A single (assessor) blinded, randomized, parallel-group, monotherapy trial to evaluate the pharmacokinetics and safety of tralokinumab in children (age 6 to <12 years) with moderate to-severe atopic dermatitis.

In this study, the main purpose is to investigate what happens to the trial
drug in the body and to confirm that it is safe when used in children. The
medicine being tested is called Tralokinumab. It is approved in the European
Union, the United Kingdom and by the FDA for the treatment of
moderate-to-severe atopic dermatitis (also called eczema) in adults.

Tralokinumab is an antibody, a type of a biological drug, which binds to a
human protein called IL-13. IL-13 is involved in the body*s immune responses to
fight diseases. By binding to IL-13, tralokinumab may improve or clear the
symptoms of eczema.
Tralokinumab has already been tested in 26 clinical trials with more than 4,700
persons exposed to tralokinumab, including more than 300 adolescents.
These subjects were either healthy or had eczema or other chronic inflammatory
diseases.

Primary objective: To establish the PK profile after multiple SC
administrations of tralokinumab in children with moderate-to-severe AD.

Secondairy objectives:
- To assess the safety and tolerability of multiple SC administrations of
tralokinumab in children with moderate to-severe AD.
- To evaluate the efficacy of tralokinumab on severity and extent of AD, and on
patient-reported outcomes, in children with moderate-to-severe AD.

other objectives:
- To evaluate the efficacy of tralokinumab on severity and extent of AD, and on
patient-reported outcomes, in children with moderate-to-severe AD.

This is a single (assessor) blinded, randomized, parallel-group, monotherapy
trial to evaluate the PK and safety of tralokinumab in children (aged 6 to <12
years) with moderate-to-severe AD.
The trial will consist of a 2- to 6-week screening period, a 16-week initial
treatment period, a 52 week open-label treatment period, and a 14-week safety
follow-up period.
Subjects will be enrolled in 2 sequential age cohorts (cohort 1: 6 to <12
years; cohort 2: 2 to <6 years).

Screening period (Week -6/-2 to Week 0)
The screening period has a duration of 2 to 6 weeks depending on the need for
wash-out. Eligibility will be assessed at the screening visit and at baseline
prior to start of treatment.

Initial washout period: During the initial washout period the below atopic
dermatitis treatments are disallowed at the indicated timepoints prior to
baseline:
Not allowed 4 weeks prior to baseline: Use of tanning beds or phototherapy,
systemic immunosuppressive/immunomodulating drugs, systemic corticosteroid us
(excludes topical, inhaled, or intranasal delivery) and three or more bleach
baths during any week.
Not allowed 2 weeks prior to baseline: Topical PDE 4 inhibitors.
During the entire washout period, up untill start of the initial treat-ment
period at week 0, topical treatment with both corticosteroids and calcineurin
inhibitors would be allowed.

Initial treatment period (Week 0 to Week 16)
Approximately 28 subjects will enter baseline (6 to <12 years ) to receive
either a low fixed dose or a high fixed dose of tralokinumab. There will be at
least 24 subjects in the cohort. For each subject, the age and weight at
baseline will determine the dose for the entire duration of the trial.
The low dose and the high dose will not necessarily be the same in the 2
cohorts.
After the 2- to 6 week screening period, each cohort will be randomized 1:1 to
a 16 week treatment period. Doses will be administered by SC injection starting
with a loading dose of tralokinumab followed by either Q2W or Q4W dosing.
Cohort 1 (aged 6 to <12 years):
• Tralokinumab low dose, 12 subjects.
• Tralokinumab high dose, 12 subjects.

In the initial treatment period (Week 0 to Week 16), topical corti-costeroids
and topical calcineurin inhibitors are allowed as topical rescue treatment. If
these would be deemed to be inadequate, as outlined in above, treatment with
systemic corticosteroids is al-lowed as systemic rescue at the discretion of
the investigators. Use of biological rescue treatment and the use of JAK
inhibitors and non-steroidal systemic immunosuppressive drugs (cyclosporine,
methotrexate, mycophenolate mofetil, azathioprine etc.) for res-cue treatment
will be disallowed.

Open-label treatment period (Week 16 to Week 68)
After completion of Week 16 treatment, all subjects will roll-over to
open-label tralokinumab treatment with optional TCS (Panel 10). Subjects can
use mild to moderate strength TCS and/or TCI on lesional skin as needed at the
investigator's discretion. Subjects, who in the opinion of the subject, the
subject's caregiver, or the investigator have unacceptable treatment effect of
tralokinumab may discontinue treatment at any timepoint and enter the safety
follow up period.

In the open-label treatment period (Week 16 to Week 68), partic-ipants are
allowed to use mild to moderate topical corticosteroids and topical calcineurin
as needed, whereas high potency topical corticosteroids are allowed as topical
rescue treatment. If these would be deemed to be inadequate, as outlined in
above, treat-ment with systemic corticosteroids is allowed as systemic rescue
at the discretion of the investigators. Use of biological rescue treat-ment and
the use of JAK inhibitors and non-steroidal systemic immunosuppressive drugs
(cyclosporine, methotrexate, mycophe-nolate mofetil, azathioprine etc.) for
rescue treatment will be disallowed.

Long-term extension treatment period
After Week 68, subjects will continue in a long-term extension treatment
period until a global end-of-treatment visit on approximately 15-Jan-2026.
Treatment will be the same as during the open-label treatment period
(open-label tralokinumab treatment [150 mg Q2W] with optional TCS). Subjects
can use mild to moderate strength TCS and/or TCI on lesional skin as needed at
the investigator's discretion. Subjects, who in the opinion of the subject,
the subject's caregiver, or the investigator have unacceptable treatment
effect of tralokinumab may discontinue treatment at any timepoint and enter
the safety follow-up period. Visits will be performed every 6 weeks. Site
visits will be interchanged with phone
visits. Tralokinumab will be administered at home in between site visits, and
tralokinumab will be dispensed for this purpose at the site visits.

Safety follow-up period (Week 68 to 82)
After treatment completion or discontinuation of trial product, subjects will
enter a 14 week off-drug safety follow-up period for assessment of safety and
immunogenicity. During follow up, subjects will be allowed to receive standard
AD care (excluding biological treatments and JAK inhibitors) at the
investigator*s discretion, if needed.

14-week off-drug safety follow-up (Week 68 to Week 82), partici-pants are
allowed to use topical corticosteroids of any potency. In addition, other
topical medications used for the treatment of atopic dermatitis, such as
topical canlcineurin inhibitors, JAK inhibi-tors and PDE-4 inhibitors would be
allowed. Below atopic dermati-tis treatments would also be options during the
off-drug safety follow up:
1. Use of UVA or UVB, psoralen + UVA, other pho-totherapy, or tanning beds
2. 3 or more bleach baths per week
3. Systemic corticosteroid
4. Systemic treatment for AD with an immuno-suppressive/immunomodulating agent
(exam-ples include cyclosporine, mycophenolate mo-fetil, azathioprine,
methotrexate, and interfer-on-gamma)

Name of IMP: Tralokinumab
Active substance:
Dosage form: Syringe/vials
Concentration: 150mg/mL
Dose and method of administration:

Dose regimen for cohort 1 (6 to <12 years)
Dose level Low
dose High dose
Subject weight 17-<40 kg >=40 kg 17-<40
kg >=40 kg
Loading dose (Visit 3/Week 0) 300 mg 300 mg 300 mg 600 mg
Initial treatment period 150 mg Q4W 150 mg Q2W 150 mg Q2W 300 mg Q2W
Open-label treatment period 150 mg Q2W
Long term extension period 150mg Q2W

With more than 4,200 subjects exposed to tralokinumab in the completed clinical
trials in AD and additional diseases investigated, the benefit-risk ratio is
considered favorable and supports the administration of tralokinumab in adult
and adolescent subjects with moderate-to-severe AD.
In both the adult and the adolescent population, tralokinumab demonstrated
substantial improvements in a number of AD-relevant clinical parameters,
including improvements in IGA, EASI, SCORAD, and POEM. It is therefore
hypothesized that treatment with tralokinumab will result in similar
improvements in a younger population, such as children aged 2 to <12 years.

Based on the extensive clinical experience, a reassuring safety profile of
tralokinumab has been observed. No major safety concerns have been identified
and the use of tralokinumab has been well-tolerated. Generally, the overall
incidence of AEs reported for tralokinumab has been similar to that for placebo
in controlled clinical trials and the adverse drug reactions observed were
mainly non-serious and mild or moderate in severity. ADA have been detected in
only few adult subjects with AD exposed to tralokinumab for up to 1 year.
Subsequently to having demonstrated a favorable safety and efficacy profile in
adults, the efficacy and safety of tralokinumab has been investigated in an
adolescent population (age 12 to <18 years) in which 276 subjects were dosed
with tralokinumab. In this younger population, the safety profile was found to
be similar to what has previously been observed in the adult population.

In the present trial, subjects will be enrolled in 1 age cohorts, initially
securing exposure and safety data for subjects aged 6 to <12 years.

Appropriate measures have been instituted in this trial to protect subjects
from potential risks, such as:
• Exclusion of subjects with active or suspected endoparasitic infections, or
high risk of endoparasitic infection, unless clinical and (if necessary)
laboratory assessment have ruled out active infection before randomization;
neutralization of IL-13 might theoretically cause a worsening of parasitic
infestation, in particular prevention of expulsion of gastrointestinal worms
(helminths).
• Exclusion of subjects with active chronic or acute infection requiring
treatment with systemic antibiotics, antivirals, antifungals, or antiprotozoals
within 2 weeks before the baseline visit.

Altogether, the risks associated with participating in this trial are
considered low and outweighed by the benefit of potentially being able to treat
children with moderate-to-severe AD with tralokinumab. Pediatric patients
treated with dupilumab have been shown to have better outcomes than those not
treated with dupilumab. Considering the similar mechanisms of action with
tralokinumab and dupilumab and the demonstrated efficacy of tralokinumab in the
adult and adolescent populations, tralokinumab is expected to offer a similar
benefit in pediatric patients as that observed with dupilumab.