A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lebrikizumab in Patients With Persistent Moderate to Severe Atopic Dermatitis That is Inadequately Controlled by Topical Corticosteroids
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 212
- 试验地点
- 74
- 主要终点
- Percentage of Participants Achieving a 50 Percent (%) Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-50) at Week 12
研究概览
简要总结
This randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of lebrikizumab administered subcutaneously (SC) in adult participants with persistent moderate to severe atopic dermatitis (AD) who are inadequately controlled by topical corticosteroids (TCS). The study includes a screening visit, a 2-week run-in period, a 12-week blinded treatment period, and an 8-week safety follow-up period. Following screening visit, eligible participants will enter in run-in period (Days - 14 to - 1) during which a protocol-specified topical therapy regimen will be initiated. At the end of the run-in period, participants who have: 1) demonstrated compliance with the protocol-specified TCS regimen, and 2) who continue to fulfill the eligibility criteria will be randomized.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AD diagnosed by the Hanifin/Rajka criteria and that has been present for at least 1 year at screening
- •Moderate to severe AD as graded by the Rajka/Langeland criteria at screening
- •History of inadequate response to a >/= 1 month (within the 3 months prior to the screening visit) treatment regimen of at least daily TCS and regular emollient for treatment of AD
- •EASI score >/= 14 at screening and end of the run-in period
- •IGA score >/= 3 (5-point scale) at screening and end of the run-in period
- •AD involvement of >/= 10% BSA at screening
- •Pruritus VAS score >/= 3 at screening
排除标准
- •Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
- •Use of an investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is longer
- •History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
- •Use of any complementary, alternative, or homeopathic medicines including, but not limited to, phytotherapies, traditional or non-traditional herbal medications, essential fatty acids, or acupuncture within 7 days prior to the run-in period or need for such medications during the study
- •Evidence of other skin conditions; including, but not limited to, T-cell lymphoma or allergic contact dermatitis
- •Evidence of, or ongoing treatment (including topical antibiotics) for active skin infection at screening
- •Other recent infections meeting protocol criteria
- •Active tuberculosis requiring treatment within the 12 months prior to Visit 1
- •Evidence of acute or chronic hepatitis or known liver cirrhosis
- •Known immunodeficiency, including human immunodeficiency virus (HIV) infection
- •Use of a topical calcineurin inhibitor (TCI) at the time of screening, unless the participant is willing to stop TCI use during the study (including the run-in period) and, in the investigator's opinion, it is safe to do so
- •Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug or TCS to the participant
- •Known current malignancy or current evaluation for a potential malignancy, including basal or squamous cell carcinoma of the skin or carcinoma in situ
- •History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer
研究组 & 干预措施
Lebrikizumab 250 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 250 milligrams (mg) SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Lebrikizumab (Drug)
Lebrikizumab 250 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 250 milligrams (mg) SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Placebo (Drug)
Lebrikizumab 250 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 250 milligrams (mg) SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: TCS Cream (Drug)
Lebrikizumab 125 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 125 mg SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Lebrikizumab (Drug)
Lebrikizumab 125 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 125 mg SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Placebo (Drug)
Lebrikizumab 125 mg Single Dose + TCS Cream
Participants will receive lebrikizumab 125 mg SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: TCS Cream (Drug)
Lebrikizumab 125 mg Q4W + TCS Cream
Participants will receive lebrikizumab 125 mg SC every 4 weeks (Q4W) for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Lebrikizumab (Drug)
Lebrikizumab 125 mg Q4W + TCS Cream
Participants will receive lebrikizumab 125 mg SC every 4 weeks (Q4W) for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: TCS Cream (Drug)
Placebo Q4W + TCS Cream
Participants will receive placebo Q4W for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: TCS Cream (Drug)
Placebo Q4W + TCS Cream
Participants will receive placebo Q4W for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving a 50 Percent (%) Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-50) at Week 12
时间窗: Week 12
次要结局
- Change in Health-Related QoL From Baseline to Week 12, as Measured by the Dermatology Life Quality Index (DLQI)(Baseline, Week 12)
- Percentage of Participants with a >/=2 Point Reduction From Baseline in IGSA at Week 12(Week 12)
- Percentage of Participants Achieving IGA Score of 0 or 1 at Week 12 and Maintaining IGA Score of 0 or 1 at Weeks 16(Weeks 12, 16)
- Percentage of Participants Achieving IGSA Score of 0 or 1 at Week 12 and Maintaining IGSA Score of 0 or 1 at Weeks 16 and 20(Weeks 12, 16, 20)
- Percent Change From Baseline in Total % Body Surface Area (BSA) Affected At Week 12(Baseline, Week 12)
- Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 12(Week 12)
- Absolute Change From Baseline in IGSA at Week 12(Baseline, Week 12)
- Percent Change From baseline in Severity Scoring of Atopic Dermatitis (SCORAD) at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving IGSA Score of 0 or 1 at Week 12 and Maintaining IGSA Score of 0 or 1 at Weeks 16(Weeks 12, 16)
- Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12(Baseline, Week 12)
- Total Use (Grams) of TCS From Week 12 to End of Study or Early Termination(From Week 12 to end of study or early termination (up to approximately 20 weeks))
- Elimination Half-Life (t1/2) of Lebrikizumab(Pre-dose on Days 1, 8, 29, 43, 57, 85, 113, 141, study discontinuation visit (up to Day 141))
- Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12(Week 12)
- Percentage of Participants Achieving an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12(Week 12)
- Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16 and 20(Weeks 12, 16, 20)
- Total Use (Grams) of TCS From Baseline to Week 12(From Baseline to Week 12)
- Maximum Serum Concentration (Cmax) of Lebrikizumab(After first dose of lebrikizumab at Week 1)
- Percent Change From Baseline in EASI Score at Week 12(Baseline, Week 12)
- Absolute Change From Baseline in EASI Score at Week 12(Baseline, Week 12)
- Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12(Week 12)
- Absolute Change From Baseline in IGA at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving IGA Score of 0 or 1 at Week 12 and Maintaining IGA Score of 0 or 1 at Weeks 16 and 20(Weeks 12, 16, 20)
- Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16(Weeks 12, 16)
- Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16 and 20(Weeks 12, 16, 20)
- Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12(Baseline, Week 12)
- Percentage of Participants With Disease Rebound(From Week 12 up to approximately 20 weeks)
- Minimum Serum Concentration (Cmin) of Lebrikizumab(Pre-dose at Weeks 4, 8, 12)
- Absolute Change From baseline in SCORAD at Week 12(Baseline, Week 12)
- Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD-50/75 at Week 12(Week 12)
- Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16(Weeks 12, 16)
- Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12(Baseline, Week 12)
- Number of Disease Flares From Baseline to Week 12(From Baseline to Week 12)
- Change in AD Symptoms From Baseline to Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)(Baseline, Week 12)
- Change in AD-Specific HealthRelated Quality of Life (QoL) From Baseline to Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)(Baseline, Week 12)
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs)(From start of run-in period (Day -14) until study completion (up to approximately 20 Weeks))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Lebrikizumab(Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141))
- Percentage of Participants With ATA to Phospholipase B-Like 2 (PLBL2) Protein(Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141))
- Time to Reach Cmax (Tmax) of Lebrikizumab(After first dose of lebrikizumab at Week 1)