A Study of Lebrikizumab Treatment in Adults and Adolescen... | NCT06526182

ID	Type	Description	Link
2023-508235-31	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Open label (Lebrikizumab)	Experimental	Participants with moderate-to-severe AD will receive loading doses of lebrikizumab 500 mg 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.	Biological: Lebrikizumab
Part 2: Open label Run-In Period (Lebrikizumab)	Experimental	Participants who respond to lebrikizumab treatment at Week 24 of Part 1 will continue treatment in Part 2, which includes an 8-week open-label Run-In Period to confirm sustained clinical response. During this period, they will receive lebrikizumab 250 mg SC injection (1 injection) Q4W starting from the Week 24 visit of Part 1.	Biological: Lebrikizumab
Part 2: Double-Blind (Lebrikizumab)	Experimental	At the end of the Run-In Period, participants who demonstrate sustained clinical response will continue treatment in the double-blind period. They will either receive lebrikizumab 250 mg SC injection (1 injection) Q4W or switch to lebrikizumab 500 mg SC injection (2 injections) Q12W for 36 weeks.	Biological: Lebrikizumab
Part 2: Double-Blind (Placebo)	Placebo Comparator	At the end of the Run-In Period, participants who demonstrate sustained clinical response will continue treatment in the double-blind period. They will either receive lebrikizumab matching placebo 250 mg SC injection (1 injection) Q4W or switch to lebrikizumab matching placebo 500 mg SC injection (2 injections) Q12W for 36 weeks.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lebrikizumab	Biological	Lebrikizumab solution for injection administered subcutaneously.	Part 1: Open label (Lebrikizumab) Part 2: Double-Blind (Lebrikizumab)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Percentage of Participants Achieving Eczema Area and Severity Index (EASI) 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 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%).	At Week 24
Part 2: Percentage of Participants Achieving EASI 75 at Week 36	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.	At Week 36
Part 2: Percentage of Participants with an IGA Score of 0 or 1 and a Reduction >=2 Points	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).	From Baseline (Part 1) up to Week 36

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Time to Achieve an EASI Score <= 7	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.	Baseline up to Week 24
Part 1: Percentage of Participants Achieving EASI <=5, and EASI <=3 at Week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Part 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.
Chronic AD (according to Hanifin and Rajka Criteria (Hanifin 1980)) 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 Day 1/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).

Part 2:
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:

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 (Sampson 2006).
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).
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).
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 (e.g., 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 participants 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.
Any known hypersensitivity or allergic response to lebrikizumab or any component of the investigational medicinal product (IMP).
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.

Facility	Status	City	State	ZIP	Country	Contacts
Hospital General Universitario Dr. Balmis		Alicante			Spain
Hospital del Mar - Parc de Salut Mar

ID	Term
D003876	Dermatitis, Atopic
D004485	Eczema
D003872	Dermatitis
D012871	Skin Diseases
D017443	Skin Diseases, Eczematous

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D017437	Skin and Connective Tissue Diseases