A Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-ranging Phase 2 Study of Rilzabrutinib Followed by an Open-label Extension Phase in Patients With Moderate-to-severe Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite the Use of H1 Antihistamine Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 160
- 试验地点
- 253
- 主要终点
- Change from baseline in weekly urticaria activity score (UAS7) at Week 12 (except US and US reference countries)
研究概览
简要总结
The first phase of this study will be a parallel, 12-week treatment, Phase 2, double-blind, 4 arm study to assess the safety and effectiveness of 3 oral doses of SAR444671 (rilzabrutinib), i.e. dose A, B and C, compared with placebo for decreasing the frequency and severity of itch and urticaria in male and female participants aged 18 years inclusive or older with CSU.
After completion of the double-blind phase of the study, participants will be given the option of enrolling in the 40-week open label extension (OLE) phase of the study. Participants will receive open-label rilzabrutinib at dose B or dose C (the dose may be modified based on the 12-week safety and efficacy data). Due to the fact that some participants may be receiving rilzabrutinib for the first time, all participants will be monitored at Week 14, Week 16, Week 20, and Week 24. Afterwards, participants will be monitored at Week 36 and Week 52.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who had a diagnosis of CSU refractory to H1-AH at the time of randomization
- •Diagnosis of CSU ≥3 months prior to screening visit (Visit 1).
- •The presence of itch and hives for ≥6 consecutive weeks at any time prior to screening visit (Visit 1) despite the use of H1-AH during this time period.
- •Participants using a study defined H1-AH for CSU treatment. For participants on stable doses of non-study-approved H1-AH, investigators may switch participants to an equivalent dose of a study-approved H1-AH maintenance medication.
- •Participants who were omalizumab naïve OR omalizumab-incomplete responders.
- •Participants must be willing and able to complete a daily symptom e-diary for the duration of the study.
- •During the 7 days before randomization: UAS7 ≥16 and ISS7 ≥
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Clearly defined underlying etiology for CUs other than CSU (main manifestation being physical urticaria).
- •Presence of skin morbidities other than CSU that may interfere with the assessment of the study outcomes.
- •Participants with active atopic dermatitis (AD).
- •Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study.
- •Known or suspected immunodeficiency, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the Investigator.
- •History of serious infections requiring intravenous (IV) therapy with the potential for recurrence (as judged by the Site Investigator) with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher), including active coronavirus disease 2019 (COVID-19).
- •Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
- •Active malignancy or history of malignancy within 5 years.
- •Conditions that may predispose the participant to excessive bleeding
- •Any participant with an uncontrolled disease state as judged by the Investigator, such as asthma, psoriasis, or inflammatory bowel disease, etc. that are typically treated with oral or parenteral corticosteroids
- •Previous use of a BTK inhibitor.
- •Had received any investigational drug (or is currently using an investigational device) within the 30 days before Day 1, or at least 5 times the respective elimination half-life time (whichever is longer).
- •Previous exposure to another investigative drug for CSU.
- •Positive for human immunodeficiency virus (HIV) antibody test.
- •Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with positive DNA test result at screening or within 3 months prior to the screening visit.
- •Positive hepatitis C antibody test result at screening or within 3 months prior to the screening visit.
- •Tuberculosis infection.
- •Any of significant laboratory abnormalities and ECG findings at the screening visit.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Rilzabrutinib dose A
dose A
干预措施: rilzabrutinib (Drug)
Placebo
Matching placebo
干预措施: placebo (Drug)
Rilzabrutinib dose C
dose C
干预措施: rilzabrutinib (Drug)
Rilzabrutinib dose B
dose B
干预措施: rilzabrutinib (Drug)
结局指标
主要结局
Change from baseline in weekly urticaria activity score (UAS7) at Week 12 (except US and US reference countries)
时间窗: From baseline to Week 12
For US and US reference countries only: change from baseline in weekly itch severity score (ISS7) at Week 12
时间窗: From baseline to Week 12
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12
时间窗: Baseline and Week 12
The UAS7 score is a composite score containing both the hive severity score (HSS, ranging from 0 = None to 3 = more than 50 hives) and the itch severity score (ISS, ranging from 0 = None to 3 = intense). The daily UAS scores ranged from 0 to 6 points per day. Daily UAS scores were summed over a 7-day period to create the UAS7, ranging from 0 to 42, and are composed of the HSS7 and ISS7 components. A higher score indicates worse disease. Baseline is defined as the sum of the 7 days measurements obtained on and prior to the target visit day.
Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12
时间窗: Baseline and Week 12
The ISS represents the itch severity on a scale and was recorded by the participant in their e-diary ranging from 0 (None) to 3 (intense). The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch. Baseline is defined as the sum of the 7 days measurements obtained on and prior to the target visit day.
次要结局
- Change from baseline in ISS7 at Week 12 (except US and US reference countries)(From baseline to Week 12)
- Proportion of participants with UAS7 = 0 at Week 12(At Week 12)
- Change from baseline in UAS7 at Week 4(From baseline to Week 4)
- Change from baseline in weekly hives severity score (HSS7) at Week 12(From baseline to Week 12)
- Proportion of participants with UAS7 ≤6 at Week 12(At Week 12)
- For US and US reference countries only: change from baseline in UAS7 at Week 12(From baseline to Week 12)
- Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and withdrawals due to TEAEs during the double-blind period and the open label extension(Until Week 52)
- Plasma PK concentrations of rilzabrutinib in participants with CSU(Until Week 52)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs), and Withdrawals Due to Treatment-Emergent Adverse Events(From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days, approximately 13 weeks for DB period and approximately 41 weeks for OLE period)
- Change From Baseline in Weekly Urticaria Activity Score at Week 4(Baseline and Week 4)
- Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12(Baseline and Week 12)
- Percentage of Participants With Weekly Urticaria Activity Score Less Than or Equal to (≤)6 at Week 12(At Week 12)
- Percentage of Participants With Weekly Urticaria Activity Score Equal to 0 at Week 12(At Week 12)
- Plasma Concentration of Rilzabrutinib(Pre-dose and 2 hours post-dose at Day 1 and Week 4; pre-dose at Week 12 (DB period); pre-dose and 2 hours post-dose at Week 16; pre-dose at Weeks 20, 24 and 52 (OLE period))