A Global, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib 25 mg b.i.d. in Comparison to Placebo With Omalizumab 300 mg Every 4 Weeks as Active Control Over 52 Weeks in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-antihistamines and an Open-label 52-week Optional Extension to Assess Long-term Efficacy, Safety and Tolerability of Remibrutinib 25 mg b.i.d.
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 470
- 试验地点
- 111
- 主要终点
- Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
研究概览
简要总结
The purpose of the core phase of the trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).
The purpose of the open-label extension phase is to assess efficacy, safety and tolerability up to two years for patients treated with remibrutinib and patients transitioned from omalizumab to remibrutinib at Week 52. In the extension phase, treatment will be with remibrutinib only (i.e., no background therapy). The extension phase will also fulfill the Novartis commitment to provide post-trial access to participants of the previous core phase.
详细描述
The study consists of 4 periods, and the total study duration is up to 112 weeks. Approximately 468 adult participants with CSU are expected to be randomized in the study.
Screening period: A screening period of up to 4 weeks will allow for the assessment of eligibility, determination of baseline disease activity and wash-out of prohibited medications.
Core Phase Treatment Period (52 weeks):
The treatment period will be double-dummy and double-blind, with placebo injections matching omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy). At the randomization visit, eligible participants will be randomized to one of four treatment arms.
Extension Phase Treatment Period (52 weeks): Optional open-label extension where patients receive treatment with open-label remibrutinib 25 mg, for 52 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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adult participants ≥18 years of age at the time of signing the informed consent.
- •CSU duration for ≥ 6 months prior to screening.
- •Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of randomization, defined as:
- •The presence of itch and hives for ≥6 consecutive weeks prior to screening, despite the use of second-generation H1-AH during this time period.
- •UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0- 21) ≥ 6 during the 7 days prior to randomization (Day 1).
- •Documentation of hives within three months before randomization.
- •Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.
- •Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).
排除标准
- •Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies.
- •Significant bleeding risk or coagulation disorders.
- •History of gastrointestinal bleeding.
- •Requirement for anti-platelet or anti-coagulant medication.
- •History or current hepatic disease.
- •Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.
- •Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines.
- •Documented history of anaphylaxis.
- •Pregnant or nursing (lactating) women.
研究组 & 干预措施
Remibrutinib
Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.
干预措施: Remibrutinib (Drug)
Placebo to omalizumab
Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
干预措施: Placebo to omalizumab (Drug)
Placebo to remibrutinib
Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
干预措施: Placebo to remibrutinib (Drug)
Omalizumab
participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.
干预措施: Omalizumab (Drug)
结局指标
主要结局
Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
时间窗: Week 12
The UAS7 is the sum of the Weekly Hives Severity Score (HSS7 score) and the Weekly Itch Severity Score (ISS7 score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
次要结局
- Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score(Week 12)
- Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score(Week 12)
- Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)(up to 68 weeks)
- Achievement of UAS7=0 (yes/no)(Week 12)