravation/exacerbation/worsening of any 
medical condition (including the trial 
disease), compared with baseline, must be 
reported as an AE. If the AE qualifies as an 
SAE, expedited reporting is required (Section 
13.4). 
Any clinically significant 
aggravation/exacerbation/worsening of any 
medical condition(s) (including the trial 
disease), compared with baseline, must be 
reported as an (S)AE in accordance with 
Sections 13.3 and 13.4. 
To correctly specify 
the reporting of 
aggravation of 
condition. 
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Section no. and name 
Description of change 
Brief rationale 
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.  
Appendix 3J 
Panel 17 
Subjects from the parent trial LP0162-1334, 
who consented to participate in the trial 
based on protocol version 11 after May 
2021, will end treatment by end of May 2022 
in all countries. 
Subjects from the parent trials LP0162-1325, 
-1326, -1339, -1341, -1342,-1343, -1346, and 
TRA-WEI-0015-I, who consented to 
participate in the trial after May 2021 based 
on protocol version 11, will have a country-
specific end of treatment date (Panel 17).  
 
To update the 
country-specific end 
dates according to 
expected availability 
of tralokinumab in 
the countries.    
 
Throughout 
Minor editorial revisions. 
Minor, have 
therefore not been 
summarised. 
 
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Table of contents 
Protocol amendment summary of changes table ................................................................... 3 
Table of contents ..................................................................................................................... 10 
List of panels ........................................................................................................................... 14 
List of abbreviations ............................................................................................................... 16 
1 Protocol synopsis ................................................................................................................ 18 
2 Trial identification ............................................................................................................. 23 
3 Schematic of trial design ................................................................................................... 23 
4 Schedule of trial procedures ............................................................................................. 27 
4.1 ECZTEND - schedule of trial procedures until end of May 2021 .............................. 27 
4.2 ECZTEND - schedule of trial procedures after May 2021 ......................................... 34 
5 Introduction and trial rationale ....................................................................................... 40 
5.1 Atopic dermatitis ........................................................................................................ 40 
5.2 Experience with investigational medicinal product .................................................... 40 
5.3 Trial rationale .............................................................................................................. 42 
5.4 Justification for dose ................................................................................................... 42 
5.5 Ethical considerations ................................................................................................. 43 
5.6 Benefit/risk assessment ............................................................................................... 45 
6 Trial objectives and endpoints .......................................................................................... 47 
7 Trial design ......................................................................................................................... 49 
7.1 Overall trial design ..................................................................................................... 49 
7.1.1 
Overview ....................................................................................................... 49 
7.1.2 
Screening period (Week -2 to Week 0) .......................................................... 49 
7.1.3 
Treatment period (Week 0 and onwards) ...................................................... 50 
7.1.4 
Safety follow-up period (after last IMP dose) ............................................... 54 
7.2 Number of subjects needed ......................................................................................... 54 
7.3 End of trial definition.................................................................................................. 55 
7.4 Software ...................................................................................................................... 55 
8 Trial population ................................................................................................................. 56 
8.1 Subject eligibility ........................................................................................................ 56 
8.2 Inclusion criteria ......................................................................................................... 56 
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8.3 Exclusion criteria ........................................................................................................ 57 
8.4 Screening and screening failures ................................................................................ 61 
9 Treatments .......................................................................................................................... 63 
9.1 Trial product description ............................................................................................. 63 
9.2 Administration of IMP ................................................................................................ 63 
9.3 Treatment assignment ................................................................................................. 66 
9.4 Background treatment ................................................................................................. 66 
9.5 Rescue treatment ......................................................................................................... 66 
9.6 Concomitant medication and concurrent procedures ................................................. 67 
9.7 Prohibited medication and procedures........................................................................ 68 
9.8 Treatment logistics and accountability ....................................................................... 69 
9.8.1 
Labelling and packaging of trial products ..................................................... 69 
9.8.2 
Storage of trial products ................................................................................ 69 
9.8.3 
Drug accountability ....................................................................................... 70 
9.8.4 
Treatment compliance ................................................................................... 70 
9.8.5 
Trial product destruction ............................................................................... 71 
9.9 Provision for subject care following trial completion ................................................ 71 
9.10 Reporting product complaints..................................................................................... 71 
10 Discontinuation and withdrawal ...................................................................................... 73 
10.1 General principles ....................................................................................................... 73 
10.2 IMP discontinuation rules ........................................................................................... 73 
10.2.1 Stopping rules ................................................................................................ 73 
10.2.2 Reasons for withdrawal from the trial ........................................................... 74 
10.2.3 Reasons for temporary discontinuation of IMP ............................................ 75 
10.3 Early termination assessments .................................................................................... 75 
10.4 Lost to follow-up ........................................................................................................ 75 
11 Trial assessments and procedures .................................................................................... 77 
11.1 Overview..................................................................................................................... 77 
11.2 Assessments performed only at screening/baseline .................................................... 78 
11.2.1 Demographics................................................................................................ 78 
11.2.2 Medical history .............................................................................................. 79 
11.2.3 Height ............................................................................................................ 79 
11.2.4 Columbia-Suicide Severity Rating Scale ...................................................... 79 
11.3 Efficacy assessments .................................................................................................. 80 
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11.3.1 Investigator assessments ............................................................................... 80 
11.3.2 Patient-reported outcomes ............................................................................. 83 
11.4 Safety assessments ...................................................................................................... 85 
11.4.1 Weight ........................................................................................................... 85 
11.4.2 Vital signs ...................................................................................................... 85 
11.4.3 Physical examination..................................................................................... 86 
11.4.4 Electrocardiogram ......................................................................................... 86 
11.4.5 Laboratory testing ......................................................................................... 87 
11.4.6 Anti-drug antibodies measurements .............................................................. 90 
11.5 Pharmacokinetic assessments ..................................................................................... 91 
11.6 Skin biopsies (subgroup of subjects at selected sites) ................................................ 91 
11.7 Estimate of total blood volume collected ................................................................... 92 
11.8 End of trial .................................................................................................................. 92 
11.9 Storage of biological samples ..................................................................................... 93 
12 Scientific rationale for trial design and appropriateness of assessments ..................... 94 
13 Adverse events ................................................................................................................... 96 
13.1 Definition and classification of adverse events .......................................................... 96 
13.2 Collection of adverse event reports ............................................................................ 96 
13.3 Reporting of adverse events........................................................................................ 96 
13.4 Reporting of serious adverse events ........................................................................... 97 
13.4.1 Investigator reporting responsibilities ........................................................... 97 
13.4.2 LEO Pharma reporting responsibilities ......................................................... 98 
13.5 Expedited reporting of pregnancy .............................................................................. 99 
13.6 Reporting of other events............................................................................................ 99 
13.6.1 Adverse events of special interest ................................................................. 99 
13.6.2 Overdose...................................................................................................... 101 
13.6.3 Medication error .......................................................................................... 101 
13.6.4 Misuse ......................................................................................................... 101 
13.6.5 Abuse ........................................................................................................... 102 
13.6.6 Aggravation of condition ............................................................................ 102 
13.7 Follow-up for final outcome of adverse events ........................................................ 102 
13.8 Handling of an urgent safety measure ...................................................................... 102 
14 Statistical methods ........................................................................................................... 104 
14.1 Sample size ............................................................................................................... 104 
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14.2 Trial analysis sets ...................................................................................................... 104 
14.3 Statistical analysis ..................................................................................................... 104 
14.3.1 Disposition of subjects ................................................................................ 104 
14.3.2 Demographics and other baseline characteristics........................................ 104 
14.3.3 Exposure and treatment compliance ........................................................... 105 
14.3.4 Primary endpoint ......................................................................................... 105 
14.3.5 Secondary efficacy endpoints ...................................................................... 105 
14.3.6 Other endpoints ........................................................................................... 106 
14.3.7 Patient-reported outcomes ........................................................................... 107 
14.3.8 Safety ........................................................................................................... 107 
14.3.9 Pharmacokinetics ........................................................................................ 110 
14.3.10 Interim analysis ........................................................................................... 110 
14.3.11 General principles ....................................................................................... 111 
14.3.12 Handling of missing values ......................................................................... 111 
15 References ......................................................................................................................... 112 
Appendix 1: Definitions of adverse events and serious adverse events ........................... 116 
Appendix 2: Classification of adverse events ..................................................................... 118 
Appendix 3: Trial governance considerations ................................................................... 121 
Appendix 3A: Regulatory and ethical considerations .............................................. 121 
Appendix 3B: Informed consent process ................................................................. 122 
Appendix 3C: Subject and data confidentiality ....................................................... 123 
Appendix 3D: Record keeping, quality control, and data handling ......................... 124 
Appendix 3E: Registration, reporting and publication policy ................................. 128 
Appendix 3F: Insurance ........................................................................................... 129 
Appendix 3G: Financial disclosure .......................................................................... 130 
Appendix 3H: Trial and site closure ........................................................................ 130 
Appendix 3I: Responsibilities .................................................................................. 131 
Appendix 3J: Country-specific end of treatment date.............................................. 131 
Appendix 3K: COVID-19 ........................................................................................ 132 
Appendix 4: Country-specific requirements ...................................................................... 136 
Appendix 4A: Japan ................................................................................................. 136 
Appendix 4B: France ............................................................................................... 140 
Appendix 5: Eligibility criteria ........................................................................................... 141 
Appendix 6: Guidance for anaphylaxis diagnosis ............................................................. 144 
Appendix 7: Contact list ...................................................................................................... 145 
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Appendix 8: Protocol amendment history ......................................................................... 146 
Amendment 1 (27-Jun-2018) ................................................................................... 146 
Amendment 2 (31-Aug-2018) .................................................................................. 149 
Amendment 3 (13-Dec-2018) .................................................................................. 152 
Amendment 4 (28-May-2019) ................................................................................. 160 
Amendment 5 (24-Jun-2019) ................................................................................... 164 
Amendment 6 (17-Feb-2020) ................................................................................... 165 
Amendment 7 (25-Nov-2020) .................................................................................. 172 
Amendment 8 (12-Feb-2021) ................................................................................... 187 
 
List of panels 
Panel 1: Overview of scenarios for trial participation .............................................................. 24 
Panel 2: Trial design ................................................................................................................. 25 
Panel 3: ECZTEND - schedule of trial procedures (up to Week 56) until end of May 2021 .. 27 
Panel 4: ECZTEND - schedule of trial procedures (Week 64–EOT) until end of May 2021 .. 31 
Panel 5: ECZTEND – schedule of trial procedures for subjects who re-consent/consent to 
participate in the trial after May 2021 .............................................................. 34 
Panel 6: Objectives and endpoints ........................................................................................... 47 
Panel 7 Treatment completion date .......................................................................................... 52 
Panel 8: Safety follow-up visit ................................................................................................. 54 
Panel 9: Identification of investigational medicinal product (IMP) ......................................... 63 
Panel 10: Dosing regimen ........................................................................................................ 64 
Panel 11: Investigator’s Global Assessment ............................................................................ 80 
Panel 12: Calculation of the Eczema Area and Severity Index ................................................ 81 
Panel 13: EASI severity score scale and area score scale ........................................................ 81 
Panel 14: Clinical laboratory tests ............................................................................................ 88 
Panel 15: Adverse events of special interest .......................................................................... 100 
Panel 16: Transmission of electronic data .............................................................................. 127 
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Panel 17: Country-specific last subject last treatment for parent trials LP0162-1325, -1326, -
1339, -1341, -1342, -1343, -1346, and TRA-WEI-0015-I ............................. 131 
 
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List of abbreviations 
AD 
atopic dermatitis 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
CCL 
C-C motif chemokine 
CCL17 
C-C motif chemokine 17 (also known as TARC) 
CDER 
United States Center for Drug Evaluation and Research 
CDISC 
Clinical Data Interchange Standards Consortium 
CDLQI 
Children’s Dermatology Life Quality Index 
CMO 
contract manufacturing organisation 
COVID-19 
Coronavirus Disease 2019 
CRA 
clinical research associate 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTR 
clinical trial report 
CXCL 10 
C-X-C motif chemokine ligand 10 
CYP 
cytochrome P450  
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
EASI75/50 
at least 75% / 50% reduction in EASI score 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EOT 
end of treatment 
ePRO 
electronic patient-reported outcome 
EQ-5D-5L 
EuroQoL 5-Dimension Health Questionnaire 5-Level 
FAS 
full analysis set 
FDA 
Unites States Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ID 
identification number 
IEC 
independent ethics committee 
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IFNG 
interferon gamma 
IGA 
Investigator’s Global Assessment 
IgE 
immunoglobulin E 
IL 
Interleukin 
IMP 
investigational medicinal product 
IPF 
idiopathic pulmonary fibrosis 
IRB 
institutional review board 
MedDRA 
Medical Dictionary for Regulatory Activities 
nAB 
neutralising antibodies 
NIMP 
non-investigational medicinal product 
NRS 
numeric rating scale 
PK 
pharmacokinetics 
POEM 
Patient Oriented Eczema Measure 
PDE-4 
phosphodiesterase 4 
PRO 
patient-reported outcome 
Q2W 
every second week 
qPCR 
quantitative real time polymerase chain reaction 
S100A9 
S100 calcium-binding protein A9  
S100A12 
S100 calcium-binding protein A12 
SAE 
serious adverse event 
SC 
subcutaneous(ly) 
SCORAD 
Scoring Atopic Dermatitis  
SD 
standard deviation 
SFU 
safety follow-up 
SOC 
system organ class 
TCI 
topical calcineurin inhibitors 
TCS 
topical corticosteroids 
UC 
ulcerative colitis 
UK 
United Kingdom 
US 
United States 
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1 Protocol synopsis 
Trial ID 
EudraCT no. 
IND no. 
FDA center 
LP0162-1337 
2018-000746-19 
123797 
CDER 
Title of trial 
An open-label, single-arm, multi-centre, long-term extension trial to evaluate 
the safety and efficacy of tralokinumab in subjects with atopic dermatitis who 
participated in previous tralokinumab clinical trials – ECZTEND 
Short title of trial 
Long-term extension trial in subjects with atopic dermatitis who participated in 
previous tralokinumab trials – ECZTEND 
Main objectives 
and endpoints 
Primary objective 
Primary endpoint 
To evaluate the long-term 
safety of tralokinumab 
• 
Number of adverse events during the 
treatment period from baseline up to 
Week 268 
Secondary objective 
Secondary endpoint 
To evaluate the efficacy of 
tralokinumab given as 
continuous treatment, re-
treatment, or introduced for 
the first time in 
tralokinumab-naïve subjects 
• 
Investigator’s Global Assessment 
(IGA)1 score of 0 (clear) or 1 (almost 
clear) at Weeks 16, 56, 88, 104, 136, 
152, 184, 216, and 248 
• 
At least 75% reduction in Eczema Area 
and Severity Index (EASI75)2 relative 
to baseline in parent trial, at Weeks 16, 
56, 88, 104, 136, 152, 184, 216, and 
248 
1 The IGA is an instrument used in clinical trials to rate the severity of the subject's 
global atopic dermatitis (AD) and is based on a 5-point scale ranging from 0 (clear) to 
4 (severe). 
2 The EASI is a validated measure used in clinical practice and clinical trials to assess 
the severity and extent of AD. The EASI is a composite index with scores ranging from 
0 to 72, with higher values indicating more severe or more extensive condition. 
Final collection of 
data for the 
primary endpoint 
The final collection of data for the primary endpoint will occur by Q2 2024. 
• 
For subjects who did NOT re-consent to participate in the trial after 
May 2021, the final collection of data for the primary endpoint 
occurred at Week 140 or earlier, dependent on when they were 
included in the trial. 
• 
For subjects from the adolescent parent trial LP0162-1334 who 
consented to participate in the trial after May 2021, treatment was 
extended by 1 year until end of May 2022. For these subjects, the final 
collection of data for the primary endpoint will occur at Week 114 or 
earlier.  
• 
For subjects from the parent trials LP0162-1325, -1326, -1339, 
-1341,-1342, -1343, -1346, and TRA-WEI-0015-I (investigator-
initiated trial) who consented to participate in the trial after May 2021, 
trial treatment will be stopped at a country-specific treatment 
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completion date. For these subjects, the final collection of data for the 
primary endpoint will occur at Week 268 or earlier. 
Trial design 
The trial will include a screening period of 2 weeks (Week -2 to Week 0), and a 
long-term treatment period of approximately 0.5 to 5.0 years. The duration of 
the treatment period for each subject will depend on when the subject enters the 
trial after completing the parent trial, and by which treatment stop date they 
have consented to (end of May 2021, end of May 2022, or a country-specific 
end of treatment day).  
 
Notes: * Subjects from the parent trial LP0162-1334 will not perform the EQ-5D-5L.  ** Visit schedule after 
May 2021 applies to subjects who consented to continue in the trial after May 2021, or who are included in 
the trial after May 2021. Treatment will be ended at a country-specific treatment end date (see Appendix 3J), 
or by end of May 2022 (subjects from the parent trial LP0162-1334). 
Abbreviations: ADA = anti-drug antibodies; CDLQI = Children’s Dermatology Life Quality Index; DLQI = 
Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EQ-5D-5L = EuroQoL 
5 Dimension Health Questionnaire 5-Level; IGA = Investigator’s Global Assessment; IMP = investigational 
medicinal product; PK = pharmacokinetics; POEM = Patient Oriented Eczema Measure; Q2W = every 
second week; SCORAD = Scoring Atopic Dermatitis; SFU = safety follow-up; TCS = topical corticosteroids; 
w = weeks. 
 
Subjects included in the trial prior to protocol version 10 attended site visits 
every 8 weeks until end of May 2021. For subjects who did NOT re-consent to 
continue in the trial after May 2021, trial treatment was ended end of May 
2021. Subjects who re-consented to continue in the trial after May 2021 and 
subjects who consent to be included in the trial based on protocol versions 10 to 
13 will follow a modified trial visit schedule more similar to standard practice 
for home use. The modified trial schedule consists of 2 types of site visits 
(standard site visits and short site visits), interchanging with a mandatory 
telephone visit between the site visits. Dependent on the subject’s consent, 
subjects included or who continued after May 2021 complete treatment by end 
of May 2022 (subjects from LP0162-1334) or at a country-specific treatment 
end date between August 2021 and May 2024, to ensure continued treatment of 
subjects until treatment with tralokinumab is also available to patients outside 
the clinical trial setting.  
After adequate training by site staff at the first 3 visits, subjects will inject 
tralokinumab 300 mg every 2 weeks at home (or have tralokinumab injected by 
a caregiver) during the treatment period. 
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, 
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including the safety follow-up period. Subjects can use TCS (US class ≥4 or 
Europe class ≤3) or TCI at the investigator’s discretion. 
Main assessments 
Safety assessments 
Adverse event reporting, anti-drug antibodies, vital signs, physical 
examination, electrocardiograms, and laboratory tests. 
Efficacy assessments 
IGA and EASI. 
Main criteria for 
inclusion 
• 
Completed the treatment period(s) of one of the parent trials: 
LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346, and 
TRA-WEI-0015-I. 
• 
Complied with the clinical trial protocol in the parent trial to the 
satisfaction of the investigator.  
• 
Able and willing to self-administer tralokinumab treatment (or have it 
administered by a caregiver) at home after the initial 3 injection visits 
at the trial site (in this trial). 
• 
Stable dose of emollient twice daily (or more, as needed) for at least 
14 days before baseline. 
Main criteria for 
exclusion 
• 
Any condition that required permanent discontinuation of trial 
treatment in the parent trial. 
• 
More than 26 weeks have elapsed since the subject received the last 
injection of investigational medicinal product (IMP) in the parent trial 
(to be assessed at baseline). 
• 
Subjects who, during their participation in the parent trial, developed a 
serious adverse event (SAE) deemed related to tralokinumab by the 
investigator, which in the opinion of the investigator could indicate that 
continued treatment with tralokinumab may present an unreasonable 
safety risk for the subject. 
• 
Subjects who, during their participation in the parent trial, developed 
an AE that was deemed related to tralokinumab by the investigator and 
led to temporary discontinuation of trial treatment, which in the 
opinion of the investigator could indicate that continued treatment with 
tralokinumab may present an unreasonable safety risk for the subject. 
• 
Treatment with systemic immunosuppressive/immunomodulating 
drugs and/or systemic corticosteroids within 5 half-lives prior to 
baseline. 
• 
Treatment with topical phosphodiesterase 4 inhibitors or topical JAK 
inhibitors within 2 weeks prior to baseline. 
• 
Receipt of any marketed biological therapy (that is, immunoglobulin or 
anti-immunoglobulin E) including dupilumab or investigational 
biologic agents: 
o 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. 
o Other biologics: within 3 months or 5 half-lives, whichever is 
longer, prior to baseline. 
• 
Clinically significant infection within 4 weeks prior to baseline. 
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• 
A helminth parasitic infection within 6 months prior to the date when 
informed consent is obtained. 
• 
Tuberculosis requiring treatment within 12 months prior to screening. 
• 
Known primary immunodeficiency disorder. 
Investigational 
medicinal product 
• 
Name/active substance: tralokinumab (human recombinant IL-13 
monoclonal antibody of the immunoglobulin G4 subclass that 
specifically binds to human IL-13 and blocks interaction with the IL-13 
receptors). 
• 
Dosage form: solution (in accessorised pre-filled syringe, 1.0 mL fill 
volume). 
• 
Concentration: 150 mg/mL. 
• 
Dose for adult subjects from all parent trials, except the parent trial 
LP0162-1334: 600 mg initial loading dose, then 300 mg every second 
week. 
• 
Dose for subjects from the parent trial LP0162-1334*: 300 mg every 
second week. 
       *All subjects from the parent trial LP0162-1334, independent of the 
         subject’s age when included in ECZTEND. 
• 
Method of administration: subcutaneous injection. 
Duration of 
treatment 
The duration of the treatment period for each subject will depend on when the 
subject enters the trial after completing the parent trial, and by which treatment 
stop date they have consented to (end of May 2021, end of May 2022, or a 
country-specific end of treatment day): 
• 
For subjects who did NOT re-consent to participate in the trial after 
May 2021, trial treatment was stopped by end of May 2021. Treatment 
duration was maximum 140 weeks.  
• 
For subjects from the parent trial LP0162-1334 who consented to 
participate in the trial after May 2021, trial treatment will be stopped by 
end of May 2022. Treatment duration will be maximum 114 weeks.  
• 
For subjects from the parent trials LP0162-1325, -1326, -1339, -1341, 
-1342, -1343, -1346, and TRA-WEI-0015-I who consent to participate 
in the trial after May 2021, trial treatment will be stopped at a 
country-specific treatment completion date. Treatment duration will be 
maximum 268 weeks. 
Number of 
subjects 
It is assumed that approximately 1,600 subjects will be assigned to treatment. 
Number and 
distribution of 
trial sites 
Approximately 330 sites in Canada, Europe, Japan, and the US. 
Statistical 
methods 
Primary endpoint 
AEs will be summarised for all treated subjects (full analysis set) and will be 
presented by Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term and primary system organ class (SOC) as percentage of subjects 
with AEs, number of AEs, and rate of AEs (number of AEs per 100 patient-
years of exposure). 
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Secondary endpoints 
The analyses of the secondary endpoints will be made for the full analysis set 
as well as for the observed cases. 
IGA and EASI75 will be presented as response rates with 95% confidence 
intervals at each assessment visit. The results will be presented for the total 
cohort of subjects and by tralokinumab-naïve/re-treated/continuously treated 
subjects. For the re-treated and continuously treated subjects, the results will 
further be divided by responders/non-responders; clinical response is defined as 
achievement of IGA 0/1 or EASI75 at the last assessment in the parent trial. 
Signatory 
investigator 
Sponsor 
LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark 
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2 Trial identification 
EudraCT number: 2018-000746-19 
IND number: 123797 
The clinical trial protocol will be registered in local registries if required by local legislation. 
3 Schematic of trial design 
An overview illustrating the different scenarios for trial participation (subject did NOT 
re-consent to continue in the trial after May 2021, subject DID re-consent to continue in the 
trial after May 2021, or subject was included in the trial after May 2021) is presented in 
Panel 1.  
Panel 2 illustrates the trial design applicable until May 2021 (top row) and after May 2021 
(bottom row), where a number of site visits were replaced by mandatory telephone visits for 
subjects participating in the trial after May 2021 to reduce the burden of frequent site visits. It 
required a re-consent or consent to participate in the trial after May 2021 (all trials).  
In the case where a subject is unable to attend site visits due to the COVID-19 pandemic, 
please refer to Appendix 3K for guidance. 
 
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Panel 1: Overview of scenarios for trial participation  
 
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Panel 2: Trial design 
 
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Notes: Subjects can be included in ECZTEND after completion of the treatment period in the parent trial, and continue with a long-term treatment period of 
approximately 0.5 to 5 years in ECZTEND. Subjects who did NOT re-consent to participation in the trial after May 2021 stopped IMP treatment by end of May 
2021 followed by 16 weeks of SFU (top row visit schedule). * Subjects from the parent trial LP0162-1334 will not perform the EQ-5D-5L. ** Visit schedule 
after May 2021 applies to subjects who consented to continue in the trial after May 2021, or who are included in the trial after May 2021. Treatment will be 
ended at a country-specific treatment end date (see Appendix 3J), or by end of May 2022 (subjects from the parent trial LP0162-1334).  
Abbreviations: ADA = anti-drug antibodies; CDLQI = Children’s Dermatology Life Quality Index; DLQI = Dermatology Life Quality Index; EASI = Eczema 
Area and Severity Index; EQ-5D-5L = EuroQoL 5 Dimension Health Questionnaire 5-Level; IGA = Investigator’s Global Assessment; IMP = investigational 
medicinal product; PK = pharmacokinetics; POEM = Patient Oriented Eczema Measure; Q2W = every second week; SCORAD = Scoring Atopic Dermatitis; 
SFU = safety follow-up; TCS = topical corticosteroids; w = weeks. 
 
 
 
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4 Schedule of trial procedures  
In the case where a subject is unable to attend site visits due to the COVID-19 pandemic, please refer to Appendix 3K for guidance. 
4.1 ECZTEND - schedule of trial procedures until end of May 2021 
Panel 3: ECZTEND - schedule of trial procedures (up to Week 56) until end of May 2021 
 
Screening1 
Treatment period2 
References 
(protocol 
section) 
Visits 
1+2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
 
Weeks 
-2 
0 
2 
4 
8 
12 
16 
24 
32 
40 
48 
56 
Visit window (days)3 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Trial population and eligibility 
Informed consent4 
X 
 
 
 
 
 
 
 
 
 
 
 
Appendix 3B 
Subject eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
8.1, 8.2, 8.3 
Investigator assessments at screening/baseline only 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
11.2.1 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
11.2.2 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
11.2.3 
Columbia-Suicide Severity Rating Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
11.2.4 
Treatments 
 
Concomitant medication and concurrent procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.6 
Initiation of emollient5 
X 
 
 
 
 
 
 
 
 
 
 
 
9.4 
Tralokinumab administration/dispensing6 
 
X7 
X7 
X7 
X 
X 
X 
X 
X 
X 
X 
X 
9.2, 9.8.3 
Treatment compliance 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.8.4 
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Screening1 
Treatment period2 
References 
(protocol 
section) 
Visits 
1+2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
 
Weeks 
-2 
0 
2 
4 
8 
12 
16 
24 
32 
40 
48 
56 
Visit window (days)3 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Investigator assessments of efficacy 
Investigator’s Global Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.3.1.1 
Eczema Area and Severity Index 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.3.1.2 
SCORing Atopic Dermatitis 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.3.1.3 
Investigator assessments of safety 
Weight 
 
X 
 
 
 
 
 
 
 
 
 
X 
11.4.1 
Vital signs 
X 
X7 
X7 
X7 
X 
X 
X 
 
X 
 
 
X 
11.4.2 
Physical examination 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
11.4.3 
Electrocardiogram 
X 
X 
 
 
 
 
X 
 
X 
 
 
X 
11.4.4 
Hepatitis B/C, HIV 
X 
 
 
 
 
 
 
 
 
 
 
 
11.4.5 
Chemistry, haematology, immunoglobulin E 
X8 
X 
 
 
X 
 
X 
 
X 
 
 
X 
11.4.5 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
11.4.5 
Urinalysis9 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
11.4.5 
Urine pregnancy test 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.4.5 
Anti-drug antibodies 
 
X 
 
X 
 
 
X 
 
 
 
 
X 
11.4.6 
Pharmacokinetics blood sample 
 
X 
 
X 
 
 
X 
 
 
 
 
X 
11.5 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
13 
Patient-reported outcomes 
 
Patient Oriented Eczema Measure 
 
X 
 
 
 
 
X 
 
X 
 
 
X 
11.3.2.1 
Dermatology Life Quality Index (DLQI)/CDLQI10 
 
X 
 
 
 
 
X 
 
X 
 
 
X 
11.3.2.2 
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Screening1 
Treatment period2 
References 
(protocol 
section) 
Visits 
1+2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
 
Weeks 
-2 
0 
2 
4 
8 
12 
16 
24 
32 
40 
48 
56 
Visit window (days)3 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Patient-reported outcomes (continued) 
EuroQoL 5-Dimension Health Questionnaire 
5-Level11 
 
X 
 
 
 
 
X 
 
X 
 
 
X 
11.3.2.3 
Worst Weekly Pruritus numeric rating scale12 
Eczema-related Sleep numeric rating scale12 
Patient use of topical treatment13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.3.2.4 
Other assessments 
Skin biopsies14 
 
 
 
 
 
 
 
 
 
 
X 
 
11.6 
1) If screening/baseline visits are performed on the same day as visit(s) in the parent trial, the order of assessments should be adhered to, working in parallel for 
both protocols. Assessments where data are captured in different vendor systems databases (ECG, ePRO, and laboratory tests) need to be completed twice. In 
such cases, the parent trial assessment should be performed first, followed by the trial LP0162-1337 assessment. 
2) Subjects who withdraw from the trial will be followed up as described in Section 10. All subjects will have a safety follow-up period of 14 weeks, starting 
2 weeks after the last dose of tralokinumab (that is, the final safety follow-up visit will be 16 weeks after the last dose). 
3) 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. 
4) The informed consent form must be signed prior to performing any protocol-related procedures, including but not limited to screening evaluations; for 
adolescent subjects participating in ECZTEND, legal representative(s) must sign a legal representative informed consent form and the adolescent subject must 
sign an informed assent form. Adolescent subjects who become adults during participation in ECZTEND must re-consent by signing the informed consent form 
for adult subjects. Additional informed consent is required for participation in the exploratory part involving skin biopsy (selected trial sites only). 
5) All subjects must use an emollient, as background treatment, twice daily (or more, as needed) for at least 14 days before baseline and must continue this 
treatment throughout the trial (including safety follow-up). 
6) At trial visits, tralokinumab will be injected at the trial site, preferably by the subject or their caregiver, alternatively by site staff. At each trial visit from 
Week 4 onwards, subjects will be provided with tralokinumab to be administered at home until the next trial visit. In case of intercurrent illness that may 
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compromise the safety of the subject, or fever within 72 hours prior to administration, tralokinumab administration should be rescheduled. If an anaphylactic 
reaction occurs, blood samples should be drawn for the analysis of serum tryptase (see details in Section 9.2). 
7) At the first 3 tralokinumab dosing visits, subjects (or their caregiver) will be trained in how to inject tralokinumab, except for those who have already been 
trained in home use during the parent trial. In addition, if the subject and/or the caregiver is/are health care professional(s), no training is required, but the 
subject should be trained in how to handle the IMP according to the IMP handling manual and in the procedures to be followed in the event of an emergency. 
At the first 3 dosing visits, subjects (except for those who have received open-label tralokinumab treatment in the parent trial) will also be monitored for 
immediate drug reactions for a minimum of 30 minutes after dosing, with vital signs taken after 30 minutes or until stable, whichever is later. 
8) IgE will not be measured at screening. 
9) Urine samples will be tested at the trial site (dipstick). In case of abnormal dipstick results, a urine sample will be sent to the central laboratory for microscopic 
examination (leucocytes, erythrocytes, and casts) (Section 11.4.5). 
10) Adult subjects from all parent trials, except the LP0162-1334 trial, will perform the DLQI. Subjects from the parent trial LP0162-1334 will perform the 
CDLQI, independent of the age of the subject during participation in ECZTEND. 
11) Subjects from the parent trial LP0162-1334 will not perform the EuroQoL 5-Dimension Health Questionnaire 5-Level. 
12) Subjects from the parent trial LP0162-1334 will perform an adolescent’s pruritis NRS with a recall period of past 7 days, and an eczema-related sleep NRS 
with a recall period over the past 7 nights, independent of the age of the subject during participation in ECZTEND. 
13) Based on subject recall during the last week prior to each site visit (from 6 days prior to each visit and including the day of the visit). 
14) Optional at selected sites and only for subjects who had skin biopsies taken in the parent trial LP0162-1325. 
Abbreviations: CDLQI = Children’s Dermatology Life Quality Index; ECG = electrocardiogram; ePRO = electronic patient-reported outcome; DLQI = 
Dermatology Life Quality Index; IMP = investigational medicinal product; NA = not applicable; NRS = numeric rating scale. 
 
 
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Panel 4: ECZTEND - schedule of trial procedures (Week 64–EOT) until end of May 2021 
 
Treatment period1 
SFU1 
Unscheduled 
visit (if 
applicable)3 
 
 
 
 
Early 
termination 
(if 
applicable)1 
 
 
 
References 
(protocol 
section) 
 
 
 
 
Visits 
14 
20 
15 
21 
16 
22 
17 
23 
18 
 
19 
 
 
EOT visit 
 
 
SFU visit 
 
Weeks 
64 
112 
72 
120 
80 
128 
88 
136 
96 
 
104 
 
Variable2
(max 140) 
Variable2 
 
Visit window (days)4 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Treatments 
 
Concomitant medication and concurrent procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.6 
Tralokinumab administration/dispensing5 
X 
X 
X 
X 
X 
X 
 
 
X 
 
9.2, 9.8.3 
Treatment compliance 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
9.8.4 
Investigator assessments of efficacy 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
11.3.1.1 
Eczema Area and Severity Index 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
11.3.1.2 
SCORing Atopic Dermatitis 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
11.3.1.3 
Investigator assessments of safety 
Weight 
 
 
 
 
 
X 
X 
 
 
X 
11.4.1 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.4.2 
Physical examination 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.4.3 
Electrocardiogram 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.4.4 
Chemistry, haematology, immunoglobulin E 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.4.5 
Urinalysis6 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.4.5 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.4.5 
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Treatment period1 
SFU1 
Unscheduled 
visit (if 
applicable)3 
 
 
 
 
Early 
termination 
(if 
applicable)1 
 
 
 
References 
(protocol 
section) 
 
 
 
 
Visits 
14 
20 
15 
21 
16 
22 
17 
23 
18 
 
19 
 
 
EOT visit 
 
 
SFU visit 
 
Weeks 
64 
112 
72 
120 
80 
128 
88 
136 
96 
 
104 
 
Variable2
(max 140) 
Variable2 
 
Visit window (days)4 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Investigator assessments of safety (continued) 
Anti-drug antibodies 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.4.6 
Pharmacokinetics blood sample 
 
 
X 
 
 
X 
X 
X 
X 
X 
11.5 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
13 
Patient-reported outcomes 
Patient Oriented Eczema Measure 
 
 
X 
 
 
X 
X 
 
X 
X 
11.3.2.1 
Dermatology Life Quality Index (DLQI)/CDLQI7 
 
 
X 
 
 
X 
X 
 
X 
X 
11.3.2.2 
EuroQoL 5-Dimension Health Questionnaire 5-Level8 
 
 
X 
 
 
X 
X 
 
X 
X 
11.3.2.3 
Worst Weekly Pruritus numeric rating scale9 
Eczema-related Sleep numeric rating scale9 
Patient use of topical treatment10 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
11.3.2.4 
1) Subjects who withdraw from the trial will be followed up as described in Section 10. The final safety follow-up visit will be 16 weeks after the last dose (i.e. 
14 weeks after the EOT visit). 
2) The number of weeks until the EOT visit (2 weeks after the last dose of tralokinumab, maximum 140 weeks) and SFU visit (maximum 154 weeks) for each 
subject will depend on the time of their trial entry and treatment duration. 
3) Assessments and procedures to be performed at an unscheduled visit are 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) 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. 
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5) At trial visits, tralokinumab will be injected at the trial site, preferably by the subject or their caregiver, alternatively by site staff. At each trial visit, subjects 
will be provided with tralokinumab to be administered at home until the next trial visit. In case of intercurrent illness that may compromise the safety of the 
subject, or fever within 72 hours prior to administration, tralokinumab administration should be rescheduled. If an anaphylactic reaction occurs, blood samples 
should be drawn for the analysis of serum tryptase (see details in Section 9.2). 
6) Urine samples will be tested at the trial site (dipstick). In case of abnormal dipstick results, a urine sample will be sent to the central laboratory for microscopic 
examination (leucocytes, erythrocytes, and casts) (Section 11.4.5). 
7) Adult subjects from all parent trials, except the LP0162-1334 trial, will perform the DLQI. Subjects from the parent trial LP0162-1334 will perform the 
CDLQI, independent of the age of the subject during participation in ECZTEND. 
8) Subjects from the parent trial LP0162-1334 will not perform the EuroQoL 5-Dimension Health Questionnaire 5-Level. 
9) Subjects from the parent trial LP0162-1334 will perform an adolescent’s pruritis NRS with a recall period of past 7 days, and an eczema-related sleep NRS 
with a recall period over the past 7 nights, independent of the age of the subject during participation in ECZTEND. 
10) Based on subject recall during the last week prior to each site visit (from 6 days prior to each visit and including the day of the visit). 
Abbreviations: CDLQI = Children’s Dermatology Life Quality Index; DLQI = Dermatology Life Quality Index; EOT = end of treatment, 2 weeks after the last 
dose of tralokinumab; NRS = numeric rating scale; SFU = safety follow-up. 
 
 
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4.2 ECZTEND - schedule of trial procedures after May 2021 
Panel 5: ECZTEND – schedule of trial procedures for subjects who re-consent/consent to participate in the trial after May 2021 
 
Scree-
ning1 
Treatment period1 
EOT visit 
 
SFU1 
 
Un-
scheduled 
visit 
(if 
applicable)3 
Early 
termination 
(if 
applicable)1 
Refe- 
rences 
(protocol 
section) 
Weeks since 
first treatment 
in LP0162-
1337 
-2 
0 
2 
4 
8 
16 
24 
32 
64 
96 
128 
160 
192 
224 
256 
40 
72 
104 
136 
168 
200 
232 
264 
48 
80 
112 
144 
176 
208 
240 
 
56 
88 
120 
152 
184 
216 
248 
 
Variable2  
(max 268) 
SFU visit 
Variable2 
Visit type  
Site 
Site 
Site 
Site 
Site 
Site 
Site 
Tele-
phone4 
Short 
Site 
Tele-
phone4 
Standard 
Site 
Site 
Site 
Visit window 
(days)5 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Trial population and eligibility 
Informed 
consent6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix
 3B 
Subject 
eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.1; 8.2, 
8.3 
Investigator assessments at screening/baseline only 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2.1 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2.2 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2.3 
Columbia-
Suicide 
Severity Rating 
Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2.4 
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Scree-
ning1 
Treatment period1 
EOT visit 
 
SFU1 
 
Un-
scheduled 
visit 
(if 
applicable)3 
Early 
termination 
(if 
applicable)1 
Refe- 
rences 
(protocol 
section) 
Weeks since 
first treatment 
in LP0162-
1337 
-2 
0 
2 
4 
8 
16 
24 
32 
64 
96 
128 
160 
192 
224 
256 
40 
72 
104 
136 
168 
200 
232 
264 
48 
80 
112 
144 
176 
208 
240 
 
56 
88 
120 
152 
184 
216 
248 
 
Variable2  
(max 268) 
SFU visit 
Variable2 
Visit type  
Site 
Site 
Site 
Site 
Site 
Site 
Site 
Tele-
phone4 
Short 
Site 
Tele-
phone4 
Standard 
Site 
Site 
Site 
Visit window 
(days)5 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Treatments 
Concomitant 
medication and 
concurrent  
procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.6 
Initiation of 
emollient7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.4 
Tralokinumab 
administration/
dispensing8 
 
X9 
X9 
X9 
X 
X 
X 
 
X 
 
X 
 
 
X 
 
9.2, 9.8.3 
Treatment 
compliance 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
9.8.4 
Investigator assessments of efficacy 
Investigator’s 
Global 
Assessment 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
11.3.1.1 
Eczema Area 
and Severity 
Index 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
11.3.1.2 
SCORing 
Atopic 
Dermatitis 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
11.3.1.3 
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Scree-
ning1 
Treatment period1 
EOT visit 
 
SFU1 
 
Un-
scheduled 
visit 
(if 
applicable)3 
Early 
termination 
(if 
applicable)1 
Refe- 
rences 
(protocol 
section) 
Weeks since 
first treatment 
in LP0162-
1337 
-2 
0 
2 
4 
8 
16 
24 
32 
64 
96 
128 
160 
192 
224 
256 
40 
72 
104 
136 
168 
200 
232 
264 
48 
80 
112 
144 
176 
208 
240 
 
56 
88 
120 
152 
184 
216 
248 
 
Variable2  
(max 268) 
SFU visit 
Variable2 
Visit type  
Site 
Site 
Site 
Site 
Site 
Site 
Site 
Tele-
phone4 
Short 
Site 
Tele-
phone4 
Standard 
Site 
Site 
Site 
Visit window 
(days)5 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Investigator assessments of safety 
Weight 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
X 
11.4.1 
Vital signs 
X 
X 
X 
X 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
11.4.2 
Physical 
examination 
X 
X 
 
 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
11.4.3 
Electrocardio-
gram 
X 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
11.4.4 
Hepatitis B/C, 
HIV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.4.5 
Chemistry, 
haematology, 
immunoglo- 
bulin E 
X10 
X 
 
 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
11.4.5 
Serum 
pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.4.5 
Urine dip stick 
(Urinalysis)11 
X 
X 
 
 
X 
 
 
 
 
 
X 
X 
 
X 
X 
11.4.5 
Urine 
pregnancy test 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
11.4.5 
Anti-drug 
antibodies 
 
X 
 
X 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
11.4.6 
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Scree-
ning1 
Treatment period1 
EOT visit 
 
SFU1 
 
Un-
scheduled 
visit 
(if 
applicable)3 
Early 
termination 
(if 
applicable)1 
Refe- 
rences 
(protocol 
section) 
Weeks since 
first treatment 
in LP0162-
1337 
-2 
0 
2 
4 
8 
16 
24 
32 
64 
96 
128 
160 
192 
224 
256 
40 
72 
104 
136 
168 
200 
232 
264 
48 
80 
112 
144 
176 
208 
240 
 
56 
88 
120 
152 
184 
216 
248 
 
Variable2  
(max 268) 
SFU visit 
Variable2 
Visit type  
Site 
Site 
Site 
Site 
Site 
Site 
Site 
Tele-
phone4 
Short 
Site 
Tele-
phone4 
Standard 
Site 
Site 
Site 
Visit window 
(days)5 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Investigator assessments of safety (continued) 
Pharmacoki-
netics blood 
sample 
 
X 
 
X 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
11.5 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
13 
Patient-reported outcomes 
Patient 
Oriented 
Eczema 
Measure 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
11.3.2.1 
Dermatology 
Life Quality 
Index (DLQI)/ 
CDLQI12 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
11.3.2.2 
EuroQoL 
5-Dimension 
Health 
Questionnaire 
5-Level13 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
11.3.2.3 
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Scree-
ning1 
Treatment period1 
EOT visit 
 
SFU1 
 
Un-
scheduled 
visit 
(if 
applicable)3 
Early 
termination 
(if 
applicable)1 
Refe- 
rences 
(protocol 
section) 
Weeks since 
first treatment 
in LP0162-
1337 
-2 
0 
2 
4 
8 
16 
24 
32 
64 
96 
128 
160 
192 
224 
256 
40 
72 
104 
136 
168 
200 
232 
264 
48 
80 
112 
144 
176 
208 
240 
 
56 
88 
120 
152 
184 
216 
248 
 
Variable2  
(max 268) 
SFU visit 
Variable2 
Visit type  
Site 
Site 
Site 
Site 
Site 
Site 
Site 
Tele-
phone4 
Short 
Site 
Tele-
phone4 
Standard 
Site 
Site 
Site 
Visit window 
(days)5 
-3 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Patient-reported outcomes (continued) 
Worst Weekly 
Pruritus 
numeric rating 
scale 
Eczema-related 
Sleep numeric 
rating scale 
Patient use of 
topical 
treatment14 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
11.3.2.4 
1) If screening/baseline visits are performed on the same day as visit(s) in the parent trial, the order of assessments should be adhered to, working in parallel for 
both protocols. Assessments where data are captured in different vendor systems databases (ECG, ePRO, and laboratory tests) need to be completed twice. In 
such cases, the parent trial assessment should be performed first, followed by the trial LP0162-1337 assessment. For subjects included in the trial prior to 
protocol version 10, the first visit after May 2021 can be a site visit or a telephone visit.  
2) Subjects who withdraw from the trial will be followed up as described in Section 10. The final safety follow-up visit will be 4 weeks after the last dose (i.e. 
2 weeks after the EOT visit). For subjects from the parent trial LP0162-1334, the maximum number of weeks until the EOT visit will be 114 weeks.  
3) Assessments and procedures to be performed at an unscheduled visit are 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). 
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4) For subjects from the parent trial LP0162-1334, the telephone visit should preferably be performed as a video call. 
5) 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. 
6) The informed consent form must be signed prior to performing any protocol-related procedures, including but not limited to screening evaluations.  
7) All subjects must use an emollient, as background treatment, twice daily (or more, as needed) for at least 14 days before baseline and must continue this 
treatment throughout the trial (including safety follow-up). 
8) At trial visits, tralokinumab will be injected at the trial site, preferably by the subject or their caregiver, alternatively by site staff. At each trial visit from 
Week 4 onwards, subjects will be provided with tralokinumab to be administered at home until the next trial visit. In case of intercurrent illness that may 
compromise the safety of the subject, or fever within 72 hours prior to administration, tralokinumab administration should be rescheduled. If an anaphylactic 
reaction occurs, blood samples should be drawn for the analysis of serum tryptase (see details in Section 9.2). 
9) At the first 3 tralokinumab dosing visits, subjects (or their caregiver) will be trained in how to inject tralokinumab, except for those who have already been 
trained in home use during the parent trial. In addition, if the subject and/or the caregiver is/are health care professional(s), no training is required, but the 
subject should be trained in how to handle the IMP according to the IMP handling manual and in the procedures to be followed in the event of an emergency. 
At the first 3 dosing visits, subjects (except for those who have received open-label tralokinumab treatment in the parent trial) will also be monitored for 
immediate drug reactions for a minimum of 30 minutes after dosing, with vital signs taken after 30 minutes or until stable, whichever is later.  
10) IgE will not be measured at screening. 
11) 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 (Section 11.4.5). 
12) Adult subjects from all parent trials, except the LP0162-1334 trial, will perform the DLQI. Subjects from the parent trial LP0162-1334 will perform the 
CDLQI, independent of the age of the subject during participation in ECZTEND. 
13) Subjects from the parent trial LP0162-1334 will not perform the EuroQoL 5-Dimension Health Questionnaire 5-Level. 
14) Based on subject recall during the last week prior to each site visit (from 6 days prior to each visit and including the day of the visit). 
Abbreviations: AE = adverse event; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EOT = end of treatment, 2 weeks after the 
last dose of tralokinumab; IGA = Investigator’s Global Assessment; IgE = immunoglobulin E; IMP = investigational medicinal product; NA = not applicable; 
SFU = safety follow-up. 
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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. In its severe form, AD is characterised by widespread skin 
lesions, intractable itch, as well as increased susceptibility to bacterial, viral, and fungal skin 
infections (Bieber 2008, Hanifin and Reed 2007, Silverberg and Hanifin 2013, Weidinger and 
Novak 2016). AD is associated with a substantial patient burden that typically includes poor 
quality of life, sleep disturbance (Jeon et al. 2017), and reductions in work productivity 
(Kiebert et al. 2002). 
AD is characterised by an activated T-helper-2 (Th2) pathway with increased skin expression 
of key Th2 cytokines including interleukin (IL) 13 (Omori-Miyake et al. 2014, Tazawa et 
al. 2004). The expression of IL-13 is increased in lesional skin compared with non-lesional 
skin, and the proportion of CD4+ and CD8+ cells expressing IL-13 is upregulated in patients 
with AD compared with individuals without AD (Aleksza et al. 2002, Tazawa et al. 2004). 
IL-13 acts on keratinocytes to release C-C motif chemokine ligand 22 (CCL22) and recruit 
more IL-13 expressing Th2 cells, decrease differentiation, and contribute to decreased barrier 
function (Purwar et al. 2006). 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 and induces itch (Oh et al. 2013, Zheng et al. 2009). Indeed, itch is a 
key issue in AD, which drives significant mechanical damage to the skin and further 
facilitates allergen and pathogen entry. 
These effects together drive and exacerbate the disease phenotype. A review of the available 
preclinical literature from mouse and human ex vivo models suggests IL-13 as a, if not the, 
central mediator of the AD skin phenotype. Indeed, there is evidence that blocking the IL-4 
receptor (which is part of the receptor complex that also binds IL-13) with the monoclonal 
antibody dupilumab leads to clinical improvement in subjects with AD (Simpson et al. 2016). 
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 (Blanchard et al. 2005, May et al. 2012, Thom et al. 2012). 
The AD development programme investigates tralokinumab in subjects with 
moderate-to-severe AD. To date, 9 clinical trials have been completed: a phase 2b 
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dose-finding trial (trial D2213C00001), 2 phase 3 trials with tralokinumab as monotherapy 
(LP0162-1325 and LP0162-1326), a phase 3 trial with tralokinumab in combination with TCS 
(LP0162-1339), a phase 2 vaccine response trial (LP0162-1341), a phase 3 trial in adolescent 
subjects (LP0162-1334), a phase 1 drug-drug interaction trial (LP0162-1342), a phase 3 trial 
in adult subjects with severe AD ineligible to treatment with cyclosporin A (LP0162-1346), 
and a phase 3  trial with tralokinumab in combination with TCS (LP062-1343) in Japanese 
subjects with moderate-to-severe AD who are candidates for systemic therapy.  
Based on the results from the dose-finding trial, the dose of 300 mg tralokinumab was chosen 
for the phase 3 programme. 
In the pivotal phase 3 trials (LP0162-1325, -1326, and -1339), IGA, EASI, 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. Likewise, 
the efficacy of tralokinumab in combination with TCS was consistently demonstrated by 
statistically significant results on all primary and multiplicity-adjusted secondary endpoints at 
Week 16 in the phase 3 trial LP0162-1339. Non-inferiority of tralokinumab versus placebo 
with respect to immune responses to concomitantly administered, non-live vaccines was 
demonstrated in the LP0162-1341 trial.  
A total of 4,713 subjects across indications (healthy subjects, and subjects with AD, asthma, 
UC, and IPF) have been exposed to tralokinumab in 26 completed clinical trials, including 
2,524 subjects with AD in 9 completed clinical trials. A total of 2,088 subjects with AD 
received tralokinumab 300 mg, and 1026 of these were exposed to tralokinumab for 52 
weeks.  
The safety data supports that tralokinumab was well-tolerated with a favorable 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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All doses studied so far have had an acceptable benefit/risk profile, and no major safety 
concerns have been identified. Possible risks associated with use of tralokinumab are 
summarised in Section 5.6. 
5.3 Trial rationale 
The purpose of this trial is to evaluate the long-term safety of tralokinumab in adult and 
adolescent subjects as well as to evaluate the continuous response, re-treatment response, and 
response in tralokinumab-naïve subjects treated with tralokinumab. 
Subjects eligible for this trial will have received trial treatment and completed the treatment 
period(s) in one of the ‘parent trials’: LP0162-1325, -1326, -1334, -1339, -1341, 
-1342, -1343, -1346, or the investigator-initiated trial TRA-WEI-0015-I (see inclusion 
criterion no. 2). 
Subjects transferring from a blinded parent trial will enter the extension trial without their 
individual treatment allocation in the parent trial being unblinded. It is assumed that the 
majority of the subjects entering into this trial will have received tralokinumab in the parent 
trial – and will in the investigator’s opinion have gained therapeutic benefit from 
tralokinumab.  
Optional use of TCS is included in this trial, as subjects transferring from trials LP0162-1339, 
-1343, and -1346, and the open-label arms of trials LP0162-1325 -1326, and -1334 will have 
had this option during their treatment in the parent trial. Furthermore, the intended 
commercial use of tralokinumab is with or without concurrent use of TCS. 
5.4 Justification for dose 
The tralokinumab dosing regimen selected for this long-term extension trial is based on the 
dosing regimen used in the earlier trials in the tralokinumab phase 3 development programme, 
which in turn is based on the results of the phase 2b trial (D2213C00001) in subjects with 
moderate-to-severe AD.  
The dose is 300 mg administered subcutaneously (SC) Q2W. Subjects from all parent trials, 
except the parent trial LP0162-1334, will get 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, which is considered 
particularly important in those subjects who are tralokinumab-naïve or may have gone 
without tralokinumab for several weeks since their last treatment in the parent trial. 
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The subjects who will reach the highest exposure of tralokinumab after an initial loading dose 
of 600 mg tralokinumab are those who already have steady-state systemic concentrations 
when entering the trial, that is, subjects who have transferred directly from treatment with 
tralokinumab in one of the parent trials. The serum concentrations of tralokinumab after a 
600 mg loading dose on top of 300 mg steady state exposure will be lower than the serum 
concentrations at steady state after 600 mg Q2W. A tralokinumab dosing regimen of 600 mg 
Q2W for up to 12 weeks was safe and well-tolerated in a phase 2a trial in adult subjects with 
asthma. 
Subjects from the parent trial LP0162-1334, independent of the subject’s age when included 
in ECZTEND, will not receive an initial loading dose of 600 mg tralokinumab at baseline. 
Based on the LP0162-1334 trial design, it is anticipated that most of the subjects have been 
treated with 300 mg tralokinumab Q2W prior to inclusion in ECZTEND. As there are no 
safety data available for the administration of a loading dose of 600 mg tralokinumab to 
adolescent subjects who are already at steady-state after treatment with 300 mg tralokinumab 
Q2W, these subjects should not be unnecessarily exposed to an initial loading dose of 600 mg 
tralokinumab. To maintain the blinding of the parent trial LP0162-1334, all subjects 
transferring from this trial will be treated with 300 mg tralokinumab Q2W. Consequently, 
subjects who have received 150 mg tralokinumab, 300 mg tralokinumab Q4W or placebo in 
the parent trial LP0162-1334, will reach the 300 mg tralokinumab Q2W steady state 
2–4 weeks later than subjects who are already at steady state after treatment with 300 mg 
tralokinumab Q2W when included in ECZTEND. 
In subjects who have had a pause in treatment with tralokinumab since their last dose in the 
parent trial, the exposure will be lower. 
5.5 Ethical considerations  
Participation in this long-term 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 investigational medicinal product (IMP). In addition, all female subjects of childbearing 
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potential will have a pregnancy test performed before, during, and at end of treatment to 
ensure that no foetuses are exposed to the IMP. 
In this trial, all subjects will be treated with open-label tralokinumab with optional use of TCS 
or TCI. All subjects have previously participated in one of the parent trials, and the subjects 
who have received tralokinumab in these trials are likely to have gained a certain degree of 
benefit since they have agreed to participate in a long-term extension trial. Subjects will be 
under supervision by a dermatologist or allergist at least every 8 weeks during the treatment 
period until end of May 2021. For subjects who re-consent/consent to participate in the trial 
after May 2021, supervision by a dermatologist or allergist occurs at least every 16 weeks 
after May 2021 and for the remaining treatment period to reflect standard clinical practice. 
Between site visits, a telephone visit is mandatory to secure sufficient safety reporting. 
Furthermore, subjects may receive rescue therapy at the discretion of the investigator if 
medically necessary through treatment and follow-up. Stopping rules are specified for this 
trial to ensure that subjects are not continuing in a trial where they experience no benefit or 
where their safety is not ensured. 
Altogether, the risks associated with participating in this clinical trial are considered low and 
outweighed by the potential treatment benefit for each participating subject as well as the 
benefit of a potential future treatment option for moderate-to-severe AD. 
In accordance with the current version of the International Council for Harmonisation (ICH) 
Good Clinical Practice (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. 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 for this long-term safety trial with tralokinumab is 
regarded as ethically justified and adherent with ethical requirements. 
 
 
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5.6 Benefit/risk assessment 
There is an unmet medical need for new therapies for use in subjects with moderate-to-severe 
AD because current immunosuppressive medications, such as cyclosporine, methotrexate, and 
azathioprine, are associated with long-term toxicities. Based on the benefits in treating AD 
reported with dupilumab, there is a reasonable expectation that tralokinumab will prove to be 
an effective treatment of moderate-to-severe AD. Although dupilumab exhibits an acceptable 
benefit/risk profile in clinical trials in AD, the long-term efficacy and safety experience with 
dupilumab is currently limited. 
Tralokinumab has already demonstrated efficacy in moderate-to-severe AD in a phase 2b trial 
in adult subjects, and the evidence discussed in Section 5.2 further supports the hypothesis 
that adult and adolescent subjects with AD may benefit from treatment with tralokinumab. An 
important aspect in the benefit/risk evaluation is the reassuring safety profile of tralokinumab 
in AD, asthma, ulcerative colitis, idiopathic pulmonary fibrosis, and in trials with healthy 
subjects. 
In the clinical trials completed to date, tralokinumab was well-tolerated. A number of 
theoretical potential risks have been identified, including hypersensitivity reactions, immune 
complex disease, severe infections, malignancies, and interference with reproductive function; 
measures are in place in this trial to protect participating subjects as follows: 
• Close monitoring of subjects during the trial, with site visits at least every 
16 weeks (every 8 weeks until end of May 2021). Mandatory telephone visits 
will be performed between site visits to secure sufficient safety reporting after 
May 2021; for subjects from the parent trial LP0162-1334, this should 
preferably be a video call (see Panel 2 and Section 4). 
• Close monitoring of subjects* after the first 3 administrations of IMP as a 
precautionary measure against hypersensitivity reactions (further details are 
given in Section 9.2). 
• * Except for subjects transferring from the open-label trials LP0162-1342 and 
TRA-WEI-0015-I, and from the open-label tralokinumab arms of trials 
LP0162-1325, -1326, and -1334, all of whom are certain to have received 
tralokinumab. 
• Monitoring of subjects for clinical manifestations that may be associated with 
the development of specific antibodies to tralokinumab (immune complex 
disease). 
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• 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) (Bancroft et 
al. 2000). 
• Exclusion of subjects with a history of tuberculosis requiring treatment within 
12 months prior to the screening visit. 
• Exclusion of subjects with a history of a clinically significant infection 
(defined as a systemic or serious skin infection requiring parenteral antibiotics, 
antiviral, or anti-fungal medication; see Section 8.3) 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. 
In conclusion, previous clinical experience with tralokinumab shows no major safety or 
tolerability concerns, and appropriate measures have been instituted in this trial to protect 
subjects from potential risks that have been previously identified and to sufficiently monitor 
each subject. The current risk/benefit profile is considered favourable and supports the 
administration of tralokinumab with or without TCS therapy for the purposes of achieving the 
objectives of this trial. 
The current COVID-19 pandemic may warrant many subjects in the ECZTEND trial to stay at 
home to comply with authority-issued preventive measures, which may impact subjects’ 
ability to attend visits at the trial site. To follow authorities’ restrictions and to safeguard the 
subjects in the ECZTEND trial as well as providing continued therapy to secure the scientific 
integrity, the clinical trial protocol provides an opportunity for telephone visits and courier 
delivery of IMP and pregnancy tests to subjects in replacement of the site visits (see Appendix 
3K for details). 
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6 Trial objectives and endpoints 
Panel 6: Objectives and endpoints 
Objectives 
Endpoints 
Primary objective 
Primary endpoint 
To evaluate the long-term 
safety of tralokinumab 
• 
Number of adverse events during the treatment period from 
baseline up to Week 268 
Secondary objectives 
Secondary endpoints 
To evaluate the efficacy 
of tralokinumab given 
as continuous treatment, 
re-treatment, or 
introduced   
for the first time 
in tralokinumab-naïve 
subjects 
• 
IGA score of 0 (clear) or 1 (almost clear) at Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
EASI751 at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 
 
Other endpoints 
 
• 
Change in EASI score from baseline2 to Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
Change in SCORAD from baseline2 to Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
Change in POEM score from baseline2,3 to Weeks 16, 56, 80-88, 
104, 128-136, 152, 184, 216, and 248 
• 
Change in DLQI/CDLQI4 score from baseline2,3 to Weeks 16, 
56, 80-88, 104, 128-136, 152, 184, 216, and 248 
• 
Change in EQ-5D-5L score from baseline2,3,5 to Weeks 16, 56, 
80-88, 104, 128-136, 152, 184, 216, and 248  
• 
Presence of anti-drug antibodies (yes/no) 
• 
Time from first dose to permanent discontinuation of 
tralokinumab 
• 
Proportion of time with EASI751 after first occurrence of 
EASI75 during treatment 
• 
Proportion of time with EASI501 after first occurrence of 
EASI50 during treatment 
• 
Proportion of time with IGA 0/1 after first occurrence of IGA 
0/1 during treatment 
• 
Worst Weekly Pruritus NRS at Weeks 16, 56, 88, 104, 136, 152, 
184, 216, and 248 
• 
Eczema-related Weekly Sleep NRS at Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
Use of topical treatment during the last week at Weeks 16, 56, 
88, 104, 136, 152, 184, 216, and 248  
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1 EASI75 and EASI50 calculated based on baseline EASI score in parent trial. Endpoint not applicable for 
subjects from the parent trial TRA-WEI-0015-I, as data from the parent trial will not be transferred to 
LEO Pharma. 
2 ‘Change from baseline’ defined as change from baseline in parent trial. Endpoints not applicable for subjects 
from the parent trial TRA-WEI-0015-I, as data from the parent trial will not be transferred to LEO Pharma. 
3 Endpoint not applicable for subjects from the parent trial LP0162-1342, as these subjects will not have had 
POEM, DLQI/CDLQI, or EQ-5D-5L assessments in the parent trial, and thus are missing baseline 
assessments. 
4 All subjects from the parent trial LP0162-1334, independent of the subject’s age during participation in 
ECZTEND, will perform the Children’s Dermatology Life Quality Index (CDLQI), an adolescent’s pruritis 
NRS with a recall period of past 7 days, and an eczema-related sleep NRS with a recall period over the past 
7 nights (see rationale in Section 12). 
5 Endpoint not applicable for subjects from the parent trials LP0162-1334, and -1343, as these subjects will not 
have had EQ-5D-5L assessments in the parent trial and thus are missing the baseline assessment. In 
addition, the EQ-5D-5L questionnaire has not been validated for adolescents. 
Abbreviations: CDLQI = Children’s Dermatology Life Quality Index; DLQI = Dermatology Life Quality 
Index; EASI = Eczema Area and Severity Index; EASI75/EASI50 = at least 75% / 50% reduction in EASI 
score, relative to baseline in parent trial; EQ-5D-5L = EuroQoL 5-Dimension Health Questionnaire 5-Level; 
IGA = Investigator’s Global Assessment; NRS = numeric rating scale; POEM = Patient Oriented Eczema 
Measure; SCORAD = Scoring Atopic Dermatitis. 
 
 
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7 Trial design 
7.1 Overall trial design  
7.1.1 Overview 
This is an open-label phase 3 trial to study the long-term safety of tralokinumab administered 
to adult subjects (≥18 years) and adolescent subjects (12 to <18 years) with AD who 
participated in previous trials with tralokinumab. The trial will include a screening period of 
2 weeks (Week -2 to Week 0), which is expected to overlap with the last period in the parent 
trial for the majority of subjects, and a long-term treatment period of approximately 0.5 years 
to up to 5 years. The duration of the treatment period for each subject will depend on when 
they enter the trial after completing the parent trial, and by which treatment stop date they 
have consented to (end of May 2021, end of May 2022, or a country-specific end of treatment 
day according to Appendix 3J).  
The visit schedule until May 2021 is different from the visit schedule after May 2021, where a 
number of site visits were replaced by mandatory telephone visits to reduce the burden of 
frequent site visits (Panel 2 and Panel 5). 
7.1.1.1 COVID-19 pandemic guidance 
In the case where a subject is unable to attend site visits due to the COVID-19 pandemic, 
please refer to Appendix 3K for guidance. 
7.1.2 Screening period (Week -2 to Week 0) 
Prior to attending any trial procedure, a signed informed consent must be obtained from the 
subject or the adolescent subject’s legally authorised representative(s), and a signed informed 
assent must be obtained from the adolescent subject (as appropriate and according to national 
laws and regulations).  
To avoid a gap between the parent trial and extension trial, screening should ideally start 
before the end of the parent trial. Hence, the screening period is expected to overlap with the 
last period in the parent trial for the majority of subjects: the last visit in the parent trial could 
ideally coincide with the baseline visit of the extension trial. However, subjects can be 
included in the ECZTEND trial up to 26 weeks after the last IMP dose in the parent trial. 
To avoid duplicate reporting of AEs, any AE with onset before the final visit in the parent trial 
should be reported as an AE in the parent trial. If ongoing, the AE should also be recorded as 
medical history in the current extension trial (see Section 11.2.2). AEs with onset after the 
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final visit in the parent trial and after informed consent has been obtained for the extension 
trial should be recorded as an AE in the extension trial. 
The screening period has a duration of 2 weeks. Eligibility will be assessed at the screening 
visit and at baseline prior to start of treatment. Should the screening exceed a duration of 
2 weeks, the sponsor should be consulted, and approval sought before the subject can attend 
Visit 3 (baseline visit). 
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 at Week -2. On lesional skin, emollient 
should only be applied at times where TCS are not applied (that is, emollient and TCS should 
not be used on the same areas at the same time of day); on areas not treated with TCS, the 
emollient may be applied at all times. 
7.1.3 Treatment period (Week 0 and onwards) 
7.1.3.1 Treatment initiation 
Following the screening period, and at least 2 weeks after the last dose in the parent trial, 
subjects from all parent trials except the parent trial LP0162-1334, will receive an initial 
loading dose of 600 mg tralokinumab (4 mL) at baseline. Subjects from the parent trial 
LP0162-1334 will start with a dose of 300 mg tralokinumab (2 mL) at baseline. For the rest of 
the treatment period, all subjects will receive a dose of 300 mg tralokinumab Q2W (2 mL). 
Tralokinumab will be administered by subcutaneous (SC) injection. 
Subjects will self-inject tralokinumab – or have tralokinumab injected by a caregiver – in their 
home after adequate training by site staff during the 3 first treatment visits (Weeks 0, 2, and 
4). Subjects who already have experience with home use of tralokinumab from participation 
in open-label arms of trials LP0162-1325, -1326, and -1334 can start self-injecting at baseline 
without training (see also Section 9.2). At the trial visits, tralokinumab will be injected at the 
trial site, preferably by the subject or their caregiver, alternatively by site staff.  
The first 3 treatment visits will also be used for post-dose monitoring for immediate drug 
reactions (see Section 9.2), as some subjects will have received placebo in the parent trial and 
are thus naïve to tralokinumab. Subjects who have transferred from the open-label trials 
LP0162-1342 or TRA-WEI-0015-I, or the open-label arms of trials LP0162-1325, -1326, or -
1334, and who have received at least 3 doses of tralokinumab in the parent trial will not need 
to be observed. 
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Subjects can use TCS (US class ≥4 or Europe class ≤3) or TCI at the investigator’s discretion. 
If TCS are used, the subject should be monitored for signs of local or systemic TCS toxicity, 
and the safety and appropriateness of continued or repeated courses of TCS therapy should be 
evaluated by site staff. 
Treatment is described in more detail in Section 9. 
7.1.3.2 Treatment period until end of May 2021 (all subjects) 
All subjects included in the trial prior to protocol version 10, attended site visits every 
8 weeks until the last visit before end of May 2021, and followed the schedules of trial 
procedures in Section 4.1.  
At end of May 2021, the procedures applicable depended on whether the subjects did NOT or 
DID accept to continue in the trial after May 2021:  
• Subject did NOT re-consent to continue in the trial after May 2021:  
The subject continued to follow the trial procedures in Section 4.1. The subject 
had to be supplied with IMP for home dosing until end of May 2021, where 
treatment had to be stopped.  
• Subject DID re-consent to continue in the trial after May 2021:  
After signing the consent form (subject or legal authorised representative), as 
well as the assent form for adolescent subjects, the last visit before end of 
May 2021 had to be completed as a normal site visit (i.e. not as an EOT visit). 
After that, the schedule of trial procedures in Section 4.2 was followed (see 
description of treatment period after May 2021 in Section 7.1.3.3). 
 
7.1.3.3 Treatment period after May 2021 
Subjects who wanted to participate in the trial after May 2021 had to re-consent (subjects 
included based on earlier protocol versions than version 10) or consent (subjects included 
based on protocol versions 10 to 12) to participate.  
Subjects who re-consented/consented to participate in the trial after May 2021 follow the 
modified schedule of trial procedures specified in Section 4.2:  
• For subjects included in the trial based on protocol versions 10 to 13, treatment 
will be initiated as described in Section 7.1.3.1. 
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• For subjects included in the trial prior to protocol version 10, the first visit 
after May 2021 can be a site visit or a telephone visit. The first site visit may 
be after 8 weeks before starting the 16-week schedule to align individual visit 
schedules with endpoints.  
• All subjects who re-consented/consented to participate in the trial after 
May 2021: subjects will start with a 24-week period with more frequent visits, 
and then continue with site visits (standard site visits or short site visits) every 
16 weeks, interchanging with a telephone visit in between the site visits. For 
subjects from the parent trial LP0162-1334, the telephone visit should 
preferably be a video call. Visit types during the treatment period are described 
in Section 7.1.3.4.  
• Treatment completion dates are dependent on the subject’s consent and are 
done according to Panel 7. 
Panel 7 Treatment completion date 
Parent trial 
Subject did NOT consent 
to continue after May 
2021 
Subject DID re-consent or 
consent to participate after 
May 2021 
LP0162-1325, -1326, -1339, -1341, -1342, 
-1343, -1346, and TRA-WEI-0015-I 
End of May 2021 
Country-specific end date 
according to Appendix 3J 
LP0162-1334 (adolescents) 
End of May 2021 
End of May 2022 
 
7.1.3.4 Trial visits in the treatment period 
Site visits until end of May 2021 
Until end of May 2021, all subjects included in the trial prior to protocol version 10, attended 
site visits every 8 weeks. At each site visit, subject or subject’s caregiver (or investigator) 
administered tralokinumab and assessed concomitant medications and treatment compliance. 
The following assessments were performed according to the trial procedures specified in 
Section 4.1: 
• Efficacy assessments: IGA, EASI, and SCORAD. 
• Safety assessments: weight, vital signs, physical examination, ECG, laboratory 
parameters (chemistry, haematology and immunoglobulin E), urinalysis, urine 
pregnancy test (if applicable), anti-drug antibodies (ADA), pharmacokinetics 
(PK), and AEs. 
• Patient-reported outcomes: POEM, DLQI/CDLQI, EQ-5D-5L*, eczema-
related sleep NRS, worst weekly pruritus NRS/adolescent’s pruritis NRS, and 
patient use of topical treatment. 
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• *The EQ-5D-5L is not performed by subjects from the parent trial 
LP0162-1334. 
Details of assessments are described in Section 11.  
Visits after May 2021 
After May 2021, subjects who re-consented to continue or consent to be included in the trial 
after May 2021, will attend 2 types of site visits (standard site visits and short site visits), 
interchanging with a telephone visit in between the site visits, according to the trial 
procedures presented in Section 4.2. The 3 types of visits are described below. 
Standard site visit 
At each standard site visit (Weeks 56, 88, 120, 152, 184, 216, and 248), subject or subject’s 
caregiver (or investigator) will administer tralokinumab and assess concomitant medications 
and treatment compliance. In addition, the following assessments will be performed: 
• Efficacy assessments: IGA, EASI, and SCORAD. 
• Safety assessments: Weight, vital signs, physical examination, ECG, laboratory 
parameters (chemistry, haematology and immunoglobulin E), urine dipstick, 
urine pregnancy test (if applicable), ADA, PK, and AEs. 
• Patient-reported outcomes: POEM, DLQI/CDLQI, EQ-5D-5L*, eczema-
related sleep NRS, worst weekly pruritus NRS/adolescent’s pruritis NRS, and 
patient use of topical treatment. 
• *The EQ-5D-5L is not performed by subjects from the parent trial 
LP0162-1334. 
Details of assessments are described in Section 11.  
Short site visit 
At each short site visit (Weeks 40, 72, 104, 136, 168, 200, 232, and 264), subjects or subject’s 
caregiver (or investigator) will administer tralokinumab and assess concomitant medications 
and treatment compliance. In addition, the following assessments will be performed: 
• Efficacy assessments: IGA, EASI, and SCORAD. 
• Safety assessments:Vital signs, physical examination, pregnancy test (if 
applicable), and AEs. 
• Patient-reported outcomes: POEM, DLQI/CDLQI, EQ-5D-5L*, eczema-
related sleep NRS, worst weekly pruritus NRS/adolescent’s pruritis NRS, and 
patient use of topical treatment.  
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• *The EQ-5D-5L is not performed by subjects from the parent trial 
LP0162-1334. 
Details of assessments are described in Section 11.  
Telephone visit 
Subjects will be contacted via telephone (telephone visit) 8 weeks after site visits (standard 
site visit or short site visit). For subjects from the parent trial LP0162-1334, this should as far 
as possible be a video call. 
At each telephone visit, AEs, concomitant medication, treatment compliance, and pregnancy 
test result (if applicable) are assessed. The pregnancy test must be performed by the subject at 
home within 48 hours before the telephone visit, and a negative result informed to the site 
staff before the subject can continue treatment. 
Delegation of the telephone visit to qualified personnel is allowed at the discretion of the 
investigator. 
Details of assessments are described in Section 11.  
7.1.4 Safety follow-up period (after last IMP dose) 
All subjects will complete an off-treatment follow-up period for the assessment of safety, PK, 
and ADA.  
The timing of the safety follow-up visit depends on the parent trial and on whether the subject 
has consented to participate after May 2021, as summarised in Panel 8. 
Panel 8: Safety follow-up visit  
Parent trial  
Subject  did NOT consent 
to continue after 
May 2021 
Subject DID re-consent or 
consent to participate 
after May 2021 
LP0162-1325, -1326, -1334 (adolescents),  
-1339, -1341, -1342, -1343, -1346, and    
TRA-WEI-0015-I 
16 weeks after last dose 
4 weeks after last dose 
7.2 Number of subjects needed 
The assumed sample size for this trial is approximately 1,600 subjects. No formal sample size 
has been calculated; the sample size is based on the population sizes of the parent trials and 
assumptions regarding how many subjects will complete the parent trials and be eligible for / 
consent to participate in the current extension trial. 
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This trial will be conducted at approximately 330 sites in Canada, Europe, Japan, and the US. 
The number of subjects per trial site will depend on how many of the subjects in the parent 
trial meet the eligibility criteria for, and choose to participate in, the extension trial. 
7.3 End of trial definition 
The end of the trial is defined as the date of the last visit of the last subject in the trial 
globally. By the end of this trial, subjects will have been exposed to tralokinumab for up to 
5 years, which is considered appropriate for evaluating long-term safety of tralokinumab. 
The final collection of data for the primary endpoint will occur by Q2 2024.  
A subject is considered to have completed the trial if the subject has completed all periods of 
the trial, including the safety follow-up visit, according to protocol version 13 or earlier 
versions.  
The duration of the treatment period for each subject will depend on when the subject enters 
the trial after completing the parent trial, and by which treatment stop date they have 
consented to (end of May 2021, end of May 2022, or a country-specific end of treatment day 
according to Appendix 3J). Hence, a subject is considered to have completed the treatment 
period for either of the following scenarios: 
• Approximately end of May 2021 for subjects completing according to earlier 
versions than protocol version 10. 
• Approximately end of May 2022 for subjects from the parent trial 
LP0162-1334 who consented to continue in the trial after May 2021. 
• At a country-specific end of treatment date (Appendix 3J) for subjects from the 
parent trials LP0162-1325, -1326, -1339, -1341, -1342, -1343, -1346, and 
TRA-WEI-0015-I who consented to continue in the trial after May 2021.  
 
See Section 11.8 for the end of trial procedures. 
7.4 Software 
CDISC controlled terminology version 30-Mar-2018 (or newer) was used for definition of 
controlled terminology used throughout this protocol and will be used for statistical 
programming and output. Study Data Tabulation Model (SDTM) v1.4 with SDTM 
Implementation Guide 3.2 (or newer) will be used for data tabulations. 
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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 safety risk by participating in the trial and can be expected to comply with the protocol. 
It is assumed that subjects entering this trial will in the investigator’s opinion have the 
potential to gain therapeutic benefit from treatment with tralokinumab irrespectively of 
whether the subject received tralokinumab or placebo in the parent trial. 
The subject’s eligibility for the clinical trial must be verified according to the inclusion and 
exclusion criteria at visits specified in Section 4. It will be recorded in the 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/IECs, as applicable. 
8.2 Inclusion criteria 
For inclusion into this trial, subjects must fulfil all of the following criteria: 
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 (as applicable according to national laws or 
regulations). 
2. Subjects must have completed* the treatment period(s) of one of the parent trials: 
LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346, or TRA-WEI-0015-I. 
• *To be assessed on the first day of IMP administration (baseline).  
3. Subjects must have complied with the clinical trial protocol in the parent trial to the 
satisfaction of the investigator. 
4. Subjects must be able and willing to self-administer tralokinumab treatment (or have it 
administered by a caregiver) at home after the initial 3 injection visits at the trial site 
(in this trial). 
5. Subjects must have applied a stable dose of emollient twice daily (or more, as needed) 
for at least 14 days prior to baseline. 
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6. Female subjects of childbearing potential (defined as Tanner stage ≥3 or menarche)* 
must use a highly effective** form of birth control (confirmed by the investigator) 
continuously for at least 1 month prior to the pregnancy test at baseline (Week 0), 
throughout the trial, and for at least 16 weeks (5 half-lives of the IMP) after the last 
administration of IMP. 
*A female subject 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). 
• Premenarchal. 
**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), 
same-sex partner, or vasectomised partner (given that the subject is monogamous). 
 
8.3 Exclusion criteria 
Subjects must not enter the trial if any of the following exclusion criteria are fulfilled: 
1. Any condition that required permanent discontinuation of trial treatment in the parent 
trial. 
2. More than 26 weeks have elapsed* since the subject received the last IMP injection in 
the parent trial. 
* To be assessed on the first day of IMP administration (baseline). 
3. Subjects who, during their participation in the parent trial, developed a serious adverse 
event (SAE) deemed related to tralokinumab by the investigator, which in the opinion 
of the investigator could indicate that continued treatment with tralokinumab may 
present an unreasonable safety risk for the subject. 
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4. Subjects who, during their participation in the parent trial, developed an AE that was 
deemed related to tralokinumab by the investigator and led to temporary 
discontinuation of trial treatment, which in the opinion of the investigator could 
indicate that continued treatment with tralokinumab may present an unreasonable 
safety risk for the subject. 
5. Receipt of any marketed biological therapy or investigational biologic agent (other 
than tralokinumab), including immunoglobulin, anti-IgE, or dupilumab: 
• 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. 
6. Treatment with the following medications within 5 half-lives prior to baseline: 
• Systemic immunosuppressive/immunomodulating drugs (for example, 
methotrexate, cyclosporine, azathioprine, mycophenolate-mofetil, Janus kinase 
inhibitors). 
• Systemic corticosteroids (excluding topical, ophthalmic, inhaled, or intranasal 
delivery). 
7. Treatment with topical PDE-4 inhibitors or topical JAK inhibitors within 2 weeks 
prior to baseline. 
8. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody* (HBsAb), 
hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (anti-HCV) serology 
at screening. Subjects with positive HBsAb are eligible provided they are vaccinated 
against hepatitis B and have negative HBsAg and HBcAb. 
*Subjects from the parent trial LP0162-1343 with a positive HBsAb may be assigned 
treatment provided they have negative HBsAg, HBcAb, and HCV serology at 
screening. 
9. Known or suspected hypersensitivity to any component(s) of the IMP. 
• Subjects who during the parent trial have had a localised injection site reaction 
suspected to be due to hypersensitivity are eligible provided that the subject 
has been able to continue IMP administrations and there has been no sign of a 
systemic hypersensitivity reaction. 
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10. History of anaphylaxis following any biological therapy.  
11. History of immune complex disease. 
12. 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 when informed consent was obtained. 
o Subjects who during the parent trial 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 has been completed. 
• 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 when informed consent was obtained. 
13. Tuberculosis requiring treatment within 12 months prior to screening. Evaluation will 
be according to local guidelines as per local standard of care. 
14. 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 or subject’s verbal report. 
15. Current participation in any other interventional clinical trial, except for tralokinumab 
trials LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1346, -1343, or TRA-WEI-
0015-I. 
16. Previously screened in this clinical trial. 
17. Receipt of live attenuated vaccines 30 days prior to baseline and during the trial 
including the safety follow-up period. 
• Receipt of inactive/killed vaccines (for example, inactive influenza and 
inactive COVID-19 vaccines) is allowed, provided they are not administered 
within 5 days before/after any IMP injection. 
18. Receipt of blood products within 4 weeks prior to baseline. 
19. Major surgery within 8 weeks prior to baseline, or planned in-patient surgery or 
hospitalisation during the trial period. 
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20. 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. 
21. 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. 
22. Subjects who are legally institutionalised. 
23. Female subjects who are pregnant, breastfeeding, or lactating. 
24. History of attempted suicide or significant risk of suicide (either in the opinion of the 
investigator, or defined as a "yes" to suicidal ideation questions 4 or 5, or answering 
"yes" to suicidal behaviour on the Columbia-Suicide Severity Rating Scale [C-SSRS] 
screening version). 
25. 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. 
26. A helminth parasitic infection within 6 months prior to the date when informed 
consent is obtained that has not been treated with, or has failed to respond to, standard 
of care therapy. 
27. Any disorder that is not stable and in the opinion of the investigator could: 
• Affect the safety of the subject throughout the trial. 
• Influence the findings of the trial. 
• Impede the subject’s ability to complete the trial. 
Examples include but are not limited to cardiovascular, gastrointestinal, hepatic, renal, 
neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, 
immunological, and psychiatric disorders and major physical impairment. 
28. Any abnormal finding which in the opinion of the investigator may: 
• Put the subject at risk because of their participation in the trial. 
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• Influence the results of the trial. 
• Influence the subject’s ability to complete the trial. 
The abnormal finding must be clinically significant and observed during the screening 
period. Examples include abnormal findings in physical examination, vital signs, 
electrocardiogram (ECG [based on the central ECG evaluation report]), or central 
laboratory results (haematology, clinical chemistry, or urinalysis). 
8.4 Screening and screening failures 
Subject identification number 
Trial participation begins once written informed consent is obtained. Refer to Appendix 3B 
for details on the informed consent process.  
Once informed consent is obtained, a unique subject identification number (subject ID) will 
be assigned by including the subject through the EDC system, and the screening evaluations 
to assess eligibility criteria may begin. The subject ID consists of 5 digits, the first 3 of which 
refer to the site number, the latter 2 are sequential numbers, starting from 01. The subject ID 
will be different from that in the parent trial, and 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, as appropriate and according to national laws and regulation) 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 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. In addition, the investigator will maintain 
a log of all subjects considered for screening, whether they or their legal representative(s) 
have provided written informed consent (and informed assent as appropriate and according to 
national laws and regulation) or not (screening log). This log will be anonymous and will 
include the reason(s) for not entering the trial, if applicable, or the allocated subject ID. 
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 screening failure information is 
required to ensure transparent reporting of screening failure subjects to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements (Schulz 2010) and to 
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respond to queries from regulatory authorities. The following data will be collected in the 
eCRF for screening failures: 
• Date of informed consent (s). 
• Demographics (age, date of birth [or only year and month of birth as applicable to local 
legislation], sex, ethnicity, race). 
• Reason for screening failure. 
• Failure to meet eligibility criteria. 
• Lost to follow-up. 
• Withdrawal by subject. 
• Withdrawal by parent/guardian.* 
• Other. 
• Date of screen failure. 
• Any adverse events (AEs) and serious AEs (SAEs) with onset after the final visit in the 
parent trial (AEs and SAEs with onset before the final visit in the parent trial should be 
reported as an AE in the parent trial). 
*For adolescent subjects as applicable. 
 
In case of any SAEs, these must be followed-up as described in Section 13.7. 
Individuals who do not meet the criteria for participation in this trial (screening failures) may 
not be re-screened. 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 9: Identification of investigational medicinal product (IMP) 
IMP 
Dosage form 
Active ingredient and concentration 
Pack size 
Tralokinumab 
Solution for 
injection 
Nominal concentration of tralokinumab 
150 mg/mL in 
 mM sodium 
acetate/acetic acid buffer,
 mM sodium 
chloride,
% (w/v) PS-
, pH 
 
1.0 mL pre-filled 
accessorised syringe1 
1 The accessorised pre-filled syringe is a single-use, disposable system designed to administer the labelled dose 
of the system to the subcutaneous space during 1 injection and automatically provide a safety mechanism to 
reduce the occurrence of accidental needle sticks during disposal of the system. The system consists of a 
pre-filled syringe sub-assembly (1 mL pre-filled syringe barrel with a 1/2-inch, 27-gauge, thin-wall, staked-
in needle; rigid needle shield; plunger stopper), and a safety device. 
 
9.2 Administration of IMP 
The EDC system will assign the required kit number(s) for each subject at each dispensing 
visit. 
The first day of dosing with tralokinumab is considered baseline (Visit 3). At this visit, 
subjects from all parent trials except the parent trial LP0162-1334, will receive 4 SC 
injections (1.0 mL each) of 150 mg tralokinumab to receive a total initial loading dose of 
600 mg tralokinumab. At baseline, subjects from the parent trial LP0162-1334 will receive 
2 SC injections (1.0 mL each) of 150 mg tralokinumab to receive a total initial dose of 
300 mg tralokinumab. For the rest of the treatment period, all subjects will receive a total dose 
of 300 mg tralokinumab every second week (Q2W). A minimum interval of 7 days is required 
between 2 dosings. 
The dosing regimen is presented in Panel 10. 
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Panel 10: Dosing regimen 
Subjects from all parent trials except the 
LP0162-1334 trial 
Subjects from the parent trial LP0162-1334 
Initial loading dose at baseline 
• 
600 mg tralokinumab, single dose of 
4 SC injections with 1 mL of 150 mg/mL 
tralokinumab 
Dose for the rest of the treatment period 
• 
300 mg tralokinumab Q2W, 
2 SC injections with 1 mL of 150 mg/mL 
tralokinumab every second week 
Dose during the treatment period (also at baseline) 
• 
300 mg tralokinumab Q2W, 
2 SC injections with 1 mL of 150 mg/mL 
tralokinumab every second week 
Abbreviations: Q2W = every second week; SC = subcutaneous 
 
Subjects will self-inject tralokinumab – or have tralokinumab injected by a caregiver – in their 
home after adequate training by the investigator or delegated site staff during the 3 first 
treatment visits. In addition, if the subject and/or the caregiver is/are health care 
professional(s), no training is required, but the subject should be trained in how to handle the 
IMP according to the IMP handling manual and in the procedures to be followed in the event 
of an emergency. The individual who will be performing the injection (that is, the subject, 
caregiver, or both) will be trained in proper SC injection technique and procedures to be 
followed in the event of an emergency during or following home use of tralokinumab. The 
subject (and/or caregiver) must inject tralokinumab under supervision by the trainer on one or 
more occasions such that the trainer is satisfied with the individual’s understanding and 
confidence of the procedure. 
Subjects who already have experience with home use of tralokinumab from participation in 
open-label arms of trials LP0162-1325 or LP0162-1326 can start self-injection at baseline 
without training. 
At trial visits, tralokinumab will be injected at the trial site, preferably by the subject or their 
caregiver, alternatively by site staff, when all assessments have been completed. It will be 
recorded in the eCRF (for trial visits only) whether tralokinumab was injected by the 
subject/caregiver or site staff. 
Tralokinumab will be injected into the SC tissue of the upper arm, anterior thigh, or abdomen, 
separated by at least 3 cm within the same anatomical location. 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. 
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Further details on IMP administration are provided in a trial product handling manual. 
Subjects will also receive a pamphlet with instructions for IMP self-administration. IMP must 
be administered according to these instructions. 
IMP dosing/dispensing visits are shown in the schedule of trial procedures (Section 4). 
After administration of tralokinumab 
For the first 3 tralokinumab dosing visits (Weeks 0, 2, and 4), subjects will be monitored for 
immediate drug reactions for a minimum of 30 minutes after administration of tralokinumab, 
with vital signs measured after 30 minutes or until stable, whichever is later. Vital signs will 
be documented in the eCRF. Subjects who have participated in open-label tralokinumab arms 
of trials LP0162-1325, -1326, or -1334, or from one of the open-label trials LP0162-1342 and 
TRA-WEI-0015-I, and who have received at least 3 doses of tralokinumab in the parent trial, 
are exempt from this monitoring. 
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) (Johansson et al. 2004). The clinical criteria for defining anaphylaxis 
for this trial are listed in Appendix 6 (Sampson et al. 2006). 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. 
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 (for example, viral 
illness). 
• The subject is febrile (defined as ≥38°C) within 72 hours prior to 
administration of tralokinumab. 
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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 violate any 
of the exclusion criteria will be assigned to treatment with tralokinumab at baseline. 
9.4 Background treatment 
All subjects must 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 must continue their background emollient treatment throughout the trial 
(including the safety follow-up). 
9.5 Rescue treatment 
If medically necessary (that is, 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, 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 (higher potency TCS: US class <4 or Europe 
class >3) will continue treatment with IMP. If TCS are used as rescue treatment, the subject 
should be monitored for signs of local or systemic TCS toxicity, and the safety and 
appropriateness of continued use should be supervised by site staff. 
If a subject receives rescue treatment with systemic corticosteroids or non-steroidal systemic 
immunosuppressive drugs (for example, cyclosporine, methotrexate, mycophenolate mofetil, 
azathioprine), treatment with IMP will be immediately discontinued (see Section 10.2.3). 
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. 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. 
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9.6 Concomitant medication and concurrent procedures 
Any medication (except for IMP/NIMP including momethasone furoate, CYP cocktail, and 
vaccine received in the treatment periods in the parent trials) that the subject receives from 
3 months prior to screening through the safety follow-up, including any of the permitted 
concomitant medications specified below, 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, unit, and frequency. 
• Route of administration. 
Similarly, concurrent procedures must also be recorded in the subject’s medical record and the 
eCRF. Note that only surgical procedures and procedures related to AD treatment (for 
example, phototherapy or bleach baths) should be recorded. The following details will be 
recorded: procedure, body location (upper limb, lower limb, trunk, head), diagnosis, and start 
and stop date (it will also be recorded if the procedure is ongoing). 
At all site visits and telephone visits, subjects should be asked whether they have used TCS or 
TCI (see below) during the past week – to make it possible to assess whether the individual 
efficacy response is achieved with or without topical therapy and to get an impression of 
topical medication use. 
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: 
• TCS (US class ≥4 or Europe class ≤3) or TCI. 
• Oral antibiotics, antiviral, or antifungal therapy for skin infections as 
appropriate. 
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• 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 anti-histamines. 
9.7 Prohibited medication and procedures 
The medications below are prohibited during the trial. For specifications on allowed rescue 
treatment for AD symptoms, please refer to Section 9.5. 
From baseline through end of treatment: 
• Higher potency topical corticosteroids (US class < 4 or Europe class > 3). Can 
be used as rescue for intolerable AD symptoms (see Section 9.5). 
• Topical phosphodiesterase 4 (PDE-4) inhibitors. 
• Topical and systemic JAK inhibitors. 
• UVA or UVB, psoralen + UVA (PUVA), other phototherapy, or tanning beds. 
• 3 or more bleach baths per week. 
From baseline through safety follow-up: 
• Systemic corticosteroids (nasal, ophthalmic, and inhaled corticosteroids are 
allowed). 
• Systemic treatment with an immunosuppressive/immunomodulating agent (e.g. 
cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, Janus kinase 
inhibitors, interferon-gamma, dupilumab, and other biologics). 
In case prohibited systemic medications are received, IMP dosing must be suspended as 
described in Section 10.2.3.  
The sponsor’s medical expert must be notified if a subject receives any of the following 
prohibited medications from baseline through safety follow-up: 
• Investigational agents other than tralokinumab. 
• Immunoglobulin or blood products. 
• Allergen immunotherapy. 
• Live (attenuated) vaccine.* 
* Receipt of inactive/killed vaccines (for example, inactive influenza and inactive COVID-19) 
is allowed, provided they are not administered within 5 days before/after any IMP injection. 
In case any prohibited treatments are used during the trial, they must be recorded as 
concomitant medication in the eCRF.  
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9.8 Treatment logistics and accountability  
9.8.1 Labelling and packaging of trial products 
The IMP will be packaged in individually numbered kits, each containing 1 syringe 
(tralokinumab 150 mg). 
Primary and secondary packaging materials (syringe and outer carton, respectively) will be 
individually labelled. 
The labelling of IMP will be in accordance with Annex 13, local regulations, and trial 
requirements. Label text will be translated into local languages, as required. 
9.8.2 Storage of trial products  
All IMP supplied by LEO Pharma 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, for example to a hospital pharmacy, as locally applicable. 
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. 
• Damaged syringe. 
Damaged IMP should be documented in the IRT and reported as a product complaint (see 
Section 9.10). Damaged IMP may not be used. 
Further details on IMP storage (including handling of such cases as listed above) and home 
use are provided in a trial product handling manual. The pamphlet given to subjects with 
instructions for IMP self-administration also provides instruction on IMP storage during home 
use. 
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9.8.3 Drug accountability 
The investigator is fully responsible for the IMP at the trial site, for maintaining adequate 
control of the IMP, and for documenting all transactions with them. Dispensing of IMP may 
be delegated, for example to a hospital pharmacy, as locally applicable. 
An individual drug accountability form (or similar) must be kept of the IMP administered to 
and returned by each subject in the trial. This individual drug accountability form must be 
available during monitoring visits and will be checked by the CRA to verify correct 
dispensing of the IMP. Drug accountability information will be entered in the IRT, where 
inventory status of all IMP at the trial site will also be maintained. 
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. Subjects will be 
provided with sharps bins for used syringes and will return filled sharps bins to the trial site. 
Subjects will return trial kit cartons and any unused IMP at each 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 supplied by the contract manufacturing organisation (CMO) on behalf of 
LEO Pharma will be returned to the CMO. Prior to return, the IMP 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. 
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, IMP may be injected by site staff, who will also 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 or subject’s caregiver at the trial site, the site staff will 
record compliance data in the eCRF. 
Where IMP is injected by the subject or subject’s caregiver at home, the subject or subject’s 
caregiver will record the date and injection site for each administration in a log of drug 
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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 
Used syringes will be destroyed at the trial site provided the trial site has procedures in place 
for such IMP destruction. Trial sites that do not have such IMP destruction procedures in 
place will dispose used IMP in sharps bins that will be shipped to the CMO. 
Unused IMP and used syringes 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. 
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 Global Safety at LEO Pharma on the 
trial-specific (paper) Complaint Form within 3 days of first knowledge. 
Critical complaints (defined as any defect, issue, or device deficiency that has or potentially 
could have a serious impact for the subject [for example, SAE or large particles in the 
syringe]) must be reported to Global Safety at LEO Pharma within 24 hours.  
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 IMP or due to a device deficiency will be reported by the investigator as described in 
Sections 13.3 and 13.4. Where possible, a photograph of the defective device should be taken 
and submitted with the report. 
Refer to the trial product handling manual for information on how to update the kit status in 
the IRT. 
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During the investigation of the product complaint, the IMP or device must be stored at 
labelled conditions unless otherwise instructed; the trial site will be notified whether the IMP 
or device needs to be returned for further investigation or may be destroyed. 
Global Safety, LEO Pharma contact information for reporting product complaints: 
Fax number: +45 6910 2468 
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 at any time (prior to first dose or during the treatment 
period) if the subject, the subject’s legally authorised representative(s), the investigator, or 
LEO Pharma considers that it is not in the subject’s best interest to continue. 
Subjects who withdraw from the trial 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 site’s trial 
records. 
10.2 IMP discontinuation rules 
10.2.1 Stopping rules 
Since it is considered unethical to continue the treatment with IMP in subjects who gain no 
therapeutic benefit after a reasonable treatment period, subjects should permanently 
discontinue IMP and be withdrawn from the trial if, based on the investigator’s assessment, 
one of the following events occurs: 
• Continuous use of higher potency TCS (US class <4 or Europe class >3) for 
>4 weeks. 
• Continuous use of systemic rescue treatment for >3 weeks. 
• Disease severity above or equal to baseline in the parent trial for a duration of 
≥8 weeks. 
The stopping rules will be effective from Week 16. 
Subjects who (in the opinion of the subject, the subject’s legally authorised representative(s), 
or investigator) have unacceptable treatment effect of IMP may also be withdrawn from the 
trial at any time without fulfilling any of the stopping rules. Subjects withdrawn from the trial 
should complete the safety follow-up period as specified in Section 7.1. 
Reasons for withdrawal from the trial are described in Section 10.2.2. 
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10.2.2 Reasons for withdrawal from the trial 
Subjects will permanently discontinue IMP and be withdrawn from the trial 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. 
• 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: 
- 
Alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) values >3×upper limit of normal (ULN) with total bilirubin >2×ULN (unless 
elevated bilirubin is related to Gilbert-Meulengracht Syndrome). 
- 
Confirmed AST or ALT >5×ULN for >2 weeks. 
Subjects withdrawn from the trial must complete the safety follow-up period as specified in 
Section 7.1. 
Data to be recorded in the eCRF 
The primary reason for withdrawal from the trial must be recorded in the medical records and 
on the end of trial form (see Section 11.8) in the eCRF, where the following reasons are 
available: 
• Lack of efficacy. 
• Adverse event. 
• Withdrawal by subject. 
• Withdrawal by parent/guardian.* 
• Lost to follow-up. 
• Death. 
• Other. 
*For adolescent subjects as applicable. 
 
If ‘adverse event’ or ‘other’ is selected, a specification must be provided in the eCRF. 
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Stopping rules are described in Section 10.2.1. 
10.2.3 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 (for example, 
cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, Janus kinase 
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. If any of the stopping rules are met (see Section 10.2.1) or any of the 
withdrawal reasons are met (Section 10.2.2), the subject must be withdrawn from the trial. 
10.3 Early termination assessments 
Withdrawal from trial 
Subjects withdrawn from the trial for any reason should attend an early termination visit as 
soon as possible after the last administration of IMP and should return to the trial site for a 
safety follow-up visit after last administration of IMP as specified in Section 7.1.4. 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. An EOT (end of treatment) form and an end of trial form must be 
completed as specified in Section 11.8. No EOT visit is to be done for subjects who are 
withdrawn from trial. 
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. 
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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, as well as counsel the 
subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to continue in the trial. 
• 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. 
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11 Trial assessments and procedures 
11.1 Overview 
Evaluations to be done at each site visit are shown in the schedule of trial procedures in 
Section 4. Refer to Section 7.1 for further details on the trial design. 
Assessments/procedures at any site visit should be performed in the following order: 
• PROs in the following order: 
1. Patient Oriented Eczema Measure (POEM). 
2. Dermatology Life Quality Index (DLQI)/Children’s 
Dermatology Life Quality Index (CDLQI).* 
3. EuroQoL 5-Dimension Health Questionnaire 5 Level 
(EQ-5D-5L)*. 
4. Eczema-related Weekly Sleep numeric rating scale (NRS).* 
5. Worst Weekly Pruritus NRS.* 
6. Patient use of topical treatment. 
• *All subjects from the parent trial LP0162-1334, independent of the subject’s 
age during participation in ECZTEND, will perform the Children’s 
Dermatology Life Quality Index (CDLQI), an adolescent’s pruritis NRS with a 
recall period of past 7 days, and an eczema-related sleep NRS with a recall 
period over the past 7 nights; these subjects will not perform the EQ-5D-5L as 
this questionnaire has not been validated for adolescents. 
• Investigator assessments (performed only by adequately trained investigators; 
to reduce inter-rater variability, the same investigator should preferably 
perform all the evaluations for a given subject throughout the entire trial 
period) in the following order: 
1. SCORAD component C, then component A and B. 
2. IGA. 
3. EASI. 
• Safety and laboratory assessments. 
• Administration and dispensing of IMP. 
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If screening/baseline visits are performed on the same day as visit(s) in the parent trial the 
following applies: 
• The order of assessments should be adhered to, working in parallel for both 
protocols. 
• Assessments where data are captured in different vendor systems databases 
(ECG, ePRO, and laboratory tests) need to be completed twice. In such cases, 
the parent trial assessment should be performed first, followed by the trial 
LP0162-1337 assessment.  
Subjects may also need to be seen at unscheduled visits during the course of the trial. The 
assessments to be performed at an unscheduled visit are left at the investigator’s discretion 
(could include any assessment performed at an early termination visit), except if the 
unscheduled visit involves administration of rescue treatment. In that case, 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. 
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 either a physician, 
certified physician’s assistant, or advanced registered nurse practitioner. 
AEs must be assessed by medically qualified personnel (Section 13.2). 
11.2 Assessments performed only at screening/baseline 
11.2.1 Demographics 
The following demographic data will be recorded: 
• Age and date of birth (or only year and month of birth as applicable to local 
legislation). 
• Sex. 
• Race: American Indian or Alaska native, Asian, black or African American, 
native Hawaiian or other Pacific islander, white, other. 
• Ethnic origin (self-reported by the subject): Hispanic or Latino, not Hispanic or 
Latino. 
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11.2.2 Medical history 
All relevant past and concurrent medical history must be recorded and includes: 
• Any ongoing AEs from parent trial. In addition, AEs reported after completion 
of the parent trial and prior to signing the informed consent form in the present 
trial must be recorded as medical history. 
• Skin disease history: all past and current skin disease history should be 
collected, including (but not limited to) alopecia, vitiligo, and herpes simplex 
infection. 
• Atopy history: 
- 
Duration of AD in years. 
- 
Previous AD treatments.  
- 
Asthma. 
- 
Food allergy. 
- 
Hay fever. 
- 
Allergic conjunctivitis. 
- 
Atopic keratoconjunctivitis. 
- 
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 Height 
The subject’s height (without shoes) will be measured. 
11.2.4 Columbia-Suicide Severity Rating Scale  
The C-SSRS Screening version is a rater-administered instrument used to assess the lifetime 
history and severity of suicidal ideation and suicidal behaviour through a series of simple, 
plain-language questions (Posner et al. 2007). The C-SSRS must be completed at screening to 
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check that exclusion criterion no. 24 does not apply. Further details on the assessment 
according to the C-SSRS are included in the efficacy assessment & C-SSRS manual. 
11.3 Efficacy assessments 
11.3.1 Investigator assessments 
11.3.1.1 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 11). 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. 
Panel 11: Investigator’s Global Assessment 
Score 
Disease severity 
Standard IGA scale 
IGA 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). 
 
11.3.1.2 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 (Hanifin 2001). 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. 
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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 12. 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 13. For each body region, a severity sum score will be calculated 
which will be multiplied by an area score (Panel 13) and by a weighting factor. The EASI 
score equals the sum of the scores obtained for each body region (Panel 12). 
Panel 12: Calculation of the Eczema Area and Severity Index 
Body region 
Erythema 
Induration/ 
papulation 
Excoriation 
Lichenification 
Area score 
Weighting factor 
Score 
Head/neck 
( SS   + 
   SS   + 
   SS   + 
   SS ) 
x  AS 
x 0.1 
 
Trunk 
( SS   + 
   SS   + 
   SS   + 
   SS ) 
x  AS 
x 0.3 
 
Upper extremities 
( SS   + 
   SS   + 
   SS   + 
   SS ) 
x  AS 
x 0.2 
 
Lower extremities ( SS   + 
   SS   + 
   SS   + 
   SS ) 
x  AS 
x 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 the Harmonising Outcome Measures for Eczema. 
Panel 13: 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, and 2.5) 
are allowed. 
 
4 
50% to 69% affected area 
 
5 
70% to 89% affected area 
 
6 
90% to 100% affected area 
EASI = Eczema Area and Severity Index. 
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11.3.1.3 Scoring Atopic Dermatitis 
The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with 
subjective symptoms (European Task Force on Atopic Dermatitis 1993). The maximum total 
score is 103, with higher values indicating more severe disease. SCORAD 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. Whenever possible, SCORAD should be 
assessed by the same investigator at each visit to reduce inter-rater variability. 
The assessment consists of 3 components: A = extent, B = intensity, and C = subjective 
symptoms: 
Extent (A) 
The extent of AD is assessed as a percentage of each defined body area and reported as the 
sum of all areas (maximum score = 100%). 
Intensity (B) 
The intensity of 6 specific symptoms of AD (erythema, oedema/papulation, oozing/crusting, 
excoriation, lichenification, and dryness) is assessed by the investigator on an average 
representative area using the following scale: 
0 
= 
None/absent 
1 
= 
Mild 
2 
= 
Moderate 
3 
= 
Severe 
Note: dryness is evaluated on uninvolved areas. 
The sum of intensity score of the 6 symptoms will be reported (maximum score = 18). 
Subjective symptoms (C) 
A subjective assessment of the average itch and sleeplessness over the last 3 days/nights is 
recorded for each symptom by the subject on a visual analogue scale, where 0 is no itch (or 
sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum 
possible score of 20. 
The SCORAD is calculated as: A/5 + 7B/2 + C. 
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11.3.2 Patient-reported outcomes 
11.3.2.1 Patient Oriented Eczema Measure 
The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema 
patients in both clinical practice and clinical trials (Charman et al. 2004). The tool consists of 
7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, 
flaking, and dryness). Subjects 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 higher score indicates worse disease 
severity. The POEM will be completed at the trial site according to the schedule of trial 
procedures in Section 4. It will be completed electronically on the device supplied to the trial 
site and is included in the investigator trial file. 
11.3.2.2 Dermatology Life Quality Index/Children’s Dermatology Life 
Quality Index 
Adult subjects from all parent trials, except the parent trial LP0162-1334, will perform the 
Dermatology Life Quality Index, DLQI. The DLQI is a validated questionnaire with content 
specific to those with dermatology 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 (Finlay and Khan 1994). 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 higher score indicates poorer 
quality of life. The DLQI will be completed at the trial site according to the schedule of trial 
procedures in Section 4. It will be completed electronically on the device supplied to the trial 
site and is included in the investigator trial file. 
All subjects from the parent trial LP0162-1334, independent of the subject’s age during 
participation in ECZTEND, will perform the Children’s Dermatology Life Quality Index, 
CDLQI. The CDLQI questionnaire is designed and validated in subjects with dermatological 
conditions from 5 to 16 years (Lewis-Jones et al 1995, Salek et al 2013, Waters et al 2010). 
The CDLQI is available in text and cartoon versions (Holme et al 2003, Beattie and Lewis-
Jones 2006, Clayton et al 2007). 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 dermatology-related symptoms and feelings, leisure, 
school or holidays, personal relationships, sleep, and the treatment (CDLQI Information and 
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Instructions 2018). 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. The CDLQI will be completed 
by subjects from the parent trial LP0162-1334 at the trial site according to the schedule of 
trial procedures in Section 4. 
11.3.2.3 EuroQoL 5-Dimension Health Questionnaire 5-Level 
The EQ-5D-5L is a standardised measure of health status developed by the EuroQol group to 
provide a simple, general measure of health for clinical and economic appraisal (Greiner et al. 
2003). The EQ-5D-5L is a self-reported questionnaire used to assess health status ‘today’ and 
is divided into 2 sections: The first section includes 5 dimensions (mobility, self-care, usual 
activity, pain/discomfort, and anxiety/depression); each dimension will be assessed by the 
subject using a 5-point scale (no problems, slight problems, moderate problems, severe 
problems, and extreme problems). The second section consists of a vertical visual analogue 
scale anchored at 0 (the worst health you can imagine) and 100 (the best health you can 
imagine). The EQ-5D-5L will be completed according to the schedule of trial procedures in 
Section 4. It will be completed electronically on the device supplied to the trial site and is 
included in the investigator trial file. Subjects from the parent trial LP0162-1334 will not 
perform the EQ-5D-5L, as this questionnaire has not been validated for adolescents. 
11.3.2.4 Other patient-reported outcomes 
Subjects will be asked about their recalled sleep interference, itch severity, and use of topical 
treatments during the last week prior to each site visit (from 6 days prior to each visit and 
including the day of the visit, referred to below as ‘during the past week’), using the following 
PROs: 
Eczema-related Weekly Sleep numeric rating scale 
Subjects will rate how much their eczema interfered with their sleep during the past week 
using an 11-point numeric rating scale (NRS), using whole numbers only, with 0 indicating 
that it ‘did not interfere’ and 10 indicating that it ‘completely interfered’. Subjects from the 
parent trial LP0162-1334 will perform an NRS with phrasings tailored to adolescent subjects, 
independent of the subject’s age during participation in ECZTEND. 
Worst Weekly Pruritus numeric rating scale 
Subjects will assess their worst itch severity during the past week using an 11-point NRS, 
using whole numbers only, with 0 indicating ‘no itch’ and 10 indicating ‘worst itch 
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imaginable’. Subjects from the parent trial LP0162-1334 will perform an NRS with phrasings 
tailored to adolescent subjects, independent of the subject’s age during participation in 
ECZTEND. 
Patient use of topical treatment 
Subjects will state their use of TCS or TCI (‘yes’, ‘no’) during the past week. 
These PROs will be presented to subjects and recorded on paper, and site staff will transcribe 
the data into the eCRF. 
11.4 Safety assessments 
11.4.1 Weight 
The subject’s weight (in indoor clothing and without shoes) will be measured at the visits 
specified in the schedule of trial procedures (Section 4). 
11.4.2 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 supine or 
sitting position following at least 5 minutes of rest. 
For the first 3 tralokinumab dosing visits, subjects will be monitored for immediate drug 
reactions for a minimum of 30 minutes after administration of tralokinumab, with vital signs 
measured after 30 minutes or until stable, whichever is later (Section 9.2). Subjects who have 
participated in open-label tralokinumab arms of trials LP0162-1325, -1326, or -1334 or from 
one of the open-label trials LP0162-1342 and TRA-WEI-0015-I, and who have received at 
least 3 doses of tralokinumab in the parent trial, are exempt from this monitoring. 
If an abnormal vital sign at screening is considered 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. 28). 
In case of abnormal findings, the vital sign measurement can be repeated approximately 
15 minutes later with subjects resting 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 approximately 15 minutes after the second measurement with subjects 
resting in a supine or sitting position. If the third measurement verifies the second (normal) 
value, the first measurement should be considered false. If the third measurement confirms 
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the first measurement (abnormal), the second measurement will be considered false. Only the 
last value measured and considered correct will be recorded in the eCRF. 
Reporting in eCRF 
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 given. 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. 
11.4.3 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 according to the schedule of trial 
procedures (Section 4). 
If an unacceptable abnormal finding is identified during the physical examination at the 
screening visit, the subject must not be included in the trial (in accordance with exclusion 
criterion no. 28). 
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. 
Clinically significant abnormal physical examination findings at the screening visit will be 
documented as medical history in the eCRF. If an abnormal physical examination finding at 
any other visit than the screening visit is considered clinically significant by the investigator, 
it will be reported as an AE in accordance with Section 13.3. Further, 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. 
11.4.4 Electrocardiogram 
A single 12-lead resting digital ECG will be recorded after the subject has been supine for at 
least 5 minutes at the visits indicated in the schedule of trial procedures (Section 4). 
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A pre-evaluation of the ECGs will be performed by the investigators to evaluate immediate 
subject safety. At a minimum, the date of ECG collection will be recorded in the source 
documents. 
The ECG data will be transferred to a central ECG service company for central evaluation. A 
cardiologist at the ECG service company will analyse and interpret the ECG data. The ECG 
service company will provide ECG evaluation reports to the trial sites. 
The investigator must evaluate all abnormal ECG results (‘clinically significant’ or ‘not 
clinically significant’) and sign and date the evaluation. The investigator has the final decision 
on the clinical significance of ECG abnormalities. If a result is abnormal at the screening visit 
and considered 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. 28); if such a subject is included, the investigator will provide a justification in 
the medical record. 
Reporting in eCRF 
It will be recorded in the eCRF if an ECG was performed and, if applicable, the investigator’s 
assessment of ECG results (‘normal’, ‘abnormal, not clinically significant’, ‘abnormal, 
clinically significant’); if an ECG was not performed, a reason should be given. 
Clinically significant abnormal ECG findings at the screening visit will be documented as 
medical history in the eCRF. If an abnormal ECG finding at any other visit than the screening 
visit is considered clinically significant by the investigator, it will be reported as an AE in 
accordance with Section 13.3. Further, 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. 
Test dummy transmissions will be undertaken prior to trial conduct to ensure that 
transmissions can be made and that the date and time settings are correct. 
The collection and transmission of ECG data will be described in a separate ECG manual. 
11.4.5 Laboratory testing 
11.4.5.1 Overview 
Blood and urine samples will be collected according to the schedule of trial procedures 
(Section 4). The evaluations shown in Panel 14 will be performed. 
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Panel 14: Clinical laboratory tests 
Chemistry 
Haematology 
Sodium 
Potassium 
Creatinine 
Urea nitrogen 
Calcium 
Alkaline phosphatase 
Aspartate aminotransferase 
Alanine aminotransferase 
Gamma glutamyl transferase 
Bilirubin1 
Lactate dehydrogenase 
Cholesterol 
Low density lipoprotein (LDL) cholesterol 
High density lipoprotein (HDL) cholesterol 
Triglycerides 
Glucose (non-fasting) 
Albumin 
Protein 
Tryptase2 
Erythrocytes 
Haematocrit 
Haemoglobin 
Erythrocyte mean corpuscular volume 
Erythrocyte mean corpuscular haemoglobin 
concentration 
Leucocytes 
Neutrophils 
Neutrophils/leucocytes 
Lymphocytes 
Lymphocytes/leucocytes 
Monocytes 
Monocytes/leucocytes 
Eosinophils 
Eosinophils/leucocytes 
Basophils 
Basophils/leucocytes 
Thrombocytes 
Serology 
Hepatitis B virus surface antigen4 
Hepatitis B virus surface antibody4 
Hepatitis B virus core antibody4 
Hepatitis C virus antibody4 
HIV-1 antibody4 
HIV-2 antibody4 
Immunoglobulin E5 
Urinalysis3 
Serum pregnancy test4,6 
Protein 
Glucose 
Ketones 
Occult blood 
Leucocytes 
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 Urine samples will be tested at the trial site (dipstick). Until end of May 2021, in case of abnormal dipstick 
results, a urine sample will be sent to the central laboratory for microscopic examination (leucocytes, 
erythrocytes, and casts). After May 2021, a urine sample will only be sent to the central laboratory to 
perform urinalysis if considered required by the investigator based on the urine dipstick results.  
4 Measured at screening only. 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 Not measured at screening. 
6 Only female subjects of childbearing potential. 
Abbreviations: HIV = human immunodeficiency virus. 
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11.4.5.2 Urine pregnancy test 
Female subjects of childbearing potential will have a urine pregnancy test (human chorionic 
gonadotropin; dipstick) performed at the trial site at baseline prior to treatment assignment. 
The test will be repeated at Week 4 and thereafter the schedule of pregnancy testing is as 
shown in the schedule of trial procedures (Section 4). After May 2021, subjects must in 
addition to the test performed at the trial site, perform the urine pregnancy test at home within 
48 hours before the telephone visit using the kit supplied by the site staff. The subject will 
also be provided with a urine pregnancy test instruction. The result of the pregnancy test 
should be communicated to the site during the telephone visit and documented in the eCRF 
and source documents.  
For female subjects who become of childbearing potential during the trial (defined as Tanner 
stage ≥3 [Marshall 1969] or menarche), the investigator must reassess whether contraceptive 
measures are in place (if applicable), and perform the pregnancy tests according to the 
schedule of trial procedures (Section 4). 
Note that pregnant subjects must permanently discontinue IMP and be withdrawn from the 
trial immediately (see Section 10.2.2). 
11.4.5.3 Investigator evaluation of laboratory samples 
Central laboratory 
Chemistry, haematology, urinalysis (if applicable), serology, and serum pregnancy tests 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. Clinically significant abnormal tests 
at baseline or later must be repeated to confirm the abnormality. 
At each visit, the site staff will record in the eCRF if a sample was taken and, if applicable, 
the date and time as well as the investigator’s assessment of the results (‘normal’, ‘abnormal, 
not clinically significant’, ‘abnormal, clinically significant’). 
If a screening laboratory result is abnormal and of clinical significance, it will be at the 
investigator’s discretion to decide if the subject should be included in the trial (in accordance 
with exclusion criterion no. 28). 
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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 at the trial site with a dipstick. Until end of May 2021, in case of 
abnormal dipstick results, a urine sample was sent to the central laboratory for microscopic 
examination (leucocytes, erythrocytes, and casts). After May 2021, a urine sample will only 
be sent to the central laboratory to perform urinalysis if considered required by the 
investigator based on the urine dipstick results.  
At each site visit, the site staff will record in the eCRF if a urine sample was taken and, if sent 
for central laboratory analysis following an abnormal dipstick result, the investigator’s 
assessment of the central analysis result (‘normal’, ‘abnormal’). 
Reporting in eCRF 
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 as well as any new clinically significant sign, symptom or illness will 
be reported as an AE in accordance with Section 13.3. 
11.4.6 Anti-drug antibodies measurements 
Blood samples will be collected to determine tralokinumab ADA levels at pre-determined 
time points according to the schedule of trial procedures (Section 4). It will be recorded in the 
eCRF if the sample was taken; if the sample was not taken, 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 used, 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 neutralising 
antibodies (nAB). Details of the analytical method used will be described in an ADA 
bioanalytical report. 
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11.5  Pharmacokinetic assessments 
Blood samples for PK assessments should 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 the sample was not taken, a reason will be provided. 
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 validated bioanalytical methods. Details of the analytical methods used will 
be described in the bioanalytical report. 
11.6  Skin biopsies (subgroup of subjects at selected sites) 
At selected sites, the subgroup of subjects who donated skin biopsy samples in the parent trial 
LP0162-1325 will be asked to have skin biopsies taken in trial LP0162-1337 as well. The 
objective of collecting these additional biopsies is to investigate the molecular profile in the 
skin of AD patients treated for more than 1 year with tralokinumab and to document the long-
term disease control of tralokinumab. Participation in this part of the trial requires that the 
subject provides additional informed consent. 
Two 3 mm skin biopsies (1 from lesional skin and 1 from non-lesional skin) will be taken at 
Week 48 as specified in the schedule of trial procedures (Section 4). The locations of the 
biopsies taken should be in close proximity to the locations of the biopsies taken in trial 
LP0162-1325.  
Collection, handling and shipment instructions for skin biopsy samples are provided in a 
separate laboratory manual. 
The biopsies will be analysed for expression of markers of inflammation and skin barrier 
integrity by gene expression analysis. 
The biomarkers to be analysed include, but are not limited to, the following: 
Gene expression analysis 
• Global gene expression analysis by RNA sequencing.   
• Quantitative realtime polymerase chain reaction (qPCR) analysis of the 
following genes: IL-1B, IFNG, IL-13, IL-31, CCL17 (TARC), CCL26, C-X-C 
motif chemokine ligand 10 (CXCL10), CCL20, IL-17A, IL-20, IL-22, 
S100A9, S100A12. 
The results from the analyses of biopsy material will be presented in a separate report. 
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11.7 Estimate of total blood volume collected 
Blood samples will be drawn for analysis of safety (chemistry, haematology, and serology), 
PK, and ADA. 
The total volume of blood to be drawn for each subject will depend on the time of their entry 
in the trial and the local duration of the trial (Appendix 3J). For adult subjects, the total blood 
volume drawn will be approximately 265 mL until end of May 2021, plus 70 mL per year of 
trial participation after May 2021. For adolescents, the total amount of blood drawn until end 
of May 2021 will be approximately 130 mL, plus 70 mL for the 1 year extension until end of 
May 2022.  
The volume of blood drawn at any visit during the trial will be approximately 20 mL for all 
subjects. 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 (European 
Commission 2008). 
11.8 End of trial 
An end of treatment form must be completed in the eCRF for all subjects completing 
treatment. The following data will be collected: 
• Date of last administration of IMP. 
An end of trial form must be completed in the eCRF for all subjects assigned to treatment. 
The following data will be collected: 
• Did the subject complete the trial? 
• If not: primary reason for withdrawal from trial (lack of efficacy, AE, 
withdrawal by subject, withdrawal by parent/guardian*, lost to follow-up, 
death, other). 
• Did the subject attend the safety follow-up visit? 
• If not: primary reason for not attending safety follow-up visit (lack of efficacy, 
AE, withdrawal by subject, withdrawal by parent/guardian*, lost to follow-up, 
death, other). 
• Date of last contact. 
*For adolescent subjects as applicable. 
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The end of trial form will be completed when the subject has had their last visit (see 
Section 7.3). 
11.9 Storage of biological samples 
PK blood samples will be retained for as long as the quality of the material permits evaluation 
but for no longer than 12 months after completion of the clinical trial report (CTR). 
Samples for ADA evaluation will be retained for as long as the quality of the material permits 
evaluation but for no longer than 15 years after marketing authorisation. 
Skin biopsy samples will be retained for as long as the quality of the material permits 
evaluation but for no longer than 12 months after completion of the CTR unless specific 
additional consent has been obtained that allows storage for future research (see below). 
Biobank 
If consent is given by the subject, LEO Pharma will store skin biopsy samples in the biobank 
established by LEO Pharma and hosted by BioStorage Technologies, Inc. Donation of the 
samples for future research is voluntary and subjects must give their separate written consent 
to confirm donation and storage and the terms associated herewith. The samples will be 
transferred from the relevant laboratory to the biobank. The samples will be labelled with the 
trial ID, subject ID, and the sample date to protect the privacy of the subjects and to allow 
continued blinding for future analyses.  
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12 Scientific rationale for trial design and appropriateness of assessments 
This trial is open-label to ensure the generation of long-term safety data without treating 
subjects with placebo for a prolonged period of time. The trial includes adolescent and adult 
subjects who have already participated in a clinical trial (parent trial) with tralokinumab. The 
eligibility criteria are chosen to ensure that subjects from the parent trials can safely be 
included in this long-term trial. Subjects will have the possibility to use tralokinumab both 
with and without TCS (US class ≥4 or Europe class ≤3), reflecting the intended use of 
tralokinumab in real clinical practice. 
Long-term safety will be assessed using standard clinical methods of subject evaluations, such 
as AE monitoring, ECG, vital signs, and clinical laboratory measurements. Furthermore, data 
on antibodies against tralokinumab (ADAs) will be collected and the potential for 
immunogenicity will be evaluated until the end of the safety follow-up period. The serum 
samples for determination of presence or absence of ADA, along with blood concentrations of 
tralokinumab, will be analysed using validated bioanalytical methods. 
The clinical efficacy of tralokinumab treatment will be assessed using IGA, EASI, and 
SCORAD. 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 (Hanifin et al. 2001). SCORAD is a validated tool to assess the 
extent and severity of AD lesions and subjective symptoms (European Task Force on Atopic 
Dermatitis 1993). The efficacy endpoints IGA score of 0 or 1 and EASI75 are recognised as 
important endpoints in clinical trials in AD by regulators in the US, EU, and Japan. 
The clinical efficacy of tralokinumab treatment will also be assessed using PROs related to 
disease symptoms, quality of life, general health status, itch, and sleep quality. POEM is a 
validated questionnaire used to assess disease symptoms in atopic eczema patients in both 
clinical practice and clinical trials (Charman et al. 2004), and is recommended by the 
Harmonising Outcome Measures for Eczema for measuring patient-reported symptoms in 
eczema trials. DLQI/CDLQI is a validated and widely used questionnaire designed to 
measure the quality of life of dermatological patients (Finlay and Khan 1994, CDLQI 
Information and Instructions 2018). The EQ-5D-5L is a standardised measure of health status 
developed by the EuroQol group to provide a simple, general measure of health for clinical 
and economic appraisal (Greiner et al. 2003). 
In order to be able to analyse the endpoints (change from parent trial baseline), subjects from 
the parent trial LP0162-1334 will continue to assess the CDLQI independent of the age of the 
subject during participation in ECZTEND. Subjects from the parent trial LP0162-1334 will 
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perform an adolescent’s pruritis NRS with a recall period of the past 7 days, and an eczema-
related sleep NRS with a recall period over the past 7 nights with phrasings tailored to 
adolescent subjects, independent of the subject’s age during participation in ECZTEND. The 
EQ-5D-5L has not been validated for adolescents and was not assessed in trial LP0162-1334, 
and is therefore not to be performed in ECZTEND for subjects from the parent trial 
LP0162-1334. 
The trial design has been modified with protocol version 10 to secure long-term safety data of 
up to 5 years globally. The treatment extension for subjects from the parent trials 
LP0162-1325, -1326, -1339, -1341, -1342, -1343, -1346, and TRA-WEI-0015-I will be 
country-specific to allow for treatment with tralokinumab until tralokinumab is available to 
patients outside the clinical trial setting (Appendix 3J). Subjects from the ongoing adolescent 
parent trial LP0162-1334 are offered a total treatment extension of 1 year until end of May 
2022. 
The trial design was modified while the trial was ongoing (effective after May 2021) to 
decrease the burden of frequent site visits for subjects by introducing a visit schedule more 
similar to standard practice for home use. To ensure close safety monitoring throughout the 
treatment period, a mandatory telephone visit will be performed in between site visits.  
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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 
AEs must be collected from the time of first trial-related activity after the subject or subject’s 
legal representative(s) has signed the informed consent form (ICF) until completion of the 
clinical trial, as defined in Section 7.3. To avoid duplicate reporting, however, any AE with 
onset before the final visit (safety follow-up visit) in the parent trial should be reported as an 
AE in the parent trial; for subjects without a safety follow-up visit in the parent trial, any AE 
with onset before the baseline visit in ECZTEND should be reported as an AE in the parent 
trial. If ongoing, the AE should also be recorded as medical history in the current extension 
trial (see Section 11.2.2). AEs with onset after the final visit in the parent trial and after 
informed consent has been obtained for the present trial, should be recorded as an AE in 
ECZTEND. 
AEs must be assessed by medically qualified personnel. 
At all visits, the subject will be asked a non-leading question by the investigator about AEs, 
for example: “How have you felt since I saw you last?” No specific symptoms should be 
asked for. At the site visits, it is important that the investigator also observes the subject for 
any changes not reported by the subject and records these changes.  
Clinically significant abnormal findings related to vital signs, physical examination, ECGs, or 
laboratory tests after the screening visit must be reported as an AE, as described in 
Sections 11.4.2 to 11.4.5. 
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 (for 
example ‘allergic contact dermatitis’). 
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The duration of the AE must be reported by the start date and stop date of the event (it will 
also be recorded if the event is ongoing). In addition, it will be recorded if the AE started prior 
to start of IMP. 
AEs must be classified in terms of severity, causality, and outcome according to the 
definitions in Appendix 2. 
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). 
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. On the SAE form in the present extension trial, 
information regarding the subject’s ID and parent trial ID must also be provided. 
13.4.1 Investigator reporting responsibilities 
Any SAE must be reported to LEO Pharma on the (paper) SAE Form within 24 hours of first 
knowledge. This report should contain an assessment of available information on seriousness, 
severity, causal relationship to the IMP or trial procedure, the action taken, the outcome to 
date, and a narrative description of the course of the event. 
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: 
Global Safety at LEO Pharma 
E-mail address: drug.safety@leo-pharma.com  
Fax number: +45 6910 2468 
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)/IEC(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 collected. However, such events should be reported 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 or not an SAE is expected. 
The relevant reference safety information document for this clinical trial is: 
For the IMP, the Investigator’s Brochure, 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 
countries. 
The IRB(s)/IEC(s) will be notified of SAEs according to the current applicable legislation for 
the concerned countries. 
For all non-US countries, the following reporting requirements apply: all SAEs which are 
assessed as causally related to the IMP(s) by either the investigator or LEO Pharma (ICH 
E2A Guideline), and which are unexpected (Suspected, Unexpected Serious Adverse 
Reactions [SUSARs]), are subject to expedited reporting to regulatory authorities and 
IEC(s)/IRB(s) according to the current applicable legislation in the concerned countries. 
Investigators will be notified of the evolving safety profile of the IMP on an ongoing basis. 
For the US, the following reporting requirements apply: all SAEs which are assessed as 
causally related to the IMP(s) by LEO Pharma (Guidance for Industry and Investigators - 
Safety Reporting Requirements for INDs and BA/BE Studies; Guidance for Clinical 
Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs – Improving Human 
Subject Protection) 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. 
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13.5 Expedited reporting of pregnancy 
Any pregnancy occurring during the clinical 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 final outcome must be reported on the 
(paper) Pregnancy Form (Part II) within 24 hours of first knowledge. 
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 10.2.2 and 10.3). 
13.6 Reporting of other events 
13.6.1 Adverse events of special interest 
The events listed in Panel 15 are considered adverse events of special interest (AESIs) in this 
trial and will require additional details to be recorded in the eCRF. LEO Pharma may request 
that the investigator forward test results, as appropriate. An AESI may be serious (requiring 
expedited reporting, Section 13.4) or non-serious. 
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Panel 15: Adverse events of special interest 
Adverse event of special interest 
Additional data to be recorded in eCRF (if available1) 
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 infections requiring systemic 
treatment 
• 
Location (face, scalp, back, chest, upper limb, 
lower limb, genitals). 
• 
Outcome of pathogenic skin 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. 
1 The additional data to be recorded in the eCRF are not a requirement, but are to be reported by the investigator, 
if available, for example as part of standard clinical practice. 
Abbreviations: eCRF = electronic case report form; PCR = polymerase chain reaction 
 
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13.6.2 Overdose 
An overdose is defined as a subject receiving a dose of IMP in excess of that specified in this 
protocol.  
The term ‘overdose’ including a specification of why it occurred (accidental or intentional) 
must be documented on the AE form of the eCRF. In addition, AEs originating from overdose 
must be documented on a separate line. If the AE originating from the overdose qualifies as 
an SAE, expedited reporting is required (Section 13.4). 
If the overdose is accidental and due to a device deficiency, the device deficiency must be 
reported as a product complaint as described in Section 9.10. 
LEO Pharma does not recommend specific treatment for an overdose. The investigator will 
use clinical judgement to treat any overdose if necessary. 
13.6.3 Medication error 
Medication error refers to any unintentional error in the dispensing or administration of an 
IMP while in the control of the investigator or subject. Broadly, medication errors fall into 
4 categories: wrong medication, wrong dose (including strength, form, concentration, amount, 
as well as administration with an interval of less than 7 days), wrong route of administration, 
or wrong subject. 
The medication error category must be documented on the AE form in the eCRF. In addition, 
AEs originating from a medication error must be documented on a separate line. 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. 
13.6.4 Misuse 
Misuse refers to situations where the IMP is intentionally and inappropriately used not in 
accordance with the protocol. 
The term ‘misuse’ must be documented on the AE form in the eCRF. In addition, AEs 
originating from misuse must be documented on a separate line. If the AE originating from 
misuse qualifies as an SAE, expedited reporting is required (Section 13.4). 
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13.6.5 Abuse 
Abuse relates to the sporadic or persistent, intentional excessive use of an IMP which is 
accompanied by harmful physical or psychological effects. 
The term ‘abuse’ must be documented on the AE form in the eCRF. In addition, AEs 
originating from abuse must be documented on a separate line. If the AE originating from 
abuse qualifies as an SAE, expedited reporting is required (Section 13.4). 
13.6.6 Aggravation of condition 
Any clinically significant aggravation/exacerbation/worsening of any medical condition(s) 
(including the trial disease), compared with baseline, 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 of possible/probable relationship to the IMP for 
2 weeks or until the final outcome is determined, whichever comes first. 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, for 
example 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 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 
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appropriate urgent safety measures to protect the subjects against any immediate hazard” 
(European Parliament and Council of The European Union 2001). 
If the investigator becomes aware of information that necessitates an immediate change in the 
clinical trial procedure or a temporary halt to the clinical trial in order 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/IECs. 
The investigator must immediately inform LEO Pharma – by contacting the clinical project 
manager or medical expert – of this change in the clinical trial procedure or of the temporary 
halt providing 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 
The assumed size of this trial is approximately 1,600 subjects. No formal sample size has 
been calculated; the sample size is based on the population sizes of the parent trials and 
assumptions regarding how many subjects will complete the parent trials and be eligible for / 
consent to participate in the current trial. 
14.2 Trial analysis sets 
All screened subjects will be accounted for in the CTR. 
All subjects receiving tralokinumab will be included in the full analysis set (FAS) and will be 
analysed for efficacy. 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 tralokinumab from the FAS, a justification addressing ICH E9 will be given. 
The safety analysis set will be identical to the FAS and will be used for summarising safety. 
Data from the investigator-initiated parent trial TRA-WEI-0015-I will not be transferred to 
LEO Pharma. Thus, endpoints defined as change from baseline (in parent trial) will not be 
calculated for subjects from this trial, and data from this trial will not be included in tables 
summarising endpoints defined as change from baseline or where data are presented by 
responder/non-responder. Subjects from this parent trial will be contributing to the primary 
endpoint and included in summary tables where possible.  
The decisions regarding inclusion/exclusion of subjects or subject data from the trial analysis 
sets will be documented in an analysis set definition document. 
14.3 Statistical analysis 
14.3.1 Disposition of subjects 
The reasons for withdrawal from the trial will be presented for all subjects assigned treatment. 
14.3.2 Demographics and other baseline characteristics 
Descriptive statistics of demographics (age, sex, ethnicity, race) and the latest treatment 
regimen in the parent trial (placebo, tralokinumab, tralokinumab + TCS) will be presented for 
the total cohort of subjects and by tralokinumab-naïve/re-treated/continuously treated 
subjects. For the re-treated and continuously treated subjects, the presentation will further be 
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divided by responder/non-responder in the parent trial; clinical response is defined as 
achievement of IGA 0/1 or EASI75 at the last assessment in the parent trial. 
14.3.3 Exposure and treatment compliance 
Exposure 
Exposure to treatment will be presented for the safety analysis set as days of exposure in total, 
by yearly treatment period, and by parent trial. 
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 
Adherence to treatment regimen will be recorded in the eCRF. The log of drug administration 
may be used as source. If any complications or deviations in administration are observed, 
these will be described as protocol deviations. 
Adherence will be presented for the safety analysis set. 
14.3.4 Primary endpoint 
The primary endpoint in this trial is number of adverse events during the treatment period 
from baseline up to Week 268, and the analysis of this is covered in Section 14.3.8. 
14.3.5 Secondary efficacy endpoints 
The analyses of the secondary efficacy endpoints will be done for the FAS as well as for the 
observed cases. Subjects fulfilling the stopping rules (see Section 10.2.1) will be withdrawn 
from trial, and no observed data will be available after withdrawal. As a consequence, 
subjects withdrawn will be regarded as non-responders in the FAS analysis. 
IGA and EASI75 will be presented as response rates with 95% confidence intervals at each 
assessment visit. The results will be presented for the total cohort of subjects and by 
tralokinumab-naïve/re-treated/continuously treated subjects. For the re-treated and 
continuously treated subjects the results will further be divided by responder/non-responder in 
the parent trial; clinical response is defined as achievement of IGA 0/1 or EASI75 at the last 
assessment in the parent trial. 
In the evaluation of EASI75, the baseline score will be that from the parent trial. 
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14.3.6 Other endpoints 
Changes from baseline in EASI score and SCORAD will be presented as number of 
observations (N), mean, standard deviation (SD), median, minimum, and maximum at each 
assessment visit. The baseline scores used will be those from the parent trial. 
The changes from baseline in EASI score and SCORAD will be presented for the FAS as well 
as for the observed cases. 
3 endpoints addressing treatment effect during the treatment period will be included: 
• Proportion of time with EASI75 after first occurrence of EASI75 during 
treatment. 
• Proportion of time with EASI50 after first occurrence of EASI50 during 
treatment. 
• Proportion of time with IGA 0/1 after first occurrence of IGA 0/1 during 
treatment. 
The proportion of time with EASI75 for an individual subject will be calculated as the time 
with EASI75 (that is, the sum of time intervals with EASI75) divided by the observation 
period after first occurrence of EASI75. The time intervals in which EASI75 is observed at 
the start of the interval will be accumulated and normalised with the total treatment time from 
first EASI assessment with EASI75 until end of treatment. 
The proportion of time with EASI50 and with IGA = 0/1 after first occurrence during 
treatment will be determined using the same principle as for the proportion of time with 
EASI75. 
These ‘proportion of time’ endpoints will each be presented as number of observations (N), 
mean, SD, median, minimum, and maximum. The group mean comprising the summed 
nominators (of time) divided by the summed denominators will further be presented. 
As the frequency of site visits is reduced after May 2021, a sensitivity analysis excluding data 
captured after May 2021 will be performed for the ‘proportion of time’ endpoints. For 
exploratory purposes, the proportion of subjects achieving EASI75 will be plotted versus the 
proportion of time with EASI75 (ranging from 0–100% of the observation period after first 
occurrence of EASI75). Similar plots for EASI50 and IGA 0/1 will be shown in the same 
graph. 
The results for the endpoints described in this section will be presented for the total cohort of 
subjects and by tralokinumab-naïve/re-treated/continuously treated subjects. For the re-treated 
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and continuously treated subjects, the results will further be divided by responder/non-
responder in the parent trial (clinical response as defined in Section 14.3.5). 
The primary reasons for discontinuation of IMP over time will be presented relative to the 
number of subjects receiving treatment at Week 0. 
14.3.7 Patient-reported outcomes 
Changes from baseline in POEM score, DLQI/CDLQI score, and EQ-5D-5L score will be 
presented in the same way as changes from baseline in EASI score and SCORAD (see 
Section 14.3.6). The baseline scores used will be those from the parent trial. In the special 
case where a subject has an assessment at both Week 80 and Week 88, the Week 80 
assessment (corresponding to approximately 1½ years) will be used for the Week 80-88 
endpoint evaluation. Likewise, the Week 128 assessment (~ 2½ years) will be prioritised for 
the Week 128-136 endpoint evaluation. The DLQI score will be presented for subjects from 
the parent trials LP0162-1325, -1326, -1339, -1341, -1343, and -1346. The CDLQI score will 
be presented for subjects from the parent trial LP0162-1334. As subjects from the parent trial 
LP0162-1342 did not have POEM, DLQI, or EQ-5D-5L assessments in the parent trial, the 
change from baseline is not applicable. As subjects from the parent trials LP0162-1334 
and -1343 did not have EQ-5D-5L assessments in the parent trial, the change from baseline is 
not applicable. Changes from baseline will not be presented for subjects from the parent trial 
TRA-WEI-0015-I, since data from this investigator-initiated trial will not be transferred to 
LEO Pharma (see Section 14.2). 
The Worst Weekly Pruritus NRS/adolescent’s pruritis NRS score, the Eczema-related Weekly 
Sleep NRS/adolescent’s eczema-related NRS score, and the change from baseline (in the 
current trial) in both scores will be summarised descriptively by visit as mean, SD, median, 
minimum, and maximum values. 
The use of topical treatment during the last week as a binary score will be summarised 
descriptively by visit. 
14.3.8 Safety 
The analysis of safety will be based on the safety analysis set. 
14.3.8.1 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 term and primary 
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system organ class (SOC) as percentage of subjects with AEs, number of AEs, and rate of AEs 
(number of AEs per 100 patient-years of exposure). 
Only treatment-emergent AEs will be summarised; however, all AEs recorded during the 
course of the trial will be included in subject data listings. An AE will be considered 
treatment-emergent if started after the first use of IMP, or if started before the first use of IMP 
and worsened in severity after first dose of IMP. The tabulations described in the following 
will only include treatment-emergent AEs. In each of the tabulations, AEs are defined by 
MedDRA preferred term within primary SOC. 
An overall summary of the number of AEs, the rate of AEs (number of AEs per 100 patient-
years of exposure), the number (percentage) of subjects with any treatment-emergent AEs, 
deaths, SAEs, withdrawals from the trial due to AEs, treatment-related AEs, and severe AEs 
will be presented. The above summaries will also be made separately for subjects who 
transferred from the parent trial LP0162-1334. As the frequency of site visits is reduced after 
May 2021, an additional overall AE summary table will be presented that excludes events and 
exposure time after May 2021. In addition to the overall summary, the data will be presented 
by tralokinumab-naïve/re-treated/continuously treated subjects. 
The number of AEs, rate of AEs, and number of subjects with each type of AE will be 
tabulated for the total cohort of subjects and by tralokinumab-naïve/re-treated/continuously 
treated subjects. 
The severity and causal relationship to IMP for each type of AE will be tabulated.  
Related AEs are defined as AEs for which the investigator has not described the causal 
relationship to IMP as ‘not related’. 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. AESIs 
and AEs leading to withdrawal from the trial will be tabulated and listed. 
AEs leading to withdrawal from trial will be listed. 
14.3.8.2 Vital signs  
The change in vital signs (blood pressure, heart rate, body temperature) from baseline (in the 
current trial) to each visit will be summarised by visit as mean, SD, median, minimum, and 
maximum values. The changes will be presented for the total cohort of subjects and by 
tralokinumab-naïve/re-treated/continuously treated subjects. 
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14.3.8.3 Clinical laboratory evaluation 
The change in each of the laboratory parameters from baseline (in the current trial) to each 
visit will be summarised as mean, SD, median, minimum, and maximum values. The changes 
will be presented for the total cohort of subjects and by tralokinumab-naïve/re-
treated/continuously treated subjects. 
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. The changes 
will be presented for the total cohort of subjects and by tralokinumab-naïve/re-
treated/continuously treated subjects. Subjects with laboratory parameters outside the 
reference range will be listed. 
14.3.8.4 Anti-drug antibodies 
The presence of ADAs is an endpoint included to assess the immunogenicity of tralokinumab. 
The ADA status will be summarised by treatment in parent trial and visits with ADA 
measurements according to the following categories: 
ADA status 
Description 
Positive, pre-existing 
ADA positive at baseline. No post-baseline ADA 
response ≥4-fold over baseline titre level. At least 
1 non-missing post-baseline ADA assessment. 
Positive, treatment-boosted 
ADA positive at baseline. At least 1 post-baseline 
ADA response ≥4-fold over baseline titre level. 
Positive, treatment emergent 
ADA negative or missing at baseline. At least 
1 positive post-baseline ADA response. 
Negative 
ADA negative or missing at baseline. All post-baseline 
ADA assessments negative. 
 
For the entire trial, the ADA status will be summarised by treatment in parent trial according 
to the categories of ADA status as listed above and with the following subcategories of 
treatment-emergent status: 
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Treatment-emergent subcategory status 
Description 
Treatment-emergent, persistent 
Positive ADA for at least 2 consecutive visits with 
ADA measurements, at least 10 weeks apart. 
Treatment-emergent, indeterminate 
Only the last ADA response positive. 
Treatment-emergent, transient 
Neither persistent nor indeterminate. 
 
The association of ADA status across the trial (positive versus negative) with AEs/SAEs may 
be evaluated. The ADA-positive subjects across the trial may in this evaluation be divided 
into the categories given above. The associations between ADA and AE/SAEs may be 
summarised for persistently, indeterminately, and transiently positive subjects. 
Serum samples that test positive for ADA will be analysed for neutralising antibodies (nAB). 
The test sample will be deemed positive or negative for the presence of nAB to tralokinumab 
relative to a pre-determined (in assay validation) statistically derived cut point. 
For subjects in the safety analysis set with positive ADA status, the ADA titre, nAB status, 
tralokinumab concentration, IGA assessment, and EASI assessment will listed by subject and 
visit. The listing will include information about which parent trial the subjects transferred 
from and what treatment they received in the parent trial. 
14.3.9 Pharmacokinetics 
All the PK samples in the trial are trough samples. The trough concentration (Ctrough) will be 
listed and descriptive statistics will be provided. 
Ctrough values from subjects with positive ADA/nAB will be compared with values from 
subjects with negative ADA/nAB, if data permit. 
The PK data may be merged with those from other clinical trials with tralokinumab for a 
population-based meta-analysis. Results of the meta-analysis will be presented in a separate 
pharmacometrics report outside of the CTR. 
14.3.10 
Interim analysis 
Interim evaluation and reporting of trial data will be perfomed (e.g. to support submissions for 
marketing approval or sharing of results at conferences).  This will be documented. 
 
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14.3.11 
General principles 
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. 
Any changes from the statistical analysis planned in this clinical trial protocol will be 
described and justified in a protocol amendment, the statistical analysis plan update, or the 
CTR, depending on the type of change. 
14.3.12 
Handling of missing values 
Missing values will not be imputed, but will be handled as described in Sections 14.3.5 and 
14.3.6 by doing analyses on the FAS as well as on the observed cases. 
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15 References 
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Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. 
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• European Commission. Ethical considerations for clinical trials on medicinal products 
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• European Parliament and Council of The European Union. Directive 2001/20/EC of 
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measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–216. 
• Greiner W, Weijnen T, Nieuwenhuizen M, Oppe S, Badia X, Busschbach J, et al. A 
single European currency for EQ-5D health states. Results from a six country study. 
Eur J Health Econ. 2003;4(3):222–231. 
• Hanifin JM, Reed ML, Eczema Prevalence and Impact Working Group. A 
population-based survey of eczema prevalence in the United States. Dermatitis. 
2007;18(2):82–91. 
• 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. Exp 
Dermatol. 2001;10(1):11-18. 
• Harmonising Outcome Measures for Eczema (HOME). EASI scoring table for 
patients 8 years or above [homepage on the Internet]. Available from: 
http://www.nottingham.ac.uk/homeforeczema/index.aspx [cited 19-Apr-2018]. 
• Holme SA, Man I, Sharpe SL, Dykes PS, Lewis-Jones MS, Finlay AY. The Children’s 
Dermatology Life Quality Index: validation of the cartoon version. Br J Dermatol. 
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• International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH). Integrated addendum to ICH E6(R1): 
Guideline for good clinical practice E6(R2) (2016). 
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• Jeon C, Yan D, Nakamura M, Sekhon S, Bhutani T, Berger T et al. Frequency and 
management of sleep disturbance in adults with atopic dermatitis: A systematic review. 
Dermatol Ther (Heidelb). 2017;7(3):349–364. 
• Johansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, 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. 
• Kiebert G, Sorensen SV, Revicki D, Fagan SC, Doyle JJ, Cohen J, et al. Atopic 
dermatitis is associated with a decrement in health-related quality of life. Int J 
Dermatol. 2002;41(3):151–158. 
• Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life Quality Index 
(CDLQI): Initial validation and practical use. Br J Dermatol. 1995;132:942–949. 
• Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis 
Child. 1969;44(235):291–303. 
• May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH, et al. Preclinical 
development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe 
uncontrolled asthma. Br J Pharmacol. 2012;166(1):177–193. 
• Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, Zheng T. TRPA1-dependent pruritus 
in IL-13-induced chronic atopic dermatitis. J Immunol. 2013;191(11):5371–5382. 
• Omori-Miyake M, Yamashita M, Tsunemi Y, Kawashima M, Yagi J. In vitro 
assessment of IL-4- or IL-13-mediated changes in the structural components of 
keratinocytes in mice and humans. J Invest Dermatol. 2014;134(5):1342–1350. 
• 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. 
• Purwar R, Werfel T, Wittmann M. IL-13-stimulated human keratinocytes 
preferentially attract CD4+CCR4+ T cells: possible role in atopic dermatitis. J Invest 
Dermatol. 2006;126(5):1043–1051. 
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• Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson FN Jr, Bock SA, Branum 
A, et al. Second symposium on the definition and management of anaphylaxis: 
Summary report - Second National Institute of Allergy and Infectious Diseases/Food 
Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 
2006;117(2):391–397. 
• Salek MS, Jung S, Brincat-Ruffini LA, Macfarlane L, Lewis-Jones MS, Basra MK, et 
al. Clinical experience and psychometric properties of the Children’s Dermatology 
Life Quality Index (CDLQI), 1995-2012. Br J Dermatol. 2013;169:734–759. 
• Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: 
updated guidelines for reporting parallel group randomised trials. BMC Med. 
2010;8:18. 
• Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and 
other health and demographic factors: a US population-based study. J Allergy Clin 
Immunol. 2013;132(5):1132–1138. 
• Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two 
phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 
2016;375(24):2335–2348. 
• Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importance of IL-4 and IL-13 in 
lesional skin of atopic dermatitis. Arch Dermatol Res. 2004;295(11):459–464. 
• 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. 
• Waters A, Sandhu D, Beattie P, Ezughah F, Lewis-Jones S. Severity stratification of 
Children’s Dermatology Life Quality Index (CDLQI) scores. Br J Dermatol. 
2010;163(Suppl 1):121. 
• Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109–1122. 
• World Medical Association. Declaration of Helsinki – ethical principles for medical 
research involving human subjects, 7th (Fortaleza) amendment (2013). 
• Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic expression of 
interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest 
Dermatol. 2009;129:742–751. 
 
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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. (ICH Harmonized Tripartite Guideline for Good Clinical Practice, 
E6 (R1)). 
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 unless these were 
planned before the subject consented to trial participation. 
• 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 11.4.5.3). 
Serious adverse event definition 
An SAE is any untoward medical occurrence that 
• Results in death. 
• Is life-threatening. 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation. 
Planned hospitalisation or planned prolonged hospitalisation do not fulfil the 
criteria for being an SAE but should be documented in the subject’s medical 
record. 
• Results in persistent or significant disability/incapacity. 
• Is a congenital anomaly/birth defect. 
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• or  
• 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. 
• Adverse events of special interest 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. 
Causality 
The causal relation of the AE to the use of the IMP should be classified using the below 
categories of probable, possible, 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. 
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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. 
 
Outcome 
The outcome of the event according to the investigator’s clinical judgement should be 
classified using the categories below. 
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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 a 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, for example subject lost to follow-up. 
 
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. 
For SAEs which have stabilised and cannot be expected to recover during study or safety 
follow-up periods, for example chronic or stabilised conditions, the final outcome should be 
kept as ‘recovering/resolving’ or ‘not recovered/not resolved’. In addition, a statement that the 
SAE has stabilised or is chronic should be added to the narrative description of the SAE on 
the SAE form. Please note that the event should not be reported as ‘recovered’ on the SAE 
form.
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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 (World Medical Association) and 
Council for International Organizations of Medical Sciences (CIOMS) International 
Ethical Guidelines. 
• Current version of applicable International Council for Harmonisation (ICH) Good 
Clinical Practice (GCP) Guidelines. 
• EU’s General Data Protection Regulation 2016/679 of 27 April 2016. 
• Applicable laws and regulations. 
The appropriate regulatory authority(ies) must be notified of/approve the clinical trial as 
required.  
Any documents that the IRB/IEC may need to fulfil its responsibilities (such as the trial 
protocol, protocol amendments, investigator’s brochure, subject information leaflet, informed 
consent forms, or advertisements) will be submitted to the IRB/IEC. These documents must 
be reviewed and approved by the IRB/IEC before the trial is initiated. 
Any amendments to the protocol must be approved by/receive favourable opinion from 
relevant regulatory authorities and IRBs/IECs, 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/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IRB/IEC. 
• Notifying the local IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures. 
• Providing oversight of the conduct of the trial at the trial site and adherence to 
applicable national and international legislation. 
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Appendix 3B: Informed consent process  
Subjects and subjects’ 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 (4.8) and all applicable laws and regulations. The authorised person obtaining the 
informed consent must also sign the 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) (including the additional ICF for the subgroup of 
subjects having biopsy samples taken) 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. 
To participate in the ECZTEND trial after May 2021, subjects must re-consent/consent to 
protocol version 10 to 13.  
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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.  
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 and consent to 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/IEC members, and by inspectors from regulatory authorities. 
Processing of personal data 
This protocol specifies the personal data on trial subjects (for example race, ethnicity, age, 
gender, 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 as well as reporting obligations in the event of any data 
breach. 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 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 
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. Clinical 
assessments/safety evaluations must be signed by medically qualified 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. 
• A statement from the investigator to verify that each of the eligibility criteria 
are met and documented. 
• Subject ID. 
• The fact that the subject is participating in a long-term clinical trial in AD 
involving open-label treatment with tralokinumab. 
• Other relevant medical information. 
Trial monitoring 
During the course of the trial, CRA(s) will visit the trial site. These visits have the following 
objectives: (i) to continually verify source data to confirm that data entered into the eCRF by 
authorised site personnel are accurate, complete, and verifiable from source documents; (ii) to 
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confirm that the safety and rights of subjects are being protected; and (iii) to confirm that the 
trial is being conducted in accordance with the currently approved protocol and any other trial 
agreements, ICH GCP, and all applicable regulatory requirements. 
The monitoring visit intervals will depend on the trial site’s recruitment rate and the 
compliance of the trial site with the protocol and ICH GCP. 
In order to perform their role effectively, CRAs and persons involved in quality assurance and 
inspections will need direct access to source data, for example 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 (for example by telephone). 
Protocol compliance 
Protocol deviations will be documented and notified to the investigator. Protocol deviations 
will be assessed by LEO Pharma and major deviations described in the CTR. 
Sponsor audits, IRB/IEC 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/IECs. 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 must be notified 
immediately. 
Risk assessment 
In this trial, overall risks have been assessed to ensure subject safety and will be continuously 
monitored during the trial. 
To ensure consistent data with respect to investigator assessment of efficacy (IGA, EASI and 
SCORAD), all investigators will receive training. 
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Throughout the trial, data quality review meetings will be held to ensure that data collection 
can be improved and mistakes prevented. During monitoring visits to the trial sites, the CRAs 
will verify that investigators work according to the protocol. 
Data handling 
Data will be collected by means of electronic data capture unless transmitted to LEO Pharma 
or designee electronically (for example, laboratory data). The investigator or staff authorised 
by the investigator will enter subject data into electronic CRFs (eCRFs). Data recorded in the 
eCRFs will be accessible to the trial site and LEO Pharma personnel immediately after entry. 
The eCRFs 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 all eCRFs used. 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 the 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 ePRO, data will be available 
immediately after data entry and available for monitors 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 (Worst Weekly Pruritus NRS, Eczema-related Weekly Sleep NRS, and Patient 
use of topical treatment) will be recorded at each site visit and entered in the eCRF. The 
outcomes will be recorded for the period of 7 days before each site visit (from 6 days prior to 
each visit and including the day of the 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 electronic data from external data providers and of ePRO data to the clinical 
database are illustrated in Panel 16.  
Panel 16: Transmission of electronic data 
 
CTR = clinical trial report; ECG = electrocardiogram; eCRF = electronic case report form; 
ePRO = electronic patient-reported outcome. 
 
Archiving of trial documentation 
The investigator at each trial site must make arrangements to store the essential trial 
documents, including the investigator trial file (in accordance with ICH GCP). 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 (for 
example 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. 
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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 and assigned subjects included 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/ IECs. 
Appendix 3E: Registration, reporting and publication policy 
Trial disclosure 
LEO Pharma is committed to be transparent with respect to its clinical trials. 
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 on the LEO Pharma corporate website 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.   
LEO Pharma may also provide researchers access to anonymised patient level data for further 
research. Publication and access will be in accordance with LEO Pharma’s Position on Public 
Access to Clinical Trials, which can be found on the LEO Pharma website. 
Publications 
The investigator shall be entitled to make publications of the results generated by investigator 
in accordance with the process described here. 
A multi-centre publication will be submitted for publication within 18 months after the 
clinical trial has been completed or terminated at all trial sites and all data have been received, 
defined as database lock of the clinical trial. After such multi-centre publication is made 
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public, or if no multi-centre publication has been submitted with the above-described 
deadline, the investigator shall have the right to publish the results from the clinical trial 
generated by the investigator, subject to the following notice requirements: 
Prior to submission for publication or presenting a manuscript relating to the clinical trial, the 
investigator shall provide to LEO Pharma a copy of all such manuscripts and/or presentations. 
LEO Pharma shall have rights to review and comment. The investigator shall consider 
comments from LEO but is not required to modify the manuscript and/or presentation based 
on such comments, provided, however, that the investigator upon the request of LEO Pharma 
remove any confidential information (other than results generated by the investigator) prior to 
submitting or presenting the manuscripts. The investigator shall, upon the request of LEO 
Pharma withhold the publication or presentation to allow LEO Pharma to protect its 
inventions and other intellectual property rights described in any such manuscripts.  
In case no multi-centre publication has been made public at the time of investigator’s 
notification of an independent publication to LEO Pharma, LEO Pharma and the writing 
group may also delay the publication or presentation if the manuscript is deemed to harm the 
ongoing multi-centre publication. 
In case of publications made by the investigator after the first multi-centre publication has 
been published, the above-mentioned requirements must still be followed. 
Any publication must comply with Good Publication Practice (GPP3) standards. 
LEO Pharma complies with GPP3 standards and the recommendations from the International 
Committee of Medical Journal Editors. LEO Pharma complies with the positions of the 
International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), 
European Federation of Pharmaceutical Industries and Associations (EFPIA), Japan 
Pharmaceutical Manufacturers Association (JPMA), Pharmaceutical Research and 
Manufacturers of America (PhRMA), and the joint position statement by the American 
Medical Writers Association (AMWA), the European Medical Writers Association (EMWA), 
and the International Society for Medical Publication Professionals (ISMPP) on disclosure of 
information about clinical trials, trial results and authorship. LEO Pharma also follows the 
CONSORT reporting guidelines (Schulz 2010). 
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 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 site closure 
Premature termination of trial or trial site 
LEO Pharma, the investigator, the IRB/IECs 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 IRB/IECs 
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 early 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/IEC 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 
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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. 
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. 
The national coordinating investigators are responsible for national issues relating to the 
clinical trial as agreed to in a National Coordinating 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.  
Appendix 3J: Country-specific end of treatment date 
Subjects from the parent trial LP0162-1334, who consented to participate in the trial after 
May 2021, will end treatment by end of May 2022 in all countries. 
Subjects from the parent trials LP0162-1325, -1326, -1339, -1341, -1342,-1343, -1346, and 
TRA-WEI-0015-I, who consented to participate in the trial after May 2021, will have a 
country-specific end of treatment date (Panel 17).  
Panel 17: Country-specific last subject last treatment for parent trials LP0162-1325, 
-1326, -1339, -1341, -1342, -1343, -1346, and TRA-WEI-0015-I 
Country 
Approximate last treatment date in the trial* 
US 
May 2022 
Germany 
Aug 2021 
UK 
Sep 2022 
France 
Aug 2022 
Italy 
Jan 2023 
Belgium 
Nov 2022 
Canada 
May 2023 
Spain 
Jan 2023 
Poland 
May 2024 
Czech Republic 
Oct 2022 
Japan 
May 2023 
*These dates are estimates of availability of tralokinumab in the countries and could change.  
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Appendix 3K: COVID-19 
Rationale 
The current COVID-19 pandemic warrants many subjects in the ECZTEND trial to stay at 
home to comply with authority-issued preventive measures. This impacts subjects’ ability to 
attend site visits in person. To follow authorities’ restrictions and to safeguard the subjects in 
the ECZTEND trial as well as providing continued therapy to secure the scientific integrity, 
this clinical trial protocol appendix is installed to provide an opportunity for telephone visits 
and courier delivery of IMP and pregnancy tests to subjects in replacement of the site visits. 
In addition, inclusion criterion 2 is changed during COVID-19 restrictions, to allow subjects 
who are not able to attend all protocol-mandated visits of their parent trials due to COVID-19 
to participate in trial LP0162-1337, if considered eligible for continued treatment by the 
investigator. 
Subject eligibility 
Inclusion criterion 2 in trial LP0162-1337 states: 
• Subjects must have completed* the treatment period(s) of one of the parent trials: 
LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346, or TRA-WEI-0015-I. 
• * To be assessed on the first day of IMP administration (baseline).  
• In trial LP0162-1334, a subject is considered to have completed the treatment period, if 
the subject has attended the Week 52 visit on site. 
• In trials LP0162-1343 and TRA-WEI-0015-I, a subject is considered to have completed 
the treatment period, if the subject has attended the Week 16 visit on site. 
• Change to inclusion criterion 2 in trial LP0162-1337 during COVID-19 restrictions: 
The change to inclusion criterion 2 described in the following only applies to subjects coming 
from parent trials LP0162-1334, -1343, and TRA-WEI-0015-I, as these are the only parent 
trials ongoing at the time of this appendix.  
For subjects who are not able to attend the above-mentioned visits at site in their parent trials 
due to COVID-19, inclusion criterion 2 is considered fulfilled if AEs have been collected over 
the telephone and if the investigator has evaluated and documented that the subject is 
considered to benefit from continued treatment in trial LP0162-1337, despite the missed 
visit(s) in the parent trial. 
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eCRF recording 
It must be recorded in the eCRF if a site visit was converted to a telephone visit (not 
applicable for the scheduled mandatory telephone visits in protocol version 13). This should 
be done in the comments log for each visit. ‘Visit date’ must also be documented. 
If the subject is reached by telephone, use of emollients, AEs, concomitant medication and 
pregnancy test result (if applicable) must be collected. All other assessments should be 
marked ‘Not done’ in the eCRF, except for EASI, SCORAD, IGA, and weight, which should 
be left blank. The log line ‘If not done, specify reason’ in the assessment form must be 
answered with ‘COVID-19’ as well as the specific reason related to COVID-19, e.g. subject 
cannot visit site due to COVID-19 quarantine, or site is closed due to COVID-19.  
In addition, the specific COVID-19-related reason for missing visit or performing visit as 
telephone visit must be entered in the ‘Comments log’ in the eCRF on subject level. 
If no contact can be established between site and subject at a given visit, this must be recorded 
as a missed visit in the eCRF (“Not done”). The log line “If not done, specify reason” must be 
answered with the specific reason related to COVID-19, as above. 
Description of visit scenarios 
It is a requirement that all subjects attend the first 3 dosing visits (Visit 3, 4, 5) at the clinic 
according to protocol in order to ensure the 30 min. post-dose observation time for the 
3 dosing visits. This will at the same time ensure proper training prior to home use. If 
attending the first 3 dosing visits is not possible, then the subject cannot take part in the trial. 
Without compromising the safety of subjects and site personnel, it is expected that efforts are 
made to secure visit attendance at sites for visits Weeks 16, 56, 88, 104, 136, 152, 184, 216 
and 248, in order to secure important efficacy assessments for the trial. Depending on national 
guidelines regarding COVID-19 and subject preferences, the remaining visits can follow 
2 different scenarios as described below: 
1) The subject is not restricted from attending visits at the clinic and continues to follow 
all procedures specified in the protocol. 
2) Subject is not able to attend visits at the clinic, in which case the following procedure 
must be followed:  
a. Site staff informs subject about the possibility of courier delivery of IMP and 
pregnancy test, if applicable. 
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b. The subject verbally consents to providing contact details for shipping 
purposes and to receiving IMP at home (this needs to be documented in the 
subject’s medical records). 
c. Site staff allocates IMP for the subject using the EDC system (RAVE®) as per 
protocol. 
d. Site staff sends the following items by a LEO-approved courier company: 
i. Participant Information Sheet for home delivery. 
ii. Log of Drug Administration. 
iii. The appropriate amount of IMP. 
iv. One sharps container, if required. 
v. If required, sanitisers: alcohol wipes, cotton balls or gauze. 
vi. For female subjects of child-bearing potential: one urine pregnancy test 
kit and Urine Pregnancy Test Instruction. 
e. Site staff contacts the subject (by telephone) and ensures the following: 
i. The Participant Information Sheet has been read, is understood and 
agreed to. 
ii. Subject is asked about concomitant medication use, concomitant 
procedures, adverse events, and pregnancy test outcome according to 
the original schedule of trial procedures. 
f. Site staff documents all the above in the subject’s medical record at the clinic. 
g. Site staff enters all available information into the EDC system (RAVE®), see 
above Section “eCRF recording”. 
Home use of IMP 
Injections of tralokinumab 
Self-injection of tralokinumab is described in the protocol and does not change with this 
appendix. 
Subjects who miss one or more doses need to have the missed doses documented in the eCRF 
with specific reason related to COVID-19 written in the comments log for each visit in scope. 
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Further details on IMP-injection are provided in the Trial Product Handling Manual. Subjects 
will also receive a pamphlet with instructions for IMP home use and a Log of Drug 
Administration. 
TCS 
The use of TCS is described in the ECZTEND clinical trial protocol and does not change with 
this document. 
Emollients 
The use of emollients is described in the ECZTEND clinical trial protocol and does not 
change with this document.  
Urine pregnancy test 
The schedule of pregnancy testing does not change with this document. Subjects need to 
perform the urine pregnancy test kit at home if required per protocol. Urine pregnancy test kit 
is delivered by the site as per protocol. The subject will be provided with a Urine Pregnancy 
Test Instruction. Results should be communicated to the site by subject during telephone visit 
and documented in the eCRF and source documents. 
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Appendix 4: Country-specific requirements 
This appendix describes requirements and procedures that are specific for Japan 
(Appendix 4A) and France (Appendix 4B). For each section, the text from the protocol is 
presented in normal font. The specific requirements or procedures for Japan or France are 
presented below in bold font. 
Appendix 4A: Japan 
Section 9.8.3 Drug accountability 
The investigator is fully responsible for the IMP at the trial site, for maintaining adequate 
control of the IMP, and for documenting all transactions with them. 
In Japan, it is the Head of Institute who is responsible for the IMP at the trial site. 
Section 9.8.5 Trial product destruction 
Used syringes will be destroyed at the trial site provided the trial site has procedures in place 
for such IMP destruction. Trial sites that do not have such IMP destruction procedures in 
place will dispose used IMP in sharps bins that will be shipped to the CMO. 
In Japan, used syringes will be destroyed at the trial sites. 
Section 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 Global Safety at LEO Pharma on the 
trial-specific (paper) Complaint Form within 3 days of first knowledge. 
Critical complaints (defined as any issue, defect, or device deficiency that has or potentially 
could have a serious impact for the subject [for example, SAE or large particles in the 
syringe]) must be reported to Global Safety at LEO Pharma within 24 hours. 
In Japan, product complaints must be reported to Pharmacovigilance at LEO Pharma 
K.K. using the contact information below: 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-pharma.com 
 
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Section 11.1 Overview 
Assessments/procedures at any site visit should be performed in the following order: 
• PROs in the following order: 
7. Patient Oriented Eczema Measure (POEM). 
8. Dermatology Life Quality Index (DLQI)/Children’s 
Dermatology Life Quality Index (CDLQI).* 
9. EuroQoL 5-Dimension Health Questionnaire 5 Level 
(EQ-5D-5L)*. 
10. Eczema-related Weekly Sleep numeric rating scale (NRS).* 
11. Worst Weekly Pruritus NRS.* 
12. Patient use of topical treatment. 
• *All subjects from the parent trial LP0162-1334, independent of the subject’s 
age during participation in ECZTEND, will perform the Children’s 
Dermatology Life Quality Index (CDLQI), an adolescent’s pruritis NRS with a 
recall period of past 7 days, and an eczema-related sleep NRS with a recall 
period over the past 7 nights; these subjects will not perform the EQ-5D-5L as 
this questionnaire has not been validated for adolescents. 
• Investigator assessments (performed only by adequately trained investigators; 
to reduce inter-rater variability, the same investigator should preferably 
perform all the evaluations for a given subject throughout the entire trial 
period) in the following order: 
1. SCORAD component C, then component A and B. 
2. IGA. 
3. EASI. 
• Safety and laboratory assessments. 
• Administration and dispensing of IMP. 
In Japan, the order of assessments may be changed after the baseline visit to perform 
safety and laboratory assessments before the investigator assessments but after the 
PROs. The assessments must be performed in the same order for all subjects at the site. 
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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 either a physician, 
certified physician’s assistant, or advanced registered nurse practitioner. 
In Japan, investigators must be dermatologists. 
Section 13.4.1 Investigator reporting responsibilities 
Any SAE must be reported to LEO Pharma on the (paper) SAE Form within 24 hours of first 
knowledge. The completed SAE form must be faxed or scanned and e-mailed to Global 
Safety, LEO Pharma. 
In Japan, SAEs must be reported to Pharmacovigilance at LEO Pharma K.K. using the 
contact information below: 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-pharma.com  
Section 13.4.2 LEO Pharma reporting responsibilities 
Global Safety, LEO Pharma will notify the regulatory authorities and concerned investigators 
of SAEs according to the current applicable legislation for the concerned countries. 
In Japan, Pharmacovigilance, LEO Pharma K.K. will be responsible for notifying the 
regulatory authorities and concerned investigators of SAEs. 
Section 13.5 Expedited reporting of pregnancy 
Any pregnancy occurring during the clinical trial must be reported to LEO Pharma within 24 
hours of first knowledge using the (paper) Pregnancy Follow Up Form (Part I). All such 
pregnancies must be followed up until delivery or termination and final outcome must be 
reported on the (paper) Pregnancy Follow Up Form (Part II) within 24 hours of first 
knowledge. 
The completed Pregnancy Follow Up Forms must be faxed or scanned and e-mailed to Global 
Safety at LEO Pharma. 
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In Japan, any pregnancy must be reported to Pharmacovigilance at LEO Pharma K.K. 
using the contact information below: 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-pharma.com 
 
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Appendix 4B: France 
Section 11.4.5.2 Urine pregnancy test 
The test will be repeated at Week 4 and thereafter as shown in the schedule of trial procedures 
(Section 4). 
In France, urine pregnancy testing will be repeated every 4 weeks. Thus, from Week 16 
onwards, site staff will supply a pregnancy test kit for home use to female subjects of 
childbearing potential. The subjects will take the pregnancy test at home every 4 weeks 
following Week 16, and will record the results in the log of drug administration (in 
which they will record each IMP administration at home, as described in Section 9.8.4). 
In case of a positive test result, the subject must discontinue IMP use and contact site 
staff immediately. Should this occur, site staff will call the subject in for an unscheduled 
site visit. In case of a negative test result, the subject should continue administration of 
IMP at home as usual. 
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Appendix 5: Eligibility criteria 
A short form (200 characters) version of each of the eligibility criteria for the trial, using 
CDISC controlled terminology, is provided below. 
No. 
Inclusion criteria 
1 
Signed and dated informed consent has been obtained prior to any protocol-related 
procedures 
2 
Subjects must have completed the treatment period(s) of one of the parent trials: 
LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346 or TRA-WEI-0015-I 
(to be assessed at baseline) 
3 
Subjects must have complied with the clinical trial protocol in the parent trial to the 
satisfaction of the investigator 
4 
Be able and willing to self-administer tralokinumab treatment (or have it administered 
by a caregiver) at home after the initial 3 injection visits at the trial site (in this trial) 
5 
Subjects must have applied a stable dose of emollient twice daily (or more, as 
needed) for at least 14 days prior to baseline 
6 
Female subjects of childbearing potential must use highly effective birth control for at 
least 1 month before baseline, throughout the trial, and for at least 16 weeks after last 
administration of IMP 
 
 
No. 
Exclusion criteria 
1 
Any condition that required permanent discontinuation of trial treatment in the parent 
trial 
2 
More than 26 weeks have elapsed since the subject received the last IMP injection in 
the parent trial (to be assessed at baseline) 
3 
Development in the parent trial of SAE that was deemed related to IMP and, as 
judged by investigator, could indicate an unreasonable risk of continued treatment 
4 
Development in the parent trial of AE that was deemed related to IMP and led to 
temporary discontinuation of IMP and, as judged by investigator, could indicate 
unreasonable risk of continued treatment 
5 
Receipt of any marketed or investigational biologic agent (such as cell-depleting 
agents or dupilumab) within 6 months prior to baseline, or until cell counts return to 
normal, whichever is longer 
6 
Treatment with systemic immunosuppressive/immunomodulating drugs and/or 
systemic corticosteroids within 5 half-lives prior to baseline 
7 
Treatment with topical PDE-4 inhibitors or topical JAK inhibitors within 2 weeks 
prior to baseline 
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No. 
Exclusion criteria (continued) 
8 
Positive HBsAg, HBsAb*, HBcAb, or anti-HCV serology at screening. Subjects with 
positive HBsAb are eligible provided they are vaccinated against hepatitis B and have 
negative HBsAg and HBcAb 
*Subjects from the parent trial LP0162-1343 with a positive HBsAb may be assigned 
treatment provided they have negative HBsAg, HBcAb, and HCV serology at 
screening. 
9 
Known or suspected hypersensitivity to any component of the IMP 
10 
History of anaphylaxis following any biological therapy 
11 
History of immune complex disease 
12 
History of cancer 
13 
Tuberculosis requiring treatment within 12 months prior to screening. Evaluation will 
be according to local guidelines as per local standard of care 
14 
History of any known primary immunodeficiency disorder including a positive HIV 
test at screening, or use of antiretroviral medications 
15 
Current participation in any other interventional clinical trial, except for tralokinumab 
trials LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346, or TRA-WEI-
0015-I 
16 
Previously screened in this clinical trial 
17 
Receipt of live attenuated vaccines within 30 days prior to baseline and during the 
trial, including the safety follow-up period 
18 
Receipt of blood products within 4 weeks prior to screening 
19 
Major surgery within 8 weeks prior to screening, or planned in-patient surgery or 
hospitalisation during the trial period 
20 
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 
21 
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 
22 
Subjects who are legally institutionalised 
23 
Female subjects who are pregnant, breastfeeding, or lactating 
24 
History of attempted suicide or significant risk of suicide (either in the opinion of the 
investigator or according to the C-SSRS) 
25 
History of a clinically significant infection (systemic infection or serious skin 
infection requiring parenteral treatment) within 4 weeks prior to baseline 
 
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No. Exclusion criteria (continued) 
26 
A helminth parasitic infection within 6 months prior to the date when informed 
consent is obtained that has not been treated with, or has failed to respond to, standard 
of care therapy 
27 
Any disorder that 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 
28 
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 
 
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Appendix 6: Guidance for anaphylaxis diagnosis 
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., generalised hives, pruritus or flushing, swollen lips-
tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
• Respiratory compromise (e.g., dyspnoea, 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., generalised hives, itch-flush, 
swollen lips-tongue-uvula) 
• Respiratory compromise (e.g., dyspnoea, 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 7: Contact list 
Contact details for the CPM, appointed CRA, and sponsor’s medical expert are provided to 
the trial sites as a separate contact list. 
Sponsor 
LEO Pharma A/S (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 
LEO Pharma K.K. is the sponsor of the clinical trial in Japan on behalf of LEO Pharma A/S: 
LEO Pharma K.K. 
1-105 Kanda-Jinbocho 
Chiyoda-ku 
Tokyo 101-0051 
Japan 
Coordinating investigator 
 
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Appendix 8: Protocol amendment history 
The Protocol amendment summary of changes table for the current amendment is located 
directly before the table of contents. 
Amendment 1 (27-Jun-2018) 
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 an inclusion criterion that will enable all 
eligible subjects to enter this trial directly after completing the treatment period(s) in their 
parent trial. The scientific rationale for this change is given in the table below. 
In addition, the amendment includes other changes, as presented in the table below. 
Note: The table below describes the changes in each section, either summarised (in plain text) 
or marked as tracked changes (text deleted has a line through it). 
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Section no. and 
name 
Description of change 
Brief rationale 
1 Protocol 
synopsis 
5.3 Trial 
rationale 
5.4 Justification 
for dose 
8.2 Inclusion 
criteria 
Appendix 5 
Change to inclusion criterion 
no. 2: 
Subjects from ALL parent trials 
will be eligible if they have 
completed the treatment period(s) 
in the parent trial. It is no longer a 
requirement that subjects from 
trials LP0162-1325, -1326, and -
1339 must also have completed 
the safety follow-up period in the 
parent trial. 
The original protocol required subjects 
from 3 of the parent trials to complete a 
14-week, off-treatment period before they 
could enter the extension trial. This 
period was needed for tralokinumab 
concentrations to decrease to a level 
where the presence or absence of ADA 
could be determined in serum samples. 
A new ADA assay with improved 
tralokinumab tolerance has been 
developed. This means that ADA can be 
measured in serum samples with higher 
levels of tralokinumab. Therefore, the 
samples can be taken only 2 weeks after 
the last dose of tralokinumab, that is, at 
the end of treatment visit in the parent 
trials. Hence, subjects can transfer 
directly into the extension trial after 
completing the treatment periods in these 
3 parent trials. 
1 Protocol 
synopsis 
4 Schedule of 
trial procedures 
6 Trial objectives 
and endpoints 
7.3 End of trial 
definition 
14.3.4 Primary 
endpoint 
Change in timeframe for primary 
endpoint from 
up to Week 128 
to 
from baseline through the last 
treatment visit (up to Week 142). 
To ensure that all treatment-emergent 
adverse events are included in the 
primary endpoint as well as to enable 
easier data presentation and reporting, it 
has been decided to include the entire 
treatment period for all subjects within 
the timeframe for the primary endpoint. 
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Section no. and 
name 
Description of change 
Brief rationale 
4 Schedule of 
trial procedures 
Change to urinalysis schedule: 
urinalysis assessment at Week 48 
moved to Week 32. 
Error in original protocol. 
9.8.3 Drug 
accountability 
Addition of text to specify that 
site staff will record the following 
details in the eCRF: the site of 
IMP injection, as recorded by 
subjects in the log of drug 
administration for each IMP 
administration at home. 
Clarification that site staff will record 
these data in the eCRF. 
14.3.3 Exposure 
and treatment 
compliance 
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 the last IMP dose + 20 
days* OR to the date of 
permanent discontinuation of 
IMP, whichever comes first. 
* 20 days = planned time between 
2 doses (14 days) + dosing 
window (±3 days) for both doses. 
The definition of exposure end has been 
simplified, in line with updated statistical 
analysis plans for the parent trials. 
14.3.8.1 Adverse 
events 
Adverse events of special interest 
(AESIs) will be tabulated and 
listed instead of being presented 
in a narrative. 
Tabulation and listings are considered a 
more practical and informative way of 
presenting data on AESIs. This will 
enable easier overview of the individual 
cases as well as sorting and pooling of 
data from several trials. 
Throughout 
Minor editorial revisions. 
Minor, have therefore not been 
summarised. 
 
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Amendment 2 (31-Aug-2018) 
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 an inclusion criterion to also allow eligible 
subjects from trial LP0162-1346 to enter the extension trial. The scientific rationale for this 
change is given in the table below. 
In addition, the amendment includes other changes, as presented in the table below. 
Note: The table below describes the changes in each section, summarised in plain text. 
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Section no. and 
name 
Description of change 
Brief rationale 
1 Protocol synopsis 
5.3 Trial rationale 
8.2 Inclusion 
criteria 
8.3 Exclusion 
criteria 
Appendix 5: 
Eligibility criteria 
Change to inclusion criterion no. 2 
to allow eligible subjects from trial 
LP0162-1346 to enter the extension 
trial. 
Change to exclusion criterion 
no. 15, reflecting that ‘current 
participation in any other 
interventional clinical trial’ will 
also be allowed for eligible subjects 
from trial LP0162-1346. 
To also offer subjects in trial 
LP0162-1346 the possibility to 
continue treatment with tralokinumab 
in the extension trial. 
8.3 Exclusion 
criteria 
Change to exclusion criterion no. 9 
to allow entry of subjects who 
during their parent trial have had a 
localised injection site reaction 
suspected to be due to 
hypersensitivity, provided that the 
subject has been able to continue 
IMP administrations and there has 
been no sign of a systemic 
hypersensitivity reaction. 
To clarify that subjects having a 
localised injection site reaction 
suspected to be due to 
hypersensitivity during their parent 
trial are allowed to continue with 
IMP, both in the parent trial and 
extension trial, if this is considered 
safe. It will be at the investigator’s 
discretion to assess if continued 
exposure to IMP is considered safe. 
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Section no. and 
name 
Description of change 
Brief rationale 
8.3 Exclusion 
criteria 
Change to exclusion criterion 
no. 12 to allow entry of subjects 
who during their parent trial have 
had basal cell carcinoma, localised 
squamous cell carcinoma of the 
skin, or in situ carcinoma of the 
cervix, provided that the subject is 
in remission and curative therapy 
has been completed. 
To clarify that subjects being 
diagnosed with basal cell carcinoma, 
localised squamous cell carcinoma of 
the skin, or in situ carcinoma of the 
cervix during their parent trial are 
allowed to continue with IMP, both 
in the parent trial and extension trial. 
Given the nature of these 
malignancies, continued exposure to 
IMP is not considered to be a safety 
concern. 
Appendix 4: 
Country-specific 
requirements 
Appendix split into Appendix 4A: 
Japan (no other changes) and 
Appendix 4B: France (new 
appendix, see below). 
 
Appendix 4B: 
France 
Country-specific requirement added 
for France: 
In France, urine pregnancy testing 
will be repeated every 4 weeks. 
From Week 16 onwards (when site 
visits will occur every 8 weeks), 
site staff will supply a pregnancy 
test kit for home use to female 
subjects of childbearing potential, 
who will take the pregnancy test at 
home 4 weeks after each site visit. 
Requested by French regulatory 
health authorities (ANSM) during 
their protocol revew. 
Appendix 8 
New appendix added for protocol 
amendment history. Summary of 
previous amendment moved to this 
appendix. 
To keep only the most recent 
amendment summary at the start of 
the protocol. 
 
 
 
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Amendment 3 (13-Dec-2018) 
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 exclusion criterion no. 6 to reflect that a 
wash-out period is not considered necessary because subjects are allowed to resume 
investigational medicinal product following 5 half-lives after the last administration of 
systemic immunosuppressive or immunomodulating drugs and/or systemic corticosteroids. 
Clarifications on how to handle duplicate assessments (i.e. assessments performed on the 
same day) between parent trial and trial LP0162-1337 have been added. In addition, the 
amendment includes other changes, as presented in the table below. 
Note: The table below describes the changes in each section, summarised as plain text, and/or 
as tracked changes (text added to the protocol is written in bold and deleted text has a line 
through it). 
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Section no. 
and name 
Description of change 
Brief rationale 
8.3 Exclusion 
criteria 
 
6. Treatment with the following medications 
within 5 half-lives 4 weeks prior to baseline: 
• 
Systemic 
immunosuppressive/immunomodulating 
drugs (for example, methotrexate, 
cyclosporine, azathioprine, 
mycophenolate-mofetil, Janus kinase 
inhibitors). 
• 
Systemic corticosteroids (excluding 
topical, ophthalmic, inhaled, or 
intranasal delivery). 
During the parent trials 
subjects are allowed to resume 
investigational medicinal 
product following 5 half-lives 
after the last administration of 
these types of medications. A 
wash-out period is therefore 
not considered necessary.  
1 Protocol 
synopsis 
Appendix 5: 
Eligibility 
criteria 
• 
Treatment with systemic 
immunosuppressive/immunomodulating 
drugs and/or systemic corticosteroids 
within 5 half-lives 4 weeks prior to 
baseline. 
During the parent trials 
subjects are allowed to resume 
investigational medicinal 
product following 5 half-lives 
after the last administration of 
these types of medications. A 
wash-out period is therefore 
not considered necessary.  
1 Protocol 
synopsis 
Trial participation will include a screening period 
of 2 to 4 weeks (including wash-out, if 
applicable), a treatment period of approximately 
1.5 to 2.5 years, and a safety follow-up period of 
14 weeks (starting 2 weeks after last dose of 
IMP).  
To clarify that the duration of 
screening is no longer 
dependent on the need for 
wash-out in acordance with 
exclusion criteria 6 and 7. 
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Section no. 
and name 
Description of change 
Brief rationale 
4 Schedule of 
trial 
procedures 
 
If the screening period does not exceed a 
duration of 2 weeks, a single screening visit 
should preferably be performed combining the 
assessments specified for Visits 1 and 2. If the 
screening period exceeds a duration of 2 weeks 
(+7 days), the screening will consist of 2 
separate visits (Visits 1 and 2). For subjects who 
do not require a washout, visits 1 and 2 will be 
combined and screening will be reduced to 2 
weeks; hence, these subjects will only attend visit 
2 (Week  2) which will include all assessments 
shown under Week 4.  
To clarify that the duration of 
screening is no longer 
dependent on the need for 
wash-out in acordance with 
exclusion criteria 6 and 7. 
7.1 Overall 
trial design 
The screening period has a duration of 2 to 
4 weeks and includes 1 or 2 screening visits 
(Visits 1 and 2). The exact duration of the 
screening period for the individual subject 
depends on the length of any washout period 
needed, as specified in the exclusion criteria in 
Section 8.3 (that is, 4 weeks prior to Week 0 
[hereinafter ‘baseline’] for systemic 
immunosuppressive or immunomodulating drugs, 
systemic corticosteroid use; and 2 weeks prior to 
baseline for topical phosphodiesterase 4 [PDE-4] 
inhibitors).If no washout or a 2-week washout 
period is required, screening will be reduced to 
2 weeks and 1 visit (Week -2; visit 2), that is, the 
2 screening visits will be merged. If the 
screening period does not exceed a duration of 
2 weeks, a single screening visit should 
preferably be performed combining the 
assessments specified for Visits 1 and 2 in the 
schedule of procedures in Panel 2. If the 
screening period exceeds a duration of 2 weeks 
(+ 7 days), the screening will consist of 2 
separate visits (Visits 1 and 2 in the schedule of 
procedures in Panel 2). Eligibility will be 
To clarify that the duration of 
screening is no longer 
dependent on the need for 
wash-out in acordance with 
exclusion criteria 6 and 7. 
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and name 
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Brief rationale 
assessed at the (first) screening visit and at 
baseline prior to start of treatment. Should the 
screening exceed a duration of 4 weeks, the 
sponsor should be consulted and approval 
sought before the subject can attend Visit 3 
(baseline visit). 
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Section no. 
and name 
Description of change 
Brief rationale 
4 Schedule of 
trial 
procedures 
Section 11.1 
Overview 
 
 
If screening/baseline visits are performed on the 
same day as visit(s) in the parent trial, the order of 
assessments should be adhered to, working in 
parallel for both protocols. Assessments where 
data are captured in different vendor systems 
databases (ECG, ePRO and laboratory tests) need 
to be completed twice. In such cases, the parent 
trial assessment should be performed first, 
followed by the trial LP0162-1337 assessment.  
To clarify how to handle 
assessments performed on the 
same day between parent trial 
and trial LP0162-1337, and to 
avoid duplicate assessments 
when possible. 
8.4 
Screening and 
screening 
failures 
9.2 
Administration 
of IMP 
Once informed consent is obtained, a unique 
subject identification number (subject ID) will be 
assigned by enrolling the subject through the 
EDC system. The subject ID consists of 5 digits, 
the first 3 of which refer to the site number, the 
latter 2 are sequential numbers, starting from 01.  
To clarify that entry of subject 
number must be done by trial 
staff using the EDC system 
rather than by interactive 
response technology. 
4 Schedule of 
trial 
procedures 
9.2 
Administration 
of IMP 
 
If the subject and/or the caregiver is/are health 
care professional(s), no training is required, 
but the subject should be trained in how to 
handle the IMP according to the IMP handling 
manual, and in the procedures to be followed 
in the event of an emergency. 
Subjects and/or caregivers 
who are health care 
professionals are considered 
sufficiently qualified for 
performing subcutaneous 
injections and do not need 
training on this, but should 
receive training in handling the 
IMP and procedures to be 
followed in the event of an 
emergency.  
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Section no. 
and name 
Description of change 
Brief rationale 
8.1 Subject 
eligibility 
It is assumed that subjects entering into this 
trial will in the investigator’s opinion have the 
potential to gain therapeutic benefit from 
treatment with tralokinumab irrespectively of 
whether the subject received tralokinumab or 
placebo in the parent trial. It is assumed that the 
majority of the subjects entering into this trial will 
in the investigator’s opinion have gained 
therapeutic benefit from tralokinumab in the 
parent trial. 
To clarify that also subjects 
receiving placebo in the parent 
trial are expected to benefit 
from treatment with 
tralokinumab in trial LP0162-
1337. 
Appendix 4A 
Japan 
Section 9.8.5 Trial product destruction 
Used syringes will be destroyed at the trial site 
provided the trial site has procedures in place 
for such IMP destruction. Trial sites that do 
not have such IMP destruction procedures in 
place will dispose used IMP in sharps bins that 
will be shipped to the CMO. 
In Japan, used syringes will be destroyed at the 
trial sites. 
To clarify that used syringes 
will be destroyed at the trial 
site in Japan 
 
Section 9.10 Reporting product complaints  
In Japan, product complaints must be reported to 
Pharmacovigilance at LEO K.K. using the contact 
information below: 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-
pharma.com 
Note: reports sent to the above fax number and 
email address will automatically be forwarded to 
Global Pharmacovigilance, LEO. 
 
As the description of an 
internal procedure is not 
considered of relevance for the 
investigator 
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Section no. 
and name 
Description of change 
Brief rationale 
 
Section 11.1 – Order of assessments 
In Japan, the order of assessments may be 
changed after the baseline visit to perform 
safety and laboratory assessments before the 
investigator assessments but after the PROs. 
The assessments must be performed in the 
same order for all subjects at the site. 
As the standard clinical 
procedure in Japan is to 
perform safety and laboratory 
assessments before subjects 
meet the principal investigator, 
a country-specific requirement 
has been added to allow this 
change in the order of 
assessments after the baseline 
visit. 
 
In Japan, investigators must be dermatologists 
or allergists. 
 
As adolescents with atopic 
dermatitis in Japan are seen by 
dermatologists and allergists, 
the country-specific 
requirement for Japan, that the 
investigator must only be a 
dermatologist has been 
changed to include allergists.  
 
Section 13.4.1 Investigator reporting 
responsitbilities 
In Japan, SAEs must be reported to 
Pharmacovigilance at LEO K.K. using the contact 
information below: 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-
pharma.com  
Note: reports sent to the above fax number and 
email address will automatically be forwarded to 
Global Pharmacovigilance, LEO. 
As the description of an 
internal procedure is not 
considered of relevance for the 
investigator 
 
Section 13.5 Expedited reporting of pregnancy 
In Japan, any pregnancy must be reported to 
Pharmacovigilance at LEO K.K. using the contact 
information below: 
As the description of an 
internal procedure is not 
considered of relevance for the 
investigator 
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Section no. 
and name 
Description of change 
Brief rationale 
Fax number: +81 3 4243 3311 
E-mail address: clinical_trial_jp@leo-
pharma.com 
Note: reports sent to the above fax number and 
email address will automatically be forwarded to 
Global Pharmacovigilance, LEO. 
 
 
Throughout  
Global Pharmacovigilance Safety at LEO. 
The Global Pharmacovigilance 
department at LEO has 
changed name. 
Throughout  
Minor editorial revisions. 
Minor, and are therefore not 
summarised. 
 
 
 
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Amendment 4 (28-May-2019) 
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 introduce the option to take skin biopsy samples at 
selected sites in the subgroup of subjects who had skin biopsy samples in the parent trial 
LP0162-1325 and to consolidate the 2 screening visits to 1 visit. In addition, the amendment 
includes other changes, as presented in the table below. 
Note: the table below describes the changes in each section, summarised as plain text, and/or 
as tracked changes (text added to the protocol is written in bold and deleted text has a line 
through it). 
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Section no. and 
name 
Description of change 
Brief rationale 
4 Schedule of 
trial procedures 
11.6 Skin 
biopsies 
(subgroup of 
subjects at 
selected sites) 
11.9 Storage of 
biological 
samples 
Appendix 3B 
Introduction of the option at selected sites to 
take 2 skin biopsy samples at Week 48 in the 
subgroup of subjects who had skin biopsy 
samples in the parent trial LP0162-1325.  
To investigate the molecular 
profile in the skin of AD 
patients treated for more than 
1 year with tralokinumab and 
to document the long-term 
disease control of 
tralokinumab. 
1 Protocol 
synopsis 
3 Schematic of 
trial design 
4 Schedule of 
trial procedures 
7.1 Overall trial 
design 
Consolidation of the 2 screening visits. 
As it is not necessary to 
perform 2 screening visits in 
this extension trial. 
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Section no. and 
name 
Description of change 
Brief rationale 
8.3 Exclusion 
criteria 
Exclusion criterion 28: 
28. Any abnormal finding which in the opinion 
of the investigator may: 
• 
Put the subject at risk because 
of their participation in the trial. 
• 
Influence the results of the trial. 
Influence the subject’s ability to complete the 
trial. 
The abnormal finding must be clinically 
significant and observed during the screening 
period. Examples include abnormal findings in 
physical examination, vital signs, 
electrocardiogram (ECG [based on the central 
ECG evaluation report]), haematology, 
clinical chemistry, or urinalysis (based on 
results provided by the central laboratory). 
To clarify that the 
investigator’s evaluations of 
abnormal ECG and laboratory 
testing results during the 
screening period are based on 
reports prepared by a central 
ECG service company and a 
central laboratory, 
respectively. 
9.6 
Concomitant 
medication and 
concurrent 
procedures 
Any medication (except for IMP/NIMP 
including momethasone furoate, CYP 
cocktail, and vaccine received in the 
treatment periods in the parent 
trials)tralokinumab/placebo) for vaccine that 
the subject receives from 3 months prior to 
screening through the safety follow-up, 
including any of the permitted concomitant 
medications specified below, must be recorded 
in the subject’s medical record and the eCRF 
along with details such as: 
To incorporate information on 
trial medications the subject 
received in the parent trial. 
9.7 Prohibited 
medication and 
procedures 
Prohibited medication and procedures from 
baseline through safety follow-up are presented 
in text format rather than in tabular format. 
To make the guidance on 
prohibited medications during 
the different periods of the 
trial more clear. 
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Section no. and 
name 
Description of change 
Brief rationale 
Appendix 4A: 
Japan 
In Japan, investigators must be dermatologists 
or allergists. 
The country-specific 
requirement for investigators 
in Japan should only include 
dermatologists. 
Throughout  
Minor editorial revisions. 
Minor, and are therefore not 
summarised. 
 
 
 
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Amendment 5 (24-Jun-2019) 
This amendment is considered to be non-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 because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the trial.  
Overall rationale for the amendment: 
The main reason for this amendment is to correct an error in the schedule of trial procedures 
introduced with amendment 4.  
Note: the table below describes the changes in each section, summarised as plain text, and/or 
as tracked changes (text added to the protocol is written in bold and deleted text has a line 
through it). 
Section 
number and 
name 
Description of change 
Brief rationale 
4 Schedule of 
trial 
procedures 
 
Specification that the Worst Weekly Pruritus 
numeric rating scale, Eczema-related Sleep 
numeric rating scale, and Patient use of topical 
treatment must be performed at screening. 
Correction of error 
introduced with protocol 
amendment 4. 
Appendix 7 
Contact list 
LEO Pharma K.K. 
1-105 Kanda-Jinbocho3-11-6
 
Chiyoda-ku 
Tokyo 101-005132 
Japan 
As the LEO Pharma K.K. 
office will move to a new 
location as of 01-Jul-2019. 
 
 
 
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Amendment 6 (17-Feb-2020) 
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.  
As protocol version 7.0 was made obsolete prior to the effective date, this amendment 
provides an overview of the changes made from protocol version 6.0 to protocol version 8.0. 
Overall rationale for the amendment: 
The main reason for the amendment is to introduce the possibility for eligible subjects in 
selected countries of trial LP0162-1334 with adolescent subjects to continue in this long-term 
extension trial (LP0162-1337, ECZTEND). The purpose is to obtain long-term safety data for 
adolescent subjects with atopic dermatitis (AD) treated with tralokinumab.  
Additional changes included in the amendment are also presented in the table below. The 
table below describes the changes in each section, summarised as plain text, and/or as tracked 
changes (text added to the protocol is written in bold and deleted text has a line through it). 
 
 
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Section number 
and name 
Description of change 
Brief rationale 
General changes in 
whole document 
•  Female subjects replaces women. 
•  LP0162-1334 added to the list of parent 
trials (also in inclusion criterion 2 and 
exclusion criterion 15). 
•  Legal representative(s) or parent/guardian 
or caregiver added to the text when 
relevant. 
•  Specified when text only applies to adult 
subjects and/or adolescent subjects. 
Updated to reflect the 
inclusion of subjects from 
the parent trial 
LP0162-1334 in 
ECZTEND. 
1 Protocol synopsis 
7.2 Number of 
subjects tested 
14.1 Sample size 
Subject number estimate has been updated to 
approximately 1,500 subjects. 
Updated to reflect the 
expected total number of 
subjects to be enrolled in 
ECZTEND. 
1 Protocol synopsis 
3 Schematic of trial 
design 
The trial design figure has been updated to 
include the parent trial LP0162-1334 and the 
updated subject number estimate of 
approximately 1,500 in ECZTEND. Formatting 
updates has also been performed. 
Updated to reflect the 
inclusion of subjects from 
the parent trial 
LP0162-1334 in 
ECZTEND. 
4 Schedule of trial 
procedures 
5.5 Ethical 
considerations 
7.1 Overall trial 
design 
8.2 Inclusion 
criteria 
8.4 Screening and 
screening failures 
Appendix 5 
Eligibility criteria 
Inclusion criterion 1 has been updated with the 
informed consent procedure for adolescent 
subjects: 
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 (as applicable according to national 
laws or regulations). 
 
This change in inclusion criterion 1 has been 
added to all relevant sections in the protocol. It 
has further been added at relevant sections that 
adolescent subjects who become adults during 
participation in ECZTEND must re-consent 
by signing the informed consent form for 
adult subjects. 
 
Updated to reflect the 
inclusion of adolescent 
subjects in ECZTEND. 
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Section number 
and name 
Description of change 
Brief rationale 
Appendix 3B 
Informed consent 
process 
The adolescents informed consent process has 
been included and elaborated in Appendix 3B 
Informed consent process. 
8.2 Inclusion 
criteria 
Inclusion criterion 6 has been updated with 
additional details related to adolescent subjects: 
Female subjects of childbearing potential 
(defined as Tanner stage ≥3 or menarche)* 
must use a highly effective** form of birth 
control (confirmed by the investigator) 
continuously for at least 1 month prior to the 
pregnancy test at baseline (Week 0), throughout 
the trial, and for at least 16 weeks (5 half lives of 
the IMP) after the last administration of IMP. 
* A female subject 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). 
• Premenarchal or have a confirmed 
clinical history of sterility (e.g. the 
subject is without a uterus or has tubal 
ligation). 
Updated to reflect the 
inclusion of adolescent 
subjects in ECZTEND. 
1 Protocol synopsis 
6 Trial objectives 
and endpoints 
14.3.4 Primary 
endpoint 
The primary endpoint has been updated from: 
Number of adverse events from baseline through 
the last treatment visit (that is, up to Week 142). 
The primary endpoint has been updated to: 
Number of adverse events during the 
treatment period from baseline up to 
Week 142. 
To clarify that the 
primary endpoint in 
ECZTEND is the number 
of adverse events 
reported during the entire 
exposure period (planned 
to include 2 weeks [±3 
days] after last dose of 
IMP). 
1 Protocol synopsis 
8.3 Exclusion 
criteria 
Appendix 5 
Eligibility criteria 
Exclusion criterion 2 has been updated:  
More than 20 26 weeks have elapsed* since the 
subject received the last IMP injection in the 
parent trial. 
*To be assessed on the first day of IMP 
  administration (baseline). 
 
Exclusion criterion 20 has been updated: 
Updated to provide all 
subjects from the parent 
trial LP0162-1334 the 
opportunity to be enrolled 
in ECZTEND if eligible. 
 
 
 
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and name 
Description of change 
Brief rationale 
History of subject or subjects’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. 
Updated to reflect the 
inclusion of adolescent 
subjects in ECZTEND. 
1 Protocol synopsis 
5.4 Justification for 
dose 
7.1 Overall trial 
design 
9.2 Administration 
of IMP 
 
Dosing regimen. The following differences 
between the dosing regimens for subjects from 
the parent trial LP0162-1334 and the rest of the 
subjects in ECZTEND has been specified in all 
relevant sections: 
• Tralokinumab dose for adult subjects from all 
      parent trials, except the parent trial 
LP0162-1334: 
      600 mg initial loading dose, then 300 mg 
every 
      second week. 
• Tralokinumab dose for subjects from the 
parent 
      trial LP0162-1334*: 300 mg every second 
week. 
     * All subjects from the parent trial LP0162-
1334, 
     independent of the subject’s age when 
enrolled in 
     ECZTEND. 
 
The justification for the dosing regimen for 
subjects from the parent trial LP0162-1334 has 
been elaborated in Section 5.4 Justification for 
dose. 
 
Updated as there are no 
safety data available for 
the administration of a 
loading dose of 600 mg 
tralokinumab to 
adolescent subjects who 
are already at steady-state 
after treatment with 
300 mg tralokinumab 
Q2W. Based on the 
LP0162-1334 trial design, 
it is anticipated that most 
of the subjects have been 
treated with 300 mg 
tralokinumab Q2W prior 
to enrolment in 
ECZTEND, and these 
subjects should not be 
unnecessarily exposed to 
an initial loading dose of 
600 mg tralokinumab. 
4 Schedule of trial 
procedures 
6 Trial objectives 
and endpoints 
11.1 Overview 
11.3.2 
Patient-reported 
Update of description of the assessment and 
analysis of the following patient-reported 
outcomes: 
 
Dermatology Life Quality Index 
(DLQI)/Children’s Dermatology Life Quality 
Index (CDLQI): Adult subjects from all parent 
trials, except the parent trial LP0162-1334, will 
perform the DLQI. All subjects from the parent 
trial LP0162-1334, independent of the subject’s 
age during participation in ECZTEND, will 
perform the CDLQI. 
Updated to reflect 
inclusion of adolescent 
subjects in ECZTEND as 
follows. In order to 
analyse change from 
parent trial baseline to the 
end of treatment visit in 
ECZTEND, subjects from 
the parent trial 
LP0162-1334 must 
continue the CDLQI 
during participation in 
ECZTEND. 
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Section number 
and name 
Description of change 
Brief rationale 
outcomes (efficacy 
assessments) 
14.3.7 
Patient-reported 
outcomes 
(statistical 
methodology) 
12 Scientific 
rationale for trial 
design and 
appropriateness of 
assessments 
Appendix 4A 
Country-specific 
requirements, Japan 
15 References 
 
EuroQoL 5-Dimension Health Questionnaire 5 
(EQ-5D-5L): Subjects from the parent trial 
LP0162-1334 will not perfom the EQ-5D-5L. 
 
Worst Weekly Pruritus numeric rating scale 
(NRS) and the Eczema-related NRS: Subjects 
from the parent trial LP0162-1334 will perform 
an adolescent’s pruritis NRS with a recall period 
of past 7 days and an eczema-related sleep NRS 
with a recall period over the past 7 nights, 
independent of the age of the subject during 
participation in ECZTEND. 
In order to provide 
wordings tailored to 
adolescent subjects, 
subjects from the parent 
trial LP0162-1334 will 
perform an adolescent’s 
pruritis NRS with a recall 
period of past 7 days, and 
an eczema-related sleep 
NRS with a recall period 
over the past 7 nights. 
Subjects from the parent 
trial LP0162-1334 will 
not perfom the EQ-5D-
5L, as this questionnaire 
has not been validated for 
adolescents. 
4 Schedule of trial 
procedures 
An additional weight assessment and treatment 
compliance assessment at the end of treatment 
(EOT) visit have been added. An additional 
weight assessment at the early termination visit 
has been added. 
Updated to ensure that all 
subjects have a weight 
assessment and a 
treatment compliance 
assessment at the end of 
their treatment period. 
8.4 Screening and 
screening failures 
10.2.2 Reasons for 
withdrawal from 
the trial 
11.8 End of trial 
Added reason for screening failure/withdrawal 
from trial, and added reason for not completing 
the trial or attending the safety follow-up visit: 
• Withdrawal by parent/guardian.* 
*For adolescent subjects as applicable. 
Updated to reflect 
inclusion of adolescent 
subjects in ECZTEND. 
9.7 Prohibited 
medication and 
procedures 
The text in the section about prohibited 
medication and procedures has been optimised. 
To clarify the section of 
prohibited medications in 
the protocol in relation to 
rescue medications. 
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Section number 
and name 
Description of change 
Brief rationale 
11.2.2 Medical 
history 
Any ongoing AEs from parent trial. In addition, 
AEs reported after completion of the parent 
trial and prior to signing the informed 
consent form in the present trial must be 
recorded as medical history. 
 
To clarify the reporting of 
AEs with onset after 
completion of parent trial 
and before consenting to 
participation in 
ECZTEND.  
11.4.5.2 Urinary 
pregnancy test 
Added to description of pregnancy test: 
For female subjects who become of 
childbearing potential during the trial 
(defined as Tanner stage ≥3 [Marshall 1969] 
or menarche), the investigator must reassess 
whether contraceptive measures are in place 
(if applicable), and perform the pregnancy 
tests according to the schedule of trial 
procedures (Section 4). 
Updated to reflect the 
inclusion of adolescent 
subjects in ECZTEND. 
11.7 Estimate of 
total blood volume 
collected 
For the longest estimated trial participation, the 
blood volume drawn will be approximately 265 
mL for adult subjects, which is less than the 
volume of blood drawn during a blood donation 
(approximately 500 mL). For adolescents, the 
total amount of blood drawn during the trial 
will be approximately 130 mL. The volume of 
blood drawn at any visit during the trial will 
be approximately 20 mL for all subjects. 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 (European 
Commission 2008). 
To clarify that the blood 
volume drawn in 
ECZTEND is appropriate 
for adolescent subjects. 
13.2 Collection of 
adverse event 
reports 
Added sentence: for subjects without a safety 
follow-up visit in the parent trial, any AE 
with onset before the baseline visit in 
ECZTEND should be reported as an AE in 
the parent trial. 
Added sentence: AEs with onset after the final 
visit in the parent trial and after informed 
consent has been obtained for the present 
trial should be recorded as an AE in 
ECZTEND. 
To clarify the reporting of 
AEs prior to treatment in 
ECZTEND (in 
accordance with the 
current text in Section 
7.1). 
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Section number 
and name 
Description of change 
Brief rationale 
13.4 Reporting of 
serious adverse 
events 
Added sentence: On the SAE form in the 
present extension trial, information regarding 
the subject’s ID and parent trial ID must also 
be provided. 
To clarify that the 
subject’s details from the 
parent trial are also 
needed on the SAE form. 
13.7 Follow-up for 
final outcome of 
adverse events 
Appendix 2 
Classification of 
adverse events 
For SAEs which have stabilised and from which 
the subject cannot be expected to recover during 
the trial or the safety follow-up periods, for 
example chronic or stabilised conditions, the 
final outcome at the investigator's discretion 
should be reported as 'recovering/resolving' 
or ‘not recovered/not resolved’. 
To provide clarification 
on how to handle SAEs 
where the final outcome 
is recovering/resolving at 
the end of the trial. 
14.3.8.1 Adverse 
events (statistical 
methodology) 
An overall summary of the number of AEs, the 
rate of AEs (number of AEs per 100 patient-
years of exposure), the number (percentage) of 
subjects with any treatment-emergent AEs, 
deaths, SAEs, withdrawals from the trial due to 
AEs, treatment-related AEs, and severe AEs will 
be presented. The above summaries will also 
be made separately for subjects who 
transferred from the parent trial LP0162-
1334. 
Updated to clarify the 
statistical analyses after 
inclusion of the parent 
trial LP0162-1334 in 
ECZTEND. 
Appendix 4 
Country-specific 
requirements 
Added introduction: This appendix describes 
requirements and procedures that are specific 
for Japan (Appendix 4A) and France 
(Appendix 4B). For each section, the text 
from the protocol is presented in normal font. 
The specific requirements or procedures for 
Japan or France are presented below in bold 
font. 
Added for information. 
Throughout  
Minor editorial revisions. 
Minor, and are therefore 
not summarised. 
 
 
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Amendment 7 (25-Nov-2020) 
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.  
Overall rationale for the amendment: 
The main reason for this amendment is to extend the collection of long-term safety data for 
tralokinumab up to 5 years, and at the same time provide subjects the possibility to continue 
treatment until treatment with tralokinumab is also available to patients outside the clinical 
trial setting. Subjects from the parent trial LP0162-1334 will have the opportunity to continue 
for an additional 1-year extension, providing an additional year of safety data for 
adolescents/young adults. To reduce the burden of frequent site visits for subjects, the 
amendment will introduce a visit schedule more similar to standard practice for home use. 
The modified design reduces the number of site visits and instead introduces a mandatory 
telephone visit in between site visits to ensure close safety monitoring of the subjects. 
This amendment also introduces the possibility for eligible subjects from 2 new parent trials, 
LP0162-1343 and TRA-WEI-0015-I, to participate in this long-term extension trial.  
The table below describes the changes in each section, summarised as plain text, and/or as 
tracked changes (text added to the protocol is written in bold and deleted text has a line 
through it). 
Section 
number and 
name 
Description of change 
Brief rationale 
Whole 
document 
• 2 new parent trials have been added to 
protocol version 10 in all relevant 
sections: LP0162-1343 and TRA-WEI-
0015-I (investigator-initiated trial). 
• The treatment extension and the 
modified trial design have been 
included in all relevant sections.  
• Trial visits have been specified to be 
either site visits or telephone visits in 
all relevant sections. 
 
To extend the collection of long-
term safety data in adult (up to 5 
years) and adolescent subjects, as 
well as to enable continued 
treatment of subjects until 
treatment with tralokinumab is 
also available to patients outside 
the clinical trial setting (including 
subjects from 2 new parent trials 
LP0162-1343 and TRA-WEI-
0015-I). 
1 Protocol 
synopsis 
Updated according to the changes in the 
main document (see the change descriptions 
below). Changes were made to the 
paragraphs regarding the primary endpoint, 
the secondary endpoints, final collection of 
To reflect changes in the main 
document. 
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Section 
number and 
name 
Description of change 
Brief rationale 
data for the primary endpoint, trial design 
description including trial design panel, 
main criteria for inclusion, main criteria for 
exclusion, duration of treatment, number of 
subjects, and number and distribution of 
trial sites. 
3 Schematic of 
trial design 
Addition of Panel 1 to provide an overview 
of the different scenarios for participation 
introduced with protocol version 10. 
Addition of explanatory text to introduce 
the 3 panels, and a reference to guidance for 
next steps in the case of COVID-19 
pandemic restrictions. 
To give trial personnel an 
overview of the different 
scenarios for trial participation 
introduced. 
3 Schematic of 
trial design 
The trial design figure has been modified to 
reflect the visit schedule until end of 
May 2021 and after May 2021, as well as to 
include the parent trials LP0162-1343 and 
TRA-WEI-0015-I:  
• Panel 2, top: Visit schedule applicable 
until end of May 2021: The trial design 
is unchanged for all subjects until end 
of May 2021, and for subjects who do 
NOT re-consent to participate after 
May 2021. 
• Panel 2, bottom: New visit schedule 
applicable after May 2021, for subjects 
who consent to participate in the trial 
after May 2021: The trial design has 
been updated to reflect the alternating 
site and telephone visits, the extended 
duration of the trial, as well as the 
shortened safety follow-up period, 
except for subjects from the parent trial 
LP0162-1334, who will continue to 
have a safety follow-up visit 16 weeks 
after the last dose of IMP. In addition, 
the timing of the visits and assessments 
have been updated. 
The trial design has been 
modified after May 2021 to 
reduce the burden of frequent site 
visits, by implementing a visit 
schedule more similar to standard 
practice for home use.  
As tralokinumab has been shown 
to be well-tolerated with a 
favorable safety profile in the 
clinical development programme, 
a shortened safety follow-up 
period has been introduced for 
adult subjects. 
4 Schedule of 
trial procedures 
The schedule of trial procedures has been 
split into 2 sections: 
• New Section 4.1: Schedule of trial 
procedures applicable until end of May 
2021 (Panel 3 and Panel 4). The trial 
procedures are unchanged, and 
Schedule split in 2 to give trial 
personnel an easy access to the 
trial procedures applicable to a 
subject. 
The trial procedures have been 
modified to reduce the burden of 
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Section 
number and 
name 
Description of change 
Brief rationale 
applicable for all subjects until end of 
May 2021, and for subjects who do 
NOT re-consent to participate after 
May 2021. 
• New Section 4.2: New schedule of trial 
procedures applicable for subjects who 
consent to participate in the trial after 
May 2021 (Panel 5). The trial design 
has been updated to reflect the 
alternating site and telephone visits, the 
extended duration of the trial, as well as 
the shortened safety follow-up period, 
except for subjects from the parent trial 
LP0162-1334, who will continue to 
have a safety follow-up visit 16 weeks 
after the last dose of IMP. In addition, 
timing of the visits and assessments 
have been updated.  
• After May 2021, the frequency of urine 
dipstick analysis has been reduced, and 
a urine sample will only be sent to the 
central laboratory to perform urinalysis, 
if considered required by the 
investigator based on the urine dipstick 
results.  
A reference to guidance in case of COVID-
19 pandemic restrictions have been added 
to this Section. 
frequent site visits by 
implementing a visit schedule 
more similar to standard practice 
for home use.  
As tralokinumab has been shown 
to be well-tolerated with a 
favorable safety profile in the 
clinical development programme, 
a shortened safety follow-up 
period has been introduced for 
adult subjects. As tralokinumab 
has been shown to be well-
tolerated with no safety concerns 
in relation to urinalysis, a reduced 
collection of urine samples has 
been included to reflect standard 
clinical practice for home use as 
well as only perform urinalysis if 
considered clinically relevant per 
investigator’s discretion. 
4 Schedule of 
trial procedures 
4.1 ECZTEND 
– schedule of 
trial procedures 
until end of May 
2021 
4.2 ECZTEND 
– schedule of 
trial procedures 
after May 2021 
The description of a safety follow-up period 
of 14 weeks’ duration (starting 2 weeks 
after the last dose) has been omitted.  
The safety follow-up period and the timing 
of the safety follow-up visit have been 
clarified as follows:  
• Until end of May 2021 (Panel 4): The 
final safety follow-up visit will be 
16 weeks after the last dose (i.e. 
14 weeks after the EOT visit). 
• After May 2021 (Panel 5): The final 
safety follow-up visit will be 4 weeks 
after the last dose (i.e. 2 weeks after the 
EOT visit), except for subjects from the 
parent trial LP0162-1334, where the 
safety follow-up visit will be 16 weeks 
To avoid confusion by describing 
a safety follow-up period of 14 
weeks and a safety follow-up visit 
16 weeks after the last dose. 
The safety follow-up period has 
been shortened for adult subjects, 
as tralokinumab has been shown 
to be well-tolerated with a 
favorable safety profile in the 
clinical development programme. 
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Section 
number and 
name 
Description of change 
Brief rationale 
7.1.4 Safety 
follow-up 
period (after last 
IMP) 
after the last dose (i.e. 14 weeks after 
the EOT visit). 
Addition of Panel 7: Safety follow-up visit 
5.2 Experience 
with the 
investigational 
medicinal 
product 
Experience with tralokinumab has been 
updated with the latest information about 
efficacy and safety. 
To provide updated information 
about experience with 
tralokinumab. 
5.5 Ethical 
considerations 
5.6 Benefit/risk 
assessment 
The nature and frequency of the monitoring 
of subjects in the different scenarios of the 
trial have been elaborated. 
To clarify the change to the 
frequency of  monitoring of 
subjects on site. 
5.6 Benefit/risk 
assessment 
Added information: 
The current COVID-19 pandemic may 
warrant many subjects in the ECZTEND 
trial to stay at home to comply with 
authority-issued preventive measures, 
which may impact subjects’ ability to 
attend visits at the trial site. To follow 
authorities’ restrictions and to safeguard 
the subjects in the ECZTEND trial, as 
well as providing continued therapy to 
secure the scientific integrity, the clinical 
trial protocol provides an opportunity 
for telephone visits and courier delivery 
of IMP and pregnancy tests to subjects in 
replacement of the site visits (see 
Appendix 3K for details). 
To provide guidance in case of 
COVID-19 pandemic restrictions. 
6 Trial 
objectives and 
endpoints 
It has been clarified in footnotes to Panel 5 
that some endpoints are not applicable for 
subjects from the parent trial TRA-WEI-
0015-I. 
Since data from the parent trial 
TRA-WEI-0015-I will not be 
transferred to LEO Pharma, as 
this is an investigator-initiated 
trial. 
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Section 
number and 
name 
Description of change 
Brief rationale 
6 Trial 
objectives and 
endpoints 
3 Schematic of 
trial design 
4 Schedule of 
trial procedures 
 
Primary endpoint: 
• Number of adverse events during the 
treatment period from baseline up to 
Week 142 268. 
Secondary endpoints: 
• IGA score of 0 (clear) or 1 (almost 
clear) at Weeks 16, 56,  80 88, 104, 
136, 152, 184, 216, and 128 248  
• EASI75 at Weeks 16, 56, 80 88, 104, 
136, 152, 184, 216, and 128 248 
 
Other endpoints: 
• Change in EASI score from baseline to 
Weeks 16, 56, 80 88, 104, 136, 152, 
184, 216, and 128 248 
• Change in SCORAD from baseline to 
Weeks 16, 56, 80 88, 104, 136, 152, 
184, 216, and 128 248 
• Change in POEM score from baseline to 
Weeks 16, 56, 80-88, 104, 128-136, 
152, 184, 216, and 128 248 
• Change in DLQI/CDLQI4 score from 
baseline to Weeks 16, 56, 80-88, 104, 
128-136, 152, 184, 216, and 128 248 
• Change in EQ-5D-5L score from 
baseline to Weeks 16, 56, 80-88, 104, 
128-136, 152, 184, 216, and 128 248 
• Worst Weekly Pruritus NRS at 
Weeks 16, 56,  80 88, 104, 136, 152, 
184, 216, and 128 248 
• Eczema-related Weekly Sleep NRS at 
Weeks 16, 56,  80 88, 104, 136, 152, 
184, 216, and 128 248  
• Use of topical treatment during the last 
week at Weeks 16, 56,  80 88, 104, 136, 
152, 184, 216, and 128 248 
Endpoints have been updated to 
fit with the new schedule of site 
visit assessments and to ensure 
that all subjects can contribute to 
the efficacy analyses. It has 
further been ensured that all 
subjects are assessed 
approximately after 1, 2 and 3 
years, when applicable. 
7.1 Overall trial 
design 
7.1.1 Overview 
The whole section has been updated and 
more headers added to reflect the modified 
trial design after May 2021 according to 
protocol version 10. 
 
Section 7.1.3 The treatment period Week 0 
and onwards): The section has been split 
Section split was made to reflect 
and ease the understanding of the 
different trial procedures required 
until end of May 2021 and after 
May 2021.  
The trial design was modified to 
extend the collection of long-term 
safety data in adult (up to 5 years) 
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Section 
number and 
name 
Description of change 
Brief rationale 
7.1.3 Treatment 
period (Week 0 
and onwards) 
7.1.3.1 
Treatment 
initiation 
7.1.3.2 
Treatment 
period until end 
of May 2021 
(all subjects) 
7.1.3.3 
Treatment 
period after May 
2021 (subjects 
who consent to 
protocol version 
10) 
7.1.3.4 Trial 
visits in the 
treatment period 
into Section 7.1.3.1 Treatment initiation, 
Section 7.1.3.2 Treatment period until end 
of May 2021 (all subjects), and Section 
7.1.3.3 Treatment period after May 2021 
(subjects who consent to protocol version 
10). Furthermore, descriptions of the 
different visit types have been added in a 
new Section 7.1.3.4. 
It has been clarified in the sections that 
treatment will be stopped as follows: 
• Subjects who do NOT re-consent to 
continue in the trial after May 2021 will 
stop treatment by end of May 2021.  
• Subjects from the parent trial LP0162-
1334 who re-consent or consent to 
participate in the trial after May 2021 
will stop treatment by end of May 
2022.  
• Subjects from the parent trials LP0162-
1325, -1326,  
-1339, -1341, -1342, -1343, -1346, and 
TRA-WEI-0015-I who re-consent or 
consent to participate in the trial after 
May 2021 will stop treatment at a 
country-specific completion date. 
and adolescent subjects, as well as 
to enable continued treatment of 
subjects until treatment with 
tralokinumab is also available to 
patients outside the clinical trial 
setting (including subjects from 2 
new parent trials LP0162-1343 
and TRA-WEI-0015-I). 
7.2 Number of 
subjects needed 
14.1 Sample 
size 
Updated to reflect the total number of 
subjects and sites expected after inclusion 
of the 2 additional parent trials LP0162-
1343 and TRA-WEI-0015-I:  
Number of subjects: 1,500 1,600 subjects 
Number of sites: 300 330 sites. 
To specify the new expected total 
number of subjects and sites 
included in the trial. 
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. The trial treatment will be stopped for 
all subjects in all countries by 31-May-
2021, and the subjects will have their final 
safety follow-up visit 16 weeks later. By 
31-May-2021, the majority of subjects will 
have been exposed to tralokinumab for 
Updated to reflect the new trial 
design. 
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Section 
number and 
name 
Description of change 
Brief rationale 
3 years (including the exposure in the 
parent trial), which is considered 
appropriate for evaluating long-term safety 
of tralokinumab. 
The end of the trial is defined as the date of 
the last visit of the last subject in the trial 
globally. By the end of this trial, subjects 
will have been exposed to tralokinumab 
for up to 5 years, which is considered 
appropriate for evaluating long-term 
safety of tralokinumab. 
The final collection of data for the primary 
endpoint for each subject will occur at 
Week 142 by Q2 2024.  
A subject is considered to have 
completed the trial if the subject has 
completed all periods of the trial, 
including the safety follow-up visit, 
according to protocol version 10 or 
earlier versions.  
A subject is considered to have 
completed the treatment period if the 
subject has completed the EOT visit with 
no ‘primary reason for withdrawal from 
trial’. This will be: 
• Approximately end of May 2021 for 
subjects completing according to 
protocol version 9 or earlier versions. 
• Approximately end of May 2022 for 
subjects from the parent trial 
LP0162-1334 completing according 
to protocol version 10. 
• At a country-specific end of treatment 
date (Appendix 3J) for subjects from 
the parent trials LP0162-1325, -1326, 
-1339, -1341, -1342, -1343, -1346, and 
TRA-WEI-0015-I completing 
according to protocol version 10.   
8 Trial 
population 
8.2 Inclusion 
criteria 
Inclusion criteria 2 and exclusion criteria 
15: addition of the 2 new parent trials 
LP0162-1343 and TRA-WEI-0015-I. 
Inclusion criteria 6: Female subjects of 
childbearing potential (defined as Tanner 
stage ≥3 or menarche)* must use a highly 
effective** form of birth control (confirmed 
Inclusion criteria 2 and exclusion 
criteria 8 and 15 updated to reflect 
the inclusion of subjects from the 
parent trials trials LP0162-1343 
and TRA-WEI-0015-I. 
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Section 
number and 
name 
Description of change 
Brief rationale 
8.3 Exclusion 
criteria 
by the investigator) continuously for at least 
1 month prior to the pregnancy test at 
baseline (Week 0), throughout the trial, and 
for at least 16 weeks (5 half-lives of the 
IMP) after the last administration of IMP. 
*A female subject 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). 
• Premenarchal or have a confirmed 
clinical history of sterility (e.g., the 
subject is without a uterus or has tubal 
litigation). 
**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), same-sex partner, or 
vasectomised partner (given that the subject 
is monogamous). 
Exclusion criteria 7: Treatment with topical 
PDE-4 inhibitors or topical JAK 
inhibitors within 2 weeks prior to baseline. 
Exclusion criteria 8: Positive hepatitis B 
surface antigen (HBsAg), hepatitis B 
surface antibody (HBsAb), hepatitis B* 
core antibody (HBcAb), or hepatitis C virus 
antibody (anti-HCV) serology at screening. 
Subjects with positive HBsAb are eligible 
provided they are vaccinated against 
Inclusion criteria 6 updated to 
provide more clarity. 
Exclusion criteria 7 updated to be 
consistent with available 
treatments options. 
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Section 
number and 
name 
Description of change 
Brief rationale 
hepatitis B and have negative HBsAg and 
HBcAb. 
*Subjects from the parent trial LP0162-
1343 with a positive HBsAb may be 
randomised provided they have negative 
HBsAg, HBcAb, and HCV serology at 
screening. 
9.7 Prohibited 
medication and 
procedures 
From baseline through end of treatment: 
• Higher potency topical corticosteroids 
(US class <4 or Europe class >3). Can 
be used as rescue for intolerable AD 
symptoms (see Section 9.5). 
• Topical phosphodiesterase 4 (PDE-4) 
inhibitors. 
• Topical JAK inhibitors. 
• UVA or UVB, psoralen + UVA 
(PUVA), other phototherapy, or tanning 
beds. 
• 3 or more bleach baths per week. 
To clarify the section on 
prohibited medication. 
9.8.3 Drug 
accountability 
Subjects will attend trial site visits at least 
every 8 weeks on a regular basis (see 
Section 4). 
To reflect the new visit schedule. 
10.2.1 Stopping 
rules 
Subjects withdrawn from the trial should 
complete the 14-week safety follow-up 
period as specified in Section 7.1. 
Reasons for withdrawal from the trial 
are described in Section 10.2.2. 
Updated to reflect the changed 
safety follow-up period and to 
make reference to Section 10.2.2. 
10.2.2 Reasons 
for withdrawal 
from the trial 
Subjects withdrawn from the trial should 
must complete the 14-week safety follow-
up period as specified in Section 7.1. 
Stopping rules are are described in 
Section 10.2.1. 
Updated to reflect the changed 
safety follow-up period and to 
make reference to Section 10.2.1. 
10.2.3 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: 
To provide clarity on when IMP 
may and should be temporarily 
discontinued, or must be 
withdrawn. 
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Section 
number and 
name 
Description of change 
Brief rationale 
• Treatment with systemic corticosteroids 
or non-steroidal 
immunosuppressive/immunomodulatin
g medications (for example, 
cyclosporine, methotrexate, 
azathioprine, mycophenolate mofetil, 
Janus kinase inhibitors, dupilumab, or 
other biologics). 
If any of the stopping rules are met (see 
Section 10.2.1) or any of the withdrawal 
reasons are met (Section 10.2.2), the 
subject must be withdrawn from the trial. 
10.3 Early 
termination 
assessment 
Added sentence:  
An EOT (end of treatment) form and an 
end of trial form must be completed as 
specified in Section 11.8.  
To avoid misunderstandings. 
11.4.2 Vital 
signs 
Vital signs will be measured in a supine or 
sitting position…. 
Should the repeated measurement result in 
a normal value, the measurement must be 
repeated once more approximately 15 
minutes after the second measurement 
with subjects resting in a supine or 
sitting position. 
To clarify how vital signs are to 
be measured. 
11.4.5.1 
Overview 
Footnotes updated to Panel 13: 
3 Urine samples will be tested at the trial 
site (dipstick). Until end of May 2021, in 
case of abnormal dipstick results, a urine 
sample will be sent to the central laboratory 
for microscopic examination (leucocytes, 
erythrocytes, and casts). After May 2021, a 
urine sample will only be sent to the 
central laboratory to perform urinalysis 
if considered required by the investigator 
based on the urine dipstick results.  
4 Measured at screening only. 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. 
As tralokinumab has been shown 
to be well-tolerated with no safety 
concerns in relation to urinalysis, 
a reduced collection of urine 
samples has been included to 
reflect standard clinical practice 
for home use as well as only 
perform urinalysis if considered 
clinically relevant per 
investigator’s discretion. 
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Version: 14.0 
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Section 
number and 
name 
Description of change 
Brief rationale 
11.4.5.2 Urine 
pregnancy test 
The test will be repeated at Week 4 and 
thereafter at all site visits the schedule of 
pregnancy testing is as shown in the 
schedule of trial procedures (Section 4). 
The date and the outcome ofAfter May 
2021, subjects must in addition to the test 
performed at the trial site, perform the 
urine pregnancy test at home within 48 
hours before the telephone visit using the 
kit supplied by the site staff. The subject 
will also be recorded provided with a 
urine pregnancy test instruction 
(pictogram). The result of the pregnancy 
test should be communicated to the site 
during the telephone visit and 
documented in the eCRF (‘positive’, 
‘negative’) and source documents.  
To ensure the pregnancy test is 
performed at regular intervals 
despite the longer time period 
between site visits after end of 
May 2021. 
11.7 Estimate of 
total blood 
volume 
collected 
The total volume of blood to be drawn for 
each subject will depend on the time of 
their entry into the trial and the local 
duration of the trial (Appendix 3J). For 
adult subjects, the longest estimated trial 
participation, the total blood volume drawn 
will be approximately 265 mL for adult 
subjects, until end of May 2021, plus 
70 mL per year of trial participation 
after May 2021which is less than the 
volume of blood drawn during a blood 
donation (approximately 500 mL). For 
adolescents, the total amount of blood 
drawn during the trial until end of 
May 2021 will be approximately 130 
mL.240 mL, plus 70 mL for the 1 year 
extension until end of May 2022.  
Changed to reflect the extended 
trial period and the changed blood 
drawing schedule. 
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Section 
number and 
name 
Description of change 
Brief rationale 
12 Scientific 
rationale for 
trial design and 
appropriateness 
of assessments 
Added text: 
The trial design has been modified with 
protocol version 10 to secure long term 
safety data of up to 5 years globally. The 
treatment extension for subjects from the 
parent trials LP0162-1325, -1326, -1339, -
1341, -1342, -1343, -1346, and TRA-WEI-
0015-I will be country-specific to allow 
for treatment with tralokinumab until 
tralokinumab is available to patients 
outside the clinical trial setting 
(Appendix 3J). Subjects from the 
ongoing adolescent parent trial LP0162-
1334 are offered a total treatment 
extension of 1 year until end of May 
2022. 
The trial design has been modified to 
decrease the burden of frequent site 
visits for subjects by introducing a visit 
schedule more similar to standard 
practice for home use. To ensure close 
safety monitoring throughout the 
treatment period, a mandatory telephone 
visit will be performed in between site 
visits.  
To clarify the rationale for 
extending treatment and reducing 
the frequency of site visits. 
13.4.2 LEO 
Pharma 
reporting 
responsibilities 
For the IMP, the Investigator’s Brochure, 
edition 17 19 and subsequent updates must 
be used. 
Updated to newest edition. 
13.6.3 
Medication 
error 
Broadly, medication errors fall into 
4 categories: wrong medication, wrong 
dose (including strength, form, 
concentration, amount, as well as 
administration with an interval of less 
than 7 days), wrong route of 
administration, or wrong subject. 
To clarify the definition of a 
medication error. 
14.2 Trial 
analysis sets 
Added text: 
Data from the investigator-initiated 
parent trial TRA-WEI-0015-I will not be 
transferred to LEO Pharma. Thus, 
endpoints defined as change from 
baseline (in parent trial) will not be 
calculated for subjects from this trial, 
To clarify to what extent data 
from the parent trial TRA-WEI-
0015-I will be included in 
endpoints and summarised data 
presentations. 
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Section 
number and 
name 
Description of change 
Brief rationale 
and data from this trial will not be 
included in tables summarising 
endpoints defined as change from 
baseline or where data are presented by 
responder/non-responder. Subjects from 
this parent trial will be contributing to 
the primary endpoint and included in 
summary tables where possible.  
14.3.4 Primary 
endpoint 
The primary endpoint in this trial is number 
of adverse events during the treatment 
period from baseline up to Week 142 268, 
and the analysis of this is covered in 
Section 14.3.8. 
To reflect the extended treatment 
period. 
14.3.6 Other 
endpoints 
An analysis has been added:  
As the frequency of site visits is reduced 
after May 2021, a sensitivity analysis 
excluding data captured after May 2021 
will be performed for the ‘proportion of 
time’ endpoints. 
Sensitivity analysis added as the 
less frequent assessment of 
efficacy after May 2021 could 
influence the estimation and 
precision of the 'proportion of 
time' endpoints. 
14.3.7 Patient-
reported 
outcomes 
Added text:  
In the special case where a subject has an 
assessment at both Week 80 and Week 
88, the Week 80 assessment 
(corresponding to approximately 1½ 
years) will be used for the Week 80-88 
endpoint evaluation. Likewise, the Week 
128 assessment (~ 2½ years) will be 
prioritised for the Week 128-136 
endpoint evaluation. 
Changes from baseline will not be 
presented for subjects from the parent 
trial TRA-WEI-0015-I, since data from 
this investigator-initiated trial will not be 
transferred to LEO Pharma (see Section 
14.2). 
To clarify the handling of the 
Week 80-88 and Week 128-136 
endpoints.  
To clarify that data from the 
parent trial TRA-WEI-0015-I will 
not be included in change from 
baseline endpoints for patient-
reported outcomes. 
14.3.8.1 
Adverse events 
An additional AE summary has been added, 
and some tabulations deleted: 
As the frequency of site visits is reduced 
after May 2021, an additional overall AE 
summary table will be presented that 
excludes events and exposure time after 
May 2021. 
The severity for each type of AE will be 
tabulated. Where there are several 
To evaluate the event rate of AEs 
prior to modification of the site 
visit frequency. 
Tabulations deleted as not 
possible to perform. 
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Section 
number and 
name 
Description of change 
Brief rationale 
recordings of severity for a given type of 
AE, severity will be taken as the most 
severe recording for that AE. The and 
causal relationship to IMP for each type of 
AE will be tabulated. Where there are 
several recordings of causal relationship to 
the IMP for a given type of AE, causal 
relationship will be taken as the most-
related recording from the last report of that 
AE, since that is when the investigator will 
be in possession of most information and so 
best able to judge causal relationship. 
14.3.10 Interim 
analysis 
To support submission for marketing 
approval, Interim evaluation and reporting 
of selected trial data (for example, baseline 
demographics, disease characteristics, and 
SAEs) will be performed perfomed (e.g. to 
support submissions for marketing 
approval or sharing of results at 
conferences). 
To clarify the interim evaluation. 
Appendix 3B: 
Informed 
consent process 
Added text:  
To participate in the ECZTEND trial 
after May 2021, subjects must 
re-consent/consent to protocol version 10. 
To clarify that continuing in 
ECZTEND after May 2021 
requires the subject or subject’s 
legal representative to sign the 
new version of informed consent. 
Appendix 3E: 
Registration, 
reporting, and 
publication 
policy 
Results of this clinical trial will be posted 
on the LEO Pharma corporate website in 
accordance with LEO Pharma’s Position on 
Public Access to Clinical Trial Information 
position on public access to clinical trial 
information no later than 12 6 months after 
trial completion. 
To reflect that the trial includes 
adolescent subjects. 
Appendix 3J: 
Country-specific 
end of treatment 
date 
New appendix with country-specific 
treatment end dates for subjects from the 
parent trials LP0162-1325, -1326,  
-1339, -1341, -1342, -1343, -1346, and 
TRA-WEI-0015-I.  
The end of treatment date is 
country-specific to allow for 
treatment until treatment with 
tralokinumab is also available to 
patients outside the clinical trial 
setting, except for subjects from 
the parent trial LP0162-1334, who 
will end treatment by end of May 
2022 in all countries. 
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Section 
number and 
name 
Description of change 
Brief rationale 
Subjects from the parent trial LP0162-1334 
will end treatment by end of May 2022 in 
all countries. 
Appendix 3K: 
COVID-19 
New Appendix 3K: The clinical trial 
addendum dated 21-Apr-2020 has been 
integrated as an appendix, and optimised to 
apply to protocol version 10. This appendix 
provides an opportunity for telephone visits 
and courier delivery of IMP and pregnancy 
tests to subjects that are unable to attend 
site visits due to COVID-19 restrictions. It 
further provides a modified inclusion 
criterion 2, which is only applicable for 
subjects under COVID-19 restrictions. 
To ensure the possibility of 
continued treatment despite the 
local restrictions and restricted 
site access caused by the COVID-
19 pandemic. 
Appendix 4B: 
France 
Trial specific text has been deleted so that 
the specific procedures for France are 
independent on which protocol version the 
subject follows. 
The procedures for France are 
independent of the protocol 
version followed. 
Appendix 5: 
Eligibility 
criteria 
Inclusion criteria 2 and exclusion criteria 
15: added the 2 new parent trials LP0162-
1343 and TRA-WEI-0015-I. 
Exclusion criteria 7: Treatment with topical 
PDE-4 inhibitors or topical JAK 
inhibitors within 2 weeks prior to baseline. 
Exclusion criteria 8: Positive HBsAg, 
HBsAb*, HBcAb, or anti-HCV serology at 
screening. Subjects with positive HBsAb 
are eligible provided they are vaccinated 
against hepatitis B and have negative 
HBsAg and HBcAb 
*Subjects from the parent trial LP0162-
1343 with a positive HBsAb may be 
randomised provided they have negative 
Inclusion criteria 2 and exclusion 
criteria 8 and 15 updated to reflect 
the inclusion of subjects from the 
parent trials trials LP0162-1343 
and TRA-WEI-0015-I. 
Exclusion criteria 7 updated to be 
consistent with available 
treatments options. 
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Section 
number and 
name 
Description of change 
Brief rationale 
HBsAg, HBcAb, and HCV serology at 
screening. 
Throughout  
Minor editorial revisions. The word 
enrolled has been replaced with included in 
the entire document. 
Minor, and are therefore not 
summarised. 
 
Amendment 8 (12-Feb-2021) 
This amendment is considered to be non-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 because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the trial.  
Overall rationale for the amendment: 
The main reason for this amendment is to correct a typo in Panel 1 that provides an overview 
of scenarios for trial participation in protocol version 11 and to correct the estimated total 
amount of blood drawn in adolescent subjects.  
The table below describes the changes in each section, summarised as plain text, and/or as 
tracked changes (deleted text has a line through it). 
Section number 
and name 
Description of change 
Brief rationale 
3 Schematic of trial 
design 
In Panel 1 that provides an overview of scenarios 
for trial participation in protocol version 11, the 
cross-reference to Section 4.2 has been corrected 
to Section 4.1 for subjects with last visit before 
end of May 2021 and who continue in the trial. 
The previous cross-
reference to Section 4.2 
was incorrect. 
11.7 Estimate of 
total blood volume 
collected 
For adolescents, the total amount of blood drawn 
until end of May 2021 will be approximately 240 
130 mL, plus 70 mL for the 1 year extension 
until end of May 2022.  
The previous estimated 
total blood volume drawn 
for adolescent subjects 
was incorrect. 
Throughout 
Minor editorial revisions. 
Minor, have therefore not 
been summarised. 
 
 
TMF-000057619 - Version 15.0

SAP_001.pdf: 
CONFIDENTIAL
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Statistical analysis plan 
LP0162-1337
Long-term extension trial in subjects with atopic dermatitis who 
participated in previous tralokinumab trials – ECZTEND
Design of trial:
Phase 3 – long-term extension trial
An open-label, single-arm, multi-centre, long-term extension trial to evaluate the safety and 
efficacy of tralokinumab in subjects with atopic dermatitis who participated in previous 
tralokinumab clinical trials
LEO Pharma A/S
Trial ID:
LP0162-1337
Date:
19-Jul-2024
Version:
1.0
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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 
 
 Medical Sciences 
 
 
 MD, PhD 
 
 
 
 Medical Sciences 
 
 
 
 
 PhD., MSc.Eng. 
 
 Biostatistics 
 
 
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 ................................................................................................................ 2 
Table of contents ....................................................................................................................... 3 
List of panels ............................................................................................................................. 4 
List of abbreviations ................................................................................................................. 5 
Version history .......................................................................................................................... 7 
1 
Introduction .................................................................................................................... 8 
1.1 
Trial objectives and endpoints ................................................................................. 8 
1.2 
Trial design ............................................................................................................ 10 
2 
Testing strategy ............................................................................................................. 11 
3 
Sample size .................................................................................................................... 11 
4 
Trial analysis sets .......................................................................................................... 11 
5 
Statistical analysis ......................................................................................................... 12 
5.1 
General principles .................................................................................................. 12 
5.2 
Intercurrent events ................................................................................................. 13 
5.3 
Baseline presentations............................................................................................ 13 
5.3.1 
Demographics and other baseline characteristics ........................................ 13 
5.3.2 
Medical, Skin, and Atopic disease histories ................................................ 14 
5.4 
Disposition of subjects, medication, procedures, and exposure ............................ 14 
5.4.1 
Disposition of subjects ................................................................................. 14 
5.4.2 
Concomitant medication and concurrent procedures ................................... 14 
5.4.3 
Extent of exposure and treatment compliance ............................................. 15 
5.5 
Primary analysis ..................................................................................................... 15 
5.6 
Efficacy analysis .................................................................................................... 15 
5.6.1 
Analysis of Secondary endpoints ................................................................. 15 
5.6.2 
Analysis of other endpoints ......................................................................... 19 
5.7 
Pharmacokinetics analysis ..................................................................................... 20 
5.8 
Safety analysis ....................................................................................................... 21 
5.8.1 
Adverse events ............................................................................................. 21 
5.8.2 
Vital signs .................................................................................................... 23 
5.8.3 
Physical examination ................................................................................... 23 
5.8.4 
Clinical laboratory evaluation ...................................................................... 23 
5.8.5 
ECG ............................................................................................................. 24 
5.8.6 
Anti-drug antibodies .................................................................................... 24 
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5.9 
Interim analysis ...................................................................................................... 25 
6 
Changes to analyses described in the protocol ........................................................... 26 
7 
Supporting documentation .......................................................................................... 27 
7.1 
Tralokinumab naïve, re-treated, continuously treated, and washed-out 
subjects................................................................................................................... 27 
7.2 
Safety areas of interest ........................................................................................... 27 
8 
References ...................................................................................................................... 29 
 
List of panels 
Panel 1: Trial objectives and endpoints .................................................................................. 8 
Panel 2: Trial design ............................................................................................................... 10 
Panel 3: AESIs (as defined in the CTP) ................................................................................... 22 
Panel 4: Clinical laboratory test where shift tables will be prepared for lowest/highest 
measurement in the treatment period .................................................................. 23 
Panel 5: Changes to the analyses described in the CTP ........................................................... 26 
Panel 6: AESI: ECZTEND defined AESI ................................................................................ 28 
Panel 7: Tralokinumab’s ADRs ................................................................................................ 28 
 
 
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List of abbreviations 
AD 
atopic dermatitis 
ADA 
anti-drug antibodies 
ADR 
adverse drug reaction 
ADRG 
analysis data reviewer’s guide 
AE  
adverse event 
AESI 
adverse event of special interest 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the curve 
CDLQI 
Children’s Dermatology Life Quality Index 
CI 
confidence interval 
CTP 
clinical trial protocol 
CTR 
clinical trial report 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
EASI50/75 
at last 50/75% reduction in EASI from baseline (in the parent trial) 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EQ-5D-5L 
EuroQoL 5-Dimension Health Questionnaire 5-Level 
FAS 
full analysis set 
HDL 
high density lipoprotein 
HLT 
MedDRA high level term 
hMI 
hypothetical multiple imputation of missing data and any unobserved data 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IGA 
Investigator’s Global Assessment 
IGA 0/1 
IGA score of 0 (clear) or 1 (almost clear) 
IMP 
investigations medicinal product 
LDL 
low density lipoprotein 
LOCF 
last observation carried forward 
LoE 
loss of efficacy 
MedDRA 
Medical Dictionary for Regulatory Activities 
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MI 
multiple imputation 
mNRI-MI-Hyp 
modified non-responder imputation with multiple imputation of missing and 
any unobserved data with treatment adherence multiple imputation strategy 
NRI 
non-responder imputation 
NRS 
numerical rating scale 
PCS 
potentially clinically significant 
PK 
pharmacokinetic 
PMDA 
Japan Pharmaceuticals and Medical Devices Agency 
POEM 
Patient-Oriented Eczema Measure 
PT 
preferred term 
Q2W 
every 2 weeks 
SAE 
serious adverse event 
SAF 
safety analysis set 
SAP 
statistical analysis plan 
SCORAD 
Scoring Atopic Dermatitis 
SD 
standard deviation 
SFU 
safety follow-up 
SOC 
system organ class 
TCS 
topical corticosteroids 
TEAE 
treatment-emergent adverse event 
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Version history 
The SAP for trial LP0162-1337 is based on the CTP version 14.0 dated 21-Feb-2022.  
SAP version 
Date 
Change 
Rationale 
1.0 
 
Not applicable 
Original version 
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1 
Introduction 
The statistical analysis will be performed as outlined in the CTP version 14.0. 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 CTP-planned analyses are described in Section 6. 
1.1 
Trial objectives and endpoints 
Panel 1: Trial objectives and endpoints 
Objectives 
Endpoints 
Primary objective 
Primary endpoint 
To evaluate the long-term 
safety of tralokinumab 
• 
Number of adverse events during the treatment period from 
baseline up to Week 268 
Secondary objectives 
Secondary endpoints 
To evaluate the efficacy 
of tralokinumab given 
as continuous treatment, 
re-treatment, or 
introduced   
for the first time 
in tralokinumab-naïve 
subjects 
• 
IGA score of 0 (clear) or 1 (almost clear) at Weeks 16, 56, 88, 
104, 136, 152, 184, 216, and 248 
• 
EASI751 at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 
248 
 
Other endpoints 
 
• 
Change in EASI score from baseline2 to Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
Change in SCORAD from baseline2 to Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 
• 
Change in POEM score from baseline2,3 to Weeks 16, 56, 80-
88, 104, 128-136, 152, 184, 216, and 248 
• 
Change in DLQI score from baseline2,3 to Weeks 16, 56, 80-88, 
104, 128-136, 152, 184, 216, and 248 in adult subjects7 
• 
Change in CDLQI4 score from baseline2,3 to Weeks 16, 56, 80-
88, 104, 128-136, 152, 184, 216, and 248 in adolescent 
subjects6 
• 
Change in EQ-5D-5L score from baseline2,3,5 to Weeks 16, 56, 
80-88, 104, 128-136, 152, 184, 216, and 248  
• 
Presence of anti-drug antibodies (yes/no) 
• 
Time from first dose to permanent discontinuation of 
tralokinumab 
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Notes: 
 1 EASI75 and EASI50 will be calculated based on baseline EASI score in parent trial. The endpoint is not 
applicable for subjects from the parent trial TRA-WEI-0015-I, as data from the parent trial will not be 
transferred to LEO Pharma. 
2 ‘Change from baseline’ is defined as change from baseline in the parent trial. Endpoints are not applicable for 
subjects from the parent trial TRA-WEI-0015-I, as data from the parent trial will not be transferred to LEO 
Pharma. 
3 Endpoint is not applicable for subjects from the parent trial LP0162-1342, as these subjects did not have 
POEM, DLQI/CDLQI, or EQ-5D-5L assessments in the parent trial and thus are missing baseline 
assessments. 
4 All subjects from the parent trial LP0162-1334, independent of the subject’s age during participation in 
ECZTEND, performed the CDLQI, an adolescent’s pruritis NRS with a recall period of past 7 days, and an 
eczema-related sleep NRS with a recall period over the past 7 nights. 
5 Endpoint is not applicable for subjects from the parent trials LP0162-1334 and -1343, as these subjects did not 
have EQ-5D-5L assessments in the parent trial and thus are missing the baseline assessment. 
6 Adolescent subjects are defined as subjects from the LP0162-1334 trial, regardless of their age during 
participation in ECZTEND. 
7 Adult subjects are defined as subjects not from the LP0162-1334 trial, regardless of their age during 
participation in ECZTEND. 
Abbreviations: CDLQI = Children’s Dermatology Life Quality Index; DLQI = Dermatology Life Quality 
Index; EASI = Eczema Area and Severity Index; EASI75/EASI50 = at least 75%/50% reduction in EASI 
score, relative to baseline in parent trial; EQ-5D-5L = EuroQoL 5-Dimension Health Questionnaire 5-Level; 
IGA = Investigator’s Global Assessment; NRS = numeric rating scale; POEM = Patient-Oriented Eczema 
Measure; SCORAD = Scoring Atopic Dermatitis. 
 
 
• 
Proportion of time with EASI751 after first occurrence of 
EASI75 during treatment period in ECZTEND 
• 
Proportion of time with EASI501 after first occurrence of 
EASI50 during treatment period in ECZTEND 
• 
Proportion of time with IGA 0/1 after first occurrence of 
IGA 0/1 during treatment period in ECZTEND 
• 
Worst Weekly Pruritus NRS at Weeks 16, 56, 88, 104, 136, 
152, 184, 216, and 248 in adult subjects7 
• 
Worst Weekly Pruritus NRS at Weeks 16, 56, 88, 104, 136, 
152, 184, 216, and 248 in adolescent subjects6 
• 
Eczema-related Weekly Sleep NRS at Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 in adult subjects7 
• 
Eczema-related Weekly Sleep NRS at Weeks 16, 56, 88, 104, 
136, 152, 184, 216, and 248 in adolescent subjects6 
• 
Use of topical treatment during the last week at Weeks 16, 56, 
88, 104, 136, 152, 184, 216, and 248  
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1.2 
Trial design 
Panel 2: Trial design 
 
Notes: Subjects were included in ECZTEND after completion of the treatment period in the parent trial, and 
continued with a long-term treatment period of approximately 0.5 to 5 years in ECZTEND. Subjects who 
did NOT re-consent to participation in the trial after May 2021 stopped IMP treatment by end of May 2021 
followed by 16 weeks of SFU (top row visit schedule). * Subjects from the parent trial LP0162-1334 did not 
perform the EQ-5D-5L. ** Visit schedule after May 2021 applied to subjects who consented to continue in 
the trial after May 2021, or who were included in the trial after May 2021. Treatment ended at a 
country-specific treatment end date, or by end of May 2022 (subjects from the parent trial LP0162-1334).  
Abbreviations: ADA = anti-drug antibodies; CDLQI = Children’s Dermatology Life Quality Index; 
DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EQ-5D-5L = EuroQoL 
5 Dimension Health Questionnaire 5-Level; IGA = Investigator’s Global Assessment; IMP = investigational 
medicinal product; PK = pharmacokinetics; POEM = Patient Oriented Eczema Measure; Q2W = every 
second week; SCORAD = Scoring Atopic Dermatitis; SFU = safety follow-up; TCS = topical 
corticosteroids; w = weeks. 
Protocol amendments 
The following CTP amendments significantly affected data interpretation, analyzed 
populations, or statistical analyses: 
• Amendment 2 (31-Aug-2018):  
o Allowed subjects from parent trial LP0162-1346 to enter ECZTEND. 
o Changed the timeframe of the primary endpoint from “up to Week 128” to “last 
treatment visit”. 
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• Amendment 6 (17-Feb-2020):  
o Changed the timeframe of the primary endpoint from “last treatment visit” to 
“up to Week 142”. 
o Allowed adolescent subjects from parent trial LP0162-1334 to enter 
ECZTEND including associated assessments and precautions. 
o Increased estimated sample size to 1500 subjects. 
• Amendment 7 (25-Nov-2020):  
o Updated the visit schedule after May 2021, extending the trial up to 5 years. 
o Converted every other site visit after Week 24 to telephone visits. 
o Allowed subjects from parent trial LP0162-1343 and TRA-WEI-0015-I to 
enter ECZTEND. 
o Added country specific end of treatment dates. 
o Updates to all endpoints in accordance with the extension of the trial and 
update to the schedule of assessments. 
For a complete overview of all changes introduced in protocol amendments, see the 
CTP Appendix 8. 
2 
Testing strategy 
No testing has been specified. 
3 
Sample size  
Sample size documentation is provided in the CTP Section 14.1. 
4 
Trial analysis sets 
All screened subjects will be accounted for in the CTR. 
All subjects receiving tralokinumab will be included in the FAS and will be analysed for 
efficacy. 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 
tralokinumab from the FAS, a justification addressing ICH E9 will be given. 
The SAF will be identical to the FAS, as all subjects receiving tralokinumab will be included 
in the SAF. However, subjects decided to be excluded from the FAS will not also be excluded 
in the SAF. Any exclusions from the SAF will be justified separately addressing ICH E9. 
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All subjects receiving tralokinumab and starting in the safety follow-up will be included in a 
safety follow-up analysis set. Any exclusions will be identical to the safety analysis set.  
Data from the investigator-initiated parent trial TRA-WEI-0015-I will not be transferred to 
LEO Pharma. Thus, endpoints defined as change from baseline (in the parent trial) will not be 
calculated for subjects from this trial, and data from this trial will not be included in tables 
summarising endpoints defined as change from baseline or where data are presented by 
responder/non-responder status. Subjects from TRA-WEI-0015-I will be contributing to the 
primary endpoint and included in summary tables where possible.  
The decisions regarding inclusion/exclusion of subjects or subject data from the trial analysis 
sets will be documented in the Classification Brief. 
5 
Statistical analysis 
All presentations of data will be made for the total ECZTEND population with above analysis 
sets applied as appropriate.  
5.1 
General principles 
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 observed data will be summarised using the number and percentage of subjects in 
each category and, if applicable, by tralokinumab naïve, re-treated, and continuously treated, 
and by washed-out subjects.  
Continuous observed data will be summarised using the mean, SD, median, 1st quartile, 3rd 
quartile, minimum, and maximum values and, if applicable, by tralokinumab naïve, re-treated, 
and continuously treated, and by washed-out subjects.  
Tralokinumab treatment naïve, re-treated, and continuously treated, and washed-out 
subgroups have been defined in Section 7.1.  
All endpoints derived using baseline values are derived using the parent trial baseline value 
unless otherwise indicated. 
For analyses using multiple imputation, the seed number used will be 32 and 100 MI will be 
carried out.  
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If region is used as a covariate or sub-group variable, it will be defined with the levels: North 
America, Europe, and Asia. 
5.2 
Intercurrent events 
The following intercurrent events are defined to describe the treatment effect that is targeted 
with the different estimand strategies described underneath. 
• Treatment completion: This intercurrent event occurs either when a subject 
completes the period of the trial the subject consented to or is withdrawn from the trial 
due to tralokinumab becoming commercially available in their country. This 
intercurrent event is introduced mainly due to the extension amendment introduced in 
May 2021. Notably, it was not collected in the eCRF whether a subject withdrew due 
to not consenting to continue in the extension of the trial. Subsequently, an algorithm 
was built such that withdrawals close (17 days) to the country-specific closure date 
were classified as treatment completers instead of as having permanently discontinued 
IMP. See the ADRG for a complete algorithm defining treatment completion. 
• Permanent discontinuation of IMP: This intercurrent event occurs when a subject is 
withdrawn from trial while under treatment. It can occur at the subjects’ own initiative, 
at the discretion of the investigator or the sponsor, or if the subject is lost to follow-up: 
o Due to lack of efficacy (LoE) or adverse event (AE): This intercurrent event 
occurs when it is specified that the primary reason for withdrawal from trial 
while under treatment is due to either LoE, or AE. Of note, the reasons 
“withdrawal by subject”, “lost to follow-up” and “other” were queried to 
ensure that the underlying reason was not LoE or AE. 
o Not due to LoE nor AE: the complement to the previously specified reasons. 
5.3 
Baseline presentations 
Due to safety-related analyses specified for subjects coming from the LP0162-1334 trial in 
the protocol, baseline presentations will be specified where applicable for subjects from the 
LP0162-1334 trial.  
5.3.1 
Demographics and other baseline characteristics 
Descriptive statistics of demographics and other baseline characteristics (e.g. efficacy 
variables at parent trial baseline and ECZTEND baseline [age, sex, ethnicity, race]) and the 
latest treatment regimen in the parent trial (placebo, tralokinumab, tralokinumab + TCS) will 
be presented for the SAF and by tralokinumab-naïve/re-treated/continuously treated subjects 
in the SAF. For the re-treated and continuously treated subjects, the presentation will further 
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be divided by responder/non-responder status in the parent trial; clinical response is defined 
as achievement of IGA 0/1 or EASI75 at the last assessment in the parent trial.  
In addition, due to variable country closures due to by the commercialization of tralokinumab, 
the above defined descriptive statistics will be made for those subjects still ongoing in trial 
(i.e. those who have neither withdrawn nor completed the trial) at weeks 56, 104, 152, 216, 
and 264 relative to ECZTEND baseline for the SAF.  
The above will also be made for subjects transferring in from LP0162-1334. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
5.3.2 
Medical, Skin, and Atopic disease histories 
Medical, skin, and atopic disease histories will be presented for the SAF. 
The above will also be made for subjects transferring in from LP0162-1334. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
5.4 
Disposition of subjects, medication, procedures, and exposure 
5.4.1 
Disposition of subjects 
The reasons for withdrawal from the trial will be presented for the SAF, using the 
Aalen-Johansen cumulative incidence function estimator, over both the treatment period and 
the safety follow-up period. 
In addition, reasons for withdrawal from the trial and reasons for permanent discontinuation 
of IMP will also be presented in the same manner over the treatment period for the SAF. 
A stacked bar plot will be made showing the proportion of subjects in each region ongoing in 
the trial (i.e. those who have neither withdrawn nor completed the trial) over the treatment 
period and the safety follow-up period for the SAF. 
The above will also be made for subjects transferring in from LP0162-1334. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
5.4.2 
Concomitant medication and concurrent procedures 
Concomitant medication at ECZTEND baseline will be presented for the SAF. 
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Concomitant medication in the treatment period will be presented for the SAF. 
All concomitant medications and concurrent procedures will be listed. 
The above will also be made for subjects transferring in from LP0162-1334. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
5.4.3 
Extent of exposure and treatment compliance 
Exposure 
Exposure to treatment will be presented for the SAF as days of exposure in total, by exposure 
time cutoffs, and by parent trial. 
Days of exposure will be calculated as the number of days from the date of the first IMP dose 
in ECZTEND 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 
Adherence will be presented for the SAF. 
The above will also be made for subjects transferring in from LP0162-1334. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
5.5 
Primary analysis 
The primary endpoint in this trial is the number of adverse events during the treatment period 
from baseline up to Week 268, and the analysis of this endpoint is covered in the safety 
analysis section. 
5.6 
Efficacy analysis 
All efficacy endpoints will be analysed using the FAS. In addition, to support the secondary 
objective of the trial, all efficacy analyses will be done by tralokinumab-naïve, re-treated, and 
continuously treated, and in addition for the washed-out subgroup (Section 7.1). 
5.6.1 
Analysis of Secondary endpoints 
For definitions of endpoints see Panel 1. 
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5.6.1.1 
Binary endpoints 
5.6.1.1.1 
Primary analysis 
Observed cases analysis by each scheduled visit will be performed, presenting proportions 
with a 95% Wilson CIs.  
Figures will be made of the observed proportions of responders by visit with CI and a table 
appended showing the number of subjects with observed data and number of subjects who 
have not dropped out at each visit.  
5.6.1.1.2 
Sensitivity analyses 
The strategies used in these sensitivity analyses use hypothetical assumptions to investigate 
potential survival bias and do not necessarily represent the truth if all subjects had continued. 
The goal is to provide multiple hypothetical scenarios, of which some will reflect extreme 
assumptions and some will be closer to the expected true estimate. Examining both extreme 
and realistic hypothetical scenarios should allow for a reasonable discussion of where the true 
estimate is.  
All analyses will be presented by all planned assessments with 95% Wilson CIs, and where 
data is being multiply imputed, Rubin’s rule will be applied using Lott and Reiter’s formula 
for Wilson CIs with MI (1). 
5.6.1.1.2.1 
Hypothetical MI of missing data and any unobserved data (hMI) 
This sensitivity analysis seeks to mitigate possible survival bias by estimating the response if  
all subjects had continued in the trial like they were before they dropped out.  
The proportion of responders will be calculated by each scheduled visit based on both 
observed, and multiply imputed missing or unobserved assessment data. The missing 
assessment data will be imputed using a 2-step MI strategy involving both a regression-based 
approach imputing data up to the 1st year (Week 56 visit) in the trial and a within-subject 
approach imputing data after the 1st year in the trial. For the complete technical definition of 
the 2-step MI strategy please see section 5.6.1.1.2.3. The split at 1 year was chosen for several 
reasons: 
1. Subjects will enter the trial differently, some being untreated or washed-out of 
tralokinumab and others may be under continuous treatment with tralokinumab when 
starting the trial. A visit-sequential full conditional specification regression-based 
approach is ideal to reflect this expected change over time in the overall proportion of 
response. 
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2. Survival bias affecting the proportion of responders can within reason be 
mitigated/minimized provided suitable adjustment in the 1st year. This is because a 
sizable part and broadly defined population were followed-up without interruptions 
during the first year. 
3. After 1 year, the population can be assumed to have regressed to its mean while under 
continuous treatment with tralokinumab.  
This hypothetical assumption applied to the imputation of missing data from subjects who 
either completed treatment (e.g. due to commercialization of tralokinumab in their country) or 
permanently discontinued IMP is strong. However, assuming that these subjects continued as 
if they had regressed to their within-subject mean is appropriate under this hypothetical 
sensitivity scenario as it attempts to estimate the proportion of responders under minimal 
influence of survival bias. 
5.6.1.1.2.2 
mNRI-MI with treatment adherence MI strategy (mNRI-MI-Hyp) 
This sensitivity analysis seeks to estimate a lower bound of the response by estimating the 
response achieved without permanent discontinuation of IMP due to LoE or AE if all subjects 
who withdrew for other reasons had continued in the trial like they were before they 
dropped out. 
The response at each scheduled visit will be calculated based on both observed and multiply 
imputed missing or unobserved assessment data, with those having permanently discontinue 
IMP due to LoE or AE prior to the analysed visit imputed as non-responders. Missing 
assessment data will be imputed using the same 2-step MI strategy (see section 5.6.1.1.2.3) as 
in the hMI sensitivity analysis. Permanent discontinuations of IMP due to LoE or AE of 
subjects who permanently discontinued IMP for other reasons or completed the trial will be 
imputed using the hypothetical treatment adherence MI strategy (see section 5.6.1.1.2.3) onto 
subjects who either completed treatment or permanently discontinued IMP for other reasons 
than LoE or AE after the time they discontinue. 
This hypothetical scenario sets out to estimate a lower bound of efficacy by assuming that 
subjects who are either observed or imputed to permanently discontinue of IMP due to LoE or 
AE are perpetually considered non-responders. In dealing with subjects who drop-out early, it 
sets a strong assumption that regression-to-the-mean can be assumed when imputing 
assessment data. But in doing so, this sensitivity strategy targets the same underlying target of 
estimation established in trials of other similar drugs in AD long-term extension trials (2) 
where subjects have been non-responder imputed based only on observed permanent 
discontinuation of IMP due to LoE or AE, with assessment data imputed using last 
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observation carried forward. However, last observation carried forward will not be used as it 
is not appropriate, see e.g., “Fallacies of Last Observation Carried Forward” (3). 
5.6.1.1.2.3 
Imputation strategies 
2-step MI strategy  
A 2-step MI strategy will be employed to mitigate potential survival bias as reasoned above. 
MI of missing data and data unobserved after intercurrent events can be used by the different 
sensitivity analyses per the need of the various estimation requirements: 
1. Data up until the Week 56 visit will be imputed using a Full Conditional Specification 
gaussian regression-based MI model adjusting for previous visit (if planned visit 
exist), next visit (if planned visit exist), parent trial, and region. If the score being 
imputed is ordinal or binary, an ordinal logistic regression model will be used instead. 
The assumption here is that the data used in the MI regression model are robust 
enough. 
2. Data after the Week 56 visit will be imputed using a within-subject non-parametric 
approach leveraging the proportion of response each subject has achieved estimated 
using linear interpolation across observed and (in the previous step) imputed scores. 
This proportion of response could also be called a within-subject AUC of days in 
response. The imputation will be derived in the following 3 steps:  
1. All days between observed and imputed visits will be imputed on the 
assessment’s scale by using linear interpolation between visits. For binary and 
ordinal scores, the imputed value will be rounded.  
2. Then all days will be transformed into the binary endpoint and an average of 
those 1s (response) and 0s (non-response) going one year back (but not further 
back than the Week 16 visit) will be the AUC of days in response.  
This assumes that from the Week 16 visit that all subjects have regressed to 
their individual mean while under long-term treatment with tralokinumab (due 
to the safety follow-up between parent trials and ECZTEND with no dosing). 
3. An imputed response at each day, including planned visits, after the 
intercurrent event will then be drawn from the Bernoulli distribution by using 
the AUC of days in response as a probability.  
Hypothetical treatment adherence MI strategy (Hyp) 
MI of treatment adherence status at end of the treatment period, 𝑡EoTrt, for subjects 
experiencing an intercurrent event, at time tICE, will be imputed based on the semi-parametric 
Cox proportional hazard model. The model will provide an estimated probability 𝑝̂(𝑡EoTrt, 
region, parent trial) of being on treatment at the later time 𝑡EoTrt conditional on being on 
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treatment at the earlier time 𝑡ICE in the hypothetical scenario where permanent discontinuation 
of IMP due to pandemic restrictions would not occur. The conditional probability 𝑝̂ will be 
calculated as the estimated survival function evaluated at 𝑡EoTrt divided by the same function 
evaluated at time tICE (with tICE < 𝑡EoTrt) and imputed using random draws from an exponential 
distribution with rate 𝑝̂. For specific regional analyses, 𝑡EoTrt may vary depending on the 
scarcity of data at the end the treatment period, but for summaries of the main populations 
Week 264 will be used.  
5.6.1.1.3 
Supplemental analysis 
To evaluate the efficacy of tralokinumab given as continuous treatment, re-treatment, or 
introduced for the first time in tralokinumab-naïve subjects, each specified analysis above will 
also be done within each of the tralokinumab naïve, re-treated, continuously treated, and 
washed-out sub-populations. 
5.6.2 
Analysis of other endpoints 
Due to the changed visit structure introduced in May 2021, some endpoints have been 
specified as combining data from 2 possible visits, e.g., Change in DLQI/CDLQI score from 
baseline to Weeks 80-88. The rule for handling these endpoints will be to calculate the 
endpoint based on the first existing data. Hence, where a subject had an assessment at both 
Week 80 and Week 88, the Week 80 assessment (corresponding to approximately 1½ years) 
will be prioritised for the Week 80-88 endpoint evaluation. Likewise, the Week 128 
assessment (~ 2½ years) will be prioritised for the Week 128-136 endpoint evaluation.  
The DLQI score will be presented for subjects from the parent trials LP0162-1325, -1326,  
-1339, -1341, -1343, and -1346. The CDLQI score will be presented for subjects from the 
parent trial LP0162-1334. As subjects from the parent trial LP0162-1342 did not have POEM, 
DLQI, or EQ-5D-5L assessments in the parent trial, the change from baseline is not 
applicable. As subjects from the parent trials LP0162-1334 and -1343 did not have EQ-5D-5L 
assessments in the parent trial, the change from baseline is not applicable. Changes from 
baseline will not be presented for subjects from the parent trial TRA-WEI-0015-I since data 
from this investigator-initiated trial have not been transferred to LEO Pharma (see the CTP 
Section 14.2). 
5.6.2.1 
Continuous endpoints 
5.6.2.1.1 
Primary analysis 
As observed according to general principles. 
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Figures will be made with the median and 1st and 3rd quartiles and an table appended showing 
the number of subjects with observed data at each visit. 
5.6.2.1.2 
Sensitivity analysis 
No sensitivity analysis will be made for continuous other endpoints. 
5.6.2.1.3 
Supplemental analysis 
To evaluate the efficacy of tralokinumab given as continuous treatment, re-treatment, or 
introduced for the first time in tralokinumab-naïve subjects, each specified analysis above will 
also be done by tralokinumab naïve, re-treated, continuously treated, and washed-out 
sub-populations. 
5.6.2.2 
Proportion of response over time endpoints 
5.6.2.2.1 
Primary analysis 
The proportion of response over time will be estimated by the AUC over daily responses 
estimated through linear interpolation between observed assessments made at scheduled 
visits. The analysis will calculate the mean proportion (assumed continuous) and 95% Wald 
CI appended, with the standard deviation, median, 1st and 3rd quartiles, and minimum and 
maximum values appended as well. 
5.6.2.2.2 
Sensitivity analysis/analyses 
No sensitivity analyses have been defined. 
5.6.2.2.3 
Supplemental analyses 
A supplementary analysis will be appended for the primary analysis, where each estimated 
percentage of days in response will be used to analyse the endpoint rephrased in to “subjects 
with ≥x% of days in response” where x is defined as the whole numbers 0, 1, 2, …,100. The 
subsequent proportion of subjects with ≥x% of days in response will be estimated with 95% 
Wilson CIs. 
The second supplementary analysis, will be re-made for the primary and the above 
supplemental analysis over the following periods: Week 0-<16, Week 16-<104, 
Week 104-<200, and Week 200-264, in addition to the overall treatment period. 
5.7 
Pharmacokinetics analysis 
The pharmacokinetics analysis is tabulated as described in the CTP Section 14.3.9. 
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5.8 
Safety analysis 
Safety endpoints will be analysed using the SAF.  
5.8.1 
Adverse events 
AEs will be coded during the course of the trial according to MedDRA version 20.0 but 
analysed in MedDRA version 27.0. 
Only TEAEs will be summarized in this trial. AEs were considered treatment emergent if they 
started after first dose of IMP or started before first dose of IMP and worsened in severity 
after first dose of IMP. All AEs recorded during the trial will be listed. 
For the treatment and SFU periods, presentations of AEs by SOC and PT will include 
summaries of the following categories of AEs:  
• All AEs. 
• Frequent AEs (≥5% of subjects reporting the AE in the total population). 
• Frequent AEs (occurring with an incidence rate ≥ 2.5 in the total population). 
• SAEs. 
• AEs leading to withdrawal from the trial. 
• Probably or possibly related AEs. 
• Severity of AEs (mild, moderate, and severe AEs presented separately). 
Summaries will include the percentage and number of subjects with an AE, number of AEs, 
patient-years of exposure up until the first event, incidence rate of AEs (rate of new 
events/occurrences, calculated as the number of subjects with an AE per 100 patient-years of 
exposure at risk defined as patient-years up until the first event or end of exposure [whichever 
came first]), and occurrence rate of AEs (rate of events/occurrences calculated as the number 
of AEs per 100 patient-years of exposure up until end of exposure).  
Overviews of AEs will be appended for the above-mentioned categories of AEs and will 
include the following information: SAEs, severity (mild, moderate, or severe), relationship to 
IMP (probably, possibly, and not related), AEs probably or possibly related to IMP, AEs 
leading to withdrawal from trial and/or permanent discontinuation of IMP, outcome, and 
action taken with IMP. 
For the SFU period, all AEs and SAEs will be presented by an overview summary and by 
SOC and PT using the safety follow-up analysis set. 
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The above summaries will also be made separately for subjects who transferred from the 
parent trial LP0162-1334. Secondly, as the frequency of site visits is reduced after May 2021, 
2 additional overall AE summary tables will be presented, one will exclude events and 
exposure time after May 2021 and the second will only include events and exposure time after 
May 2021. Thirdly, the data will be presented by tralokinumab naïve, re-treated, and 
continuously treated, and by washed-out subjects using the above defined summaries. 
5.8.1.1 
ECZTEND defined adverse events of special interest (ECZTEND-AESI) 
ECZTEND-AESIs will be presented overall within each AESI, and by SOC and PT, as 
defined for TEAEs. Additionally collected information for each of the defined 
ECZTEND-AESIs will be summarised. For their definition see Panel 6. 
Panel 3: AESIs (as defined in the CTP) 
AESIs 
Reason for inclusion 
Eczema herpeticum 
Eczema herpeticum is a well-known severe skin infection in 
patients with AD. 
Eczema herpeticum occurs in lesioned AD skin – the 
additional information collected can be used to adjudicate 
the events, if needed. 
Malignancy diagnosed after 
treatment assignment, excluding 
basal cell carcinoma, localised 
squamous cell carcinoma of the skin, 
and carcinoma in situ of the cervix 
There has been no indication of a higher risk of malignancy 
with tralokinumab treatment compared with placebo. 
However, as is typical for immunomodulating biologics, 
malignancy is considered an important potential risk for 
tralokinumab. 
Skin infections requiring systemic 
treatment 
The skin barrier is expected to improve during treatment 
with tralokinumab. Additional information is collected to 
better describe location and pathogen. 
Conjunctivitis** 
Important potential risk in the tralokinumab risk 
management plan. 
Due to focus on eye disorders. 
Keratoconjunctivitis** 
Due to focus on eye disorders. 
Keratitis** 
Due to focus on eye disorders. 
**: grouped in AESI ‘Eye disorders’ 
5.8.1.2 
Adverse drug reactions 
These ADRs of tralokinumab (as of writing this SAP) will be presented in the same way as 
for the AESIs. The ADRs of tralokinumab are defined in Panel 7. 
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5.8.2 
Vital signs 
Vital signs will be tabulated as described in the CTP Section 14.3.8.2. However, only 
presenting summaries of the total, tralokinumab naïve, re-treated, and continuously treated, 
not the washed-out subjects.  
Additionally, vital sign values will be considered potentially clinically significant if satisfying 
the PCS criteria specified in the ADRG. All post-baseline measurements (including samples 
from unscheduled visits) will be included in the search for PCS values. Number and 
percentage of subjects with at least one post-baseline PCS value will be summarised with the 
denominator being all subjects with at least one post-baseline assessment. All PCS values will 
be included in the listings. 
5.8.3 
Physical examination 
Physical examinations reported as ‘abnormal, clinical significant’ will be listed. 
5.8.4 
Clinical laboratory evaluation 
Clinical laboratory evaluations will be tabulated as described in the CTP Section 14.3.8.3. 
However, only presenting summaries of the total, tralokinumab naïve, re-treated, and 
continuously treated, not the washed-out subjects.  
Additionally, shift tables will be produced for relevant laboratory tests showing categories at 
baseline against highest or lowest test measurement in the treatment period (see Panel 4).  
Panel 4: Clinical laboratory test where shift tables will be prepared for lowest/highest 
measurement in the treatment period 
Clinical laboratory test 
Shift table to lowest 
Shift table to highest 
Chemistry 
Sodium 
Yes 
Yes 
Potassium 
Yes 
Yes 
Creatinine 
- 
Yes 
Calcium 
Yes 
Yes 
Alkaline phosphatase 
- 
Yes 
Aspartate aminotransferase 
- 
Yes 
Alanine aminotransferase 
- 
Yes 
Bilirubin 
- 
Yes 
Cholesterol 
- 
Yes 
LDL cholesterol 
- 
Yes 
HDL cholesterol 
Yes 
Yes 
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Clinical laboratory test 
Shift table to lowest 
Shift table to highest 
Triglycerides 
- 
Yes 
Glucose (non-fasting) 
Yes 
Yes 
Hematology 
Hemoglobin 
Yes 
Yes 
Neutrophils, segmented 
Yes 
- 
Lymphocytes 
Yes 
Yes 
Monocytes 
Yes 
Yes 
Eosinophils 
- 
Yes 
Basophils 
- 
Yes 
Platelets 
Yes 
Yes 
Abbreviations: HDL = high density lipoprotein; LDL = low density lipoprotein; - = not applicable. 
Laboratory values will be considered potentially clinically significant if satisfying the PCS 
criteria specified in the ADRG. All post-baseline measurements (including samples from 
unscheduled visits) will be included in the search for PCS values. For haematology and 
chemistry laboratory parameters, the number and percentage of subjects with at least one 
post-baseline PCS value will be summarised with the denominator being all subjects with at 
least one post-baseline assessment. All PCS values will be included in the listings. 
Subjects fulfilling Hy’s law will be presented. 
5.8.5 
ECG 
The overall central evaluation of ECGs will be summarised and listed. The overall central 
evaluation of ECG data will be presented using shift tables. However, only presenting 
summaries of the total, tralokinumab naïve, re-treated, and continuously treated, not the 
washed-out subjects.  
All other ECG parameters collected will be listed. 
5.8.6 
Anti-drug antibodies 
The ADA status categories are updated compared to the CTP Section 14.3.8.4 to incorporate 
ADA data from the parent trial. 
The ADA status will be categorized as below, where all ADA assessments from the parent 
trial and ECZTEND are taken into account. For subjects who received tralokinumab treatment 
in the parent trial, ‘first tralokinumab dose’ refers to the first tralokinumab dose in the parent 
trial, if applicable. 
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The ADA status will be categorised as follows: 
ADA positive 
• Pre-existing: At least 1 positive ADA assessment before first tralokinumab dose, no 
post-tralokinumab ADA response greater or equal to 4-fold over the maximum 
pre-tralokinumab titre level. At least 1 positive post-tralokinumab ADA assessment. 
• Treatment-boosted: At least 1 positive ADA assessment before first tralokinumab 
dose, at least 1 post-tralokinumab ADA response greater or equal to 4-fold over the 
maximum pre-tralokinumab titre level. 
• Treatment-emergent: All ADA assessments negative or missing before first 
tralokinumab dose, at least 1 positive ADA response after first tralokinumab dose. 
o Persistent: Positive ADA for at least 2 consecutive visits at least 10 weeks 
apart. 
o Indeterminate: Only the last ADA response positive. 
o Transient: Neither persistent nor indeterminate. 
ADA negative 
• All ADA assessments negative or missing. At least one non-missing ADA assessment 
after first tralokinumab dose. 
Perishing ADA 
• At least 1 positive ADA assessment before first tralokinumab dose, all ADA 
assessments negative after first tralokinumab dose. 
No post-baseline 
• No ADA assessments after first tralokinumab dose. 
 
For subjects with an ADA positive measurement during the trial, the development in EASI 
and neutralising antibodies (nAB) will be presented graphically and listed (IGA included). 
Presentations will only present the total, tralokinumab naïve, re-treated, and continuously 
treated, not the washed-out subjects. 
5.9 
Interim analysis 
At the time of writing this SAP several analyses have been conducted. Mainly, an interim 
report was prepared for EMA which delivered a comprehensive analysis focused solely on 
safety analyses. Japanese subjects in ECZTEND have been analysed for submission to 
PMDA. Several abstracts, posters, oral presentations, and articles have been presented and/or 
published featuring analyses from ECZTEND both in terms of safety and efficacy analyses on 
differing data-cuts. 
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6 
Changes to analyses described in the protocol 
Panel 5 summarises the changes to the analyses planned in the protocol. 
Panel 5: Changes to the analyses described in the CTP 
Section in the CTP 
Description of change 
Brief rational3 
14.3.5 
The specified strict NRI sensitivity 
analysis has been replaced by 
2 sensitivity analyses. 
The specified sensitivity analysis was not 
reasonable as it was not possible to 
distinguish causes based on the original 
intent, and due to the amendment extending 
the trial causing some subjects to not consent 
to continuing in the trial. A modified NRI 
method has been introduced as a 
replacement together with appropriate MI 
method.  
14.3.5 
No split on response vs non-response 
based on the last assessment in parent 
trials. 
The last assessment is not necessarily 
representable of a fluctuating disease like 
AD and is conditioned by a lot of other 
factors, e.g. differing parent trial treatment 
periods and procedures. 
Abbreviations: AD = atopic dermatitis; CTP = clinical trial protocol; MI = multiple imputation; 
NRI = non-responder imputation. 
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7 
Supporting documentation 
7.1 
Tralokinumab naïve, re-treated, continuously treated, and 
washed-out subjects 
For summary tables grouped by tralokinumab naïve, re-treated, continuously treated subjects 
the grouping is based on the following principle: 
• Tralokinumab naïve subjects have not received any planned tralokinumab treatment in 
parent trial.  
• Continuously treated subjects have had a period shorter than 16 weeks (5 half-lives of 
tralokinumab) between last tralokinumab administration in parent trial and first 
tralokinumab administration in ECZTEND.  
• Re-treated subjects have had a period of 16 weeks or longer between last 
tralokinumab administration in parent trial and first tralokinumab administration in 
ECZTEND. Thus, full washout between treatment in ECZTEND and parent trial.  
The combined group of tralokinumab naïve and re-treated subjects, which consists of those 
new to tralokinumab or washed out from tralokinumab will be called ‘washed-out subjects’. 
As data from the TRA-WEI-0015-I study have not been transferred to this study, subjects 
from the study will not be classified in these groupings. 
7.2 
Safety areas of interest 
Two types of AESIs are defined: 
• AESI: ECZTEND defined AESI (defined in the CTP Panel 15). These AEs are marked 
by the investigator in the eCRF, and these AEs require additional details to be recorded 
in the eCRF. See Panel 6. 
• Tralokinumab ADRs: Defined using Adtralza® Company Core Data Sheet version 5.0, 
dated 14-Nov-2022. See Panel 7. 
The searches described in this document are based on MedDRA version 27.0. 
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Panel 6: AESI: ECZTEND defined AESI 
AESI* 
Description 
Eczema herpeticum 
No additional description  
Malignancy 
Diagnosed after treatment assignment, excluding basal 
cell carcinoma, localised squamous cell carcinoma of 
the skin, and carcinoma in situ of the cervix. 
Skin infections 
Requiring systemic treatment. 
Conjunctivitis** 
No additional description 
Keratoconjunctivitis** 
No additional description 
Keratitis** 
No additional description 
*: as defined in the CTP Panel 15; **: grouped in AESI ‘Eye disorders’ 
 
Panel 7: Tralokinumab’s ADRs 
ADRs 
Description 
Upper respiratory tract infection  
Preferred terms: Viral upper respiratory tract 
infection, Upper respiratory tract infection, 
Pharyngitis, Nasopharyngitis 
Injection site reactions  
All preferred terms under the high level term (HLT): 
Injection site reactions 
Eosinophilia  
Preferred terms: Eosinophilia, Eosinophil count 
increased 
Conjunctivitis/Conjunctivitis allergic  
Preferred terms: Conjunctivitis, Conjunctivitis allergic 
Keratitis 
Preferred terms: Keratitis 
 
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8 
References 
1. 
Lott A, Reiter JP. Wilson Confidence Intervals for Binomial Proportions With Multiple 
Imputation for Missing Data. The American Statistician. 2020;74(2):109-115. 
 
2. 
Beck LA, Thaçi D, Deleuran M, Blauvelt A, Bissonnette R, de Bruin-Weller M, Hide 
M, Sher L, Hussain I, Chen Z, et al. Dupilumab Provides Favorable Safety and 
Sustained Efficacy for up to 3 Years in an Open-Label Study of Adults with Moderate-
to-Severe Atopic Dermatitis. Am J Clin Dermatol. 2020;21(4):567-577. 
 
3. 
Lachin JM. Fallacies of last observation carried forward analyses. Clin Trials. 
2016;13(2):161-168. 
 
 
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