Atopic Dermatitis
Conditions
Keywords
Eczema, Dermatitis, Dermatitis, Atopic, Skin Diseases
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-group study which is 52 weeks in duration. The study is designed to confirm the safety and efficacy of lebrikizumab as monotherapy for treatment of moderate-to-severe atopic dermatitis utilizing a 16-week induction treatment period and a 36-week long-term maintenance treatment period.
Interventions
BIOLOGICALLebrikizumab
Subcutaneous injection
OTHERPlacebo
Subcutaneous Injection
Sponsors
Dermira, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Randomized, double-blind, parallel group, placebo controlled
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults and adolescents (≥12 years and ≥40 kg) * Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit * Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit * Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit * ≥10% body surface area (BSA) of atopic dermatitis involvement at the baseline visit * History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable
Exclusion criteria
* Prior treatment with dupilumab or tralokinumab * Treatment with topical corticosteroids, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit * Treatment with any of the following agents within 4 weeks prior to the baseline visit: * Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) * Phototherapy and photochemotherapy (PUVA) for AD * Treatment with the following prior to the baseline visit: * An investigational drug within 8 weeks or within 5 half-lives (if known) of baseline, whichever is longer * Cell-depleting biologics, including to rituximab, within 6 months of baseline * Other biologics within 5 half-lives (if known) or 16 weeks of baseline, whichever is longer * Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study * Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma * Evidence of active acute or chronic hepatitis * History of human immunodeficiency virus (HIV) infection or positive HIV serology * 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 non-metastatic squamous or basal cell carcinoma of the skin * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | Baseline to Week 16 | The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16 | Baseline to Week 16 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% reduction from baseline in the EASI score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | Baseline to Week 16 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16 | Baseline to Week 16 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score. |
| Percentage Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | Baseline, Week 16 | 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. Least Squares (LS) Mean was calculated using analysis of covariance (ANCOVA) model with treatment and randomization strata (region, disease severity, age) as fixed factors and baseline value as covariate. |
| Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | Baseline to Week 16 | 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 a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | Baseline to Week 16 | 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 Change in EASI Score From Baseline to Week 16 | Baseline, Week 16 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). LS Mean was calculated using ANCOVA model with treatment, stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors baseline value as covariate. |
| Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | Baseline, Week 16 | The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD. |
| Percentage of Participants Achieving EASI-90 From Baseline to Week 4 | Baseline to Week 4 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline, Week 16 | The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. |
| Percentage of Participants Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | Baseline to Week 16 | The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. |
| Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | Baseline to Week 16 | The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. |
| Percentage Change in Sleep-loss Score From Baseline to Week 16 | Baseline, Week 16 | Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. |
| Change From Baseline in Sleep-loss Score at Week 16 | Baseline, Week 16 | Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. |
| Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline to Week 16 | Baseline to Week 16 | Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. |
| Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | Baseline to Week 1 | 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 a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | Baseline to Week 2 | 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 a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | Baseline to Week 4 | 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 a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | Baseline to Week 1 | 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 an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2 | Baseline to Week 2 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | Baseline to Week 4 | 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 Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16 | Baseline, Week 16 | SCORAD is validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on visual analog scale (VAS), where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7\*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Pharmacokinetics (PK): Trough Serum Concentrations of Lebrikizumab in Maintenance Period (C-trough) | Predose at Week 52 | C-trough was the concentration of study drug in the blood immediately before the next dose was administered. Trough serum concentration of Lebrikizumab was assessed at predose week 52. |
| Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score) | Baseline to Week 52 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% reduction from baseline in the EASI score. |
| Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52 | Baseline to Week 52 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | Baseline to Week 52 | 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 From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | Baseline to Week 52 | 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 Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52 | Baseline, Week 52 | SCORAD is a validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on VAS, where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7\*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index | Baseline, Week 16 | The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a is a 2-part questionnaire which measure health status of the participant. The first component (Health state) is a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS) | Baseline, Week 16 | The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | Baseline, Week 16 | POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed. |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16-Adolescents | Baseline, Week 16 | PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in PROMIS Anxiety at Week 16 - Adults | Baseline, Week 16 | PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in PROMIS Depression at Week 16- Adolescents | Baseline, Week 16 | PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in PROMIS Depression at Week 16- Adults | Baseline, Week 16 | PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma | Baseline, Week 16 | The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicate lower asthma control. LS Mean was calculated using ANCOVA with treatment, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate. |
| Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 | Baseline, Week 16 | The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors. |
| Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | Baseline to Week 2 | 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 an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4 | Baseline to Week 4 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
Countries
Bulgaria, Canada, Germany, Mexico, Singapore, Taiwan, Ukraine, United States
Participant flow
Recruitment details
During the Induction period (16-weeks): Participants were randomly assigned to either 250 mg lebrikizumab Q2W or placebo; At week 16, participants who responded to treatment, defined as having an Investigator Global Assessment (IGA) of 0 or 1 or a 75% reduction in Eczema Area and Severity Index (EASI-75) from Baseline to Week 16 entered Maintenance Period and were re-randomized (2:2:1) to: lebrikizumab 250 mg Q2W, lebrikizumab 250 mg Q4W, or placebo (Continued)
Pre-assignment details
(Continued) Induction non-responder (i.e.) participants who do not achieve an IGA of 0 or 1 or an EASI-75 at Week 16 and maintenance non-responders (i.e.) those not maintaining an EASI-50 response at week 24, 32, 40, and 48 following week 16 re-randomization were assigned to an Escape Arm and received lebrikizumab 250 mg as open-label treatment Q2W through Week 52.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Induction Period (Baseline-Week 16):
Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14. | 150 |
| Lebrikizumab Q2W Induction Period (Baseline-Week 16):
500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14. | 295 |
| Total | 445 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Period | Adverse Event | 4 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Due to Epidemic/Pandemic | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lack of Efficacy | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lost to Follow-up | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Participant Missed Study Visits | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Protocol Violation | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Withdrawal by Subject | 6 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Entered Escape Arm | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 6 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Sponsor Decision | 0 | 0 | 1 | 1 | 1 | 1 | 4 | 6 | 0 | 0 | 0 |
| Maintenance Blinded Treatment Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 4 | 0 | 0 | 0 |
| Maintenance Open Label Escape Arm | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 0 |
| Maintenance Open Label Escape Arm | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 27 | 2 |
| Maintenance Open Label Escape Arm | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Open Label Escape Arm | Participant Missed Study Visits | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Open Label Escape Arm | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Open Label Escape Arm | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 9 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Lebrikizumab Q2W |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 50 Participants | 33 Participants |
| Age, Categorical >=65 years | 10 Participants | 33 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 123 Participants | 362 Participants | 239 Participants |
| Age, Continuous | 35.6 years STANDARD_DEVIATION 17.15 | 36.2 years STANDARD_DEVIATION 16.8 | 36.5 years STANDARD_DEVIATION 16.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 44 Participants | 122 Participants | 78 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 36 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 89 Participants | 270 Participants | 181 Participants |
| Region of Enrollment Bulgaria | 7 Participants | 22 Participants | 15 Participants |
| Region of Enrollment Canada | 16 Participants | 58 Participants | 42 Participants |
| Region of Enrollment Germany | 28 Participants | 81 Participants | 53 Participants |
| Region of Enrollment Mexico | 3 Participants | 9 Participants | 6 Participants |
| Region of Enrollment Singapore | 8 Participants | 19 Participants | 11 Participants |
| Region of Enrollment Taiwan | 21 Participants | 60 Participants | 39 Participants |
| Region of Enrollment Ukraine | 3 Participants | 11 Participants | 8 Participants |
| Region of Enrollment United States | 64 Participants | 185 Participants | 121 Participants |
| Sex: Female, Male Female | 79 Participants | 226 Participants | 147 Participants |
| Sex: Female, Male Male | 71 Participants | 219 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 149 | 0 / 295 | 0 / 30 | 0 / 59 | 0 / 59 | 0 / 5 | 0 / 9 | 0 / 11 | 0 / 108 | 1 / 125 | 0 / 11 |
| other Total, other adverse events | 97 / 149 | 157 / 295 | 15 / 30 | 32 / 59 | 36 / 59 | 3 / 5 | 4 / 9 | 8 / 11 | 68 / 108 | 77 / 125 | 5 / 11 |
| serious Total, serious adverse events | 4 / 149 | 2 / 295 | 1 / 30 | 0 / 59 | 2 / 59 | 0 / 5 | 2 / 9 | 0 / 11 | 1 / 108 | 5 / 125 | 0 / 11 |
Outcome results
Primary
Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% reduction from baseline in the EASI score.
Time frame: Baseline to Week 16
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16 | 18.1 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16 | 52.1 percentage of participants |
p-value: <0.00000195% CI: [24.4, 42.2]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Baseline to Week 16
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to Good Clinical Practice (GCP) issues. Markov Chain Monte Carlo Multiple Imputation (MCMC-MI) was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | 10.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | 33.2 percentage of participants |
p-value: 0.00000495% CI: [14.2, 29.6]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma
The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicate lower asthma control. LS Mean was calculated using ANCOVA with treatment, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, with non-missing baseline ACQ-5 score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma | 0.19 score on a scale | Standard Error 0.14 |
| Lebrikizumab Q2W | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma | 0.19 score on a scale | Standard Error 0.108 |
p-value: 0.97441795% CI: [-0.27, 0.26]ANCOVA
Secondary
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16
The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors.
Time frame: Baseline, Week 16
Population: All randomized, adolescent participants, with non-missing baseline CDLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MMRM was used to handle all missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 | -3.4 score on a scale | Standard Error 2.1 |
| Lebrikizumab Q2W | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 | -7.6 score on a scale | Standard Error 1.13 |
p-value: 0.08476995% CI: [-9.1, 0.6]Mixed Models Analysis
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time frame: Baseline, Week 16
Population: All randomized participants, with non-missing baseline DLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -2.4 score on a scale | Standard Error 1.17 |
| Lebrikizumab Q2W | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -7.3 score on a scale | Standard Error 1.16 |
p-value: <0.00000195% CI: [-6.3, -3.5]ANCOVA
Secondary
Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)
The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, with non-missing EQ-5D-5L-VAS data at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS) | 5.2 millimeters (mm) | Standard Error 1.62 |
| Lebrikizumab Q2W | Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS) | 9.7 millimeters (mm) | Standard Error 1.36 |
p-value: 0.00530495% CI: [1.3, 7.6]ANCOVA
Secondary
Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index
The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a is a 2-part questionnaire which measure health status of the participant. The first component (Health state) is a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, with non-missing EQ-5D-5L- Health State Index data at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing Values were imputed using last observation carried forward (LOCF) method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index | Health State Index US | 0.0 score on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index | Health State Index UK | 0.0 score on a scale | Standard Error 0.02 |
| Lebrikizumab Q2W | Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index | Health State Index UK | 0.1 score on a scale | Standard Error 0.02 |
| Lebrikizumab Q2W | Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index | Health State Index US | 0.1 score on a scale | Standard Error 0.01 |
Comparison: UKp-value: 0.00000195% CI: [0.1, 0.1]ANCOVA
Comparison: USp-value: 0.00000195% CI: [0, 0.1]ANCOVA
Secondary
Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed.
Time frame: Baseline, Week 16
Population: All randomized participants, with observed POEM data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MMRM was used to handle all missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | -3.5 score on a scale | Standard Error 0.77 |
| Lebrikizumab Q2W | Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | -9.5 score on a scale | Standard Error 0.52 |
p-value: <0.00000195% CI: [-7.7, -4.3]Mixed Models Analysis
Secondary
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16-Adolescents
PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized, adolescent participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16-Adolescents | 0.12 T-score | Standard Error 2.129 |
| Lebrikizumab Q2W | Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16-Adolescents | -2.79 T-score | Standard Error 1.55 |
p-value: 0.24127595% CI: [-7.85, 2.03]ANCOVA
Secondary
Change From Baseline in Percent Body Surface Area (BSA) at Week 16
The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD.
Time frame: Baseline, Week 16
Population: All randomized participants, with observed BSA data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. The MMRM included treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, geographic region, age group, baseline IGA score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | -14.0 percentage of BSA | Standard Error 1.94 |
| Lebrikizumab Q2W | Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | -30.2 percentage of BSA | Standard Error 1.33 |
p-value: <0.00000195% CI: [-20.3, -12]Mixed Models Analysis
Secondary
Change From Baseline in PROMIS Anxiety at Week 16 - Adults
PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized, adults participants, with Week 16 PROMIS anxiety data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing Values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PROMIS Anxiety at Week 16 - Adults | -0.45 T-score | Standard Error 0.58 |
| Lebrikizumab Q2W | Change From Baseline in PROMIS Anxiety at Week 16 - Adults | -3.18 T-score | Standard Error 0.422 |
p-value: 0.00011695% CI: [-4.12, -1.36]ANCOVA
Secondary
Change From Baseline in PROMIS Depression at Week 16- Adolescents
PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized, adolescent participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PROMIS Depression at Week 16- Adolescents | -0.57 T-score | Standard Error 2.047 |
| Lebrikizumab Q2W | Change From Baseline in PROMIS Depression at Week 16- Adolescents | -1.67 T-score | Standard Error 1.493 |
p-value: 0.64513295% CI: [-5.86, 3.67]ANCOVA
Secondary
Change From Baseline in PROMIS Depression at Week 16- Adults
PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized, adult participants, with Week 16 PROMIS Depression data, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PROMIS Depression at Week 16- Adults | 0.16 T-score | Standard Error 0.54 |
| Lebrikizumab Q2W | Change From Baseline in PROMIS Depression at Week 16- Adults | -2.59 T-score | Standard Error 0.392 |
p-value: 0.00003195% CI: [-4.03, -1.47]ANCOVA
Secondary
Change From Baseline in Sleep-loss Score at Week 16
Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time frame: Baseline, Week 16
Population: All randomized participants, with non-missing baseline Sleep-loss score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sleep-loss Score at Week 16 | -0.35 score on a scale | Standard Error 0.095 |
| Lebrikizumab Q2W | Change From Baseline in Sleep-loss Score at Week 16 | -1.05 score on a scale | Standard Error 0.08 |
p-value: <0.00000195% CI: [-0.9, -0.5]ANCOVA
Secondary
Percentage Change in EASI Score From Baseline to Week 16
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). LS Mean was calculated using ANCOVA model with treatment, stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in EASI Score From Baseline to Week 16 | -27.96 percent change | Standard Error 3.893 |
| Lebrikizumab Q2W | Percentage Change in EASI Score From Baseline to Week 16 | -61.53 percent change | Standard Error 3.3 |
p-value: <0.00000195% CI: [-41.2, -26]ANCOVA
Secondary
Percentage Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
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. Least Squares (LS) Mean was calculated using analysis of covariance (ANCOVA) model with treatment and randomization strata (region, disease severity, age) as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, with a Baseline Pruritus NRS score \>0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | -9.02 percentage change | Standard Error 3.868 |
| Lebrikizumab Q2W | Percentage Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | -36.56 percentage change | Standard Error 3.321 |
p-value: <0.00000195% CI: [-34.9, -20.2]ANCOVA
Secondary
Percentage Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52
SCORAD is a validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on VAS, where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7\*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 52
Population: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period and had evaluable data at week 52. Missing Values were imputed using LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52 | -67.60 percent change | Standard Error 3.767 |
| Lebrikizumab Q2W | Percentage Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52 | -73.89 percent change | Standard Error 2.718 |
| Maintenance Blinded Treatment - Lebrikizumab Responder/Lebrikizumab 250 Q2W | Percentage Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52 | -73.85 percent change | Standard Error 2.764 |
p-value: 0.17674895% CI: [-15.46, 2.87]ANCOVA
p-value: 0.18315195% CI: [-15.48, 2.99]ANCOVA
Secondary
Percentage Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16
SCORAD is validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on visual analog scale (VAS), where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7\*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Time frame: Baseline, Week 16
Population: All randomized participants, with baseline SCORAD \>0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. Missing Values were imputed using last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16 | -13.81 percent change | Standard Error 3.197 |
| Lebrikizumab Q2W | Percentage Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16 | -44.57 percent change | Standard Error 2.677 |
p-value: <0.00000195% CI: [-36.93, -24.59]ANCOVA
Secondary
Percentage Change in Sleep-loss Score From Baseline to Week 16
Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time frame: Baseline, Week 16
Population: All randomized participants, with baseline sleep-loss score \>0, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Sleep-loss Score From Baseline to Week 16 | -11.29 percent change | Standard Error 5.393 |
| Lebrikizumab Q2W | Percentage Change in Sleep-loss Score From Baseline to Week 16 | -48.37 percent change | Standard Error 4.59 |
p-value: <0.00000195% CI: [-47.4, -26.8]ANCOVA
Secondary
Percentage of Participants Achieving ≥4-point Improvement in DLQI From Baseline to Week 16
The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.
Time frame: Baseline to Week 16
Population: All randomized participants, with non-missing baseline DLQI score, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | 32.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | 65.4 percentage of participants |
p-value: 0.00000195% CI: [22.2, 43.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score.
Time frame: Baseline to Week 16
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16 | 9.5 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16 | 30.7 percentage of participants |
p-value: 0.00000895% CI: [13.3, 28.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving EASI-90 From Baseline to Week 4
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score.
Time frame: Baseline to Week 4
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving EASI-90 From Baseline to Week 4 | 1.5 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants Achieving EASI-90 From Baseline to Week 4 | 6.3 percentage of participants |
p-value: 0.02292195% CI: [1.4, 8.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% reduction from baseline in the EASI score.
Time frame: Baseline to Week 52
Population: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period and had evaluable EASI-75 data at week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score) | 72.0 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score) | 84.7 percentage of participants |
| Maintenance Blinded Treatment - Lebrikizumab Responder/Lebrikizumab 250 Q2W | Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score) | 77.4 percentage of participants |
p-value: 0.23824595% CI: [-9.5, 35.1]Cochran-Mantel-Haenszel
p-value: 0.61242795% CI: [-17.8, 27.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Baseline to Week 52
Population: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period and had evaluable IGA data at week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52 | 49.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52 | 80.6 percentage of participants |
| Maintenance Blinded Treatment - Lebrikizumab Responder/Lebrikizumab 250 Q2W | Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52 | 64.6 percentage of participants |
p-value: 0.03387695% CI: [2.6, 62.5]Cochran-Mantel-Haenszel
p-value: 0.40741795% CI: [-17.5, 44.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52
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.
Time frame: Baseline to Week 52
Population: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period and had evaluable data at week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 67.6 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 88.1 percentage of participants |
| Maintenance Blinded Treatment - Lebrikizumab Responder/Lebrikizumab 250 Q2W | Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 90.3 percentage of participants |
p-value: 0.15928195% CI: [-11.4, 52]Cochran-Mantel-Haenszel
p-value: 0.1649595% CI: [-10.6, 51.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52
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.
Time frame: Baseline to Week 52
Population: All participants who were randomized to Lebrikizumab 250 mg Q2W at Baseline Visit and re-randomized to Lebrikizumab 250 mg Q2W, Lebrikizumab 250 mg Q4W or placebo at Week 16 and received at least 1 dose of study treatment during the maintenance period and had evaluable data at week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 67.6 percentage of partcipants |
| Lebrikizumab Q2W | Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 87.4 percentage of partcipants |
| Maintenance Blinded Treatment - Lebrikizumab Responder/Lebrikizumab 250 Q2W | Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52 | 94.4 percentage of partcipants |
p-value: 0.17970495% CI: [-12.2, 51.2]Cochran-Mantel-Haenszel
p-value: 0.0830895% CI: [-6.5, 55.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16
The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. 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, over the previous week. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.
Time frame: Baseline to Week 16
Population: All randomized participants, with a DLQI Total Score of ≥4-point at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | 33.6 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16 | 66.3 percentage of participants |
p-value: 0.00000195% CI: [22.2, 43.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Baseline to Week 16
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | 10.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 | 33.2 percentage of participants |
p-value: 0.00000495% CI: [14.2, 29.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Baseline to Week 2
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2 | 0 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2 | 0.7 percentage of participants |
p-value: 0.30846395% CI: [-0.3, 1.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Baseline to Week 4
Population: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4 | 1.4 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4 | 9.0 percentage of participants |
p-value: 0.00160795% CI: [4.1, 12]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
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.
Time frame: Baseline to Week 1
Population: All randomized participants, with a Pruritus NRS Score of ≥4 Points at baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | 0.0 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | 0.4 percentage of participants |
p-value: 0.46922195% CI: [-0.4, 1.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
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.
Time frame: Baseline to Week 2
Population: All randomized participants, with a Pruritus NRS Score of ≥4 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | 0.7 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | 3.6 percentage of participants |
p-value: 0.11319495% CI: [-0.1, 5.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
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.
Time frame: Baseline to Week 4
Population: All randomized participants, with a Pruritus NRS Score of ≥4 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | 3.0 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | 16.8 percentage of participants |
p-value: 0.0002395% CI: [7.7, 18.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16
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.
Time frame: Baseline to Week 16
Population: All randomized participants, with a Baseline Pruritus NRS score ≥4, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | 11.5 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | 39.8 percentage of participants |
p-value: <0.00000195% CI: [20, 36.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
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.
Time frame: Baseline to Week 1
Population: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | 0.0 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1 | 0.4 percentage of participants |
p-value: 0.4681695% CI: [-0.4, 1.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
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.
Time frame: Baseline to Week 2
Population: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | 0.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2 | 3.9 percentage of participants |
p-value: 0.1157795% CI: [-0.1, 5.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
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.
Time frame: Baseline to Week 4
Population: All randomized participants, with a Pruritus NRS Score of ≥5 Points at Baseline, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | 3.3 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4 | 18.1 percentage of participants |
p-value: 0.00025295% CI: [8.2, 20.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16
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.
Time frame: Baseline to Week 16
Population: All randomized participants, with Baseline Pruritus NRS score ≥ 5, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | 11.8 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16 | 41.6 percentage of participants |
p-value: <0.00000195% CI: [21, 38.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline to Week 16
Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary.
Time frame: Baseline to Week 16
Population: All randomized participants, with baseline sleep-loss score ≥2 Points, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with eighteen participants was excluded from analysis due to GCP issues. MCMC-MI was used to handle missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline to Week 16 | 8.2 percentage of participants |
| Lebrikizumab Q2W | Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline to Week 16 | 28.0 percentage of participants |
p-value: 0.00057195% CI: [9.6, 28.1]Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics (PK): Trough Serum Concentrations of Lebrikizumab in Maintenance Period (C-trough)
C-trough was the concentration of study drug in the blood immediately before the next dose was administered. Trough serum concentration of Lebrikizumab was assessed at predose week 52.
Time frame: Predose at Week 52
Population: All participants who received 250 mg Q2W or 250 mg Q4W in the Maintenance Period and had evaluable PK data at Week 52. The 250 mg Q2W PK population also includes participants from the Escape Arm (Induction period non-responders and Maintenance Period non-responders who received open-label 250 mg Q2W dosing).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Trough Serum Concentrations of Lebrikizumab in Maintenance Period (C-trough) | 46.7 micrograms/milliliter (µg/mL) | Standard Deviation 24.8 |
| Lebrikizumab Q2W | Pharmacokinetics (PK): Trough Serum Concentrations of Lebrikizumab in Maintenance Period (C-trough) | 90.5 micrograms/milliliter (µg/mL) | Standard Deviation 40.1 |