Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis

Almirall, S.A.260 enrolled

Overview

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 atopic dermatitis (AD).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

260

Conditions

Atopic Dermatitis Eczema

Interventions

LebrikizumabBIOLOGICAL

Lebrikizumab solution for injection administered subcutaneously.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults and adolescents (aged \>=12 to less than \[\<\] 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 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. * 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). 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, example, 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 of Screening or develop any 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 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). * Known current or chronic infection with hepatitis B virus. * Known liver cirrhosis and/or chronic hepatitis of any aetiology. * Known active endoparasitic infections or at high risk of these infections. * Known or suspected history of immunosuppression, including history of invasive opportunistic infections (example, 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.

Locations (33)

Site 34

Augsburg, Germany

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) Total Score Less Than or Equal to (<=) 7 at Week 24

The EASI is used to assess the severity and extent of AD; it is a composite index with total score ranging from 0 to 72, with higher values indicating more severe and extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%). Percentage of participants who achieved EASI total \<= 7 at Week 24 was reported.

Time frame: At Week 24

Secondary Outcomes

Percentage of Participants Who Achieved EASI Total Score <=7, EASI <=5, and EASI <=3 by Visit

Time frame: At Weeks 2, 4, 16, and 24

Percentage of Participants Who Achieved EASI 75 and EASI 90 by Visit

The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. EASI 75 is defined as 75% reduction from baseline in the EASI score. EASI 90 is defined as 90% reduction from baseline in the EASI score. Percentage of participants who achieved EASI 75 and EASI 90 at each visit was reported.

Data from ClinicalTrials.gov

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Site 29

Bonn, Germany

Site 27

Dresden, Germany

Site 28

Düsseldorf, Germany

Site 11

Erlangen, Germany

Site 37

Frankfurt, Germany

Site 32

Freiburg im Breisgau, Germany

Site 5

Göttingen, Germany

Site 15

Hamburg, Germany

...and 23 more locations

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points From Baseline by Visit

The IGA is an instrument used to globally rate the severity of the participant's AD. It is based on a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe), and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting (minimal, palpable induration and significant induration). Percentage of participants with an IGA Score of 0 or 1 and a reduction \>=2 points from baseline at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants Who Achieved Scoring Atopic Dermatitis (SCORAD) 75 and SCORAD 90 by Visit

SCORAD is a validated clinical tool for assessing the extent and intensity of AD. There are 3 components: surface involvement, intensity part and subjective assessment. Surface involvement is assessed as proportion of involved surface area segment by segment by applying the rule of 9s. Intensity part of the SCORAD consists of 6 items: erythema, oedema, oozing/crusting, excoriation, lichenification, and dryness. Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points). Subjective assessment of itch and of sleeplessness is recorded for each symptom using a VAS, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), for maximum possible score of 20. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition. SCORAD 75 is defined as 75% reduction in SCORAD from baseline. SCORAD 90 is defined as 90% reduction in SCORAD from baseline.

Time frame: At Week 2, 4, 16 and 24

Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) (Hands) From Baseline by Visit

mTLSS combines an evaluation of hand eczema lesions severity including 6 key signs (erythema, desquamation, lichenification/hyperkeratosis, vesiculae, oedema, fissures) and the intensity of pruritus and pain. The seven features of AD of the hands (erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, fissures, pruritus/pain) form the composite scale of mTLSS' strength and each one of them scores from (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The scores are summed, extending from a base estimation of 0 (no signs or symptoms) to the most extreme of 21 (more serious disease). Percentage change from baseline was calculated as: (\[Observed or imputed value at post-baseline time point (i.e. Visit) - Observed value at Baseline\]/Observed value at Baseline) \*100.

Time frame: Baseline, Week 2, 4, 16, and 24

Percentage of Participants With Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Who Achieved >=4-Point Improvement in Pruritus NRS From Baseline by Visit

The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity score over the past 24 hours, with 0 (No itch) to 10 (Worst itch imaginable). Assessments will be recorded by the participant using an eDiary. Percentage of participants with pruritus NRS \>=4 at baseline who achieved \>=4-Point improvement in pruritus NRS from baseline at each visit was reported

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants Who Achieved Dermatology Life Quality Index (DLQI) 0-1 by Visit

The DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL. DLQI scores indicates 0-1 (no effect on patient's life), 2-5 (small effect on patient's life), 6-10 (moderate effect on patient's life), 11-20 (very large effect on patient's life), 21-30 (extremely large effect on patient's life). Percentage of participants who achieved DLQI 0-1 at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants With DLQI >=4 at Baseline Who Achieved >=4-Point Improvement in DLQI From Baseline by Visit

DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. High score is indicative of a poor QoL. Percentage of participants with DLQI \>=4 at Baseline who achieved \>=4-Point improvement in DLQI from baseline at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants Who Achieved Children Dermatology Life Quality Index (cDLQI) 0-1 by Visit

cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced. Percentage of participants who achieved cDLQI 0-1 at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants With cDLQI >=6 at Baseline Who Achieved >=6-Point Improvement in cDLQI From Baseline by Visit

Time frame: At Week 2, 4, 16 and 24

Percentage of Participants With a Sleep-Loss Scale of >=2 Points at Baseline Who Achieved at Least 2-point Reduction From Baseline by Visit

Sleep loss will be assessed by all participants using a patient-related outcome (PRO) instrument. Participants (and if applicable, with help of parents/caregiver if required) will rate their sleep on a 5-point Likert scale (with scores ranging from 0 \[not at all\] to 4 \[unable to sleep at all\]). Assessments will be recorded by the participant using an eDiary.The baseline Sleep-Loss Scale score will be determined based on the average of daily Sleep-Loss Scale scores during the 7 days immediately before the Day 1 or Baseline visit. Percentage of participants with a Sleep-Loss scale of \>=2 points at baseline who achieved at least 2-point reduction from baseline at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Percentage of Participants With Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Who Achieved >=4-Point Improvement in POEM From Baseline by Visit

The POEM is a 7-item, validated questionnaire completed by the participant (and, if applicable, with help of parents/caregiver if required) to assess disease symptoms. Participants are asked to respond to questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping. All answers carry equal weight, with a total possible score ranging from 0 to 28 (answers scored as: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; every day = 4. A high score is indicative of a poor quality of life. POEM responses are captured weekly using an eDiary. Percentage of participants with POEM \>=4 at baseline who achieved \>=4-Point improvement in POEM from baseline at each visit was reported.

Time frame: At Weeks 2, 4, 16 and 24

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related TEAEs, TEAEs Leading to Study Treatment Discontinuation, and Treatment-emergent Adverse Events of Special Interest (TEAESIs)

TEAEs are undesirable events that first occurred or worsened in severity after the date of first IMP injection in the study, and on or prior to the date of the last visit within the treatment period. An SAE are AE, which falls into any of the following categories: death, is life-threatening, requires in-patient hospitalisation or prolongs existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect, or any other medically important event that may jeopardise the participant or may require intervention to prevent one of the other above outcomes. Related TEAEs includes events considered related or possibly related to study treatment by the Investigator. The following treatment-emergent AEs are being designated as AESIs: conjunctivitis, herpes simplex or zoster infection and parasitic infections.

Time frame: Baseline up to follow-up (Week 28)