Pharmacokinetics and Safety Evaluation of Tralokinumab in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis: A Randomized, Assessor-Blinded Study

Trial ID: 2024-512791-36-00
Protocol: LP0162-1335
Sponsor: Leo Pharma A/S

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this clinical trial is to establish the **pharmacokinetic (PK) profile** after multiple subcutaneous (SC) administrations of tralokinumab in children aged 6 to less than 12 years with moderate-to-severe atopic dermatitis (AD). Understanding the PK profile is clinically relevant as it provides critical information on the absorption, distribution, metabolism, and excretion of tralokinumab, which is essential for optimizing dosing regimens and ensuring therapeutic efficacy and safety in the pediatric population.

Secondary objectives include:

Assessing the safety and tolerability of multiple SC administrations of tralokinumab in children with moderate-to-severe AD. This is crucial for identifying potential adverse effects and ensuring the treatment is well-tolerated in the target population.
Evaluating the efficacy of tralokinumab on the severity and extent of AD, as well as on patient-reported outcomes. This objective aims to determine the therapeutic benefits of tralokinumab in reducing disease severity and improving quality of life, which are important measures of treatment success.

Participants

The clinical trial involves a total of **4 participants** diagnosed with moderate-to-severe **Atopic dermatitis**. The study population consists of children aged 6 to less than 12 years, with both male and female subjects included. Participants were selected based on specific criteria, including a body weight of at least 17 kg and a history of atopic dermatitis for 12 months or more. The trial targets individuals who have experienced treatment failure with topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) or for whom these treatments are medically inadvisable. Participants are required to have at least 10% body surface area involvement of atopic dermatitis and an Eczema Area and Severity Index (EASI) score of 16 or higher. Additionally, an Investigator's Global Assessment (IGA) score of 3 or more is necessary. Prior to baseline, participants must have used emollients twice daily or more for at least 14 days. The trial includes a vulnerable population, ensuring careful consideration of ethical standards and participant safety.

Plans and Procedures

The clinical trial is designed to evaluate the **pharmacokinetics** and safety of **tralokinumab** in children aged 6 to less than 12 years with moderate-to-severe **atopic dermatitis**. This is a Phase 4, single (assessor) blinded, randomized, parallel-group, monotherapy trial. The trial will involve multiple subcutaneous administrations of tralokinumab, with the primary objective of establishing the pharmacokinetic profile in the target population. The trial is expected to last until April 2026, with participant involvement spanning up to 194 days, depending on individual response and adherence to the protocol.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and history of atopic dermatitis. The inclusion criteria require a diagnosis of atopic dermatitis as defined by the Hanifin and Rajka criteria, a body weight of at least 17 kg, and a history of treatment failure with topical corticosteroids or calcineurin inhibitors. Following the screening, participants will be randomized and begin the initial treatment period, which extends from Week 0 to Week 16. During this period, primary endpoints such as Ctrough at Week 16 and Cmax between Week 12 and Week 14 will be assessed.

Secondary endpoints include the number of treatment-emergent adverse events and the status of anti-drug antibodies throughout the trial. The trial also includes an open-label treatment period from Week 16 to Week 68, and a long-term extension treatment period, with the end-of-study visit occurring two weeks after the last dose of the investigational medicinal product. Participants may be withdrawn from the study early due to adverse events, non-compliance with the study protocol, or at the discretion of the investigator for safety reasons. The trial aims to provide comprehensive data on the safety and efficacy of tralokinumab in the pediatric population with moderate-to-severe atopic dermatitis.

Treatment

The clinical trial involves the administration of **Adtralza**, a pharmaceutical product containing the active substance **tralokinumab**. Adtralza is formulated as a **solution for injection in a pre-filled syringe**. Each syringe contains 150 mg of tralokinumab, a protein-based therapeutic agent. The medication is administered via **subcutaneous injection**. The dosing regimen for this trial involves multiple administrations, with a maximum daily dose of 600 mg. The total treatment period extends up to 194 days. The pre-filled syringe is equipped with a single-use, disposable, needle-based injection system that includes a passive needle safety guard, ensuring safe and effective delivery of the medication.

Tralokinumab, the active ingredient in Adtralza, is a monoclonal antibody designed to target and neutralize interleukin-13, a cytokine involved in the inflammatory process of **atopic dermatitis**. The trial aims to evaluate the pharmacokinetics and safety of tralokinumab in pediatric patients aged 6 to less than 12 years with moderate-to-severe atopic dermatitis. The investigational product used in the trial is 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 to ensure compliance with trial protocols.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial is conducted under a single (assessor) blinded, randomized, parallel-group, monotherapy design, focusing on establishing the pharmacokinetic profile of tralokinumab in the specified pediatric population.

Efficacy

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include pharmacokinetic parameters such as **Ctrough** at Week 16, **Cmax** between Week 12 and Week 14 for Q2W dosing (and Week 12 to Week 16 for Q4W dosing), **AUC** between Week 12 and Week 14 for Q2W dosing (and Week 12 to Week 16 for Q4W dosing), and **Tmax** between Week 12 and Week 14 for Q2W dosing (and Week 12 to Week 16 for Q4W dosing). These endpoints will be summarized by dosing interval within the low dose level.

Secondary endpoints include the number of treatment-emergent adverse events and the status of anti-drug antibodies across different treatment periods: the initial treatment period (Week 0 to Week 16), the open-label treatment period (Week 16 to Week 68), and the long-term extension treatment period (Week 68 to the end-of-treatment visit). Additionally, changes in clinical assessment scores such as SCORAD, POEM, and EASI from Week 0 to Week 68 will be evaluated. These assessments will provide a comprehensive evaluation of the efficacy of tralokinumab in children with moderate-to-severe atopic dermatitis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Diagnosis of AD (as defined by Hanifin and Rajka criteria for AD).
Age 6 to <12 years.
Body weight at baseline of ≥17 kg.
History of AD for ≥ 12 months at screening.
History of TCS and/or TCI treatment failure (due to inadequate response or intolerance) or subjects for whom these topical AD treatments are medically inadvisable.
AD involvement of ≥10% body surface area at screening and baseline.
An EASI score of ≥16 at screening and at baseline.
An IGA score of ≥3 at screening and at baseline.
Emollient twice daily (or more) for at least 14 days prior to baseline.

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Exclusion Criteria

Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment.
Treatment with topical PDE-4 inhibitor within 2 weeks prior to randomization.
Treatment with the following immunomodulatory medications or bleach baths within 4 weeks prior to baseline: 3a. Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, JAK inhibitors). 3b. Systemic corticosteroid use (excludes topical, inhaled, ophthalmic, or intranasal delivery). 3c. 3 or more bleach baths during any week within the 4 weeks.
Receipt of any marketed biological therapy or investigational biologic agents (including immunoglobulin, anti-IgE, or dupilumab): 4a. 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. 4b. Other biologics (including dupilumab): within 3 months or 5 half-lives, whichever is longer, prior to baseline.
Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals, or antiprotozoals within 2 weeks before the baseline visit.
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).
History of past or current tuberculosis or other mycobacterial infection.
Established diagnosis of a primary immunodeficiency disorder.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Not Recruiting	07 Sept 2022	5
France	Not Recruiting	07 Sept 2022	1
The Netherlands	Not Recruiting	07 Sept 2022	—
Spain	Not Recruiting	07 Sept 2022	5
Netherlands	—	—	9