Intervention With Tralokinumab in Patients With Moderate-to-severe Atopic Dermatitis With Genital Impact
Conditions: Atopic Dermatitis (Moderate-to-severe) Involving the Genital Region
Sponsor: University Hospital Schleswig-Holstein

 
 
 
 
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Intervention with Tralokinumab in patients with moderate-to-severe Atopic 
Dermatitis with genital impact 
Version 1.1, 15.05.2025 
 
Sponsor 
Institute and Comprehensive Center for 
Inflammation Medicine (CCIM) of the 
University Medical Center Schleswig-
Holstein (UKSH), Campus Lübeck, Lübeck, 
Germany and Department of Dermatology 
of the University Hospital Augsburg (UKA), 
Augsburg, Germany. 
Sponsor (representative) 
UKSH/University of Lübeck 
Represented by Director of Institute 
Prof. Dr. med. Diamant Thaçi 
Principal Investigator 
Prof. Dr. med. Diamant Thaçi 
Protocol written  
Dr. med. Cristian Papara 
Inga Catharina Brouer 
Prof. Dr. med. Dr. h.c. Andreas Wollenberg 
In collaboration with 
Dr. rer. nat. Antje Maaß 
Dr. med. David Aldo De Luca Laredo 
Dr. med. Cristian Papara 
Julia Schumacher  
Lena Pommerien 
 
 

 
 
 
 
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Protocol Synopsis 
Study title 
A non-interventional, prospective 52-week clinical study investigating 
improvements in patient-reported outcomes (PROs) in individuals with 
moderate-to-severe atopic dermatitis (AD) involving the genital region, 
treated with tralokinumab as part of routine care. 
Hypothesis 
Treatment with tralokinumab in patients with moderate-to-severe AD 
involving the genital region is expected to lead to significant 
improvements in PROs and clinical disease severity. These 
improvements will be assessed using genital-specific scoring systems, 
validated PRO instruments, and non-invasive imaging techniques, 
including optical coherence tomography (OCT), confocal microscopy, or 
line-field optical coherence tomography (LC-OCT). 
Objectives 
To investigate improvements in genital scores and PROs in patients with 
moderate-to-severe AD involving the genital region during treatment 
with tralokinumab in routine clinical care. Clinical assessment of genital 
AD severity will be conducted using genital-specific scoring systems 
[e.g., Genital-Numerical Rating Scale (g-NRS), Genital-Investigator 
Global Assessment (g-IGA)], validated PRO instruments [e.g., Patient-
Oriented Eczema Measure (POEM), Atopic Dermatitis Control Tool 
(ADCT)], and non-invasive imaging techniques (e.g., confocal 
microscopy, OCT, LC-OCT). 
Study design 
This is a prospective, open, exploratory, non-randomized, non-blinded 
study. A total of 30 patients diagnosed with moderate-to-severe AD 
involving the genital region will be treated with tralokinumab in routine 
clinical care, in accordance with the tralokinumab Summary of Product 
Characteristics, over a period of 52 weeks. Data acquisition will take 
place at treatment initiation and during routine follow-up visits at 
baseline, week 4, week 16, week 24, and week 52. 
Timelines 
First patient first visit: October 2025 
Patient recruiting: 12 months 
Last patient last visit: October 2027 
Study Closure: June 2028 
Sample size 
A total of 30 patients with moderate-to-severe AD involving the genital 
region, for whom the clinical decision to initiate treatment with 
tralokinumab has been made independently of the study, will be offered 
enrollment. Patients will be recruited at two centers: approximately two-

 
 
 
 
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thirds at the Institute and Comprehensive Center for Inflammation 
Medicine (CCIM) of the University Medical Center Schleswig-Holstein 
(UKSH), Campus Lübeck, Lübeck, Germany and approximately one-
third at the Department of Dermatology of the University Hospital 
Augsburg (UKA), Augsburg, Germany. 
Study site 
location 
The study will be conducted at two centers: primarily at the Institute and 
Comprehensive Center for Inflammation Medicine at the University of 
Lübeck, Lübeck, Germany, and additionally at the Department of 
Dermatology, University Hospital Augsburg, Augsburg, Germany. 
Subject eligibility 
criteria 
Inclusion 
• 
Subjects must be able to understand and communicate with the 
investigator and comply with the requirements of the study and must 
give written, signed and dated informed consent before any study 
related activity is performed.  
• 
Subjects must be at least 18 years of age at time of enrollment. 
• 
Subjects starting treatment with tralokinumab and for whom the 
clinical decision has been made independent of the study according 
to licensed product specifications and treatment guidelines prior to 
participation in the study. 
• 
Subjects diagnosed with moderate-to-severe AD and genital 
involvement eligible for systemic therapy according to the local label. 
Subject eligibility 
criteria 
Exclusion 
• 
Exclusion criteria will comply with the licensed specifications for 
tralokinumab.  
• 
Subjects incapable of giving full informed consent.  
• 
Current participation in another study with any investigational 
products (noninterventional or registries are allowed).  
• 
Currently pregnant or nursing women will be excluded from this 
study. 
• 
Subjects without genital involvement. 
Early termination 
• 
Treatment failure, defined as no improvement or worsening of EASI 
at week 16. 
• 
Change in therapy. 
• 
More than 20% of the total treatment duration (i.e., >73 cumulative, 
non-consecutive days) without receiving the study drug. 
 
 

 
 
 
 
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Table of contents 
Protocol Synopsis ............................................................................................................ 2 
List of abbreviations ......................................................................................................... 5 
1. 
Background/Rationale ............................................................................................. 6 
2. 
Study Purpose ......................................................................................................... 7 
3. Study Objectives .......................................................................................................... 7 
4. 
Study Design ........................................................................................................... 8 
5. Study Population.......................................................................................................... 8 
5.1. Inclusion Criteria ................................................................................................... 8 
5.2. Exclusion Criteria .................................................................................................. 9 
5.3. Reproductive Status .............................................................................................. 9 
5.4. Management and Reporting of Adverse Events and Other Experiences ............... 9 
5.5. Recruitment of Study Participants ........................................................................12 
6. 
Study Timeline .......................................................................................................12 
7. 
Visit Schedule and Assessments ............................................................................12 
7.1. Procedures for Informing and Obtaining Consent .................................................12 
7.2. Study Methodology ...............................................................................................13 
7.3. First Visit ..............................................................................................................13 
7.4.1. Clinical, demographic and imaging assessments ...........................................14 
7.4.2. Clinical documentation and safety ..................................................................14 
7.4.3. Scores Assessing Clinical Signs ....................................................................15 
7.4.4. Scores Assessing Symptoms .........................................................................16 
7.4.5. Scores Assessing Quality of Life of Patients ..................................................17 
7.4.6. Imaging ..........................................................................................................19 
8. 
Data Handling ........................................................................................................20 
9. 
Termination of the Study ........................................................................................20 
10. Statistical analysis ..................................................................................................21 
11. References .............................................................................................................22 
 

 
 
 
 
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List of abbreviations 
AD         
    Atopic Dermatitis   
ADCT           Atopic Dermatitis Control Tool   
AE         
    Adverse Event   
BMI        
    Body Mass Index   
BSA            Body Surface Area   
CCIM           Comprehensive Center for Inflammation Medicine   
DLQI           Dermatology Quality of Life Index   
EASI           Eczema Area and Severity Index   
GCP            Good Clinical Practice   
g-IGA            Genital- Investigator Global Assessment 
g-NRS 
    Genital-Numeric Rating Scale 
HADS           Hospital Anxiety and Depression Scale   
IGA 
    Investigator Global Assessment 
IL-13      
    Interleukin-13   
l-SCORAD    localized SCORing Atopic Dermatitis 
LC-OCT        Line-field Optical Coherence Tomography   
MGISD         Mean Global Index of Sexual Dysfunction  
OCT            Optical Coherence Tomography   
POEM           Patient-Oriented Eczema Measure   
PRO            Patient-Reported Outcomes   
SAE            Serious Adverse Event   
SBQ-G          Sexual Behavior Questionnaire   
SCORAD      SCORing Atopic Dermatitis 
UKA            University Hospital Augsburg   
UKSH           University Medical Center Schleswig-Holstein 
   
 
 

 
 
 
 
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1. Background/Rationale 
Atopic dermatitis (AD) is a common, chronic, and highly pruritic inflammatory skin disease 
that significantly impacts quality of life and poses a considerable socioeconomic burden (1). 
It is often associated with reduced health-related quality of life, sleep disturbances, and 
impaired work productivity (2,3). 
Genital involvement in AD, reported in 10.3% to 45% of cases, can severely affect patients’ 
well-being, particularly sexual health (4, 5). However, genital examination is often omitted in 
routine clinical practice, and patients may hesitate to disclose symptoms in this area. As a 
result, genital AD remains frequently overlooked and under-reported. 
Tralokinumab is a fully human IgG4 monoclonal antibody that specifically neutralizes 
interleukin-13 (IL-13) by inhibiting its binding to IL-13 receptors (6). IL-13 plays a central role 
in AD pathogenesis and is a key driver of inflammation and skin barrier dysfunction (7). 
Tralokinumab is approved for the treatment of moderate-to-severe AD. 
Certain anatomical regions, such as the head and neck and the genital area, are considered 
difficult-to-treat areas in AD. While treatment efficacy in the head-and-neck region can be 
assessed retrospectively through regional EASI analysis, evaluating the impact of treatment 
on genital involvement and its associated patient-reported outcomes (PROs) requires 
prospective study designs. 
A post hoc analysis of adult patients with moderate-to-severe AD has shown that 
tralokinumab provides sustained improvement in head-and-neck involvement for up to four 
years, including in patients with severe baseline disease (8). These improvements were 
accompanied by enhanced quality of life, particularly regarding reductions in skin discomfort 
and feelings of self-consciousness or embarrassment due to visible skin involvement (8). 
In contrast, data on genital involvement remain limited. A recent case series by Paolino et al. 
suggested that tralokinumab may be particularly effective in this area (9). After four months 
of treatment in 12 patients with genital AD, the genital Investigator Global Assessment (IGA) 
score was reduced by approximately 60% (p = 0.001), with a median decrease from 3 to 1 (p 
= 0.001). 
Further studies with larger patient populations are warranted to confirm these findings, 
assess long-term clinical benefits, and investigate the corresponding improvements in 
patient-reported outcomes. 

 
 
 
 
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2. Study Purpose 
This study aims to investigate improvements in genital PROs in patients with moderate-to-
severe AD involving the genital region during treatment with tralokinumab in routine clinical 
care over a 52-week period. Additionally, the study will assess changes in both local (genital-
specific) and general clinical scoring systems, as well as evaluate skin changes using non-
invasive imaging techniques such as confocal microscopy, optical coherence tomography 
(OCT), or line-field optical coherence tomography (LC-OCT). 
3. Study Objectives 
Primary Endpoint 
Improvement of ≥50% in Genital-Numerical Rating Scale 
(g-NRS) or ≥2 points in Genital-Investigator Global 
Assessment (g-IGA) in patients with moderate-to-severe 
AD treated with tralokinumab over a 52-week period. 
Secondary Endpoints 
Improvement in general PRO instruments [e.g., Patient-
Oriented Eczema Measure (POEM), Atopic Dermatitis 
Control Tool (ADCT), Dermatology Life Quality Index 
(DLQI), Hospital Anxiety and Depresssion Scale (HADS)] 
in patients with moderate-to-severe AD undergoing 
treatment with tralokinumab over a 52-week period. 
Improvement in overall disease severity [e.g., Eczema 
Area and Severity Index (EASI), SCORing Atopic 
Dermatitis (SCORAD), Investigator Global Assessment 
(IGA)] in patients with moderate-to-severe AD 
undergoing treatment with tralokinumab over a 52-week 
period. 
Exploratory assessment of skin changes using non-
invasive imaging techniques (OCT, confocal microscopy, 
or LC-OCT) will be performed, where feasible and 
acceptable to participants, in patients with moderate-to-
severe AD receiving tralokinumab over a 52-week period. 
Imaging will be conducted at both centers. Image 
analysis will be carried out at the Department of 
Dermatology, University Hospital Augsburg (UKA), 
Augsburg, Germany. 

 
 
 
 
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4. Study Design 
This is a prospective, open-label, exploratory, non-randomized, non-blinded study. A total of 
30 patients diagnosed with moderate-to-severe AD involving the genital region will be treated 
with tralokinumab as part of routine clinical care, in accordance with the Summary of Product 
Characteristics for tralokinumab, over a 52-week period. 
Tralokinumab is prescribed in accordance with the terms of its marketing authorization. The 
decision to prescribe tralokinumab is clearly independent of the decision to include the patient 
in the study. The medicinal product is obtained through standard distribution channels. 
Data will be collected at treatment initiation and during routine follow-up visits at baseline, week 
4, week 16, week 24, and week 52. 
5. Study Population  
The study will consist of a total of 30 patients (both male and female) with moderate-to-
severe AD involving the genital region, for whom the clinical decision to initiate treatment with 
tralokinumab has been made independently of the study in accordance with the terms of the 
marketing authorization and local clinical guidelines. Patients will be recruited at two centers: 
approximately two-thirds at the Institute and Comprehensive Center for Inflammation 
Medicine (CCIM) of the University Medical Center Schleswig-Holstein (UKSH), Campus 
Lübeck, Lübeck, Germany, and approximately one-third at the Department of Dermatology of 
the UKA, Augsburg, Germany.  
Participation in the study is entirely voluntary, and subjects may withdraw at any time without 
providing a reason and without any consequences to their ongoing medical care. 
5.1. Inclusion Criteria 
The investigator must ensure that only patients who meet the following inclusion criteria and 
do not fulfill any of the exclusion criteria are offered enrollment in the study. 
Subjects eligible for inclusion in this study must fulfill all of the following criteria: 
• 
Subjects must be able to understand and communicate with the investigator and 
comply with the requirements of the study and must give written, signed and dated 
informed consent before any study related activity is performed.  
• 
Subjects must be at least 18 years of age at time of enrollment. 

 
 
 
 
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• 
Subjects starting treatment with tralokinumab and for whom the clinical decision has 
been made independent of the study according to licensed product specifications and 
treatment guidelines prior to participation in the study.  
• 
Subjects diagnosed with moderate-to-severe AD and genital involvement eligible for 
systemic therapy according to the local label. 
5.2. Exclusion Criteria 
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study:  
• 
Subjects not fullfilling the approved (licensed) indication for treatment with 
tralokinumab.  
• 
Subjects incapable of giving full informed consent.  
• 
Current 
participation 
in 
another 
study 
with 
any 
investigational 
products 
(noninterventional or registries are allowed).  
• 
Currently, pregnant and nursing women, or those planning to become pregnant or 
breastfeed, will be excluded from this study. 
• 
Subjects without genital involvement. 
5.3. Reproductive Status 
Data on tralokinumab use during pregnancy are limited. Animal studies have shown no 
evidence of reproductive toxicity; however, as a precaution, use during pregnancy should be 
avoided. It is unknown whether tralokinumab is excreted in human milk; therefore, use during 
lactation is not recommended. Regarding fertility, animal studies revealed no adverse effects 
on male or female reproductive organs or on sperm parameters (count, motility, or 
morphology).  
5.4. Management and Reporting of Adverse Events and Other Experiences 
An Adverse Event (AE) is defined, in accordance with Good Clinical Practice (GCP) 
regulations, as any novel medical occurrence or worsening of a preexisting medical condition 
in a participant that does not necessarily have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of investigational product, 
whether or not considered related to the investigational product. 
The causal relationship of AEs to the study drug is determined by a physician for all AEs. The 
causal relationship can be one of the following:  

 
 
 
 
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Related: There is a reasonable causal relationship between study drug administration and the 
AE. The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship. 
Not related: There is not a reasonable causal relationship between study drug administration 
and the AE. 
Following the subject’s written consent to participate in the study, all non-serious AEs and 
Serious Adverse Event (SAEs), whether related or not related to study drug, are collected and 
will be reported as described in the following sections. 
A non-serious AE is an AE not classified as serious. The collection of non-serious AE 
information begins following the subject’s written consent to participate in the study. All non-
serious adverse events (not only those deemed to be treatment-related) should be collected 
continuously during the treatment period and for a minimum of 30 days following the last dose 
of study treatment. Non-serious AEs should be followed to resolution or stabilization, or 
reported as SAEs if they become serious. Follow-up is also required for non-serious AEs that 
cause interruption or discontinuation of study drug and for those present at the end of study 
treatment as appropriate. Non-serious AE are to be provided to BMS and to health authorities 
as per applicable law. AEs will be reported by using the adverse event reporting form and will 
be documented within the case report form. 
A SAE is defined, in accordance with GCP regulations, as any medical occurrence that at any 
dose: 
• 
results in death 
• 
is life-threatening (defined as an event in which the participant was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe 
• 
requires inpatient hospitalization or causes prolongation of existing hospitalization 
• 
results in persistent or significant disability/incapacity  
• 
is a congenital anomaly/birth defect 
• 
is an important medical event (defined as a medical event(s) that may not be 
immediately life-threatening or result in death or hospitalization but, based upon 
appropriate medical and scientific judgment, may endanger the subject or may require 
intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed 
in the definition above. Examples of such events include, but are not limited to, 
intensive treatment in an emergency room or at home for allergic bronchospasm; blood 
dyscrasias or convulsions that do not result in hospitalization. 

 
 
 
 
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The following hospitalizations are not considered SAEs in this study: 
• 
a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)  
• 
elective surgery, planned prior to signing consent  
• 
admissions as per protocol for a planned medical/surgical procedure  
• 
routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)  
• 
Medical/surgical admission other than to remedy ill health and planned prior to entry 
into the study. Appropriate documentation is required in these cases.  
• 
Admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason). 
 
A SAE report will be completed for any event where doubt exists regarding its seriousness and 
for the above-mentioned criteria. In this trial SAEs will be documented following the subject´s 
written consent to participate in the study through 30 days of discontinuation of dosing and the 
completed report will be sent within 24 hours of awareness to LEO Pharma Global Safety via 
drug.safety@leo-pharma.com in the form of a list according to current regulations. If a follow-
up SAE report is necessary, SAE changes in its intensity or relationship to study drug or if new 
information becomes available, a follow-up SAE report will be sent within 24 hours of 
awareness to drug.safety@leo-pharma.com. All SAE will be followed to resolution or 
stabilization.  
Pregnancy 
After initiation of the investigational product, it is subsequently discovered that a study 
participant is pregnant or may have been pregnant at the time of investigational product 
exposure, the investigational product will be immediately and permanently discontinued. 
A pregnancy will be reported to LEO Pharma Global Safety and the completed report will be 
sent within 24 hours of awareness to drug.safety@leo-pharma.com. 
Any pregnancy that occurs in a female partner of a male study participant will be reported to 
LEO Pharma if the female partner has signed an informed consent for disclosure of pregnancy 
information. Follow-up information regarding the course of the pregnancy, including perinatal 
and neonatal outcome and, where applicable, offspring information must be reported to LEO 
Pharma. 
Product Quality Complaints 
Product Quality Complaints are any communication about Tralokinumab that alleges 
deficiencies related to identity, quality, durability, reliability, safety, effectiveness, performance, 

 
 
 
 
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tampering, diversion, or counterfeiting/falsification of a drug, combination product, or device 
after it is released for distribution to market or clinic by either: (1) LEO Pharma or (2) distributors 
or partners for whom LEO Pharma manufactures the material. This includes all components 
co-packaged with the drug, such as drug containers, delivery system, labelling, and inserts.  
Product Quality Complaints will be reported to LEO Pharma within one business day of 
awareness. The report should include as much product information as possible (e.g. 
description of quality complaint, impacted batch number, photographs). 
The affected product will be quarantined immediately at the investigational site and should not 
disposed unless retention presents a risk to personnel (e.g. cytotoxic).  
5.5. Recruitment of Study Participants 
Recruitment is expected to take approximately 12 months. Eligible patients will be identified 
and recruited at two study sites: approximately two-thirds at the Institute and CCIM of the 
UKSH, Campus Lübeck, Lübeck, Germany, and approximately one-third at the Department of 
Dermatology of the UKA, Augsburg, Germany. 
Eligible patients are those initiating systemic treatment with tralokinumab for moderate-to-
severe AD, independently of the study, as part of routine clinical care. Patients are identified 
by their treating physician and are informed about the study during regular consultation hours. 
Initial study information is provided through a short information leaflet (Kurzinformation). 
6. Study Timeline 
The study is planned to commence with the first patient’s first visit in October 2025. The 
recruitment period will span 12 months, during which eligible patients will be screened and 
enrolled. The last patient’s last visit is anticipated in October 2027. Following this, data analysis 
and reporting will be conducted, with study closure expected by June 2028. 
7. Visit Schedule and Assessments 
7.1. Procedures for Informing and Obtaining Consent 
Eligible patients will be asked during their regular consultation whether they are interested in 
participating in the study. If they express interest, they will receive detailed written patient 
information and a general introduction to the study. Patients will be informed both verbally 
and in writing. Sufficient time will be provided for them to review the study information, 
consider their participation, and ask any questions during or after the consultation. If the 
patient decides to participate, the informed consent form will be signed and dated by both the 
patient and the physician. The study will only commence after full and independent informed 

 
 
 
 
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consent has been obtained. Written informed consent is a mandatory prerequisite for study 
participation. 
7.2. Study Methodology 
The study involves clinical documentation, clinical scoring, PRO instruments, safety 
monitoring, and imaging techniques including OCT, confocal microscopy, or LC-OCT. 
Local/genital assessment tools include the patients‘ g-NRS, g-IGA, the Lindenmeyer Sexuality 
Questionnaire, the Sexual Behavior Questionnaire (SBQ-G), and the localized SCORAD (l-
SCORAD). 
Clinical 
scores 
include 
the 
EASI, 
IGA, 
SCORAD. 
Patient-reported outcomes will be assessed using the DLQI, POEM, ADCT, and HADS. 
7.3. First Visit                                                                                                                     
During the regular consultation, participants will be screened for eligibility according to the 
inclusion and exclusion criteria. A complete physical examination will be performed, and 
eligibility for treatment with tralokinumab will be assessed. Informed consent will then be 
obtained and signed by both the participant and the physician. 
Following consent, clinical documentation will be completed, including demographics, disease 
history, concomitant medications, clinical scores, and patient-reported outcomes. Imaging 
assessments will also be conducted. Upon completion of baseline assessments, participants 
will begin treatment with tralokinumab as per the product's summary of characteristics. 
7.4. Schedule of Visits 
The schedule of visits, including timelines for clinical documentation, clinical scoring, patient 
questionnaires, and imaging procedures, is outlined in Table 1. All procedures listed in Table 
1 represent standard clinical assessments routinely performed in the care of patients with 
atopic dermatitis. The Genital-Investigator Global Assessment (g-IGA) is a scale used to 
evaluate the severity of genital skin inflammation in affected patients. Assessment of skin 
changes using non-invasive imaging techniques (OCT, confocal microscopy, or LC-OCT) will 
be performed, where feasible and acceptable to participants. OCT is a non-invasive, non-
injurious imaging modality that is safe for patients and is frequently employed in routine 
dermatological care. Imaging will be conducted at both centers. Image analysis will be 
carried out at the Department of Dermatology, UKA, Augsburg, Germany. 
Table 1: Schedule of visits, clinical documentation, clinical scores, patient 
questionnaires, and imaging. 

 
 
 
 
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Visit 
1 
2 
3 
4 
5 
Week 
0 
4 
16 
24 
52 
Procedure: 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
Confirmation of eligibility 
X 
 
 
 
 
Patient demographics  
X 
 
 
 
 
Medical history, prior and concomitant therapies 
as well as surgeries 
X 
 
 
 
 
Weight, Height, body mass index (BMI) 
X 
 
 
 
 
Genital-Investigator Global Assessment (g-IGA) 
X 
X 
X 
X 
X 
Eczema Area and Severity Index (EASI) 
X 
X 
X 
X 
X 
Investigator Global Assessment (IGA) 
X 
X 
X 
X 
X 
SCORing Atopic Dermatitis (SCORAD) 
X 
X 
X 
X 
X 
Localized SCORing Atopic Dermatitis (l-SCORAD) 
X 
X 
X 
X 
X 
Genital-Numeric Rating Scale (g-NRS) 
X 
X 
X 
X 
X 
Sexuality Questionnaire Lindenmeyer 
X 
X 
X 
X 
X 
Sexual Behavior Questionnaire (SBQ-G) 
X 
X 
X 
X 
X 
Dermatology Life Quality Index (DLQI) 
X 
X 
X 
X 
X 
Patient-Oriented Eczema Measure (POEM) 
X 
X 
X 
X 
X 
Atopic Dermatitis Control Tool (ADCT) 
X 
X 
X 
X 
X 
Hospital Anxiety and Depression Scale (HADS) 
X 
 
X 
 
X 
Non-invasive imaging* 
X 
X 
X 
X 
X 
*Exploratory assessment of skin changes using non-invasive imaging techniques (OCT, 
confocal microscopy, or LC-OCT) will be performed, where feasible and acceptable to 
participants. Imaging will be conducted at both centers. Image analysis will be carried out at 
the Department of Dermatology, UKA, Augsburg, Germany. 
7.4.1. Clinical, demographic and imaging assessments 
The following assessments will be conducted during the study. Items 1 to 5 focus on gathering 
general patient information. Clinical signs will be assessed using the g-IGA, EASI, IGA, 
SCORAD and l-SCORAD for the genital area. Symptoms will be evaluated with the Genital-
NRS. Quality of life will be assessed using the Sexuality Questionnaire Lindenmeyer, SBQ-G, 
DLQI, POEM, ADCT, and HADS. 
7.4.2. Clinical documentation and safety 
Clinical Documentation & Safety will be asked at first visit on week 0 and until week 52 
depending on the item. Data is consisting of:  
• 
Date of birth / age  
• 
Gender  
• 
Medical/Surgical history and previous medications  
• 
Adverse Events / SAEs  
• 
Concomitant therapy  
• 
Initial diagnosis of AD 
• 
AD treatment history  

 
 
 
 
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• 
Weight  
• 
Height  
Patients’ height will be measured and documented in the beginning, the weight throughout the 
study. The body mass index (BMI) will be calculated using the formula.  
BMI= (weight in kilograms / (height in meters x height in meters)). 
 
7.4.3. Scores Assessing Clinical Signs 
The following scores will be recorded at baseline and at each scheduled follow-up visit 
throughout the study. 
Genital-Investigator Global Assessment (g-IGA) 
The g-IGA is a clinician-reported tool used to assess the severity of genital involvement in AD, 
as previously described (9). It utilizes a 5-point scale developed, incorporating morphological 
criteria: 
• 
0 – Clear: No signs of inflammation (e.g., erythema, induration, lichenification, 
oozing, or crusting). Postinflammatory hyper-/hypopigmentation may be present. 
• 
1 – Almost Clear: Minimal erythema and slight induration or lichenification; no oozing 
or crusting. 
• 
2 – Mild: Mild erythema (pink), slight induration or lichenification; no oozing or 
crusting. 
• 
3 – Moderate: Noticeable erythema (dull red), induration, or lichenification; 
oozing/crusting may occur. 
• 
4 – Severe: Marked erythema (bright/deep red), pronounced thickening, and/or 
widespread lesions; oozing or crusting may be present. 
Eczema Area and Severity Index (EASI) 
The EASI is used to assess the severity and extent of signs of AD in patients. It evaluates four 
key parameters: Erythema, infiltration, excoriation, and lichenification, each rated on a scale 
of 0 to 3 (0 = none, 3 = severe). These parameters are assessed across four body regions: 
Head/neck, upper limbs, trunk, and lower limbs.  

 
 
 
 
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The total EASI score is calculated by combining the severity of the four parameters with the 
affected body surface area (BSA) (expressed as a percentage of the total body surface area). 
The resulting score ranges from 0 to 72, with higher scores indicating more severe eczema. 
Investigator’s Global Assessment (IGA)                                                                                           
The IGA is a clinician-assessed scale used to evaluate the overall severity of AD. The IGA is 
based on a visual inspection of the patient’s skin and is rated on a 5-point scale: 
0 = Clear (no signs of AD) 
1 = Almost Clear (few residual lesions) 
2 = Mild (slight redness, itching, and/or scaling) 
3 = Moderate (moderate redness, itching, and/or scaling) 
4 = Severe (intense redness, itching, scaling, and/or thickened skin) 
SCORing Atopic Dermatitis (SCORAD) 
The SCORAD is a validated clinical tool used to assess the extent and severity of AD. It 
integrates both objective clinical signs and patient-reported symptoms into a composite score 
ranging from 0 to 103. The extent of the disease is calculated using the "rule of nines" to 
estimate the percentage of body surface area affected. Intensity is assessed based on six 
clinical signs: erythema, edema/papulation, excoriation, lichenification, oozing/crusts, and 
dryness, each scored on a 4-point scale: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. 
Subjective symptoms, specifically pruritus and sleep disturbance, are recorded by the patient 
using visual analogue scales ranging from 0 to 10.  
Localized SCORAD for the Genital Area (l-SCORAD) 
The l-SCORAD is an adapted version of the SCORAD designed to evaluate the severity of AD 
in the genital area. This tool focuses solely on the intensity of skin lesions within the localized 
site and excludes overall body surface area and patient-reported symptoms. The same six 
clinical signs (erythema, edema/papulation, excoriation, lichenification, oozing/crusts, and 
dryness) are assessed and scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = 
severe).  
7.4.4. Scores Assessing Symptoms 
The following scores will be recorded at baseline and at each scheduled follow-up visit 
throughout the study. 

 
 
 
 
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Genital-Numeric Rating Scale (Genital-NRS) 
The Genital Numeric Rating Scale (g-NRS) is a patient-reported measure that subjectively 
assesses the severity of genital involvement in AD on a scale from 0 to 10, as previously 
described (9).  
Patient-Oriented Eczema Measure (POEM) 
The POEM is a questionnaire designed to evaluate the symptoms of AD over the past week. 
It consists of seven questions addressing symptoms such as itching, sleep disturbance, 
bleeding, oozing, skin cracks, scaling, and dryness. For each question, the patient indicates 
the number of days in the past week they experienced the symptom (0 to 7 days). Each 
response is scored from 0 to 4 (0 = no days, 4 = every day), and the total score is the sum of 
these individual scores. The total score ranges from 0 to 28, with higher scores reflecting a 
greater symptom burden and more severe disease.  
Atopic Dermatitis Control Tool (ADCT) 
The ADCT is a patient-reported measure to assess the control of AD symptoms over the past 
week. It includes six questions on itching, sleep disturbance, daily activities, and emotional 
impact, with responses scored from 0 to 4 (0 = no symptoms, 4 = extreme symptoms). The 
total score, ranging from 0 to 24, indicates the level of control. A score of 7 or higher, or an 
increase of 5 points or more since the last assessment, suggests poor disease control.  
7.4.5. Scores Assessing Quality of Life of Patients 
The following scores will be recorded at baseline and at each scheduled follow-up visit 
throughout the study, except for the HADS, which will be assessed at Visits 1, 3, and 5 only. 
Sexuality Questionnaire Lindenmeyer 
The Sexuality Questionnaire Lindenmeyer is designed to assess various aspects of an 
individual's sexual health and well-being. It includes questions about the respondent's 
relationship status, satisfaction with their partnership, and the frequency of sexual contact. It 
also explores the individual's sexual behaviour, including their satisfaction with sexual activity 
and whether they use contraception. The questionnaire addresses any perceived sexual 
problems, including whether these issues may be related to alcohol or drug use. Finally, it asks 
whether the individual has sought medical or psychological treatment for sexual difficulties in 
the past and whether they currently wish for help in managing these issues. Through a 
combination of multiple-choice and open-ended questions, the questionnaire collects 
information to better understand the respondent's sexual health and identify areas where 
therapeutic support may be needed. 

 
 
 
 
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Sexual Behaviour Questionnaire SBQ-G 
The SBQ-G is a standardized tool used to assess sexual function and satisfaction over the 
past three months. It includes questions on various aspects of sexuality, such as sexual desire, 
frequency of sex and masturbation, arousal, enjoyment, and overall satisfaction. Additionally, 
it addresses specific sexual problems like erectile dysfunction in men, premature or delayed 
ejaculation, orgasm ability in women, and pain during intercourse. For men, the questionnaire 
also includes questions about the ability to achieve and maintain an erection, as well as 
satisfaction with orgasm. For women, it covers orgasm frequency and satisfaction, pain during 
sex, and menstrual regularity. Responses are scored on a scale from 0 to 3, and a Mean Global 
Index of Sexual Dysfunction (MGISD) is calculated by summing specific items and computing 
a weighted average. Higher scores indicate greater sexual dysfunction.  
Dermatology Life Quality Index (DLQI) 
The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six 
domains including symptoms and feelings, daily activities, leisure, work and school, personal 
relationships and treatment (10). The DLQI has a one-week recall period. 
Response categories include: 
not relevant = score of 0 
not at all = score of 0 
a little = score of 1 
a lot = score of 2 
very much = score of 3 
 
The DLQI will be self-administered by the patient at visits indicated in the activity schedule. 
The DLQI will be analyzed under six headings (10 questions) as follows: 
Table 2: Analysis of DLQI. 
Domain 
Question number  
Score  
Symptoms and feelings 
Question 1 and 2 
Score maximum 6 
Daily activities 
Question 3 and 4 
Score maximum 6 
Leisure 
Question 5 and 6 
Score maximum 6 
Work and school 
Question 7 
Score maximum 3 
Personal relationships 
Question 8 and 9 
Score maximum 6 
Treatment 
Question 10 
Score maximum 3 
Hospital Anxiety and Depression Scale (HADS) 
The HADS is a self-report tool designed to assess the levels of anxiety and depression 
experienced over the past week. Participants are asked to select a score between 0 and 3 for 

 
 
 
 
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each statement. The scale includes questions related to feelings of tension, enjoyment, 
restlessness, and panic. Based on the total scores, the results are interpreted as follows: A 
score between 0 and 7 indicates normal levels, 8 to 10 suggests borderline abnormal levels, 
and a score between 11 and 21 indicates abnormal levels, which may require further 
evaluation. This tool helps to identify individuals who may be experiencing anxiety or 
depression, aiding in the decision for further assessment or intervention. 
7.4.6. Imaging 
Assessment of skin changes using non-invasive imaging techniques (OCT, confocal 
microscopy, or LC-OCT) have become an optional routine analysis of inflammatory skin 
diseases and will be performed on an availability-dependent basis. These assessments will be 
conducted depending on patient willingness and availability at the respective visits. Confocal 
microscopy, OCT, and LC-OCT will be performed at the Department of Dermatology, 
University Hospital Augsburg (UKA), Germany. OCT will also be conducted at the Institute and 
CCIM, University Hospital Schleswig-Holstein (UKSH), Lübeck, Germany. 
All imaging data will be analyzed at the Department of Dermatology in Augsburg. To facilitate 
this, anonymized image data will be securely transferred to Augsburg on encrypted storage 
devices for extraction and analysis. 
Confocal microscopy 
Confocal microscopy is a high-resolution imaging technique, allowing non-invasive 
examination of skin, mucosa, hair, and nails (11). In dermatology, confocal microscopy is 
effective for identifying various cutaneous infections and infestations, as well as for monitoring 
treatment progress (12).  
OCT Imaging 
The VivoSight OCT System (Michelson Diagnostics Ltd, Kent, UK) will be utilized in this study. 
According to the manufacturer’s specifications, the laser product is laser class 1 and eye safe 
meaning that safety goggles are not required. The emission wavelength is 1.305 nm. The 
optical resolution is <7.5 μm lateral and <5 μm axial. The scan area is 6 mm x 6 mm. The 
penetration depth is about 1-2 mm. Images will be acquired as vertical B-scans and en-face 
scans. The images will be saved as TIFF, TIFF stack, and DICOM formats. OCT scans will be 
obtained of a non-lesional skin site and a lesional skin site at investigaors and subjects 
discretion: 
• 
The non-lesional skin site will be at the left or right volar forearm. The same skin site 
will be used for all evaluations throughout the study. A body map will be used for 
reference so that the location is used consistently for all subsequent evaluations. 

 
 
 
 
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• 
The AD lesional skin site will be at predilection site e.g. at the elbow. The same skin 
site will be used for all evaluations throughout the study. A body map will be used for 
reference so that the location is used consistently for all subsequent evaluations. 
LC-OCT Imaging 
The LC-OCT is a non-invasive imaging technique that combines the depth penetration of OCT 
with the high lateral resolution of confocal microscopy, allowing for real-time, high-resolution 
visualization of skin architecture in both cross-sectional and en-face modes. 
8. Data Handling 
During the study, the protocol and GCP guidelines will be strictly followed. Study data will be 
initially documented as source data in the patient’s medical records and study-specific 
documents by the designated study personnel immediately after each visit.Pseudonymized 
data, using identifiers such as 'P01' for Lübeck and 'P51' for Augsburg, followed by the 
corresponding visit number (e.g., P01V2), will be annotated and transferred to a paper-based 
case report form. Pseudonymized data will also be stored electronically using Microsoft Excel. 
Standard security measures for using Microsoft Excel will be implemented, including password 
protection of files, restricted access to authorized personnel only, regular data backups, and 
storage on secure, access-controlled institutional servers to ensure data confidentiality and 
integrity. To minimize transcription and transfer errors, a two-step internal monitoring process 
will be implemented: a second independent study team member will review and verify all data 
entries on the CRFs against the original source documents, as well as the electronic entries 
against the paper CRFs. Any discrepancies identified will be resolved promptly through source 
data verification. All source data will remain at the Institute and CCIM Lübeck. Electronic data 
may be exchanged between the UKSH, Campus Lübeck, and the UKA Augsburg via secure 
systems and may be accessed by authorized study personnel for analysis. Image analysis will 
be carried out at the Department of Dermatology, UKA, Augsburg, Germany. Access to 
electronic data will be restricted to authorized study personnel only.  
9. Termination of the Study 
Study participation may be discontinued early in the following cases:  
• 
if treatment failure occurs, defined as no improvement or a worsening of the EASI score 
at week 16. 
• 
if there is a change in therapy. 
• 
if the participant misses more than 20% of the total treatment duration, corresponding 
to more than 73 cumulative, non-consecutive days without receiving the study drug. 

 
 
 
 
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10. Statistical analysis 
Descriptive and inferential statistical analyses will be conducted to evaluate the efficacy of 
tralokinumab in patients with moderate-to-severe AD over a 52-week period. For the primary 
endpoint, changes in genital/local patient-reported outcome (PRO) instruments (e.g., Genital-
NRS) will be analyzed using paired t-tests or Wilcoxon signed-rank tests, depending on data 
distribution, to assess within-subject improvement from baseline to week 52. Repeated 
measures ANOVA or mixed-effects models may be applied to assess longitudinal trends over 
multiple time points. For the secondary endpoints, similar methods will be used to analyze 
changes in general PROs (e.g., POEM, ADCT, DLQI, HADS) and clinical severity scores (e.g., 
EASI, SCORAD, IGA). Missing data will be handled using appropriate imputation methods or 
sensitivity analyses. For the exploratory imaging analyses, changes in structural and 
morphological features as measured by confocal microscopy and OCT will be evaluated 
descriptively and, where possible, compared over time using non-parametric tests or image-
derived quantitative metrics. All statistical tests will be two-sided, and a p-value of <0.05 will 
be considered statistically significant. All questionnaires and clinical scores used in this study, 
except the newly developed Genital-Investigator Global Assessment (g-IGA), are standardized 
and validated instruments widely applied in dermatological research and practice. The 
selection of these instruments was made by Prof. Dr. Andreas Wollenberg and Prof. Dr. 
Diamant Thaci in consultation with Prof. Dr. Uwe Gieler to ensure clinical relevance. Prof. 
Gieler will also be involved in the data analysis to ensure appropriate interpretation of the 
results.
 
 
 
 
 
 
 
 
 

 
 
 
 
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11. References 
 
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2020 position paper on diagnosis and treatment of atopic dermatitis in adults and 
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