A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Upadacitinib in Adult and Adolescent Subjects With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,328
- 试验地点
- 856
- 主要终点
- Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 50
研究概览
简要总结
Hidradenitis suppurativa (HS) is an inflammatory skin disease that causes painful lesions in the axilla (underarm), inguinal (groin) and anogenital (anal/genital) regions. This study will assess how safe and effective upadacitinib is in treating adult and adolescent participants with moderate to severe HS who have failed to respond to or are intolerant of anti-tumor necrosis factor (TNF) therapy. Adverse events and change in disease activity will be assessed.
Upadacitinib is an approved drug for ulcerative colitis, atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, and axial spondylarthritis and is being developed for the treatment of HS. This study is "double-blinded", meaning that neither the trial participants nor the study doctors will know who will be given upadacitinib and who will be given placebo. This study is comprised of 3 periods. In Period 1, participants are randomized into 2 groups called treatment arms where each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. In Period 2, participants are placed into 6 different groups depending on their placement and results in Period 1. Period 3 is the long-term extension period where participants will continue treatment from Period 2. Approximately 1328 adult and adolescent participants diagnosed with HS will be enrolled in approximately 300 sites worldwide.
Participants will receive oral tablets of upadacitinib or placebo once daily for 36 weeks in Period 1 and Period 2. Eligible participants from Period 1 and Period 2 will enter Period 3 and receive oral tablets of upadacitinib or placebo once daily for 68 weeks. Participants will be followed up for approximately 30 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular outpatient visits during the study. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of hidradenitis suppurativa (HS) for at least 6 months prior to Baseline, as determined by the investigator (i.e., through medical history and interview of participant).
- •Documented history of previous use of >= 1 tumor necrosis factor (TNF) inhibitor for HS for at least 12 weeks and/or 1 approved non-anti-TNF biologic therapy for HS for at least 16 weeks characterized by inadequate response or for any duration characterized by intolerance as determined by the investigator.
- •Participant must have a total abscess and inflammatory nodule (AN) count of >= 5 at Baseline.
- •HS lesions must be present in at least 2 distinct anatomic areas at Baseline.
- •At least 1 anatomic area of HS involvement characterized as Hurley Stage II or higher at Baseline.
- •Draining fistula count of <= 20 at Baseline.
排除标准
- •History of active skin disease other than HS that could interfere with the assessment of HS, including skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline visit.
- •Treatment with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug or be currently enrolled in another interventional clinical study. Investigational drugs are also prohibited during the study.
- •Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 (e.g., rituximab) within 12 months prior to Baseline or until B cell count returns to normal level or pre-treatment level.
- •Use of prescription topical therapies (including topical antibiotics) that can also be used to treat HS within 14 days prior to the Baseline visit.
- •Received any systemic (including oral) antibiotic treatment for HS or any other chronic inflammatory disorder within 14 days prior to the Baseline visit.
研究组 & 干预措施
Period 2: Group 2 - Placebo
Participants who were randomized to placebo in Period 1 who achieve HiSCR 50 (clinical responder, CR) at Week 16 will continue to receive placebo once daily for 20 weeks.
干预措施: Placebo (Drug)
Period 2: Group 1 - Upadacitinib Dose A
Participants who were randomized to placebo in Period 1 who did not achieve HiSCR 50 (clinical non-responder, CNR) at Week 16 will receive Upadacitinib Dose A once daily for 20 weeks.
干预措施: Upadacitinib (Drug)
Period 1: Placebo
Participants will receive Placebo once daily for 16 weeks.
干预措施: Placebo (Drug)
Period 3: Long-Term Extension
Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days.
干预措施: Placebo (Drug)
Period 2: Group 6 - Placebo
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive placebo once daily for 20 weeks.
干预措施: Placebo (Drug)
Period 1: Upadacitinib Dose A
Participants will receive Upadicitinib Dose A once daily for 16 weeks.
干预措施: Upadacitinib (Drug)
Period 2: Group 4 - Upadacitinib Dose A
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose A once daily for 20 weeks.
干预措施: Upadacitinib (Drug)
Period 2: Group 3 - Upadacitinib Dose A
Participants who were randomized to upadacitinib Dose A in Period 1 who did not achieve HiSCR 50 (CNR) at Week 16 will continue to receive upadacitinib Dose A once daily for 20 weeks.
干预措施: Upadacitinib (Drug)
Period 2: Group 5 - Upadacitinib Dose B
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose B once daily for 20 weeks.
干预措施: Upadacitinib (Drug)
Period 3: Long-Term Extension
Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 50
时间窗: Baseline to Week 16
HiSCR 50 is defined as at least a 50% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline.
Number of Participants with Adverse Events (AEs)
时间窗: Up to Approximately Week 108
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
次要结局
- Change from Baseline in Draining Fistula Count(Baseline to Week 16)
- Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 75(Baseline to Week 16)
- Percentage of Participants Achieving Numeric Rating Scale 30 (NRS30) at Week 4 Among Participants with NRS ≥ 3 at Baseline(Baseline to Week 4)
- Change from Baseline in Hidradenitis Suppurativa Symptom Assessment (HSSA)(Baseline to Week 16)
- Change from Baseline in Hidradenitis Suppurativa Impact Assessment (HSIA)(Baseline to Week 16)
- Change from Baseline in Dermatology Life Quality Index (DLQI) for Adult Participants and Adolescent Participants Age ≥16 Years Old and Older(Baseline to Week 16)
- Change from Baseline in Hidradenitis Suppurativa (HS)-Related Odor, Based on Hidradenitis Suppurativa Symptom Assessment (HSSA) Question 8(Baseline to Week 16)
- Change from Baseline in the Patient's Global Assessment of Hidradenitis Suppurativa (HS)-Related Skin Pain NRS(Baseline to Week 8)
- Occurrence of Hidradenitis Suppurativa (HS) Flare During Period 1(Baseline to Week 16)