A Study of Lebrikizumab in Combination With Topical Corticosteroids in Patients With Atopic Dermatitis (AD) That Are Not Adequately Controlled With or Are Non-eligible for Cyclosporine

Phase 3

Completed

Conditions: Dermatitis, Atopic
Eczema

Interventions: Biological: Lebrikizumab
Drug: Lebrikizumab-matching Placebo

Registration Number: NCT05149313

Lead Sponsor: Almirall, S.A.

Brief Summary: The main purpose of this study is to evaluate the efficacy of lebrikizumab compared with placebo in participants not adequately controlled with cyclosporine or for whom cyclosporine is not medically advisable up to Week 16.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 331

Inclusion Criteria

Adults and adolescents (aged greater than or equal to (>=) 12 to <18 years at the time of Informed Consent Form (ICF)/Informed Assent Form (IAF) and weighing >=40 kilograms).
Chronic AD that has been present for >=1 year before the Screening visit.
EASI score >=16 at the Baseline Visit.
IGA score >=3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
>=10% BSA of AD involvement at the Baseline visit.
Inadequate response to existing topical medications
Failure to cyclosporine or non-medically advisable to receive/continue receiving cyclosporine
Signed ICF (and informed assent for adolescents as required)

Exclusion Criteria

Treatment with TCS within 1 week before the Baseline visit.
Treatment with topical calcineurin inhibitors, phosphodiesterase-4 inhibitors such as crisaborole, or cannabinoids within 2 week before the Baseline visit.
Treatment with interleukin 4 (IL-4) or interleukin 13 (IL-13) antagonists biological therapies before the Baseline visit. Exception: previous treatment with dupilumab will be allowed in a subset of patients
Treatment with immunosuppressive/immunomodulating drugs, phototherapy and photochemotherapy within 4 weeks before the Baseline visit
Uncontrolled chronic disease that might require bursts of oral corticosteroids
Serious, opportunistic, chronic or recurring infections within 3 months of Screening or before randomization
Current or chronic infection with hepatitis B virus, current infection with hepatitis C virus, known liver cirrhosis and/or chronic hepatitis of any etiology
Known or suspected history of immunosuppression, history of HIV infection or positive HIV serology at Screening
Any clinically significant laboratory test results obtained at the Screening visit
Presence of skin comorbidities that may interfere with study assessments
Have had an important side effect to TCS that would prevent further use.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lebrikizumab	Lebrikizumab	Lebrikizumab administered subcutaneously (SC), participants will receive 2 injections of lebrikizumab 250 mg at Baseline and Week 2, followed by 1 injection of lebrikizumab 250 milligram (mg) once every two weeks (Q2W) in the induction period up to week 16. Participants who received lebrikizumab 250 mg Q2W during the Induction Period will continue to receive lebrikizumab 250 mg Q2W during the Maintenance Period. In order to maintain the double blind, participants from the lebrikizumab 250 mg Q2W arm will be administered a second injection of blinded placebo during Week 16 and Week 18. From Week 20 up to Week 52, all participants will receive 1 injection of lebrikizumab 250 mg Q2W in Open-label maintenance period.
Lebrikizumab-matching Placebo	Lebrikizumab-matching Placebo	Lebrikizumab-matching Placebo administered SC, 250 mg dose, Q2W in the induction period for 16 weeks. Participants will receive 2 injections of lebrikizumab 250 mg at Week 16 and Week 18 followed by 1 injection of lebrikizumab 250 mg Q2W from Week 20 up to Week 52 in Open-label maintenance period.

Primary Outcome Measures

Name	Time	Method
Double-blind Induction Period: Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) 75 (>=75% Reduction From Baseline in EASI Score) at Week 16	At Week 16	The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. The severity of the clinical signs of AD for each of 4 body regions was scored on a 4-point scale: 0=absent, 1=mild, 2=moderate and 3=severe. The area of AD involvement on each of the 4 anatomic regions was assessed as a percentage by body area: 0=no eruption, 1=1% to 9%, 2=10% to 29%, 3=30% to 49%, 4=50% to 60%, 5=70% to 80% and 6=90% to 100%. The composite index with total score ranged from 0 to 72, where higher scores indicates more severe and or extensive disease.

Secondary Outcome Measures

Name	Time	Method
Double-blind Induction Period: Percentage of Participants Who Achieved Investigator Global Assessment (IGA) Score of 0 or 1 and 2-point Improvement at Week 16	At Week 16	The IGA is an instrument used to globally rate the severity of the participants 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). Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear).
Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Pruritus Numeric Rating Score (NRS) at Week 16	At Week 16	The Pruritus NRS is an 11-point scale used by participants to rate their worst pruritus (itch) severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable. Higher score indicates more severity.
Double-blind Induction Period: Percentage of Participants Who Achieved EASI 75 (>=75% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, and 12	At Weeks 2, 4, 8, and12	The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. The severity of the clinical signs of AD for each of 4 body regions was scored on a 4-point scale: 0=absent, 1=mild, 2=moderate and 3=severe. The area of AD involvement on each of the 4 anatomic regions was assessed as a percentage by body area: 0=no eruption, 1=1% to 9%, 2=10% to 29%, 3=30% to 49%, 4=50% to 60%, 5=70% to 80% and 6=90% to 100%. The composite index with total score ranged from 0 to 72, where higher scores indicates more severe and or extensive disease. Percentage of participants who achieved EASI 75 (\>=75% reduction from baseline in EASI score) at Weeks 2, 4, 8, and 12 were reported
Double-blind Induction Period: Percentage of Participants Who Achieved EASI 90 (>=90% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, 12 and 16	At Weeks 2, 4, 8, 12 and 16	The EASI score is used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. The severity of the clinical signs of AD for each of 4 body regions was scored on a 4-point scale: 0=absent, 1=mild, 2=moderate and 3=severe. The area of AD involvement on each of the 4 anatomic regions was assessed as a percentage by body area: 0=no eruption, 1=1% to 9%, 2=10% to 29%, 3=30% to 49%, 4=50% to 60%, 5=70% to 80% and 6=90% to 100%. The composite index with total score ranged from 0 to 72, where higher scores indicates more severe and or extensive disease.
Double-blind Induction Period: Percentage of Participants Who Achieved EASI 50 (>=50% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, 12 and 16	At Weeks 2, 4, 8, 12 and 16	The EASI score is used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. The severity of the clinical signs of AD for each of 4 body regions was scored on a 4-point scale: 0=absent, 1=mild, 2=moderate and 3=severe. The area of AD involvement on each of the 4 anatomic regions was assessed as a percentage by body area: 0=no eruption, 1=1% to 9%, 2=10% to 29%, 3=30% to 49%, 4=50% to 60%, 5=70% to 80% and 6=90% to 100%. The composite index with total score ranged from 0 to 72, where higher scores indicates more severe and or extensive disease.
Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Dermatology Life Quality Index (DLQI) at Weeks 2, 4, 8, 12 and 16	At Weeks 2, 4, 8, 12 and 16	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 quality of life (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 was scored on a 4-point scale (ranged from 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, giving a total score ranging from 0 (not at all) to 30 (very much). A high score is indicative of a poor QoL.
Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Children's Dermatology Life Quality Index (CDLQI) at Weeks 2, 4, 8, 12 and 16	At Weeks 2, 4, 8, 12 and 16	The 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 to measure the impact of AD disease on QoL in children during the previous week. Each question is scored as follows: 0=not at all or unanswered, 1 = only a little, 2 = quite a lot and 3 = very much. Question 7 has an added possible response, which was scored as 3. CDLQI equals the sum of the score of each question, ranged from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL). Higher scores indicate higher impact on QoL.
Double-blind Induction Period: Percentage of Participants Who Achieved a 4- Point Improvement in Skin Pain NRS at Week 16	At Week 16	The Skin Pain NRS is an 11-point scale completed by participants to rate their worst skin pain (example, discomfort or soreness) severity over the past 24 hours, with 0 (indicating "No pain") and 10 (indicating "Worst pain imaginable). Higher scores indicated worse pain.
Double-blind Induction Period: Change From Baseline in Body Surface Area (BSA) at Weeks 2, 4, 8, 12 and 16	Baseline, Weeks 2, 4, 8, 12 and 16	The BSA assessment estimates the extent of disease or skin involvement with respect to AD and is expressed as a percentage of total body surface. BSA was determined by the Investigator or designee using the participant palm = 1% BSA rule. The participant's palm is measured from the wrist to the proximal interphalangeal and thumb. This higher the BSA %, the more active atopic dermatitis is present. Percent of BSA for a body region = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA for an individual is arithmetic mean of % BSA of all 4 body regions and ranges from 0% to 100% with higher values representing greater severity of AD and negative change from baseline indicate no severity.
Double-blind Induction Period: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at Weeks 8 and 16	Baseline, Weeks 8 and 16	SCORAD is a validated clinical tool for assessing the extent and intensity of AD. There are 3 components: A) Surface involvement is assessed as proportion of involved surface area segment by segment by applying the rule of 9s and reported as the sum of all areas, with a score ranging from 0-100. B) Intensity part of the SCORAD consists of 6 items: erythema, oedema, oozing/crusting, excoriation, lichenification, and dryness. Each item graded as: none (0), mild (1), moderate (2), or severe (3). C) Subjective assessment of itch and of sleeplessness is recorded for each symptom using a visual analogue scale (VAS), where 0=no itch (or no sleeplessness) and 10= worst imaginable itch (or sleeplessness), with maximum score of 20. Formula is: A/5+7B/2+C, A: extent (0-100), B: intensity (0-18), C: subjective symptoms (0-20). SCORAD total score ranged from 0 (no disease) to 103 (severe disease). Higher values represent worse outcome and negative change from baseline indicate improvement.
Double-blind Induction Period: Change From Baseline in Pruritus NRS by Week up to Week 16	Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16	The Pruritus NRS is an 11-point scale used by participants to rate their worst pruritus (itch) severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable." Higher scores indicated greater severity and negative change from baseline indicate no severity.
Double-blind Induction Period: Change From Baseline in the Sleep Loss at Week 16 Using Patient-related Outcome (PRO) by Week up to Week 16	Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16	Sleep loss was assessed by all participants using a PRO instrument. Participants (and if applicable, with help of parents/caregiver if required) rate their sleep on a 5-point Likert scale (with scores ranging from 0 \[not at all\] to 4 \[unable to sleep at all\]). Higher scores indicated a greater impact and worse outcome; therefore, negative change from baseline indicate less impact.
Double-blind Induction Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Weeks 4, 8, 12 and 16	Baseline, Weeks 4, 8, 12 and 16	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 to 2 days = 1; 3 to 4 days = 2; 5 to 6 days = 3; every day = 4. Higher scores indicated more severe disease and poor quality of life (QoL); therefore, negative change from baseline indicate improvement in QoL.
Double-blind Induction Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 2. 4, 8, 12 and 16	Baseline, Weeks 2, 4, 8, 12 and 16	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 was scored on a 4-point scale (ranged from 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, giving a total score ranging from 0 (not at all) to 30 (very much). A high score is indicative of a poor QoL and negative change from baseline indicate improvement in QoL.
Double-blind Induction Period: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2. 4, 8, 12 and 16	Baseline, Weeks 2, 4, 8, 12 and 16	The 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 to measure the impact of AD disease on QoL in children during the previous week. Each question is scored as follows: 0=not at all or unanswered, 1 = only a little, 2 = quite a lot and 3 = very much. Question 7 has an added possible response, which was scored as 3. CDLQI equals the sum of the score of each question, ranged from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL). Higher scores indicate higher impact on QoL and negative change from baseline indicate low impact on QoL.
Double-blind Induction Period: Change From Baseline in Skin Pain NRS by Week up to Week 16	Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16	The Skin Pain NRS is an 11-point scale completed by participants to rate their worst skin pain (example, discomfort or soreness) severity over the past 24 hours, with 0 (indicating "No pain") to 10 (indicating "Worst pain imaginable). Higher scores indicated worse pain and negative change from baseline indicate no pain.
Double-blind Induction Period: Median Time (Days) to TCS-Free Use	Baseline up to Week 16	Days from first study drug injection to the day participant stopped using all TCS.
Double-blind Induction Period: Proportion of Topical Corticosteroids (TCS) Medication Free Days	Baseline up to Week 16	TCS free days proportion = Number of days participant did not take TCS medication / Number of days from Baseline to Week 16 Date or early discontinuation

Trial Locations

Locations (48): Alm Site 12
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Reims, France
Alm Site 35
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Utrecht, Netherlands
Alm Site 19
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Lille, France
Alm Site 26
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Hamburg, Germany
Alm Site 13
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Martigues, France
Alm Site 29
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Kiel, Germany
Alm Site 1
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Graz, Austria
Alm Site 2
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Gent, Belgium
Alm Site 30
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Berlin, Germany
Alm Site 20
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Lille, France
Alm Site 16
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Nantes, France
Alm Site 24
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Blankenfelde, Germany
Alm Site 28
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Bad Bentheim, Germany
Alm Site 32
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Bonn, Germany
Alm Site 33
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Rotterdam, Netherlands
Alm Site 25
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Marburg, Germany
Alm Site 34
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Bergen Op Zoom, Netherlands
Alm Site 48
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Ostrowiec Świętokrzyski, Poland
Alm Site 10
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Alicante, Spain
Alm Site 21
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Southampton, United Kingdom
Alm Site 4
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Bilbao, Spain
Alm Site 8
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Barcelona, Spain
Alm Site 7
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Sevilla, Spain
Alm Site 22
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Salford, United Kingdom
Alm Site 3
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Badalona, Spain
Alm Site 9
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Zaragoza, Spain
Alm Site 23
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Poole, United Kingdom
Alm Site 6
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Barcelona, Spain
Alm Site 5
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Madrid, Spain
Alm Site 14
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Bordeaux, France
Alm Site 17
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Le Mans, France
Alm Site 15
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Nice, France
Alm Site 18
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Pierre-Bénite, France
Alm Site 27
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Göttingen, Germany
Alm Site 31
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Frankfurt, Germany
Alm Site 43
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Chorzów, Poland
Alm Site 46
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Kraków, Poland
Alm Site 39
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Lublin, Poland
Alm Site 44
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Rzeszów, Poland
Alm Site 11
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Mieres, Spain
Alm Site 41
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Kraków, Poland
Alm Site 36
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Szczecin, Poland
Alm Site 42
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Warsaw, Poland
Alm Site 37
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Łódź, Poland
Alm Site 38
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Katowice, Poland
Alm Site 40
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Wrocław, Poland
Alm Site 45
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Białystok, Poland
Alm Site 47
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Warszawa, Poland