A phase 3 multi-center trial to evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids in children (age 2 to <12 years) and infants (age 6 months to <2 years) with moderate-to-severe atopic dermatitis. The trial is randomized, double blind, placebo-controlled, and parallel-group for children (age 2 to <12 years) and open-label and single-group for infants (age 6 months to <2 years).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leo Pharma A/S

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

20 Nov 2024 → ongoing

Decision date (initial)

2024-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

LEO Pharma A/S

External identifiers

EU CT number

2023-503630-44-00

WHO UTN

U1111-1285-6559

ClinicalTrials.gov

NCT06311682

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of this trial is to evaluate whether tralokinumab+TCS provides more effective control of the skin manifestations of AD than placebo+TCS in subjects aged 2 to <12 years. In addition, key secondary endpoints are included that address symptom scores and extent of AD, severity of itching or scratching, the impact of AD on the subjects’ quality of life, and the impact of AD on the subjects’ and their caregiver’s daily life and well-being in subjects aged 2 to <12 years. As an exploratory component, this trial will also investigate the impact of tralokinumab+TCS on skin colonization with Staphylococcus aureus and stratum corneum lipid composition (an indirect measure of skin barrier function) in subjects aged 2 to <12 years.

Secondary objectives 1

1. The objectives and endpoints will be evaluated separately in subjects aged 2 to <12 years and subjects aged 6 months to <2 years. All objectives and endpoints will be considered secondary for subjects aged 6 months to <2 years as there will be no placebo-comparison in this cohort and the endpoints will not be subject to multiplicity adjustment.

Conditions and MedDRA coding

Treatment of moderate-to-severe Atopic dermatitis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001900-PIP02-17

Plan to share IPD

No

IPD plan description

Not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Signed and dated informed consent
2. 2. Age 6 months to <12 years at screening, with the following exceptions for countries outside of North America (US/Canada): • Age 2 years to <12 years at screening in the EU and the UK. • Age 6 years to <12 years at screening in South-Korea.
3. 3. Body weight ≥9 kg at screening
4. 4. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (27)
5. 5. History of AD for: • ≥12 months for subjects aged ≥6 years at screening. • ≥3 months for subjects aged 6 months to <6 years at screening
6. 6. Documented inadequate response* to mid-strength** TCS within 6 months before the screening visit. * Inadequate response to topical treatment is defined as either of the below: • Failure to achieve and maintain remission or low disease activity state despite topical AD treatment. • Documented systemic treatment for AD within 6 months before the screening visit. ** Mid-strength TCS is defined as below, see Section 10.4 for details: • Europe: TCS classified as ‘Potent (Class 3)’ or ‘Very potent (Class 4)’. • US: TCS classified as ‘Moderate (Class 4)’, ‘High (Class 2 or 3)’, or ‘Ultra-high (Class 1)’
7. 7. AD involvement of ≥10% body surface area at screening and baseline according to component A of SCORAD
8. 8. An EASI score of ≥16 at screening and baseline
9. 9. An IGA score of ≥3 at screening and baseline
10. 10. A Child Worst Itch NRS average score* of ≥4 (subjects aged ≥6 years at screening) or a Scratch ObsRO average score* of ≥4 (subjects aged <6 years at screening) during the week prior to baseline. * Average Child Worst Itch NRS and average Scratch ObsRO at baseline will be calculated from daily assessments of each score during the 7 days immediately preceding baseline. Scores must be provided on at least 4 days during the 7 days immediately preceding baseline to calculate the baseline average score. For subjects who do not provide scores on at least 4 days during the 7 days immediately preceding the planned baseline date, randomization or assignment to treatment should be postponed until this requirement is met, but without exceeding the 4 weeks’ maximum duration for screening
11. 11. Subject and caregiver(s) are able to comply with clinic visits and trial requirements and procedures, as assessed by the investigator
12. 12. Female subjects who have been assessed by the investigator to be of childbearing potential (i.e. post-menarcheal and not permanently sterile, see Section 10.3.1 for details) and 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 (5 half-lives) after discontinuation of treatment with IMP. *: 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 the below (see Section 10.3.2 for details): • Sexual abstinence (when this is in line with the preferred and usual lifestyle of the subject [periodic abstinence, e.g. calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception]). • Bilateral tubal occlusion. • Intrauterine device (IUD). • Intrauterine hormone-releasing system (IUS). • Combined (estrogen 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). • Vasectomized azoospermic partner (given that the subject is monogamous)

Exclusion criteria 33

1. 1.Treatment with the following topical medications within 1 week prior to baseline: • TCS. • TCI. • Topical PDE-4 inhibitor. •Topical JAK inhibitors.
2. 2. Treatment with bleach baths within 1 week prior to baseline.
3. 3.Treatment with the following immunomodulatory medications within 4 weeks prior to baseline: • Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, JAK inhibitors). • Systemic corticosteroids (excludes inhaled, ophthalmic, or intranasal delivery).
4. 4. Use of tanning beds or phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen+ultraviolet A [PUVA]) within 4 weeks prior to baseline.
5. 5.Treatment with a live (attenuated) or non-live vaccine within 30 days prior to the baseline visit. Subjects should preferably be brought up-to-date on their vaccinations according to local vaccination programs before being randomized in the trial.
6. 6. Receipt of any marketed biological therapy or investigational biologic agents (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. • Dupilumab: within 12 weeks prior to baseline. • Other biologics: within 8 weeks or 5 half-lives, whichever is longer, prior to baseline.
7. 7. Treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 3 months or 5 half-lives, whichever is longer, prior to baseline.
8. 8. Receipt of blood products within 4 weeks prior to screening.
9. 9. Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as seborrheic dermatitis, active skin infection, scabies, cutaneous T cell lymphoma, or psoriasis.
10. 10. Eczema as part of a genodermatosis syndrome, such as Netherton’s syndrome, hyper IgE syndrome, Wiskott–Aldrich syndrome, etc.
11. 11. Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
12. 12. Clinically significant active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals or antiprotozoals within 2 weeks before the baseline visit*. *: If the infection resolves, the screening period may be prolonged after approval by the sponsor's medical expert.
13. 13. History of malignancy at any time before the baseline visit.
14. 14. History of anaphylaxis following any biological therapy.
15. 15. History of immune complex disease.
16. 16. Active or suspected endoparasitic infections (including helminthic infections), or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization. Evaluation will be according to local guidelines as per local standard of care.
17. 17. History of past or current tuberculosis or other mycobacterial infection.
18. 18. History of known HIV infection, confirmed HIV seropositivity at the screening visit, or the subject taking antiretroviral medications as determined by medical history and/or verbal report from the caregiver(s).
19. 19. Established diagnosis of a primary immunodeficiency disorder (e.g. severe combined immunodeficiency, Wiskott–Aldrich syndrome, DiGeorge syndrome, X-linked agammaglobulinemia, common variable immunodeficiency) or secondary immunodeficiency. Subjects suspected to have immunodeficiency based on their clinical presentation (history of invasive opportunistic infections, e.g. tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, chronic mucocutaneous candidiasis, etc. or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the investigator) will also be excluded from the trial.
20. 20. History of past or current hepatitis B or C including a positive hepatitis B or C test at screening.
21. 21. Known or suspected hypersensitivity to any component of the IMP.
22. 22. Any other medical or psychological condition which in the investigator’s opinion 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, hematologic, immunological, and psychiatric disorders, major physical impairment, drug or alcohol dependency, or unwillingness or lacking ability to understand and comply with the trial related procedures.
23. 23. Pregnant, breastfeeding, or lactating female subjects.
24. 24. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN) at screening.
25. 25. Any clinically significant abnormal findings in physical examination, vital signs, hematology, or clinical chemistry during the screening period, which in the opinion of the investigator, may put the subject at risk because of their participation in the trial, may influence the results of the trial, or may affect the subject’s ability to complete the entire duration of the trial.
26. 26. Current participation in any other interventional clinical trial.
27. 27. Previously randomized or assigned to treatment in this clinical trial.
28. 28. Previously randomized in any clinical trials with tralokinumab.
29. 29. Planned major surgical procedure during the subject's participation in this trial.
30. 30. Subjects with severe needle phobia or a history of vasovagal reactions following injections or blood withdrawal, or subjects who are unwilling to comply with the assessments of the trial.
31. 31. Inability or unwillingness to receive IMP injections at randomization and throughout the trial.
32. 32. Subjects who are legally institutionalized.
33. 33. Employees at the trial site*, or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals. *: When the trial site is a department at a hospital, this exclusion criterion only applies to family members of employees in the department that participates in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. IGA 0/1 at Week 16
2. EASI75 at Week 16

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leo Pharma A/S

Sponsor organisation

Leo Pharma A/S

Address

Industriparken 55

City

Ballerup

Postcode

2750

Country

Denmark

Scientific contact point

Organisation

Leo Pharma A/S

Contact name

LEO Pharma Clinical Trials mailbox

Public contact point

Organisation

Leo Pharma A/S

Contact name

LEO Pharma Clinical Trials mailbox

Third parties 1

Locations

12 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 281 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications