Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Percent Change in CD4+ T Effector Cells Expressing IL4 in Dupilumab-treated Subjects at Week 12 vs Week 0
研究概览
简要总结
This is a single-arm, open-label study to examine the effect of dupilumab on the immunologic and genetic environment within atopic dermatitis skin lesions.
详细描述
Fifteen subjects with moderate to severe AD will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). Biopsy samples from AD subjects and surgical discard samples will undergo molecular profiling. Skin swabs and stool samples will be collected and banked for future analysis. The reason to treat patients for 52 weeks is to have the ability to correlate early molecular events with clinical outcomes at week 52.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide written informed consent and comply with the protocol.
- •At least 18 years of age.
- •Diagnosis of chronic atopic dermatitis for at least 3 years prior to enrollment.
- •Subject is considered a candidate for phototherapy or systemic therapy
- •Eczema Area and Severity Index (EASI) score ≥ 12
- •Investigator Global Assessment (IGA) ≥ 3
- •10% body surface area (BSA) or greater
- •Subject is unlikely to conceive due to male, post-menopausal, or using adequate contraceptive (barrier, hormonal, implant, or permanent sterilization methods).
- •Physical exam within clinically acceptable limits.
排除标准
- •Subject is unable to provide written informed consent or comply with the protocol.
- •Subject is younger than 18 years of age.
- •Subject has had atopic dermatitis for less than 3 years prior to enrollment.
- •Subject with mild atopic dermatitis (EASI<12 and IGA<3) or is not a candidate for phototherapy or systemic treatments.
- •Subject with current, or a history of, severe atopic dermatitis well controlled on current therapy.
- •Serious known infection.
- •History of immunosuppression (including human immunodeficiency virus (HIV))
- •History of malignancy 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.
- •Severe concomitant illnesses.
- •Having used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) or phototherapy within 4 weeks before the baseline visit.
- •Treatment with topical corticosteroid or topical calcineurin inhibitor within 1 week before the baseline visit.
- •Treatment with any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer, or use of other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer.
- •Physical or laboratory exam not within clinically acceptable limits.
- •Subjects possess other diagnoses that, in the investigator's opinion, preclude him/her from safely participating in this study or interfere with the evaluation of the subject's atopic dermatitis.
- •History of known or suspected intolerance to any of the ingredients of the investigational study product.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>10 mIU/mL).
研究组 & 干预措施
Dupilumab treatment
15 subjects will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). All subjects will undergo skin biopsies for molecular profiling.
干预措施: Dupilumab (Drug)
结局指标
主要结局
Percent Change in CD4+ T Effector Cells Expressing IL4 in Dupilumab-treated Subjects at Week 12 vs Week 0
时间窗: 12 weeks
The percent change in CD4+ T effector cells expressing IL-4 in dupilumab-treated subjects at week 12 vs week 0 was calculated as follows. A single value was derived for the entire population with pooled samples from pre- and post-intervention time points, which was then used to calculate a percent change between the two periods. Specifically, the mean M1 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 0. The mean M2 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 12. The final result was calculated as: (M1-M2)/M1\*100. Therefore, the result is a number and there is no central tendency metric.
次要结局
- Number of Differentially Expressed Genes in Cutaneous CD4+ T Cells Between Week 0 and Week 12 in Dupilumab-treated Subjects(12 weeks)