A Multi-center, Double-blinded and Open-label Extension Study to Evaluate the Efficacy and Safety of Ligelizumab as Retreatment, Self-administered Therapy and Monotherapy in Chronic Spontaneous Urticaria Patients Who Completed Studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 1,033
- Locations
- 1
- Primary Endpoint
- Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in Core Studies and Who Achieved UAS7≤ 6 at Week 12 in Core Studies, With Well-controlled Disease (UAS7 ≤ 6) at Week 12 of the Extension Study
Study Overview
Brief Summary
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).
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
Participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) were treated in a double-blind manner for the first 12 weeks of treatment. Thereafter, they were treated in an open-label manner.
No blinding was required for participants transitioning from CQGE031C1301 (NCT03907878) and CQGE031C2202 (NCT03437278)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
Ligelizumab 72 mg LIVI -ligelizumab 120 mg PFS
Participants received 72 mg of ligelizumab liquid in vial (LIVI) subcutaneously every 4 weeks for the first 12 weeks. Thereafter, participants received 120 mg of ligelizumab pre-filled syringe (PFS) subcutaneously every 4 weeks for up to 92 additional weeks (continuous or interrupted if the participant entered the observation period 2).
Intervention: Ligelizumab (Drug)
Ligelizumab 120 mg LIVI -ligelizumab 120 mg PFS
Participants received 120 mg of ligelizumab liquid in vial (LIVI) subcutaneously every 4 weeks for the first 12 weeks. Thereafter, participants received 120 mg of ligelizumab pre-filled syringe (PFS) subcutaneously every 4 weeks for up to 92 additional weeks (continuous or interrupted if the participant entered the observation period 2).
Intervention: Ligelizumab (Drug)
Outcomes
Primary Outcomes
Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in Core Studies and Who Achieved UAS7≤ 6 at Week 12 in Core Studies, With Well-controlled Disease (UAS7 ≤ 6) at Week 12 of the Extension Study
Time Frame: Week 12 of the extension study
The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals and the intensity of the pruritus over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the UAS7 was missing for that week. Missing data was considered as non-responder. The percentage of subjects transitioning from core studies (CQGE031C2302 and CQGE031C2303) and receiving the same dose regimen as in the core studies who achieved UAS7 ≤ 6 at week 12 in the core studies with UAS7≤ 6 at Week 12 of the extension study was estimated based on observed data.
Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Well-controlled Disease (UAS7 ≤ 6) at Week 12
Time Frame: Week 12 of the extension study
The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. The percentage of subjects transitioning from CQGE031C2302 and CQGE031C2303 and receiving the same dose regimen as in the core studies with UAS7≤ 6 at Week 12 was estimated using multiple imputation method. The 95% confidence interval was derived based on the Wilson score method with continuity correction.
Secondary Outcomes
- Change From Extension Study Baseline in the HSS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies(Extension study baseline (Week 0), Week 12 of the extension study)
- Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Completely Controlled Disease (UAS7 =0) at Week 12(Week 12 of the extension study)
- Change From Extension Study Baseline in the UAS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies(Extension study baseline (Week 0), Week 12 of the extension study)
- Change From Extension Study Baseline in the ISS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies(Extension study baseline (Week 0), Week 12 of the extension study)
- Cumulative Number of Angioedema-free Weeks (AAS7=0) up to Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies(From extension study baseline (Week 0) up to Week 12 of the extension study)
- Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With DLQI = 0-1 at Week 12(Week 12 of the extension study)
- Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration(Week 24 of the extension study)