A Study of of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis

Phase 3

Recruiting

• Conditions: Dermatitis, Atopic; Eczema
• Interventions: Biological: Lebrikizumab

• Registration Number: NCT06526182
• Lead Sponsor: Almirall, S.A.

Brief Summary

The main purpose of this study is to evaluate the effectiveness and safety of 24 weeks of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe AD.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-07
• Study Start: 2024-07-03
• Study First Submitted: 2024-07-24
• Study First Submitted QC: 2024-07-24
• Last Update Submitted: 2024-07-24
• Study First Posted: 2024-07-29
• Last Update Posted: 2024-07-29
• Primary Completion: 2026-04
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 520

Inclusion Criteria

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.

   NOTE: A woman of childbearing potential (WOCBP) is defined as a post menarcheal amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (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 (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.

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).

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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)) NOTE: Herpes zoster is considered active and ongoing until all vesicles are dry and crusted over;
   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. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lebrikizumab	Lebrikizumab	Participants with moderate-to-severe AD will receive loading doses of lebrikizumab 500 milligrams (mg) subcutaneous (SC) injection (2 injections) at Day 1 and Week 2 followed by 250 mg (1 injection) every 2 weeks (Q2W) after Week 4 to Week 16 followed by 250 mg (1 injection) every 4 weeks (Q4W) after Week 16 to Week 24.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less than or Equal to (<=) 7 at Week 24	At Week 24	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. 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%).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving EASI 75 and EASI 90 by Visit	Baseline up to Week 24	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 with Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Achieving >=4-Point Improvement in Pruritus NRS	Baseline up to Week 24	The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable.
Percentage of Participants With DLQI >=4 at Baseline Achieving >=4-Point Improvement in DLQI	Baseline up to Week 24	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.
Time to EASI Score <= 7	Baseline up to Week 24	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.
Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) From Baseline by Visit	Baseline up to Week 24	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 hand (erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, fissures, pruritus/pain) form the composite scale of mTLSS' strength and each one of them scores from 0 (mild) to 3 (severe). The scores is summed, extending from a base estimation of 0 (no signs or symptoms) to the most extreme of 21 (more serious disease).
Percentage of Participants Achieving Children Dermatology Life Quality Index (cDLQI) 0-1 by Visit	Baseline up to Week 24	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 With cDLQI >=6 at Baseline Achieving >=6-Point Improvement in cDLQI	Baseline up to Week 24	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 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)	Baseline up to follow-up (Week 28)	An AE is defined as any untoward medical occurrence in a clinical trial participant, regardless of the administration of the IMP and its causal relationship to it. An AE can therefore be any unfavourable/unintended medical occurrence during the participation in the trial, including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, ECG abnormality, or an abnormal finding in the physical examination. An SAE is an 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. The following treatment-emergent AEs are being designated as AESIs: conjunctivitis, herpes simplex or zoster infection and parasitic infections.
Percentage of Participants with an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points by Visit	Baseline up to Week 24	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 a Sleep-Loss Scale of >=2 Points at Baseline Achieving >= 2 Point Improvement	Baseline up to Week 24	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 Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Achieving >=4-Point Improvement in POEM	Baseline up to Week 24	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 will be captured weekly using an eDiary.
Percentage of Participants Achieving EASI Score <=7, <=5, and <=3 by Visit	Baseline up to Week 24	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. 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 Achieving Scoring Atopic Dermatitis (SCORAD) 75, and 90 by Visit	Baseline up to Week 24	The SCORAD is a validated measure of the extent and severity of atopic dermatitis lesions, along with subjective symptoms. 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.
Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) 0-1 by Visit	Baseline up to Week 24	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)

Trial Locations

Locations (4)

Hospital del Mar - Parc de Salut Mar; 🇪🇸 Barcelona, Spain

Hospital General Universitario Dr. Balmis; 🇪🇸 Alicante, Spain

Hospital Universitario Clínico San Cecilio; 🇪🇸 Granada, Spain

Consorci Hospital General Universitari de València; 🇪🇸 Valencia, Spain