A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 3 Study to Compare Efficacy and Safety of CT-P39 and Xolair in Patients With Chronic Spontaneous Urticaria Who Remain Symptomatic Despite H1 Antihistamine Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celltrion
- 入组人数
- 634
- 试验地点
- 1
- 主要终点
- Therapeutic Equivalence Based on Change From Baseline in ISS7 at Week 12 in 300 mg Groups
研究概览
简要总结
A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 3 Study to Compare Efficacy and Safety of CT-P39 and Xolair in Patients with Chronic Spontaneous Urticaria Who Remain Symptomatic despite H1 antihistamine Treatment
详细描述
CT-P39, containing the active ingredient omalizumab, is a recombinant humanized monoclonal antibody that is being developed and manufactured as a proposed biosimilar to Xolair (omalizumab) by the Sponsor. CT-P39 is identical to Xolair with respect to concentration and presentation. The 150 mg of drug product (CT-P39) will have the same pharmaceutical form and strength as 150 mg Xolair (in a prefilled syringe [PFS] for subcutaneous injection) and is intended to have a similar quality profile compared with Xolair.
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 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with CSU
- •Diagnosed as CSU refractory to H1-antihistamine
排除标准
- •Chronic urticaria with clearly defined underlying etiology
- •Clinically significant allergic reaction and/or hypersensitivity to any component of omalizumab
- •History of anaphylactic shock
- •History of and/or concomitant immune complex disease (including Type III hypersensitivity)
- •Parasitic diseases or colonization on stool evaluation for ova and parasites
- •Unable to receive background therapy with protocol-defined antihistamines or contraindicated to epinephrine
研究组 & 干预措施
Arm 1
Planned to receive CT-P39 300 mg every 4 weeks in Treatment Period 1 (TP1) and maintain CT-P39 300 mg in TP2
干预措施: CT-P39 (Biological)
Arm 2
Planned to receive Xolair 300 mg every 4 weeks in TP1 and be re-randomized at Week 12 to Arm 2-1 or Arm 2-2
干预措施: EU-approved Xolair (Biological)
Arm 2-1
Planned to receive Xolair 300 mg every 4 weeks in TP1 and be re-randomized to switch to CT-P39 300 mg in TP2
干预措施: CT-P39 (Biological)
Arm 2-1
Planned to receive Xolair 300 mg every 4 weeks in TP1 and be re-randomized to switch to CT-P39 300 mg in TP2
干预措施: EU-approved Xolair (Biological)
Arm 2-2
Planned to receive Xolair 300 mg every 4 weeks in TP1 and be re-randomized to maintain Xolair 300 mg in TP2
干预措施: EU-approved Xolair (Biological)
Arm 3
Planned to receive CT-P39 150 mg every 4 weeks in Treatment Period 1 (TP1) and increase to CT-P39 300 mg in TP2
干预措施: CT-P39 (Biological)
Arm 4
Planned to receive Xolair 150 mg every 4 weeks in Treatment Period 1 (TP1) and increase to Xolair 300 mg in TP2
干预措施: EU-approved Xolair (Biological)
结局指标
主要结局
Therapeutic Equivalence Based on Change From Baseline in ISS7 at Week 12 in 300 mg Groups
时间窗: Week 12
The primary efficacy evaluation was comparison of mean change from baseline in ISS7 of 300 mg of CT-P39 (Arm 1) and 300 mg of Xolair (Arm 2) at Week 12, calculated as ISS7 at Week 12 minus the baseline ISS7. The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome. The analysis was conducted by analysis of covariance (ANCOVA). The ANCOVA model included the treatment group as a fixed effect and baseline ISS7, body weight on Day 1 and country as covariates.
Relative Potency of CT-P39 Compared With Xolair Based on Change From Baseline in ISS7 at Week 12
时间窗: Week 12
The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome. The relative potency was not calculated due to the assumption of parallel-line assay not being met. A parallel-line assay assumes that dose-efficacy response relationships are linear and parallel on log-dose scale which requires the equal slope in the regression model used to estimate relative potency. However, the slopes of the two treatment groups were estimated to be different, indicating a violation of the parallelism assumption. As a result, the relative potency was not computed.
次要结局
- Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12(Week 12)
- Time to Minimally Important Difference (MID) in ISS7 by Week 12(Up to Week 12)
- Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 24(Week 24)
- Percentage of Minimally Important Difference (MID) Responders in ISS7 at Week 12(Week 12)
- Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12(Week 12)
- Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 24(Week 24)
- Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12(Week 12)
- Change From Baseline in Number of Tablets/Week of Rescue Therapy at Week 24(Week 24)
- Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12(Week 12)
- Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 24(Week 24)
- Change From Baseline in the Overall Chronic Urticaria Quality of Life Questionnaire Score (CU-Q2oL) Score at Week 12(Week 12)
- Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 24(Week 24)
- Change From Baseline in the Overall Chronic Urticaria Quality of Life Questionnaire Score (CU-Q2oL) Score at Week 24(Week 24)
- Trough Serum Concentration (Ctrough) of Omalizumab at Week 12(Week 12)
- Trough Serum Concentration (Ctrough) of Omalizumab at Week 24(Week 24)
- Immunogenicity Result at Week 12(Week 12)
- Immunogenicity Result at Week 24(Week 24)
- Percentage of Patients With UAS7 of ≤ 6 Points and Complete Responders in Weekly Urticaria Activity Score at Week 12(Week 12)
- Percentage of Patients With UAS7 of ≤ 6 Points and Complete Responders in Weekly Urticaria Activity Score at Week 24(Week 24)
- Percentage of Angioedema-Free Days From Week 4 to Week 12(Week 4 to 12)
- Change From Baseline in Number of Tablets/Week of Rescue Therapy at Week 12(Week 12)