A Seamless Phase 2a/2b, Randomized, Double-Blind, Placebo- and Active-Controlled, Multiple-Arm, Multiple-Stage, Adaptive Study Evaluating the Efficacy and Safety of LAD191 in Adults With Moderate-to-Severe Hidradenitis Suppurativa
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Proportion of Participants Achieving 50 Percent (%) Reduction from Baseline in Hidradenitis Suppurativa Clinical Response (HiSCR-50)
研究概览
简要总结
The main purpose of this study is to assess the efficacy of multiple dosing regimens of LAD191 compared to placebo in participants with moderate-to-severe Hidradenitis Suppurativa (HS) and to access the safety, tolerability, pharmacokinetic and immunogenicity in participants with moderate-to-severe HS.
详细描述
The purpose of this study is to assess the multiple dosing regimens of LAD191 compared to placebo in participants with moderate-to-severe Hidradenitis Suppurativa (HS). The study has a prospectively defined adaptive design that will utilize interim data for futility evaluation.
The study includes up to 4 weeks screening period 16-week double-blind, placebo-controlled period (Treatment period 1), 16-weeks LAD191 double-blind period (Treatment period 2), and 12-week safety follow-up.
The study participants will be randomized to one of the following treatment arms: LAD191 dose A, LAD191 dose B; LAD191 dose C, Adalimumab or Placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged greater than or equal to (>=) 18 to less than or equal to (<=) 65 years.
- •A diagnosis of moderate-to-severe HS defined as a total of >= 5 inflammatory lesions (i.e., number of abscesses plus number of inflammatory nodules) at both the Screening and Baseline/Day 1 visits, with signs and symptoms of HS for at least 6 months.
- •HS lesions present in at least 2 distinct anatomic areas (e.g., left and right axilla), one of which must be at least Hurley Stage II or Hurley Stage III at both the Screening and Baseline/Day 1 visits.
- •History of inadequate response, intolerance, or contraindication to a course of a systemic antibiotics for treatment of HS at the screening visit.
- •Regular use of over-the-counter topical antiseptics on HS lesions and agrees to regular use, throughout the entirety of the study.
- •Participants who are women of child-bearing potential (WOBCP) and male participants must agree to the requirements for the avoidance of pregnancy and exposure of the participant's partner to LAD191 during the study.
排除标准
- •HS with >20 draining tunnels at the Screening or Baseline/Day 1 visit.
- •Ongoing medical conditions requiring systemic immunosuppressive/immunomodulating treatments during the study.
- •Known hypersensitivity to LAD191 or any of its excipients.
- •Known hypersensitivity to adalimumab or biosimilar or any of its excipients or meeting any warning or contraindication to adalimumab treatment as per the approved product information, and as per the Investigator's judgment.
- •Hypersensitivity or systemic reaction to a prior biologic (antibody-based) therapy, regardless of indication, that was clinically significant, as per the Investigator's judgment.
- •Prior treatment with LAD
- •Live or attenuated vaccinations 4 weeks prior to Baseline/Day 1 or is planning to receive any such vaccine during the study.
- •Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
- •Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to meet the required washout period for a particular prohibited medication prior to Baseline/Day 1.
研究组 & 干预措施
Placebo
Participants will receive matching LAD191 placebo SC injection during Treatment Period 1 and will begin treatment with the highest available dose of LAD191 during Treatment Period 2.
干预措施: Placebo (Other)
LAD191 Dose B
Participants will receive dose B LAD191 SC injection during both Treatment Period 1 and Treatment Period 2, unless if Dose B is eliminated after interim analysis, participants will receive the highest available dose of LAD191 during Treatment Period 2.
干预措施: LAD191 (Drug)
LAD191 Dose C
Participants will receive dose C LAD191 SC injection during both Treatment Period 1 and Treatment Period 2, unless if Dose C is eliminated after interim analysis, participants will receive the highest available dose of LAD191 during Treatment Period 2.
干预措施: LAD191 (Drug)
LAD191 Dose A
Participants will receive dose A LAD191 subcutaneous (SC) injection during both Treatment Period 1 and Treatment Period 2, unless if Dose A is eliminated after interim analysis, participants will receive the highest available dose of LAD191 during Treatment Period 2.
干预措施: LAD191 (Drug)
Placebo
Participants will receive matching LAD191 placebo SC injection during Treatment Period 1 and will begin treatment with the highest available dose of LAD191 during Treatment Period 2.
干预措施: LAD191 (Drug)
Adalimumab
Participants will receive adalimumab SC injection during Treatment Period 1 and will begin treatment with the highest available dose of LAD191 during Treatment Period 2.
干预措施: LAD191 (Drug)
Adalimumab
Participants will receive adalimumab SC injection during Treatment Period 1 and will begin treatment with the highest available dose of LAD191 during Treatment Period 2.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Proportion of Participants Achieving 50 Percent (%) Reduction from Baseline in Hidradenitis Suppurativa Clinical Response (HiSCR-50)
时间窗: At Week 16
HiSCR-50 is defined as ≥50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline.
Proportion of Participants Achieving 50 Percent (%) Reduction from Baseline in Hidradenitis Suppurativa Clinical Response (HiSCR-50)
时间窗: At Week 16
HiSCR-50 is defined as ≥50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline.
次要结局
- Proportion of Participants Achieving 75% Reduction from Baseline in HiSCR-75 at Week 16(At Week 16)
- Proportion of Participants Achieving 90% Reduction from Baseline in HiSCR-90 at Week 16(At Week 16)
- Proportion of Participants Achieving 55% Reduction from Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4-55) at Week 16(At Week 16)
- Change from Baseline in Skin Pain Numerical Rating Scale (NRS) at Week 16(At Week 16)
- Change from Baseline in Hidradenitis Suppurativa Quality of Life (HiSQOL) at Week 16(At Week 16)