A Phase 2a/2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, Double-Blind, Dose-ranging Study to Evaluate the Safety and Efficacy of Bermekimab (JNJ-77474462) for the Treatment of Subjects With Moderate to Severe Hidradenitis Suppurativa
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 151
- 试验地点
- 54
- 主要终点
- Part 1: Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at Week 16
研究概览
简要总结
The purpose of this study is to evaluate the clinical efficacy of bermekimab in participants with moderate to severe Hidradenitis Suppurativa (HS).
详细描述
Hidradenitis suppurativa (HS) is a chronic skin disease of unclear etiology that affects 1 percent (%) to 4% of the general population. JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 alpha (IL-1 alpha) and is an effective blocker of IL-1 alpha biological activity. IL-1 alpha is a key mediator of sterile inflammatory responses. Skin is a significant reservoir of preformed IL-1 alpha, and it has been postulated that IL-1 alpha may play a role in the pathophysiology of multiple inflammatory skin disorders, including HS. Part 1 of this study contains 4 study periods: up to 6 weeks screening period (Period 1), 16-week placebo-controlled period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow-up (Period 4). Part 2 of this study also contains 4 study periods: up to 6 weeks screening period (Period 1), 12-week placebo-controlled period (Period 2), 20-week cross over period (Period 3), and 4-week safety follow up (Period 4). Safety will be assessed by adverse events (AEs), serious adverse event (SAEs), physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, allergic reaction, injection-site reactions, and tuberculosis evaluations. The total duration of study participation will be up to 42 weeks.
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
- •Have hidradenitis suppurativa (HS) for at least 1 year (365 days) prior to the baseline visit as determined by the investigator through participant interview and/or review of the medical history
- •Have Hurley Stage II or Hurley Stage III HS as determined by the investigator at screening and baseline visits
- •Have HS lesions present in at least 2 distinct anatomic areas (examples include but are not limited to left and right axilla; or left axilla and left inguinocrural fold) at screening and baseline visits
- •Have a total abscess and inflammatory nodule (AN) count of greater than or equal to (>=) 5 at the screening and baseline visit
- •Agree not to receive a live virus or live bacterial vaccination during the study and for 90 days after the last administration of study intervention
排除标准
- •Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Has unstable cardiovascular disease, defined as a recent clinical deterioration (that is, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months
- •Has or has had herpes zoster within the 2 months before screening
- •Has a transplanted organ (with exception of a corneal transplant greater than [>] 3 months before the first administration of study intervention)
- •Has known allergies, hypersensitivity, or intolerance to bermekimab or adalimumab or its excipients
研究组 & 干预措施
Part 1 (Group 1): Placebo
Participants will receive placebo subcutaneously (SC) at Week 0 through Week 15. At Week 16, participants will cross over to receive bermekimab dose 1 SC every week thereafter through Week 31.
干预措施: Bermekimab (Drug)
Part 1 (Group 1): Placebo
Participants will receive placebo subcutaneously (SC) at Week 0 through Week 15. At Week 16, participants will cross over to receive bermekimab dose 1 SC every week thereafter through Week 31.
干预措施: Placebo (Drug)
Part 1 (Group 2): Adalimumab
Participants will receive adalimumab 160 milligrams (mg) SC at Week 0, placebo SC at Week 1, followed by adalimumab 80 mg SC and placebo SC at Weeks 2 and 3. Participants will then receive adalimumab 40 mg SC and placebo SC at Week 4 and every week thereafter through Week 31.
干预措施: Adalimumab (Drug)
Part 1 (Group 2): Adalimumab
Participants will receive adalimumab 160 milligrams (mg) SC at Week 0, placebo SC at Week 1, followed by adalimumab 80 mg SC and placebo SC at Weeks 2 and 3. Participants will then receive adalimumab 40 mg SC and placebo SC at Week 4 and every week thereafter through Week 31.
干预措施: Placebo (Drug)
Part 1 (Group 3): Bermekimab Dose 1
Participants will receive bermekimab dose 1 SC and placebo SC at Week 0, followed by bermekimab dose 1 SC at Week 1 and every week thereafter through Week 31.
干预措施: Bermekimab (Drug)
Part 1 (Group 3): Bermekimab Dose 1
Participants will receive bermekimab dose 1 SC and placebo SC at Week 0, followed by bermekimab dose 1 SC at Week 1 and every week thereafter through Week 31.
干预措施: Placebo (Drug)
Part 2 (Group 1): Placebo
Participants will receive placebo SC from Week 0 through Week 11. At Week 12, participants will cross over to receive bermekimab dose 1 SC weekly through Week 31.
干预措施: Bermekimab (Drug)
Part 2 (Group 1): Placebo
Participants will receive placebo SC from Week 0 through Week 11. At Week 12, participants will cross over to receive bermekimab dose 1 SC weekly through Week 31.
干预措施: Placebo (Drug)
Part 2 (Group 2): Bermekimab Dose 1
Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 31.
干预措施: Bermekimab (Drug)
Part 2 (Group 3): Bermekimab Dose 1
Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 1 SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31.
干预措施: Bermekimab (Drug)
Part 2 (Group 3): Bermekimab Dose 1
Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 1 SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31.
干预措施: Placebo (Drug)
Part 2 (Group 4): Bermekimab Dose 2
Participants will receive bermekimab dose 2 SC and placebo SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 2 SC and placebo SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31.
干预措施: Bermekimab (Drug)
Part 2 (Group 4): Bermekimab Dose 2
Participants will receive bermekimab dose 2 SC and placebo SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 2 SC and placebo SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at Week 16
时间窗: Week 16
HiSCR50 was defined as at least 50 percent (%) reduction in total abscess and inflammatory nodule counts (AN count) with no increase in abscess count and no increase in draining fistula count relative to baseline.
次要结局
- Part 1: Change From Baseline in the Abscess and Inflammatory Nodule (AN) Count at Week 16(Baseline, Week 16)
- Part 1: Change From Baseline in Number of Abscess at Week 16(Baseline, Week 16)
- Part 1: Change From Baseline in Number of Draining Fistula at Week 16(Baseline, Week 16)
- Part 1: Percentage of Participants Who Achieved HiSCR75 at Week 16(Week 16)
- Part 1: Percentage of Participants Who Achieved HiSCR90 at Week 16(Week 16)
- Part 1: Percentage of Participants With Hidradenitis Suppurativa-Investigator's Global Assessment (HS-IGA) Score of Inactive (0), Almost Inactive (1), or Mild Activity (2) and With at Least 2-grade Improvement Relative to Baseline at Week 16(Baseline, Week 16)
- Part 1: Change From Baseline in Number of Inflammatory Nodules at Week 16(Baseline, Week 16)
- Part 1: Change From Baseline in International Hidradenitis Suppurativa Severity Score (IHS4) at Week 16(Baseline up to Week 16)
- Part 1: Change From Baseline in Hidradenitis Suppurativa (HS)-Related Pain Symptom Score in the Past 24 Hours Based on Hidradenitis Suppurativa Symptom Diary (HSSD) Questionnaire at Week 16(Baseline, Week 16)
- Serum Concentration of Bermekimab(Weeks 0, 1, 4, 8, 12, 16, 20, 24, 28, 32, 36)
- Number of Participants With Antibodies to Bermekimab(From baseline up to Week 36)