Study of Efficacy and Safety of Ligelizumab in Chronic Spontaneous Urticaria Patients Who Completed a Previous Study With Ligelizumab

The purpose of this extension study was to establish efficacy and safety of ligelizumab. This was assessed in adult and adolescent chronic spontaneous urticaria (CSU) patients who had completed a preceding ligelizumab study and have relapsed, following treatment in these preceding studies, despite standard of care H1-antihistamine (H1-AH) treatment.

This study also fulfilled the Novartis commitment to provide post-trial access to patients who had completed studies: CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878).

This was a Phase IIIb multi-center, double-blinded and open-label extension study to evaluate efficacy and safety of ligelizumab retreatment with H1-AHs background therapy with an option for ligelizumab monotherapy (i.e., discontinuation of background H1-AH) in adult and adolescent CSU participants who had completed one of the preceding studies, in the setting of retreatment and self-administration.

Participants with weekly urticaria activity score (UAS7) \< 16 during screening entered the first (investigational treatment-free) observation period (OBS1), with a duration up to 36 weeks.

Participants with UAS7 ≥ 16 during screening or OBS1 were assigned to 1 of the 2 treatment arms and entered the treatment period (first half treatment period, referred to as TRT1). The first half treatment period (TRT1) was 52 weeks (from Week 0 to Week 52). Participants remained on the same H1-AH background medication they were taking in the preceding studies. TRT1 was divided into:

* The first 12 weeks in TRT1:

  i. participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) previously treated with ligelizumab 72 mg liquid in vial subcutaneously (s.c.) every 4 weeks (Q4W) were treated with the same dose regimen in a double-blind manner in this extension study; ii. all other participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) were treated with ligelizumab 120 mg liquid in vial s.c., Q4W, in a double-blind manner in this extension study; iii. participants transitioning from CQGE031C1301 (NCT03907878) and CQGE031C2202 (NCT03437278) were treated with ligelizumab 120 mg liquid in vial s.c., Q4W in an open-label manner in this extension study.
* After the first 12 weeks in TRT1 (and up to Week 52), all participants were switched to ligelizumab 120 mg s.c. pre-filled syringe (PFS) Q4W in an open-label manner and they were offered an opportunity to self-administer ligelizumab outside the clinic.

The second half of the treatment period (TRT2) was 52 weeks (from Week 52 to Week 104). Participants with UAS7\>6 and \<16 or with UAS7 ≥ 16 for whom the benefit-risk was deemed as positive by the investigator at Week 52 of TRT1 were transitioned to the TRT2 (ligelizumab 120 mg s.c. Q4W PFS) unless a decision to stop treatment was made based on a risk-benefit assessment. They were not allowed to discontinue H1- AH background medication.

Participants with UAS7 ≤ 6 at Week 52 of TRT1 entered the second (investigational treatment-free) observation period (OBS2) for up to 52 weeks and remained on the same H1-AH background medication they were taking in the preceding studies. Participants with UAS7 ≤ 6 at Week 52 of TRT1 who entered the second observation period (OBS2) and relapsed (UAS7 ≥ 16) were transitioned to the TRT2 and were also offered the opportunity to discontinue their H1-AH background medication (i.e. ligelizumab 120 mg s.c. q4w PFS monotherapy) after 12 weeks in TRT2. Participants who entered the OBS2 and did not relapse (UAS7\<16) exited the study at the end of the OBS2 period.

Finally, participants who were in TRT2 entered the post-treatment follow-up period after treatment discontinuation, with duration of 12 weeks (for participants who did not complete a continuous 104-week treatment) or 52 weeks (for participants who completed the full 104-week treatment period without interruption). Participants who decided to remain on H1-AH background medication continued to use H1-AH background medication. Participants who decided to go off H1- AH background medication continued to remain off.

Eligibility Criteria:
Key Inclusion Criteria:

* Written informed consent
* Subjects who successfully completed all of the treatment period and the follow-up period in any of the following studies: CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878)
* Male and female, adult and adolescent subjects ≥12 years of age
* Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedule

Key Exclusion Criteria:

* Use of investigational drugs, other than those in use in the preceding studies, at the time of enrollment
* Use of omalizumab within 16 weeks of Screening
* History of hypersensitivity to the study drug ligelizumab or its components, or to drugs of similar chemical classes
* New onset or signs and symptoms of any form of chronic urticarias other than CSU during the preceding studies CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356) or CQGE031C2202 (NCT03437278).
* Diseases with possible symptoms of urticaria or angioedema
* Subjects with evidence of helminthic parasitic infection
* Documented history of anaphylaxis
* Pregnant or nursing (lactating) women