OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in CSU Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 314
- 试验地点
- 1
- 主要终点
- Number of Participants Who Were Clinically Well-controlled (UAS7<=6) After the Initial Dosing Period, Relapsed (UAS7>=16) When Treatment Was Discontinued, and Who Achieved a UAS7 Score <=6 at the End of the Second Dosing Period (Retreatment A2 and B2)
研究概览
简要总结
This trial assessed the efficacy of optimized re-treatment therapy with omalizumab (150mg or 300mg) after relapse, in participants with Chronic Spontaneous Urticaria who were clinically well-controlled following their first course of treatment with omalizumab (150mg or 300mg). The study also assessed the benefit of uptitrating to 300mg dose in participants who were not well-controlled following their initial course of treatment with omalizumab 150mg, as well as the benefit of treatment extension of those patients who were not well-controlled following their initial course of treatment with omalizumab 300mg.
详细描述
The study consisted of 5 phases.
Phase 1 (Screening): At the first visit (Screening Visit), the participant was provided informed consent and then completed all screening visit assessments. During this visit, all CIU/CSU treatments taken by the participant were documented. Any protocol-defined prohibited CIU/CSU treatments were stopped at this visit, and the participant underwent a wash-out period of 1-5weeks (refer to study protocol for medication wash-out times) prior to Phase 2 Visit1. Only non-sedating H1- antihistamines, at locally-approved dosages, were allowed to be continued during the Screening Period and throughout the rest of the study. All participants also needed to complete daily diary during the entire screening period.
Phase 2 (Initial Dosing Period): Following completion of Phase 1, eligible participants were randomly assigned (in a 4:3 ratio) to either Group A or Group B. Participants in Group A were treated with omalizumab 150mg by subcutaneous (SC) injection every 4 weeks during the 24-week Phase 2 (Initial Dosing Period), while participants in Group B were treated with omalizumab 300mg every 4 weeks during this period. Randomization to treatment groups was stratified at Phase 2 Visit 1 by geographic location of the study site (i.e. Canada or Latin America), baseline presence/absence of angioedema and baseline UAS7 score (collected at Phase 2 Visit 1). At the end of Phase 2, all participants with a UAS7 score ≤ 6 entered Phase 3 (Study Treatment Withdrawal Period). Group A participants who had a UAS7 > 6 at any visit of Phase 2 starting at Week 8 (Phase2-Visit3) skipped Phase 3 and moved directly to Phase 4 (Second Dosing Period) and received 300 mg Omalizumab (step-up). Group B participants who had a UAS7 >6 at the end of Phase 2 skipped Phase 3 and moved directly to Phase 4.
Phase 3 (Study Treatment Withdrawal Period): During Phase 3 (Study Treatment Withdrawal Period), no study treatment (omalizumab) was given and participants continued to visit the study center at 4-week intervals (to a maximum of 8 weeks). If a UAS7 score ≥16 was observed during Phase 3 (Study Treatment Withdrawal Period), the participant moved directly to Phase 4 (Second Dosing Period). If a participant completed the full 8 weeks of Phase 3 (Study Treatment Withdrawal Period) with a UAS7 score <16, the participant was moved directly to Phase 5 (Follow-up Period).
Phase 4 (Second Dosing Period)
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
- None
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
- •Men or women at least 18 years of age at time of screening.
- •Having a diagnosis of CSU and the presence of symptoms for ≥6 months prior to the screening visit.
- •Presence of itch and hives for ≥6 consecutive weeks at any time prior to the screening visit despite concurrent use of non-sedating H1-antihistamine treatment
- •Patient must have been on an approved dose of non-sedating H1-antihistamine for CSU, and no other concomitant CSU treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must document current use on the day of the randomization visit.
排除标准
- •Patients having a clearly defined underlying etiology for chronic urticaria other than CSU including the following urticarias: acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact
- •Patients with other skin disease associated with itch that could interfere with study outcomes and/or compromise the safety of the patient
- •Patients with evidence of parasitic infection
- •Patients with a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- •Pregnant or nursing (lactating) women,
- •Women of child-bearing potential, unless they are using effective methods of contraception during dosing of study treatment.
- •Patients who are unable or unwilling to comply with study procedures, attend scheduled study visits, complete questionnaires and daily diaries, or who may otherwise be unable to comply with the study requirements.
研究组 & 干预措施
omalizumab 150mg
Participants received 150mg omalizumab every 4 weeks during the initial dosing phase (24 weeks). A second dosing period (at 150mg or 300mg) may have been implemented based on protocol-defined assessment criteria.
干预措施: omalizumab (Drug)
omalizumab 300mg
Participants received 300mg omalizumab every 4 weeks during the initial dosing phase (24 weeks). A second dosing period may have been implemented based on protocol-defined assessment criteria.
干预措施: omalizumab (Drug)
结局指标
主要结局
Number of Participants Who Were Clinically Well-controlled (UAS7<=6) After the Initial Dosing Period, Relapsed (UAS7>=16) When Treatment Was Discontinued, and Who Achieved a UAS7 Score <=6 at the End of the Second Dosing Period (Retreatment A2 and B2)
时间窗: Last 7 days of second dosing period, 44 weeks
The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the last 7 days of the second dosing period.
次要结局
- The Difference in Urticaria Activity Score Over 7 Days (UAS7) Between the Start and End of the Second Dosing Period, in Participants That Step-up Treatment Dose During the Initial Dosing Period (Step-up A3)(7 days prior to start of second dosing period and last 7 days of Second Dosing Period)
- Time to Relapse (Urticaria Activity Score Over 7 Days (UAS7) ≥ 16) After Drug Withdrawal in Participants Who Responded to Initial Dosing Period (Retreatment A2 and B2)(study drug withdrawal period, weeks 24 through 32)
- The Change in Urticaria Activity Score Over 7 Days (UAS7) From Baseline to Week 24 in Group B Participants(7 days prior to Baseline visit, and last 7 days prior to week 24 of the initial dosing period)
- Number of Participants With Urticaria Activity Score Over 7 Days (UAS7)≤6 at the End of the Second Dosing Period, in Participants Who Stepped-up Treatment Dosing (Step-up A3)(Last 7 days of the second dosing period)
- Difference in Urticaria Activity Score Over 7 Days (UAS7) Between End of Initial Dosing Period and the End of the Second Dosing Period, in Group B3 Participants Who Did Not Respond to the Initial Dosing Period(last 7 days of initial dosing period, week 24, and last 7 days of second dosing period, week 36)
- Change in Urticaria Activity Score Over 7 Days (UAS7) Between Baseline and End of Second Dosing Period(7 days prior to Baseline visit, and last 7 days of second dosing period)
- The Number of Participants Who Remained Well-controlled (UAS7<=6) or Who Had Achieved UAS=0 at Phase 4 (Second Dosing Period) Week 8 During Retreatment After Being Well Controlled or Achieving UAS7=0 at Phase 2 (Initial Dosing Period) Week 8(Week 8 of initial dosing phase and week 8 of second dosing phase)