A Phase 2 Multicenter Platform Trial of Targeted Immunomodulator Therapies for Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 83
- 试验地点
- 62
- 主要终点
- Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16
研究概览
简要总结
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. The purpose of this study is to evaluate the clinical efficacy and safety of single therapies and/or combination therapies for moderate to severe AD through multiple substudies.
This study will consist of multiple substudies. Substudy 1 will have a randomized, open-label period 1 followed by a lutikizumab treatment period 2 enrolling 80 participants at a 1 to 1 ratio.
In Substudy 1, participants will receive subcutaneous (SC) injections of lutikizumab or matching placebo every other week for 16 weeks followed by an additional 32 weeks of SC injections of lutikizumab every other week for a total of 52 weeks.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and biomarker collections.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of AD with onset of symptoms at least 1 year prior to the Baseline Visit and participant meets Hanifin and Rajka criteria.
- •Participant has applied non-medicated, additive-free bland emollient twice daily for at least 7 days before the Baseline Visit.
- •History of inadequate response to topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or topical JAK inhibitors, OR systemic treatment for AD, OR participants for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
排除标准
- •Use of the following AD treatments within the specified washout period prior to the Baseline Visit:
- •-- Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4) inhibitors, IFN-γ, and mycophenolate mofetil within 5 half-lives [if known] or within 4 weeks, whichever is longer;
- •-- Any biologic treatments, (within 5 half-lives [if known]) or within 12 weeks (whichever is longer), or as specified below: < 8 weeks for dupilumab; < 12 weeks for nemolizumab; < 16 weeks for tralokinumab and lebrikizumab.
- •Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks.
- •Herbal treatments (e.g., traditional Chinese medicines) within 4 weeks.
- •Topical treatments (with the exception of non-medicated, additive-free bland emollients), including but not limited to TCS, TCIs, or topical PDE-4 inhibitors within 7 days.
- •Topical JAK inhibitor within 14 days.
- •Systemic JAK inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, upadacitinib, abrocitinib [PF-04965842], and filgotinib) within 5 half-lives [if known] or within 14 days, whichever is longer.
研究组 & 干预措施
Substudy 1: Lutikizumab Monotherapy
In Period 1, participants will be receive lutikizumab Dose A at Baseline randomization, followed by Dose B every other week starting at Week 2 for 16 weeks. Participants will continue into Period 2 at Week 16 with Dose C every other week until Week 52.
干预措施: Lutikizumab (Drug)
Substudy 1: Placebo to Lutikizumab
In Period 1, participants will be receive a matching placebo Dose A at Baseline randomization, followed by matching placebo Dose B every other week starting at Week 2 for 16 weeks. At Week 16, participants that were assigned placebo will then enter Period 2 and receive open-label lutikizumab Dose A, followed by lutikizumab Dose B every other week starting at Week 18, and lutikizumab Dose C every other week starting at Week 32 until Week 52.
干预措施: Placebo (Drug)
Substudy 1: Placebo to Lutikizumab
In Period 1, participants will be receive a matching placebo Dose A at Baseline randomization, followed by matching placebo Dose B every other week starting at Week 2 for 16 weeks. At Week 16, participants that were assigned placebo will then enter Period 2 and receive open-label lutikizumab Dose A, followed by lutikizumab Dose B every other week starting at Week 18, and lutikizumab Dose C every other week starting at Week 32 until Week 52.
干预措施: Lutikizumab (Drug)
结局指标
主要结局
Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16
时间窗: At Week 16
EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.
Percentage of Participants Who Reported Adverse Events
时间窗: Up to Week 52
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
次要结局
- Percentage of Participants Achieving an Improvement (Reduction) of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Percent Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement(At Week 16)
- Percentage of Participants Achieving an EASI 50 Response(At Week 16)
- Percent Change From Baseline in EASI Score(At Week 16)
- Absolute Change from Baseline in Investigator Global Assessment for Atopic Dermatitis (vIGA-AD)(At Week 16)
- Percentage of Participants Achieving a Validated Investigator´s Global Assessment for AD (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points(At Week 16)
- Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Absolute Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Absolute Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement(At Week 16)
- Percentage of Participants Achieving an Improvement (Reduction) of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Percentage of Participants Achieving an EASI 50 Response(At Week 16)
- Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Percentage of Participants Achieving an EASI 90 Response(At Week 16)
- Percentage of Participants Achieving an EASI 100 Response(At Week 16)
- Absolute Change from Baseline for EASI(At Week 16)
- Absolute Change from Baseline in Investigator Global Assessment for Atopic Dermatitis (vIGA-AD)(At Week 16)
- Percent Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement(At Week 16)
- Percent Change From Baseline in EASI Score(At Week 16)
- Percentage of Participants Achieving a Validated Investigator´s Global Assessment for AD (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points(At Week 16)
- Absolute Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 16)
- Absolute Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement(At Week 16)
- Percentage of Participants Achieving an Improvement (Reduction) of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS)(At Week 4)