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 (ADvantage)

April 30, 2025 updated by: Almirall, S.A.

A Randomised, Double-Blind, Placebo-Controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adult and Adolescent Patients With Moderate-To-Severe Atopic Dermatitis That Are Not Adequately Controlled With Cyclosporine or For Whom Cyclosporine is Not Medically Advisable.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

331

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: Lebrikizumab
Lebrikizumab solution for injection administered subcutaneously.
Placebo Comparator: 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.
Drug: Lebrikizumab-matching Placebo
Matching Placebo solution for injection administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
At Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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).
At Week 16
Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Pruritus Numeric Rating Score (NRS) at Week 16
Time Frame: 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.
At Week 16
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
Time Frame: 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
At Weeks 2, 4, 8, and12
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
Time Frame: 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.
At Weeks 2, 4, 8, 12 and 16
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
Time Frame: 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.
At Weeks 2, 4, 8, 12 and 16
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
Time Frame: 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.
At Weeks 2, 4, 8, 12 and 16
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
Time Frame: 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.
At Weeks 2, 4, 8, 12 and 16
Double-blind Induction Period: Percentage of Participants Who Achieved a 4- Point Improvement in Skin Pain NRS at Week 16
Time Frame: 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.
At Week 16
Double-blind Induction Period: Change From Baseline in Body Surface Area (BSA) at Weeks 2, 4, 8, 12 and 16
Time Frame: 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.
Baseline, Weeks 2, 4, 8, 12 and 16
Double-blind Induction Period: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at Weeks 8 and 16
Time Frame: 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.
Baseline, Weeks 8 and 16
Double-blind Induction Period: Change From Baseline in Pruritus NRS by Week up to Week 16
Time Frame: 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.
Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16
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
Time Frame: 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.
Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16
Double-blind Induction Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Weeks 4, 8, 12 and 16
Time Frame: 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.
Baseline, Weeks 4, 8, 12 and 16
Double-blind Induction Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 2. 4, 8, 12 and 16
Time Frame: 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.
Baseline, Weeks 2, 4, 8, 12 and 16
Double-blind Induction Period: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2. 4, 8, 12 and 16
Time Frame: 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.
Baseline, Weeks 2, 4, 8, 12 and 16
Double-blind Induction Period: Change From Baseline in Skin Pain NRS by Week up to Week 16
Time Frame: 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.
Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16
Double-blind Induction Period: Proportion of Topical Corticosteroids (TCS) Medication Free Days
Time Frame: 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
Baseline up to Week 16
Double-blind Induction Period: Median Time (Days) to TCS-Free Use
Time Frame: Baseline up to Week 16
Days from first study drug injection to the day participant stopped using all TCS.
Baseline up to Week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Almirall, S.A.

Investigators

  • Study Director: Study Director, Almirall, S.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 23, 2021

Primary Completion (Actual)

January 30, 2023

Study Completion (Actual)

May 7, 2024

Study Registration Dates

First Submitted

November 26, 2021

First Submitted That Met QC Criteria

November 26, 2021

First Posted (Actual)

December 8, 2021

Study Record Updates

Last Update Posted (Estimated)

May 20, 2025

Last Update Submitted That Met QC Criteria

April 30, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M-17923-30
  • 2021-002967-23 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe