A Study of Lebrikizumab in Combination With Topical Corticosteroids in Participants Having Atopic Dermatitis (AD) That Are Not Adequately Controlled or Non-eligible for Cyclosporine
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lebrikizumab Lebrikizumab administered subcutaneously (SC), 250 milligram (mg) dose once every two weeks (Q2W) in the induction period for 16 weeks. Participants achieving EASI75 at Week 16 will receive 1 injection each of 250 mg lebrikizumab and placebo at Week 16, no injections at Week 18 followed by 1 injection of lebrikizumab 250 mg once every four weeks (Q4W) after Week 20 up to Week 36. Participants not achieving EASI75 at Week 16 will receive 1 injection each of 250 mg lebrikizumab and placebo at Week 16 and 18, followed by 1 injection of lebrikizumab 250 mg Q2W after Week 20 up to Week 52. |
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 each of 250 mg lebrikizumab-matching placebo at Week 16, no injections at Week 18 followed by 1 injection of lebrikizumab- matching placebo 250 mg Q4W after Week 20 up to Week 36. |
Drug: Lebrikizumab-matching Placebo
Matching Placebo solution for injection administered subcutaneously.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving EASI 75 (>=75% Reduction From Baseline in EASI Score) at Week 16 [Baseline, Week 16]
The Eczema Area and Severity Index (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.
Secondary Outcome Measures
- Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and 2-point Improvement at Week 16 [Week 16]
The IGA is an instrument used to globally rate the severity of the participants'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 4-point Improvement in Pruritus Numeric Rating Score (NRS) [Week 16]
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 Achieving EASI90 [Week 16]
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 90 is defined as 90% reduction from baseline in the EASI score.
- Percentage of Participants Achieving EASI 75, 90 and 50 [Up to Week 16]
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. EASI 50 is defined as 50% reduction from baseline in the EASI score.
- Change From Baseline in Body Surface Area (BSA) [Baseline up to Week 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 will be 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.
- Change From Baseline in Scoring Atopic Dermatitis (SCORAD) [Baseline up to Week 16]
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 and reported as the sum of all areas, with a score ranging from 0 to 100. 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 visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), for maximum possible score of 20. Formula is: A/5+7B/2+C, A: extent (0-100), B: intensity (0-18), C: subjective symptoms (0-20). The maximum score is 103 (higher values worse outcome).
- Change From Baseline in Pruritus NRS [Baseline up to Week 16]
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."
- Change From Baseline in the Sleep Loss Using PRO [Baseline up to Week 16]
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 electronic Diary.
- Change from Baseline in Patient-Oriented Eczema Measure (POEM) [Baseline up to Week 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; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; every day = 4. A high score is indicative of a poor quality of life (QoL). POEM responses will be captured weekly using an electronic Diary.
- Change From Baseline in Dermatology Life Quality Index (DLQI)/Children Dermatology Life Quality Index (CDLQI) [Up to Week 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 is scored from 0 to 3 ("not at all," "a little," "a lot," and "very much"), giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL. 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. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
- Percentage of Participants Achieving a 4-point Improvement in DLQI/CDLQI [Up to Week 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 is scored from 0 to 3 ("not at all," "a little," "a lot," and "very much"), giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL. 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. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
- Percentage of Participants with Topical Corticosteroids (TCS)-free Days [Baseline up to Week 16]
Proportion of participants TCS- free days will be reported
- Time to TCS-free Use [Up to Week 16]
Time to TCS- free Use (days) will be reported
- Change from Baseline in Skin Pain NRS [Up to 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.
- Percentage of Participants Achieving a 4- point Improvement in Skin Pain NRS [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 O indicating "No pain" and 10 indicating "Worst pain imaginable.
Eligibility Criteria
Criteria
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 3 (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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alm Site 1 | Graz | Austria | ||
| 2 | Alm Site 2 | Gent | Belgium | ||
| 3 | Alm Site 14 | Bordeaux | France | ||
| 4 | Alm Site 17 | Le Mans | France | ||
| 5 | Alm Site 19 | Lille | France | ||
| 6 | Alm Site 20 | Lille | France | ||
| 7 | Alm Site 13 | Martigues | France | ||
| 8 | Alm Site 16 | Nantes | France | ||
| 9 | Alm Site 15 | Nice | France | ||
| 10 | Alm Site 18 | Pierre-Bénite | France | ||
| 11 | Alm Site 12 | Reims | France | ||
| 12 | Alm Site 28 | Bad Bentheim | Germany | ||
| 13 | Alm Site 30 | Berlin | Germany | ||
| 14 | Alm Site 24 | Blankenfelde | Germany | ||
| 15 | Alm Site 32 | Bonn | Germany | ||
| 16 | Alm Site 31 | Frankfurt | Germany | ||
| 17 | Alm Site 27 | Göttingen | Germany | ||
| 18 | Alm Site 26 | Hamburg | Germany | ||
| 19 | Alm Site 29 | Kiel | Germany | ||
| 20 | Alm Site 25 | Marburg | Germany | ||
| 21 | Alm Site 34 | Bergen Op Zoom | Netherlands | ||
| 22 | Alm Site 33 | Rotterdam | Netherlands | ||
| 23 | Alm Site 35 | Utrecht | Netherlands | ||
| 24 | Alm Site 45 | Białystok | Poland | ||
| 25 | Alm Site 43 | Chorzów | Poland | ||
| 26 | Alm Site 38 | Katowice | Poland | ||
| 27 | Alm Site 41 | Kraków | Poland | ||
| 28 | Alm Site 46 | Kraków | Poland | ||
| 29 | Alm Site 39 | Lublin | Poland | ||
| 30 | Alm Site 48 | Ostrowiec Świętokrzyski | Poland | ||
| 31 | Alm Site 44 | Rzeszów | Poland | ||
| 32 | Alm Site 36 | Szczecin | Poland | ||
| 33 | Alm Site 42 | Warsaw | Poland | ||
| 34 | Alm Site 47 | Warszawa | Poland | ||
| 35 | Alm Site 40 | Wrocław | Poland | ||
| 36 | Alm Site 37 | Łódź | Poland | ||
| 37 | Alm Site 10 | Alicante | Spain | ||
| 38 | Alm Site 3 | Badalona | Spain | ||
| 39 | Alm Site 6 | Barcelona | Spain | ||
| 40 | Alm Site 8 | Barcelona | Spain | ||
| 41 | Alm Site 4 | Bilbao | Spain | ||
| 42 | Alm Site 5 | Madrid | Spain | ||
| 43 | Alm Site 11 | Mieres | Spain | ||
| 44 | Alm Site 7 | Sevilla | Spain | ||
| 45 | Alm Site 9 | Zaragoza | Spain | ||
| 46 | Alm Site 23 | Poole | United Kingdom | ||
| 47 | Alm Site 22 | Salford | United Kingdom | ||
| 48 | Alm Site 21 | Southampton | United Kingdom |
Sponsors and Collaborators
- Almirall, S.A.
Investigators
- Study Director: Study Director, Almirall, S.A.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M-17923-30
- 2021-002967-23