Evaluation of Lebrikizumab Efficacy and Safety in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Phase 3b Open-label Study

Trial ID: 2023-505558-16-00
Protocol: M-17923-33
Sponsor: Almirall S.A.

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this study is to evaluate the **effectiveness** of 24 weeks of **lebrikizumab** treatment in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe **Atopic Dermatitis** (AD). This is clinically relevant as it aims to assess the therapeutic potential of lebrikizumab, a monoclonal antibody, in managing a chronic inflammatory skin condition that significantly impacts patients' quality of life.

Secondary objectives include:

Evaluating the impact of 24 weeks of lebrikizumab treatment on patient-reported and investigator-reported outcome measures in adults and adolescents with moderate-to-severe AD.

Participants

The clinical trial involves a total of **57 participants** diagnosed with **Atopic Dermatitis**. The study population includes both male and female subjects, comprising adults and adolescents aged 12 to less than 18 years, who are candidates for systemic therapy. Participants are required to have a chronic form of the disease, as defined by the Hanifin and Rajka Criteria, with a history of at least one year prior to the screening visit. The trial population was selected based on specific criteria, including an EASI score of 12 or higher and an IGA score of 3 or more at baseline, indicating moderate-to-severe disease severity. Additionally, participants must have at least 10% body surface area involvement and a history of inadequate response to topical treatments. The study includes individuals who are willing and able to comply with all study-related procedures and requirements. Both genders are represented, and the trial includes a vulnerable population, ensuring a comprehensive evaluation of the treatment's effectiveness across diverse demographic groups.

Plans and Procedures

The clinical trial is a **Phase 3b** open-label study designed to evaluate the effectiveness and safety of **lebrikizumab** treatment in adults and adolescents with moderate-to-severe **atopic dermatitis**. The trial will involve a single arm, with participants receiving **lebrikizumab** as a **solution for injection** administered subcutaneously. The primary objective is to assess the improvement in disease severity, signs, and symptoms over a 24-week treatment period. The trial is expected to commence recruitment on October 1, 2023, and conclude by May 16, 2025.

Participants will be involved in the study for a maximum of 24 weeks, during which they will attend several study visits. The sequence of visits includes an initial screening visit to confirm eligibility based on criteria such as age, weight, and disease characteristics. Participants must have a history of chronic **atopic dermatitis** for at least one year, an EASI score of 12 or higher, and an IGA score of 3 or more at baseline. Following the screening, eligible participants will proceed to the baseline visit, where they will receive their first dose of **lebrikizumab**. Subsequent follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse events.

The primary endpoint is the percentage of participants achieving an EASI score of 7 or less at Week 24. Secondary endpoints include various measures of disease improvement, such as EASI 75 and EASI 90 scores, IGA score reductions, and improvements in quality of life indices like DLQI and POEM. Participants will be required to complete electronic diaries to record pruritus and sleep-loss data, which will be used to assess treatment efficacy. The end-of-study visit will involve a final assessment of the participants' condition and the collection of any remaining data.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. Women of childbearing potential must adhere to strict contraceptive measures during the study and for a specified period after the last dose of **lebrikizumab**. The trial is not categorized as low intervention, given its focus on safety and efficacy in a patient population requiring systemic therapy for **atopic dermatitis**.

Treatment

The clinical trial involves the administration of **Lebrikizumab**, a monoclonal antibody, as the experimental medication. Lebrikizumab is provided in the pharmaceutical form of a **solution for injection**. The active substance, lebrikizumab, is a protein of other origin, specifically designed for subcutaneous use. The medication is delivered in a pre-filled syringe containing 250 mg of lebrikizumab, with a concentration of 125 mg/mL. The syringe is equipped with a needle safety device, forming a drug-device combination product. The maximum daily dose of lebrikizumab is 500 mg, with a total maximum dose of 3000 mg over the treatment period. The treatment duration is set for a maximum of 24 weeks, with the administration schedule determined by the study protocol.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the effectiveness and safety of lebrikizumab in participants with moderate-to-severe atopic dermatitis. Compliance with the dosing schedule and administration is monitored throughout the trial to ensure adherence to the protocol. Participants are required to follow the instructions provided in the package leaflet, which accompanies the medication, to ensure proper administration and handling of the drug-device combination product.

Efficacy

The efficacy of lebrikizumab in the treatment of moderate-to-severe **Atopic Dermatitis** will be assessed through a series of primary and secondary endpoints over a 24-week period. The primary endpoint is the percentage of participants achieving an Eczema Area and Severity Index (EASI) score of ≤7 at Week 24. Secondary endpoints include various measures of symptom improvement and quality of life, such as the percentage of participants achieving EASI scores of ≤7, ≤5, and ≤3 by visit, as well as EASI 75 and EASI 90. Additional secondary endpoints involve the Investigator's Global Assessment (IGA) score, with a focus on participants achieving a score of 0 or 1 and a reduction of ≥2 points by visit.

Other secondary endpoints include the percentage of participants achieving SCORAD 75 and SCORAD 90, percentage change from baseline in modified Total Lesion Symptom Score (mTLSS) for hands, and improvements in Pruritus Numeric Rating Scale (NRS) and Dermatology Life Quality Index (DLQI). The study will also evaluate the percentage of participants with a Sleep-Loss Scale reduction of at least 2 points, improvements in Patient-Oriented Eczema Measure (POEM), and scores from the Itch Controlled Days questionnaire and Treatment Satisfaction Questionnaire for Medication (TSQM-9) by visit. These efficacy parameters will be collected and analyzed at various timepoints throughout the study to determine the effectiveness of lebrikizumab in improving disease severity, signs, and symptoms in the target population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adults and adolescents (aged ≥12 to <18 years at the time of informed consent form (ICF)/informed assent form (IAF) signature and weighing ≥40 kg) who are candidates for systemic AD therapy.
Chronic AD (according to Hanifin and Rajka Criteria) that has been present for ≥1 year before the Screening visit.
EASI score ≥12 at the Day 1/Baseline Visit.
IGA score ≥3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
≥10% BSA of AD involvement at the Day 1/Baseline visit.
History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or to use a highly effective contraceptive method during the treatment period and for at least 4 weeks or 1 menstrual period after the last dose of lebrikizumab. NOTE: A woman of childbearing potential (WOCBP) is defined as a postmenarcheal woman, who has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilisation (removal of ovaries and/or uterus). NOTE: The following contraceptive methods are highly effective: combined (oestrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) associated with inhibition of ovulation, progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, or sexual abstinence. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enrol in the study and sign and date either a separate IAF or the ICF signed by the parent/legal guardian (as appropriate based on local regulations and requirements).

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Exclusion Criteria

Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication.
History of anaphylaxis as defined by the Sampson criteria.
Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, co-morbid severe uncontrolled asthma (defined by an Asthma Control Questionnaire-5 score ≥1.5 or a history of ≥2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalisation for >24 hours).
Occurrence of the following types of infection within 3 months before or during screening or development of these infections before Day 1 / Baseline: a. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator’s opinion); b. Opportunistic (as defined by Winthrop et al. (Winthrop 2015)) NOTE: Herpes zoster is considered active and ongoing until all vesicles are dry and crusted over; c. Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer); d. Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).
Known current or chronic infection with any hepatitis virus.
Known liver cirrhosis and/or chronic hepatitis of any aetiology.
Known active endoparasitic infection or at high risk of these infections.
Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator’s judgement.
History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
Any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit that would jeopardise the patient’s participation in the study, per the Investigator’s judgement.
Presence of skin comorbidities that may interfere with study assessments.
History of malignancy, including mycosis fungoides, within 5 years before the Screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin with no evidence of recurrence in the past 12 weeks.
Severe concomitant illness(es) that in the Investigator’s judgement would adversely affect the participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant because of his/her participation in this clinical trial, may make participation unreliable, or may interfere with study assessments.
Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.