Phase 3 Multicenter Evaluation of Tralokinumab with Topical Corticosteroids in Pediatric Moderate-to-Severe Atopic Dermatitis
- Trial ID
- 2023-503630-44-00
- Protocol
- LP0162-1336
- Sponsor
- Leo Pharma A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase 3 multi-center trial is to evaluate the efficacy and safety of **tralokinumab** in combination with topical corticosteroids (TCS) compared to placebo plus TCS in children aged 2 to less than 12 years with moderate-to-severe atopic dermatitis. This objective is clinically relevant as it aims to determine the potential of tralokinumab to provide more effective control of the skin manifestations of atopic dermatitis, which is crucial for improving patient outcomes in this age group.
Secondary objectives include evaluating the symptom scores and extent of atopic dermatitis, the severity of itching or scratching, and the impact of atopic dermatitis on the quality of life of subjects and their caregivers. Additionally, the trial will assess the impact of tralokinumab plus TCS on skin colonization with Staphylococcus aureus and stratum corneum lipid composition in subjects aged 2 to less than 12 years. For subjects aged 6 months to less than 2 years, all objectives and endpoints are considered secondary, as there is no placebo comparison in this cohort, and endpoints will not be subject to multiplicity adjustment.
Participants
The clinical trial involves a total of **79 participants** who are being studied for the treatment of moderate-to-severe **atopic dermatitis**. The study population consists of both male and female subjects aged 2 to less than 12 years. Participants were selected based on specific criteria, including a documented diagnosis of atopic dermatitis as defined by the Hanifin and Rajka criteria, and a history of the condition for at least 12 months for those aged 6 years and older, or at least 3 months for those aged 6 months to less than 6 years. The trial includes subjects who have shown an inadequate response to mid-strength topical corticosteroids within the 6 months prior to screening. Participants are required to have at least 10% body surface area involvement and an EASI score of 16 or higher at screening and baseline. The trial population is characterized by a vulnerable group, given the young age of the participants. Lifestyle considerations such as diet and physical activity are not specified in the available data. The selection process ensures that participants and their caregivers can comply with clinic visits and trial requirements, as assessed by the investigator.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **tralokinumab** in combination with topical corticosteroids in children and infants with moderate-to-severe atopic dermatitis. This phase 3 trial employs a randomized, double-blind, placebo-controlled, and parallel-group design for children aged 2 to less than 12 years, while an open-label, single-group design is used for infants aged 6 months to less than 2 years. The trial is expected to commence recruitment on August 20, 2024, and conclude by April 28, 2028, with a maximum treatment period of 150 days for participants.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, body weight, and a documented history of atopic dermatitis. Following successful screening, participants will be randomized to receive either the investigational medicinal product (IMP) or placebo, both administered via subcutaneous injection. The primary endpoints include achieving an Investigator's Global Assessment (IGA) score of 0/1 and a 75% improvement in the Eczema Area and Severity Index (EASI75) by Week 16.
Study visits will be scheduled at regular intervals to monitor the participants' response to treatment, assess safety, and collect data on secondary endpoints, which include symptom scores, the extent of atopic dermatitis, and the impact on quality of life. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted. Participants are expected to be involved in the trial for the duration of the treatment period, with conditions for early termination including non-compliance with trial procedures or adverse events that necessitate withdrawal.
Treatment
The clinical trial involves the administration of **Adtralza**, a 150 mg solution for injection in a pre-filled syringe, containing the active substance **tralokinumab**. This investigational medicinal product (IMP) is designed for **subcutaneous use** and is administered via a single-use, disposable, needle-based injection system with a passive needle safety guard. The maximum daily dose is 600 mg, and the treatment period extends up to 150 days. The IMP batches used in the trial are representative of the commercial product, with minor differences in manufacturing processes and packaging. The clinical material is assembled, labeled, and packaged in a specific order distinct from the commercial product. The IMP is manufactured by LEO Pharma A/S and is not a pediatric formulation.
The trial also includes a placebo, which is a pre-filled syringe containing the same excipients in the same amounts as the IMP, but without the active substance. The placebo is used to maintain the double-blind nature of the study for participants aged 2 to <12 years. The placebo presentation is identical in appearance to the active treatment to ensure blinding is maintained throughout the trial. The placebo does not have a specific pharmaceutical form or active substance, and it is not a pediatric formulation.
Efficacy
The efficacy of tralokinumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-severe **atopic dermatitis** in children aged 2 to <12 years will be assessed using specific primary endpoints. These endpoints include achieving an Investigator's Global Assessment (IGA) score of 0 or 1 and a 75% improvement in the Eczema Area and Severity Index (EASI75) at Week 16. The trial is designed as a randomized, double-blind, placebo-controlled, and parallel-group study for children, while it is open-label and single-group for infants aged 6 months to <2 years.
Secondary endpoints will address symptom scores, the extent of atopic dermatitis, severity of itching or scratching, and the impact on the quality of life of both the subjects and their caregivers. Additionally, exploratory analyses will investigate the impact of tralokinumab+TCS on skin colonization with Staphylococcus aureus and stratum corneum lipid composition, which serves as an indirect measure of skin barrier function. Efficacy assessments will be conducted at specified timepoints, with the primary focus on Week 16 outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent
- 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.
- Body weight ≥9 kg at screening
- Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (27)
- 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
- 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)’
- AD involvement of ≥10% body surface area at screening and baseline according to component A of SCORAD
- An EASI score of ≥16 at screening and baseline
- An IGA score of ≥3 at screening and baseline
- 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
- Subject and caregiver(s) are able to comply with clinic visits and trial requirements and procedures, as assessed by the investigator
- 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
- 1.Treatment with the following topical medications within 1 week prior to baseline: • TCS. • TCI. • Topical PDE-4 inhibitor. •Topical JAK inhibitors.
- Treatment with bleach baths within 1 week prior to baseline.
- 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).
- 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.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.
- 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.
- 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.
- Receipt of blood products within 4 weeks prior to screening.
- 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.
- Eczema as part of a genodermatosis syndrome, such as Netherton’s syndrome, hyper IgE syndrome, Wiskott–Aldrich syndrome, etc.
- Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
- 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.
- History of malignancy at any time before the baseline visit.
- History of anaphylaxis following any biological therapy.
- History of immune complex disease.
- 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.
- History of past or current tuberculosis or other mycobacterial infection.
- 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).
- 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.
- History of past or current hepatitis B or C including a positive hepatitis B or C test at screening.
- Known or suspected hypersensitivity to any component of the IMP.
- 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.
- Pregnant, breastfeeding, or lactating female subjects.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN) at screening.
- 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.
- Current participation in any other interventional clinical trial.
- Previously randomized or assigned to treatment in this clinical trial.
- Previously randomized in any clinical trials with tralokinumab.
- Planned major surgical procedure during the subject's participation in this trial.
- 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.
- Inability or unwillingness to receive IMP injections at randomization and throughout the trial.
- Subjects who are legally institutionalized.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 20 Aug 2024 | 8 |
 Croatia | Not Recruiting | 20 Aug 2024 | 14 |
 Czechia | Not Recruiting | 20 Aug 2024 | 4 |
 Denmark | Not Recruiting | 20 Aug 2024 | 2 |
 Germany | Not Recruiting | 20 Aug 2024 | 14 |
 Ireland | Not Recruiting | 20 Aug 2024 | 6 |
 Italy | Not Recruiting | 20 Aug 2024 | 12 |
 The Netherlands | Not Recruiting | 20 Aug 2024 | — |
 Poland | Not Recruiting | 20 Aug 2024 | 18 |
 Portugal | Not Recruiting | 20 Aug 2024 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The placebo presentation is a pre-filled syringe containing the same excipients in the same amounts as the IMP. | Placebo | N/A | — | — | — | N/A |
Adtralza 150 mg solution for injection in pre-filled syringe | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 600 | 150 | PRD9019038 |