Conditions: Chronic Spontaneous Urticaria
Keywords: chronic spontaneous urticaria, CSU, chronic idiopathic urticaria, CIU, hives, angioedema, itch
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 314
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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)

* Group A participants who relapsed (UAS7 ≥16) during Phase 3 (Study Treatment Withdrawal Period) were retreated with omalizumab 150mg by SC injection every 4 weeks during the 12-week Phase 4 (Second Dosing Period)
* Group A participants who were not clinically well-controlled at week 8 of Phase 2 (Initial Treatment Period) or any subsequent visit in Phase 2 moved to Phase 4 (Second Dosing Period) immediately during which their study treatment was up-titrated to 300mg by SC injection every 4 weeks for 12 weeks.
* Group A participants who had their symptoms well controlled at week 24 (UAS7≤6) but did not relapse during the 8 weeks Study Treatment withdrawal period (UAS7\<16) moved directly to Phase 5, Follow up period.
* Group B participants who relapsed during Phase 3 (Study Treatment Withdrawal Period) were retreated with omalizumab 300mg by SC injection every 4 weeks during the 12- week Phase 4 (Second Dosing Period)
* Group B participants who were not clinically well-controlled at week 24 of Phase 2 (Initial Treatment Period) moved to Phase 4 (Second Dosing Period) immediately during which their study treatment remained 300mg by SC injection every 4 weeks for 12 weeks. In case the treating physician and the participant decided not to extend treatment, they could move directly from Phase 2 (Initial Treatment Period) to Phase 5 (Follow- up Period).
* Group B participants who had their symptoms well controlled at week 24 (UAS7≤6) but did not relapse during the 8 weeks Study Treatment withdrawal period (UAS7\<16) moved directly to Phase 5, Follow up period.

Phase 5 (Follow-up Period)

* Participants who did not relapse (UAS7 \<16) following completion of Phase 3 (Study Treatment Withdrawal Period) entered the 4-week Phase 5 (Follow-up Period).
* Group B participants who did not respond during their initial 24-week treatment period (Phase 2), and who did not wish to extend their treatment into Phase 4 (Second Dosing Phase) were allowed to move directly into the 4-week Phase 5 (Follow-up Period).
* All participants who completed Phase 4 (Second Dosing Period) entered the 4-week Phase 5 (Follow-up Period).

During Phase 5 (Follow-up Period), participants continued to only receive non-sedating H1- antihistamines at approved dosages. Omalizumab was not allowed to be administered during this period.

Arms:
arm 1: 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. arm 2: 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.

Interventions: intervention 1: omalizumab intervention 2: omalizumab
Intervention descriptions: intervention 1: 150mg omalizumab via sub-cutaneous injection once every 4 weeks intervention 2: 300mg omalizumab via sub-cutaneous injection once every 4 weeks

Protocol document: