Clinical trial NCT06526182: A Study of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis
Official title: A Phase 3, 2-Part, Open-Label and Double-Blind, Randomised Study to Evaluate the Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dermatitis, Atopic
Eczema
Keywords: Dermatitis
Skin Diseases
Skin Diseases, Eczematous
Moderate-to-severe atopic dermatitis
Lead sponsor: Almirall, S.A.
Sponsor class: INDUSTRY
First posted: 2024-07-29
Enrollment: 520
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 and Part 2 (Run-In Period): Open label; Part 2: Randomized and Double-Blind.
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the effectiveness of 24 weeks of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe AD in Part 1 and to describe how similar is the current maintenance dosing regimen of lebrikizumab 250 mg every 4 weeks (Q4W) to the new proposed; lebrikizumab 500 mg every 12 weeks (Q12W), in terms of efficacy, safety, PK, ADA and blood biomarkers.

Detailed description: This study consists of two parts. Part 1 is a single-arm, open-label design, where participants will receive lebrikizumab subcutaneous (SC) injections up to Week 24. Part 2 is a randomized, double-blind design, in which participants who achieve clinical response in Part 1 will continue receiving lebrikizumab treatment across two periods: a Run-in period and a Double-blind period. Participants who do not maintain at least a 50% reduction in Eczema Area and Severity Index (EASI) from baseline during Double-Blind Period will enter an Escape Arm.

Eligibility criteria: Inclusion Criteria:

Part 1:

1. Adults and adolescents (aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 at the time of informed consent form \[ICF\]/informed assent form \[IAF\] signature and weighing 40 \>= kilograms \[kg\]) who are candidates for systemic AD therapy.
2. Chronic AD (according to Hanifin and Rajka Criteria (Hanifin 1980)) that has been present for \>= 1 year before the screening visit.
3. EASI score \>= 12 at the Day 1/Baseline Visit.
4. IGA score \>= 3 (moderate) (scale of 0 \[clear\] to 4 \[severe\]) at the Day 1/Baseline visit.
5. \>= 10% BSA of AD involvement at the Day 1/Baseline visit.
6. History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
7. Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
8. Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
9. 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.
10. Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enroll 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).

    Part 2:
11. Demonstrate clinical response to treatment at Week 24 of Part 1, defined as achieving EASI 75 or IGA 0/1 without the use of high-potency TCS within the prior 4 weeks or systemic corticosteroids at any time post baseline.

Exclusion Criteria:

1. Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
2. 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.
3. History of anaphylaxis as defined by the Sampson criteria (Sampson 2006).
4. Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, comorbid 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).
5. Occurrence of the following types of infection within 3 months before or during screening or development of these infections before Day 1/Baseline:

   1. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator's opinion);
   2. Opportunistic (as defined by Winthrop et al. (Winthrop 2015))
   3. Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer);
   4. Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).
6. Known current or chronic infection with any hepatitis virus.
7. Known liver cirrhosis and/or chronic hepatitis of any aetiology.
8. Known active endoparasitic infection or at high risk of these infections.
9. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgement.
10. History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
11. Any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit that would jeopardise the participants participation in the study, per the Investigator's judgement.
12. Presence of skin comorbidities that may interfere with study assessments.
13. 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.
14. 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.
15. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
16. Any known hypersensitivity or allergic response to lebrikizumab or any component of the investigational medicinal product (IMP).
17. For the scratch sensor substudy only: a history of allergic response to skin adhesives, active skin or systemic infection, active AD on the back of the hand, or a pre-existing sleep disorder, including insomnia, obstructive sleep apnea, or restless leg syndrome, or currently taking prescription sleep medications.

Primary outcomes:
measure: Part 1: Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less than or Equal to (<=) 7 at Week 24
timeFrame: At Week 24
measure: Part 2: Percentage of Participants Achieving EASI 75 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with an IGA Score of 0 or 1 and a Reduction >=2 Points
timeFrame: From Baseline (Part 1) up to Week 36
Secondary outcomes:
measure: Part 1: Time to Achieve an EASI Score <= 7
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants Achieving EASI <=5, and EASI <=3 at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants Achieving EASI 75 and EASI 90 at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants with an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) 75, and SCORAD 90 at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants with Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Achieving >=4-Point Improvement in Pruritus NRS
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) 0-1 at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants Achieving Children Dermatology Life Quality Index (cDLQI) 0-1 at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants with DLQI >=4 at Baseline Achieving >=4-Point Improvement in DLQI
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants with cDLQI >=6 at Baseline Achieving >=6-Point Improvement in cDLQI
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants with a Sleep-Loss Scale of >=2 Points at Baseline Achieving >= 2 Point Improvement at Week 24
timeFrame: At Week 24
measure: Part 1: Percentage of Participants with Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Achieving >=4-Point Improvement in POEM
timeFrame: Baseline up to Week 24
measure: Part 1: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, AEs Leading to Study Treatment Discontinuation, and Adverse Events of Special Interest (AESIs)
timeFrame: Baseline up Week 24
measure: Part 2: Percentage of Participants Achieving EASI Scores <=7, and <=3 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants Achieving EASI 90 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with Pruritus NRS >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in Pruritus NRS at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with Pruritus NRS 0 or 1 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants Achieving DLQI 0-1 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants Achieving cDLQI 0-1 at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with DLQI >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in DLQI at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with cDLQI >=6 at Baseline (Part 1) Achieving >=6-Point Improvement in cDLQI at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with a Sleep-Loss Scale of >=2 Points at Baseline (Part 1) Achieving >= 2 Point Improvement at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with POEM >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in POEM at Week 36
timeFrame: At Week 36
measure: Part 2: Percentage of Participants with TEAEs, SAEs, Related AEs, AEs Leading to Study Treatment Discontinuation, and AESIs
timeFrame: From Week 24 up to Week 68
Other outcomes:
Locations:
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Barcelona
country: Spain
facility: Hospital del Mar - Parc de Salut Mar
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Valencia
country: Spain
facility: Consorci Hospital General Universitari de València
Study officials:
affiliation: Almirall, S.A.
name: Study Director
role: STUDY_DIRECTOR
References: