A Study of Lebrikizumab (LY3650150) in Participants With Moderate-to-Severe Atopic Dermatitis
- Conditions
- Atopic Dermatitis
- Interventions
- Biological: LebrikizumabDrug: Placebo
- Registration Number
- NCT03443024
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of lebrikizumab compared with placebo in participants with moderate-to-severe atopic dermatitis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 280
- Male or female, 18 years or older.
- Chronic AD as defined by Hanifin and Rajka (1980) that has been present for ≥1 year before the screening visit .
- Eczema Area and Severity Index (EASI) score ≥16 at the screening and the baseline visit.
- Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the screening and the baseline visit.
- ≥10% body surface area (BSA) of AD involvement at the screening and 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 topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week prior to the baseline visit.
- Treatment with:
- An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to the baseline visit.
- Dupilumab within 3 months prior to baseline visit.
- Cell-depleting biologics, including rituximab, within 6 months prior to the baseline visit.
- Other biologics within 5 half-lives (if known) or 16 weeks prior to baseline visit (whichever is longer).
- Use of prescription moisturizers within 7 days of the baseline visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 125 milligrams (mg) Lebrikizumab - Every 4 Weeks (Q4W) Lebrikizumab 125 mg Lebrikizumab administered subcutaneously (SC) once Q4W. Baseline: Loading dose 250 mg Lebrikizumab SC (two injections SC 1-milliliter (mL) of 125 mg/mL Lebrikizumab and 1-mL placebo). Week 2: Four 1-mL SC injections placebo. Weeks 4, 8, 12: 125 mg SC Lebrikizumab and 1-mL SC placebo. Weeks 6, 10, 14: Two 1-mL SC placebo. 125 milligrams (mg) Lebrikizumab - Every 4 Weeks (Q4W) Placebo 125 mg Lebrikizumab administered subcutaneously (SC) once Q4W. Baseline: Loading dose 250 mg Lebrikizumab SC (two injections SC 1-milliliter (mL) of 125 mg/mL Lebrikizumab and 1-mL placebo). Week 2: Four 1-mL SC injections placebo. Weeks 4, 8, 12: 125 mg SC Lebrikizumab and 1-mL SC placebo. Weeks 6, 10, 14: Two 1-mL SC placebo. 250 mg Lebrikizumab - Q4W Lebrikizumab 250 mg Lebrikizumab administered SC once Q4W. Baseline: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 2: Four 1-mL SC injections of placebo. Weeks 4, 8, 12: 250 mg (two 1-mL injections of 125 mg/mL Lebrikizumab). Weeks 6, 10, 14: Two 1-mL injections of placebo. 250 mg Lebrikizumab - Q4W Placebo 250 mg Lebrikizumab administered SC once Q4W. Baseline: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 2: Four 1-mL SC injections of placebo. Weeks 4, 8, 12: 250 mg (two 1-mL injections of 125 mg/mL Lebrikizumab). Weeks 6, 10, 14: Two 1-mL injections of placebo. 250 mg Lebrikizumab - Every 2 Weeks (Q2W) Lebrikizumab 250 mg Lebrikizumab administered SC once Q2W. Baseline and Week 2: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 4, 6, 8, 10, 12, 14: 250 mg (two 1-mL SC injections of 125 mg/mL Lebrikizumab). 250 mg Lebrikizumab - Every 2 Weeks (Q2W) Placebo 250 mg Lebrikizumab administered SC once Q2W. Baseline and Week 2: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 4, 6, 8, 10, 12, 14: 250 mg (two 1-mL SC injections of 125 mg/mL Lebrikizumab). Group 4 - Placebo Placebo Placebo administered SC once Q2W. Baseline and Week 2: Four 1-mL SC injections of placebo. Week 4, 6, 8, 10, 12, 14: Two 1-mL SC injections of placebo.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Eczema Area and Severity Index (EASI) Baseline, Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - 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).
Least Square (LS) Means were calculated using analysis of covariance (ANCOVA) with the factor of treatment and the baseline EASI as covariate.
Note: Missing values were imputed using Markov Chain Monte Carlo (MCMC) multiple imputation.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a 75% Improvement From Baseline in EASI (EASI75) at Week 16 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - 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 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥2 Points From Baseline to Week 16 (5-point Scale) 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 With EASI <7 at Week 16 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - 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).
Percentage of Participants Achieving EASI50 at Week 16 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - 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 responder is defined as a participant who achieves a ≥ 50% improvement from baseline in the EASI score.Percentage of Participants Achieving EASI90 at Week 16 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - 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 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI scorePercent Change From Baseline in Pruritus Numeric Rating Score (NRS) Baseline, Week 16 The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Pruritus assessments were recorded daily by the participant using an electronic diary.
LS Means were calculated using ANCOVA with the factor of treatments and the baseline pruritus NRS as covariates.Percentage of Participants With Pruritus NRS Change of ≥3 at Week 16 Week 16 The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary.
The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 3-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test.Percentage of Participants With Pruritus NRS Change of ≥4 From Baseline to Week 16 Week 16 The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary.
The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 4-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test.Change From Baseline in Body Surface Area (BSA) Involved With Atopic Dermatitis (AD) Baseline, Week 16 The body surface area (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.
Percent Change From Baseline in the Sleep Loss Scale Score Baseline, Week 16 The Sleep Loss Scale is used by the participants to report the impact of itching on their sleep every night. Participants responded to the question to what extent did your itching interfere with your sleep last night. The scale ranged from 0 to 4, with 0 (not at all) to 4 (unable to sleep at all). Higher scores indicated a greater impact and worse outcome. Assessments were recorded daily by the participant using an electronic diary.
Least Squares (LS) Means were calculated using ANCOVA with the factor of treatment and the baseline sleep-loss scale as covariates.Change From Baseline in Atopic Dermatitis Impact Questionnaire (ADIQ) Score Baseline, Week 16 The ADIQ is a 17-item questionnaire used to assess the participant's AD-specific health-related quality of life. Each item is rated on a 5-point scale from 0 to 4, with higher numbers indicating greater burden. The questionnaire assesses AD's impact on emotions, energy, activities of daily living, and social activities. The ADIQ has a recall specification of 7 days. Assessments were recorded by the participant using an electronic diary and transferred to the clinical database.The ADIQ score is calculated by summing the score of each of the 14 questions resulting in a maximum of 56 and a minimum of 0, with higher scores indicating greater burden.
Trial Locations
- Locations (57)
Menter Dermatology Research
🇺🇸Dallas, Texas, United States
Integrated Clinical Research, LLC
🇺🇸West Palm Beach, Florida, United States
Arlington Research Center, Inc.
🇺🇸Arlington, Texas, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Dermatology Research Associates
🇺🇸Los Angeles, California, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸Indianapolis, Indiana, United States
Dermatology Associates of Seattle
🇺🇸Seattle, Washington, United States
UCSD Dermatology
🇺🇸San Diego, California, United States
Progressive Clinical Research, PA
🇺🇸San Antonio, Texas, United States
Total Vein and Skin
🇺🇸Boynton Beach, Florida, United States
Florida Academic Centers Research and Education, LLC
🇺🇸Coral Gables, Florida, United States
Academic Dermatology Associates
🇺🇸Albuquerque, New Mexico, United States
Clear Dermatology & Aesthetics Center
🇺🇸Scottsdale, Arizona, United States
Wake Research Associates, LLC
🇺🇸Raleigh, North Carolina, United States
TCR Medical Corporation
🇺🇸San Diego, California, United States
International Clinical Research - US, LLC
🇺🇸Sanford, Florida, United States
Dundee Dermatology
🇺🇸West Dundee, Illinois, United States
Clinical Science Institute
🇺🇸Santa Monica, California, United States
JDR Dermatology Research
🇺🇸Las Vegas, Nevada, United States
Advanced Medical Research, PC
🇺🇸Sandy Springs, Georgia, United States
Dermatology and Skin Cancer Specialists, LLC
🇺🇸Rockville, Maryland, United States
Icahn School of Medicine
🇺🇸New York, New York, United States
Marietta Dermatology Clinical Research, Inc.
🇺🇸Marietta, Georgia, United States
Meridian Clinical Research, LLC
🇺🇸Baton Rouge, Louisiana, United States
Wilmington Dermatology Center
🇺🇸Wilmington, North Carolina, United States
Kansas City Dermatology, PA
🇺🇸Overland Park, Kansas, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Tennessee Clinical Research Center
🇺🇸Nashville, Tennessee, United States
Dermatology Trial Associates
🇺🇸Bryant, Arkansas, United States
Northwest Arkansas Clinical Trials Center
🇺🇸Rogers, Arkansas, United States
Center for Dermatology Clinical Research, Inc.
🇺🇸Fremont, California, United States
Stanford Medicine Outpatient Center-Medical Dermatology Clinic
🇺🇸Redwood City, California, United States
George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Tory Sullivan, MD PA
🇺🇸North Miami Beach, Florida, United States
Olympian Clinical Research
🇺🇸Largo, Florida, United States
The Indiana Clinical Trials Center
🇺🇸Plainfield, Indiana, United States
ActivMed Practices & Research, Inc.
🇺🇸Portsmouth, New Hampshire, United States
Sadick Research Group, LLC.
🇺🇸New York, New York, United States
Piedmont Plastic Surgery and Dermatology
🇺🇸Charlotte, North Carolina, United States
Schweiger Dermatology, PLLC
🇺🇸New York, New York, United States
DermResearchCenter of New York, Inc.
🇺🇸Stony Brook, New York, United States
Clinical Partners, LLC
🇺🇸Johnston, Rhode Island, United States
Rivergate Dermatology Clinical Research Center
🇺🇸Goodlettsville, Tennessee, United States
International Clinical Research - Tennessee LLC
🇺🇸Murfreesboro, Tennessee, United States
Bellaire Dermatology Associates
🇺🇸Bellaire, Texas, United States
The University of Texas Health
🇺🇸Houston, Texas, United States
Center for Clinical Studies, LTD. LLP
🇺🇸Webster, Texas, United States
Virginia Clinical Research, Inc.
🇺🇸Norfolk, Virginia, United States
Premier Clinical Research
🇺🇸Spokane, Washington, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Center for Dermatology and Laser Surgery
🇺🇸Sacramento, California, United States
Skin Sciences, PLLC
🇺🇸Louisville, Kentucky, United States
Oregon Medical Research Center
🇺🇸Portland, Oregon, United States
Clinical Research Center of the Carolinas
🇺🇸Charleston, South Carolina, United States
Westlake Dermatology Clinical Research Center
🇺🇸Austin, Texas, United States
Somerset Skin Centre
🇺🇸Troy, Michigan, United States