Randomised, Double-blind, Placebo-controlled, Phase IIb/Phase III Study to Evaluate the Efficacy and Safety of Spesolimab in Patients With Moderate to Severe Hidradenitis Suppurativa. Lunsayil 1.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 209
- 试验地点
- 162
- 主要终点
- Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8
研究概览
简要总结
This study is open to adults with moderate to severe hidradenitis suppurativa (HS). The purpose of this study is to find out whether a medicine called spesolimab helps people with HS. People who have previously taken specific medicines such as immunosuppressive biologics other than Tumor necrosis factor (TNF) inhibitors cannot take part.
This study has 2 parts. In Part 1, participants are divided into 4 groups of almost equal size. 3 groups get different doses of spesolimab, 1 group gets placebo. All participants get injections into a vein or under the skin. Placebo injections look like spesolimab injections, but do not contain any medicine. Every participant has an equal chance of being in each group. In the beginning, participants get the study medicine every week and later every 2 weeks. After 4 months, participants in the placebo group switch to spesolimab treatment.
In Part 2, participants are divided into 2 groups. One group gets a suitable dose of spesolimab that was found in Part 1 of the study. The other group gets placebo. After 4 months, participants in the placebo group switch to spesolimab treatment.
Participants join only one of the two parts. They are in the study for about 1 year. During this time, they visit the study site in the beginning every week and later every 2 weeks. Some of the visits can be done at the participant's home instead of the study site. The doctors regularly check participants' HS symptoms. The results are compared between the groups to see whether spesolimab works. The doctors also regularly check participants' general health and take note of any unwanted effects.
详细描述
Main endpoints for Part 2 will be supported by Part 1 results available at time of primary analysis.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Of full age of consent at screening.
- •Signed and dated written informed consent in accordance with International Council on Harmonisation-Good clinical practice (ICH-GCP) and local legislation prior to admission to the trial.
- •Moderate to severe HS.
- •HS lesions in at least 2 distinct anatomic areas.
- •Biologic naive or Tumor Necrosis Factor inhibitor (TNFi)-exposed for HS.
- •For biologic naïve, inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS in the last 1 year prior to the Baseline visit, as per investigator discretion. All participants must have previous exposure to antibiotics for HS.
- •Total AN count of greater than or equal to
- •Total dT count of at least 1 at Baseline visit. Further inclusion criteria apply.
排除标准
- •Participants who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
- •Prior exposure to any immunosuppressive/immunomodulatory biologic other than TNFi for HS.
- •Prior exposure to Interleukin 36 receptor (IL-36R) inhibitors including spesolimab.
- •Treated with any investigational device or investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug, whichever is longer.
- •Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- •Participants with history of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.
- •Participants with a transplanted organ (with exception of a corneal transplant >12 weeks prior to screening) or who has ever received stem cell therapy (e.g., Remestemcel-L).
- •Participants with any documented active or suspected malignancy or history of malignancy within 5 years prior to the screening visit, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix.
- •Further exclusion criteria apply.
研究组 & 干预措施
Spesolimab low dose group
Patients with moderate to severe HS were administered an initial weekly low dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
From Week 16, if patients had inadequate clinical response defined as 25% increase in the ANdT count compared to baseline, the dose could be increased every two weeks to a pre-determined concentration.
干预措施: Spesolimab i.v. (Drug)
Spesolimab low dose group
Patients with moderate to severe HS were administered an initial weekly low dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
From Week 16, if patients had inadequate clinical response defined as 25% increase in the ANdT count compared to baseline, the dose could be increased every two weeks to a pre-determined concentration.
干预措施: Spesolimab s.c. (Drug)
Spesolimab medium dose group
Patients with moderate to severe HS were administered an initial weekly medium dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
干预措施: Spesolimab i.v. (Drug)
Spesolimab medium dose group
Patients with moderate to severe HS were administered an initial weekly medium dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
干预措施: Spesolimab s.c. (Drug)
Spesolimab high dose group
Patients with moderate to severe HS were administered an initial weekly high dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
干预措施: Spesolimab i.v. (Drug)
Spesolimab high dose group
Patients with moderate to severe HS were administered an initial weekly high dose of spesolimab via i.v. (Week 0 to Week 3). Afterwards, patients were administered a lower weekly s.c. dose of spesolimab for 4 weeks (Week 4 to Week 7). Patients were then administered a maintenance s.c. dose of spesolimab every two weeks until the end of the treatment (Week 8 to Week 48).
干预措施: Spesolimab s.c. (Drug)
Placebo
Patients with moderate to severe Hidradenitis suppurativa (HS) were administered an initial weekly dose of placebo via intravenous infusion (i.v.) (Week 0 to Week 3). Afterwards, patients were administered a subcutaneous injection (s.c.) dose of placebo once a week for 4 weeks (Week 4 to Week 7), and once every 2 weeks for the following 7 weeks (Week 8 to Week 14).
From Week 16 until the end of treatment (Week 48), patients were switched to the same s.c. dose of spesolimab administered to patients in the medium and high dose groups (starting with 3 loading s.c. doses of spesolimab every week and then maintenance s.c. dose of spesolimab every 2 weeks).
干预措施: Spesolimab s.c. (Drug)
Placebo
Patients with moderate to severe Hidradenitis suppurativa (HS) were administered an initial weekly dose of placebo via intravenous infusion (i.v.) (Week 0 to Week 3). Afterwards, patients were administered a subcutaneous injection (s.c.) dose of placebo once a week for 4 weeks (Week 4 to Week 7), and once every 2 weeks for the following 7 weeks (Week 8 to Week 14).
From Week 16 until the end of treatment (Week 48), patients were switched to the same s.c. dose of spesolimab administered to patients in the medium and high dose groups (starting with 3 loading s.c. doses of spesolimab every week and then maintenance s.c. dose of spesolimab every 2 weeks).
干预措施: Placebo matching Spesolimab i.v. (Drug)
Placebo
Patients with moderate to severe Hidradenitis suppurativa (HS) were administered an initial weekly dose of placebo via intravenous infusion (i.v.) (Week 0 to Week 3). Afterwards, patients were administered a subcutaneous injection (s.c.) dose of placebo once a week for 4 weeks (Week 4 to Week 7), and once every 2 weeks for the following 7 weeks (Week 8 to Week 14).
From Week 16 until the end of treatment (Week 48), patients were switched to the same s.c. dose of spesolimab administered to patients in the medium and high dose groups (starting with 3 loading s.c. doses of spesolimab every week and then maintenance s.c. dose of spesolimab every 2 weeks).
干预措施: Placebo matching Spesolimab s.c. (Drug)
结局指标
主要结局
Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 8
时间窗: The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8.
Percent change from baseline in draining fistula/tunnel (dT) count at Week 8 is reported. Tunnel/fistula/sinus were counted as dT only if draining. Percent change was calculated as follows: (dT count at week 8 - dT count at baseline)/ dT at baseline. Least square means and standard errors were estimated by Mixed effect model for repeated measurements (MMRM). The MMRM included fixed categorical effects of treatment at each visit, Tumor Necrosis Factor inhibitor (TNFi) status at baseline, and categorical baseline dT count at each visit. Visit were treated as the repeated measure with an unstructured covariance structure used to model the within-trial participant measurements.
次要结局
- Part 1 - Percent Change From Baseline in Draining Fistula/Tunnel (dT) Count at Week 16(The MMRM model incorporates dT count from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16.)
- Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 8(The MMRM model incorporates IHS4 value from baseline (Week 0), Week 2, Week 4, Week 6 and Week 8. The data represent the Least Squares Means at Week 8.)
- Part 1 - Absolute Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) Value at Week 16(The MMRM model incorporates IHS4 from baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14 and Week 16. The data represent the Least Squares Means at Week 16.)
- Part 1 - Occurrence of Treatment Emergent Adverse Events (TEAEs)(From first drug administration until end of exposure, plus residual effect period, up to approximately 68 weeks.)