Study to Evaluate the Efficacy, Safety, Tolerability, and Immunogenicity of TEV-45779 Compared to XOLAIR (Omalizumab) in Patients With Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine (H1) Treatment.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 608
- 试验地点
- 18
- 主要终点
- Change From Baseline in the ISS7 at Week 12, TEV-45779 High Dose Compared to XOLAIR High Dose (For European Medicines Agency [EMA] Submission)
研究概览
简要总结
The purpose of the study is to compare the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity of TEV-45779 compared to XOLAIR in patients with Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) who remain symptomatic on H1 antihistamine treatment.
详细描述
This is a multicenter, randomized, double-blind study to demonstrate similar efficacy and safety of TEV-45779 compared to XOLAIR administered sc at doses of 300 mg or 150 mg every 4 weeks for 24 weeks (6 treatments) in patients with Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite antihistamine (H1) treatment. This study will consist of a screening period (up to 2 weeks), a 24-week treatment period consisting of a 12-week double-blind main treatment period and a 12-week double-blind transition period, which is followed by a 16-week follow-up period. The total duration of the study is up to 42 weeks.
At baseline, patients will be randomized in a 2:2:1:1 ratio to receive the first 3 treatments of TEV-45779 300 mg, XOLAIR 300 mg, TEV-45779 150 mg or XOLAIR 150 mg (main treatment period). At Week 12, prior to receiving their fourth dose of study medication, patients in the XOLAIR 300 mg and the XOLAIR 150 mg treatment groups will be randomized 1:1 to receive 3 additional doses of XOLAIR (at the same dose level as prior to randomization, or switch to 3 doses of TEV-45779 (transition period) at the same dose level as prior to randomization. All patients in the TEV-45779 groups will continue to receive TEV-45779 at the same dose levels.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CIU refractory to H1 antihistamines for ≥3 months
排除标准
- •Chronic urticaria with clearly defined underlying etiology
- •Other skin disease associated with itch
- •Evidence of parasitic infection on stool evaluation for ova and parasites
- •History of anaphylactic shock
- •Hypersensitivity to omalizumab or any component of the formulation
- •Required background therapy with other than protocol-defined antihistamines
- •Any medical condition that could jeopardize or would compromise the patient's safety or ability to participate in this study
结局指标
主要结局
Change From Baseline in the ISS7 at Week 12, TEV-45779 High Dose Compared to XOLAIR High Dose (For European Medicines Agency [EMA] Submission)
时间窗: Baseline, Week 12
The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching. Least square (LS) mean and 95% confidence interval (CI) were calculated using analysis of covariance (ANCOVA) model. Multiple imputation performed both for the participants having missing ISS7 at week 12 and for participants using any disallowed concomitant medication.
Change From Baseline in the ISS7 at Week 12, TEV-45779 High Dose Compared to XOLAIR High Dose (For Food and Drug Administration [FDA] Submission)
时间窗: Baseline, Week 12
The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching. LS mean and 90% CI were calculated using ANCOVA model. Multiple imputation performed for the participants having missing ISS7 at week 12.
次要结局
- Change From Baseline in the ISS7 at Weeks 4 and 12(Baseline, Weeks 4 and 12)
- Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12(Baseline, Week 12)
- Percentage of Participants With a UAS7 Score ≤6 at Week 12(Week 12)
- Percentage of Complete Responders (UAS7 Score = 0) at Week 12(Week 12)
- Change From Baseline in the Physician's (In-clinic) Assessment of UAS at Week 12(Baseline, Week 12)
- Change From Baseline in the Weekly Number of Wheals Score at Week 12(Baseline, Week 12)
- Change From Baseline in the Weekly Size of the Largest Wheals Score at Week 12(Baseline, Week 12)
- Time to Minimally Important Difference (MID) Response in ISS7 Score(Baseline up to Week 12)
- Percentage of ISS7 MID Responders at Week 12(Week 12)
- Percentage of Angioedema-Free Days From Week 4 to Week 12(Week 4 to Week 12)
- Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12(Baseline, Week 12)
- Change From Week 12 in ISS7 at Weeks 24 and 40(Week 12, Weeks 24 and 40)
- Change From Week 12 in the UAS7 at Week 24(Week 12, Week 24)
- Change From Week 12 in the Physician's (In-clinic) Assessment of UAS7 at Week 24(Week 12, Week 24)
- Change From Week 12 in the Weekly Number of Wheals Score at Weeks 24 and 40(Week 12, Weeks 24 and 40)
- Change From Week 12 in the Weekly Size of the Largest Wheals Score at Weeks 24 and 40(Week 12, Weeks 24 and 40)
- Percentage of Angioedema-Free Days From Week 12 to Week 24(Week 12 to Week 24)
- Change From Week 12 in the Overall DLQI Score at Weeks 24 and 40(Week 12, Weeks 24 and 40)
- Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) in the Main Treatment Period(Baseline up to Week 12)
- Number of Participants With at Least One TEAE Week 12 up to Week 24(Week 12 up to Week 24)
- Number of Participants With Antidrug Antibodies (ADAs) in the Main Treatment Period(Baseline up to Week 12)
- Number of Participants With ADAs From Week 12 to Week 24(Week 12 up to Week 24)