Chronic Spontaneous Urticaria
Conditions
Keywords
Anti-IgE, chronic spontaneous urticaria, hives severity score, itch severity score, urticaria activity score, CSU
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. 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.
Interventions
DRUGLigelizumab
For the first 12 weeks of treatment: i) participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) previously treated with ligelizumab 72 mg LIVI s.c. Q4W were treated with the same dose regimen in a double-blind manner; ii) all other participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) were treated with ligelizumab 120 mg LIVI s.c. Q4W in a double-blind manner; iii) participants transitioning from CQGE031C1301 (NCT03907878) and CQGE031C2202 (NCT03437278) were treated with ligelizumab 120 mg LIVI s.c. Q4W in an open-label manner. Thereafter, all participants were switched to ligelizumab 120 mg s.c. PFS Q4W in an open-label manner and they were offered an opportunity to self-administer ligelizumab. The longest possible treatment was 104 weeks, however this treatment might not be continuous and might span over a period of 156 weeks due to the possibility of entering the intervening observation period.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The Itch Severity Score (ISS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 preceding days. The ISS7 ranged from 0 to 21. A higher ISS7 indicated more severe itching. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the ISS7 values. Otherwise, the weekly score was missing for that week. The absolute 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 was estimated using multiple imputation method. |
| 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 | The Hive Severity Score (HSS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 preceding days. The HSS7 ranged from 0 to 21 A higher HSS7 indicated a greater number of hives. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the HSS7 values. Otherwise, the weekly score was missing for that week. The absolute 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 was estimated using multiple imputation method. |
| 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 | 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 core studies (CQGE031C2302 and CQGE031C2303) and receiving the same dose regimen as in the core studies with UAS7 = 0 at Week 12 was estimated using multiple imputation method. |
| 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 | The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score was calculated and ranged from 0 to 30. Higher scores indicated worse disease-related QoL. A DLQI score of 0 or 1 indicated that there was no impact of a skin disease on the patient's life. The 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 was estimated using multiple imputation method. |
| Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration | Week 24 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. Missing data was considered as non-responder in the analysis. The percentage of subjects with UAS7≤ 6 at Week 24 (i.e., 12 weeks after starting self-administration) was estimated based on observed data. |
| 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 | The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reported the occurrence of angioedema (opening question) with no, AAS score for this day was 0. If yes was the answer to the opening question, the subject continued to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. A score between 0 and 3 was assigned to every answer field. The AAS7 was the weekly sum of the daily AAS. AAS7 scores ranged from 0-105. Higher score indicated more severe disease. AAS7 in all subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies was estimated using multiple imputation method. The imputed AAS7 = 0 was used for the cumulative number of weeks that subjects achieved AAS7 = 0 response calculation |
| 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 | 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 negative change score from extension study baseline indicates improvement. 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 absolute change from extension study baseline in the UAS7 at Week 12 was estimated using multiple imputation method. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, France, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Japan, Lebanon, Malaysia, Mexico, Netherlands, Oman, Peru, Philippines, Poland, Puerto Rico, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, Tunisia, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Pre-assignment details
A total of 1457 participants who completed preceding studies (CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878)) entered the screening period. 515 participants with weekly urticaria activity score (UAS7) \<16 during screening entered the OBS1 period (treatment-free period). A total of 1033 participants with UAS7≥ 16 during screening or OBS1 period were assigned to 1 of the 2 treatment arms and entered the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 290 |
| 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) | 743 |
| Total | 1,033 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Half Treatment Period (52 Weeks) | Adverse Event | 1 | 11 |
| First Half Treatment Period (52 Weeks) | Death | 0 | 2 |
| First Half Treatment Period (52 Weeks) | Lack of Efficacy | 0 | 2 |
| First Half Treatment Period (52 Weeks) | Lost to Follow-up | 4 | 2 |
| First Half Treatment Period (52 Weeks) | Physician Decision | 0 | 3 |
| First Half Treatment Period (52 Weeks) | Pregnancy | 0 | 1 |
| First Half Treatment Period (52 Weeks) | Protocol deviation | 0 | 3 |
| First Half Treatment Period (52 Weeks) | Study terminated by sponsor | 134 | 322 |
| First Half Treatment Period (52 Weeks) | Subject decision | 11 | 28 |
| Follow-up Period (up to 12 or 52 Weeks) | Adverse Event | 1 | 6 |
| Follow-up Period (up to 12 or 52 Weeks) | Lack of Efficacy | 0 | 2 |
| Follow-up Period (up to 12 or 52 Weeks) | Lost to Follow-up | 0 | 5 |
| Follow-up Period (up to 12 or 52 Weeks) | New therapy for study indication | 2 | 1 |
| Follow-up Period (up to 12 or 52 Weeks) | Physician Decision | 4 | 16 |
| Follow-up Period (up to 12 or 52 Weeks) | Pregnancy | 0 | 1 |
| Follow-up Period (up to 12 or 52 Weeks) | Protocol deviation | 0 | 1 |
| Follow-up Period (up to 12 or 52 Weeks) | Subject decision | 16 | 32 |
| Observation Period 2 (up to 52 Weeks) | Adverse Event | 0 | 1 |
| Observation Period 2 (up to 52 Weeks) | Lost to Follow-up | 0 | 1 |
| Observation Period 2 (up to 52 Weeks) | Study terminated by sponsor | 45 | 107 |
| Observation Period 2 (up to 52 Weeks) | Subject decision | 0 | 1 |
| Second Half Treatment Period (52 Weeks) | Lost to Follow-up | 0 | 1 |
| Second Half Treatment Period (52 Weeks) | Study terminated by sponsor | 71 | 195 |
| Second Half Treatment Period (52 Weeks) | Subject decision | 5 | 8 |
Baseline characteristics
| Characteristic | Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | Total |
|---|---|---|---|
| Age, Continuous | 42.4 Years STANDARD_DEVIATION 13.98 | 42.8 Years STANDARD_DEVIATION 14.4 | 42.7 Years STANDARD_DEVIATION 14.28 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 11 Participants | 20 Participants | 31 Participants |
| Race/Ethnicity, Customized Asian | 66 Participants | 199 Participants | 265 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 13 Participants | 14 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 209 Participants | 506 Participants | 715 Participants |
| Sex: Female, Male Female | 190 Participants | 525 Participants | 715 Participants |
| Sex: Female, Male Male | 100 Participants | 218 Participants | 318 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 288 | 0 / 745 | 0 / 1,033 | 0 / 263 | 3 / 684 | 3 / 947 | 0 / 77 | 0 / 206 | 0 / 283 | 0 / 288 | 3 / 745 | 3 / 1,033 |
| other Total, other adverse events | 12 / 288 | 65 / 745 | 77 / 1,033 | 49 / 263 | 156 / 684 | 205 / 947 | 11 / 77 | 36 / 206 | 47 / 283 | 65 / 288 | 224 / 745 | 289 / 1,033 |
| serious Total, serious adverse events | 1 / 288 | 10 / 745 | 11 / 1,033 | 5 / 263 | 32 / 684 | 37 / 947 | 2 / 77 | 3 / 206 | 5 / 283 | 8 / 288 | 44 / 745 | 52 / 1,033 |
Outcome results
Primary
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
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.
Time frame: Week 12 of the extension study
Population: Ligelizumab responder retreatment subpopulation: Participants transitioning from core studies (CQGE031C2302 and CQGE031C2303) who received at least one dose of study treatment, were treated with the same dosage of ligelizumab in the extension study as in the two core studies and achieved UAS7 ≤ 6 at week 12 in the core studies. Only participants with non-missing UAS7 scores based on observed data for Week 12 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | 81.9 Percentage of participants |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | 82.6 Percentage of participants |
Primary
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
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.
Time frame: Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from core studies (CQGE031C2302 and CQGE031C2303) who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies. Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | 53.5 Percentage of participants |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | 57.5 Percentage of participants |
Secondary
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
The Hive Severity Score (HSS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 preceding days. The HSS7 ranged from 0 to 21 A higher HSS7 indicated a greater number of hives. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the HSS7 values. Otherwise, the weekly score was missing for that week. The absolute 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 was estimated using multiple imputation method.
Time frame: Extension study baseline (Week 0), Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | -10.71 Score on a scale | Standard Error 7.5 |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | -10.95 Score on a scale | Standard Error 7.11 |
Secondary
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
The Itch Severity Score (ISS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 preceding days. The ISS7 ranged from 0 to 21. A higher ISS7 indicated more severe itching. A negative change score from baseline indicates improvement. A minimum of 4 out of 7 daily scores were needed to calculate the ISS7 values. Otherwise, the weekly score was missing for that week. The absolute 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 was estimated using multiple imputation method.
Time frame: Extension study baseline (Week 0), Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | -9.12 Score on a scale | Standard Error 6.35 |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | -9.46 Score on a scale | Standard Error 6.55 |
Secondary
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
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 negative change score from extension study baseline indicates improvement. 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 absolute change from extension study baseline in the UAS7 at Week 12 was estimated using multiple imputation method.
Time frame: Extension study baseline (Week 0), Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | -19.83 Score on a scale | Standard Error 13.12 |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | -20.41 Score on a scale | Standard Error 12.94 |
Secondary
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
The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reported the occurrence of angioedema (opening question) with no, AAS score for this day was 0. If yes was the answer to the opening question, the subject continued to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. A score between 0 and 3 was assigned to every answer field. The AAS7 was the weekly sum of the daily AAS. AAS7 scores ranged from 0-105. Higher score indicated more severe disease. AAS7 in all subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies was estimated using multiple imputation method. The imputed AAS7 = 0 was used for the cumulative number of weeks that subjects achieved AAS7 = 0 response calculation
Time frame: From extension study baseline (Week 0) up to Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | 9.30 Weeks | Standard Error 0.25 |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | 9.68 Weeks | Standard Error 0.27 |
Secondary
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
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 core studies (CQGE031C2302 and CQGE031C2303) and receiving the same dose regimen as in the core studies with UAS7 = 0 at Week 12 was estimated using multiple imputation method.
Time frame: Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | 37.3 Percentage of participants |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | 41.5 Percentage of participants |
Secondary
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
The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score was calculated and ranged from 0 to 30. Higher scores indicated worse disease-related QoL. A DLQI score of 0 or 1 indicated that there was no impact of a skin disease on the patient's life. The 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 was estimated using multiple imputation method.
Time frame: Week 12 of the extension study
Population: Ligelizumab retreatment subpopulation: Participants transitioning from studies CQGE031C2302 and CQGE031C2303 who received at least one dose of study treatment and were treated with the same dosage of ligelizumab in the extension study as in the two core studies (CQGE031C2302 and CQGE031C2303). Only participants with non-missing UAS7 scores (based on the data after the missing data imputation) for Week 12 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | 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 | 45.6 Percentage of participants |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | 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 | 55.8 Percentage of participants |
Secondary
Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration
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. Missing data was considered as non-responder in the analysis. The percentage of subjects with UAS7≤ 6 at Week 24 (i.e., 12 weeks after starting self-administration) was estimated based on observed data.
Time frame: Week 24 of the extension study
Population: Self-administration subpopulation: Participants transitioning from preceding studies (CQGE031C2302, CQGE031C2303, CQGE031C2202 and CQGE031C1301) who had at least one injection of study treatment with PFS administered by the participant herself/himself or caregiver either in clinic or outside of clinic
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ligelizumab 72 mg LIVI -Ligelizumab 120 mg PFS | Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration | 69.4 Percentage of participants |
| Ligelizumab 120 mg LIVI -Ligelizumab 120 mg PFS | Percentage of Subjects With Well-controlled Disease (UAS7 ≤ 6) 12 Weeks After Starting Self-administration | 69.5 Percentage of participants |