OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in Chronic Spontaneous Urticaria (CSU) Patients

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.

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.

Eligibility Criteria:
Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.