A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in Adult Patients With Moderate-to-Severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 254
- 试验地点
- 84
- 主要终点
- Percentage of Participants Who Develop a Booster Response to Tetanus Toxoid 4 Weeks After Tdap (Tetanus-diphtheria-pertussis) Vaccine Administration
研究概览
简要总结
The reason for this study is to assess the impact of lebrikizumab on vaccine immune response in adult participants with moderate to severe atopic dermatitis (AD).
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic atopic dermatitis (AD) according to American Academy of Dermatology Consensus Criteria that has been present for ≥1 year before screening.
- •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 AD involvement at the baseline visit.
- •History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
- •Have not received any tetanus-containing vaccine within approximately 5 years of baseline.
- •Have never received a meningococcal conjugate vaccine or have received not more than 1 prior MCV dose at least 4 years prior to baseline, of a vaccine containing 1 or more meningococcal serogroups (serogroups A, C, W, Y).
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •a. Female participants of childbearing potential: must agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method during the treatment period and for at least 18 weeks after the last dose of study drug. Women of non-childbearing potential (non-WOCBP) may participate without any contraception requirements.
- •b. Male participants are not required to use any contraception except in compliance with specific local government study requirements.
排除标准
- •Recurring herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis
- •Evidence of active or chronic hepatitis
- •History of human immunodeficiency virus (HIV) infection or positive HIV serology.
- •Presence of skin comorbidities that may interfere with study assessments.
- •History of malignancy, including mycosis fungoides, within 5 years before screening, except completely treated in situ carcinoma of the cervix or completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
- •Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma.
- •Have a prior history of Guillain-Barre syndrome.
- •Allergic to latex.
- •History of past vaccination allergy or Arthus-type hypersensitivity.
- •Have an uncontrolled seizure disorder.
- •Have known hypogammaglobulinemia or a screening serum immunoglobulin G (IgG) or immunoglobulin A (IgA) concentration less than the lower limit of the reporting laboratory's reference range.
- •Treated with topical corticosteroids (TCS), calcineurin inhibitors, or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit.
- •Treated with the following prior to baseline visit:
- •a. An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer
- •b. B Cell-depleting biologics, including rituximab, within 6 months
- •c. Other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer
- •Received a Bacillus Calmette-Guerin (BCG) vaccination or treatment within 12 months of screening, or treated with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study.
- •A contraindication to the Tdap vaccine or mean corpuscular volume (MCV).
- •Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
研究组 & 干预措施
Lebrikizumab
Participants received a loading dose of 500 milligram (mg) lebrikizumab injection administered subcutaneously (SC) at baseline and week 2, and 250 mg once every two weeks (Q2W) from week 4 to 14.
干预措施: Lebrikizumab (Drug)
Placebo
Participants received placebo SC injection Q2W from baseline to week 14.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Develop a Booster Response to Tetanus Toxoid 4 Weeks After Tdap (Tetanus-diphtheria-pertussis) Vaccine Administration
时间窗: Week 16
Booster response to tetanus toxoid is defined as: ≥4-fold increase in anti-tetanus toxoid immunoglobulin G (IgG) antibody concentration if the pre-vaccination level was \>0.10 International units per milliliter (IU/mL) and ≤2.7 IU/mL; OR ≥2-fold increase in anti-tetanus toxoid IgG antibody concentration if the pre-vaccination level was \>2.7 IU/mL; OR ≥4-fold increase in anti-tetanus toxoid IgG antibody concentration and a post-vaccination level ≥0.10 IU/mL if the pre-vaccination level was ≤0.10 IU/mL
Percentage of Participants Who Have Positive Antibody Response to Meningococcus C Antigen 4 Weeks After Meningococcal Conjugate Vaccine (MCV) Administration
时间窗: Week 16
Positive antibody response to Meningococcus C antigen as measured by group C serum bactericidal antibodies is defined as: post-vaccination rabbit complement serum bactericidal assay (rSBA) titer ≥4 times the lower limit of quantitation (LLOQ), if the pre-vaccination rSBA titer is less than the LLOQ; OR post-vaccination rSBA titer ≥4 times the pre-vaccination titer, if the pre-vaccination rSBA titer is greater than or equal to the LLOQ.
次要结局
- Percentage of Participants Achieving a ≥75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI-75)(Week 16)
- Percentage of Participants Achieving an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction of ≥2 Points From Baseline(Week 16)
- Percentage of Participants Achieving ≥90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI-90)(Week 16)
- Change From Baseline in Sleep-Loss Score(Baseline, Week 16)
- Percentage of Participants Achieving ≥4-Point Improvement From Baseline in Pruritus Numeric Rating Scale (NRS) Score(Week 16)
- Change From Baseline in Percent Body Surface Area (BSA)(Baseline, Week 16)