Chronic Spontaneous Urticaria
Conditions
Keywords
Anti-IgE, CSU, chronic spontaneous urticaria, hives severity score, itch severity score, urticaria activity score
Brief summary
The purpose of this study was to establish safety and efficacy of ligelizumab in adolescent and adult subjects with Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo. The study population consisted of 1,072 male and female subjects aged ≥ 12 years who were diagnosed with CSU and who remained symptomatic despite the use of H1-antihistamines. This was a multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.
Detailed description
This was a Phase III multi-center, randomized, double-blind, active and placebo-controlled, parallel-group study. The study consisted of 3 distinct periods: * Screening period (Day -28 to Day 1): Duration of up to 4 weeks in which subjects who have given informed consent were assessed for eligibility. * Double-blind treatment period (52 weeks): The subjects were seen in the clinic every 4 weeks. * Post-treatment follow-up period (12 weeks): This period consists of 3 visits (every 4 weeks) with the final visit occurring 16 weeks after the last dose at Week 48.
Interventions
BIOLOGICALLigelizumab
Liquid in vial
BIOLOGICALOmalizumab
Lyophilized powder for solution in vial
OTHERPlacebo
Liquid in vial
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Patients, investigator staff and personnel performing the study assessments remained blinded to the identity of the treatment from the time of randomization until final database lock. The study drug was prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded study drug administrator. Neither the unblinded pharmacist nor the unblinded study drug administrator was involved in any assessments.
Intervention model description
This was a Phase III multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. The subject's, parent's or legal guardian's signed written informed consent and child's assent, if appropriate, must be obtained before any assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit. * Male and female subjects ≥ 12 years of age at the time of screening. * CSU diagnosis for ≥ 6 months. * Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization, as defined by all of the following: * The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1 (Day - 28 to Day -14) despite current use of non-sedating H1-antihistamine * UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to randomization (Visit 110, Day 1) * Subjects must be on H1-antihistamine at only locally label approved doses for treatment of CSU starting at Visit 1 (Day -28 to Day -14) * Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules. Key
Exclusion criteria
* History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes (i.e. to murine, chimeric or human antibodies). * Subjects having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic- or contact-urticaria. * Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency). * Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All subjects will be screened at Visit 1. If stool testing is positive for pathogenic organism, the subject will not be randomized and will not be allowed to rescreen. * Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.). * Prior exposure to ligelizumab or omalizumab. * H1-AH used as background medication at greater than locally label-approved doses after visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects | Baseline, Week 12 | The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement |
| Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) | Baseline, Week 12 | The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) | Baseline, Week 12 | Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement.. No Statistical Analysis was planned for adolescent population. |
| Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Baseline, Week 12 | Assessed as percentage of subjects achieving DLQI = 0-1, meaning, no impact on subjects quality of life at Week 12 The Dermatology life Quality Index (DLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). No statistical anaylsis was planned for adolescent group. |
| Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Week 12 | The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. No Statistical analysis was planned for adolescent group. |
| Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) | Baseline, Week 12 | Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. No Statistical Analysis was planned. |
| Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) | Baseline, Week 12 | Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. |
| Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) | Baseline, Week 12 | Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement. |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, Colombia, Croatia, Czechia, Denmark, France, Germany, Greece, Guatemala, Hungary, India, Malaysia, Oman, Peru, Poland, Puerto Rico, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
1,072 participants enrolled at 164 sites in 28 countries
Pre-assignment details
There were 1,034 adult subjects and 38 adolescent subjects
Participants by arm
| Arm | Count |
|---|---|
| Ligelizumab 120 mg Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w | 317 |
| Ligelizumab 72 mg Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w | 324 |
| Omalizumab 300 mg Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w | 322 |
| Placebo Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48 | 109 |
| Total | 1,072 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 0 | 14 | 1 | 6 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 0 | 7 | 0 | 2 | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 | 0 | 3 | 0 | 1 | 0 |
| Overall Study | No treatment due to mis-randomization | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 4 | 0 | 4 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 2 | 0 | 3 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 6 | 0 | 6 | 1 | 8 | 2 | 1 | 0 |
| Overall Study | Reason unknown | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Technical problems | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 19 | 0 | 17 | 0 | 16 | 1 | 7 | 0 |
Baseline characteristics
| Characteristic | Ligelizumab 72 mg | Total | Placebo | Ligelizumab 120 mg | Omalizumab 300 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 38 Participants | 3 Participants | 10 Participants | 13 Participants |
| Age, Categorical >=65 years | 15 Participants | 63 Participants | 11 Participants | 19 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 297 Participants | 971 Participants | 95 Participants | 288 Participants | 291 Participants |
| Age, Continuous Adolescents | 15.1 Years STANDARD_DEVIATION 1.62 | 14.8 Years STANDARD_DEVIATION 1.72 | 15.3 Years STANDARD_DEVIATION 2.08 | 14.6 Years STANDARD_DEVIATION 2.01 | 14.7 Years STANDARD_DEVIATION 1.65 |
| Age, Continuous Adults | 43.3 Years STANDARD_DEVIATION 13.12 | 42.7 Years STANDARD_DEVIATION 13.34 | 43.2 Years STANDARD_DEVIATION 14.06 | 42.3 Years STANDARD_DEVIATION 13.48 | 42.2 Years STANDARD_DEVIATION 13.19 |
| Race/Ethnicity, Customized Adolescent Asian | 3 Participants | 5 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Adolescent Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Adolescent Multi-racial | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Adolescent Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Adolescent Race Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Adolescents Native American | 0 Participants | 6 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Adolescent White | 8 Participants | 26 Participants | 2 Participants | 8 Participants | 8 Participants |
| Race/Ethnicity, Customized Adult Asian | 72 Participants | 218 Participants | 22 Participants | 60 Participants | 64 Participants |
| Race/Ethnicity, Customized Adult Black or African American | 4 Participants | 15 Participants | 1 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Adult Multi-racial | 4 Participants | 16 Participants | 0 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Adult Native American | 10 Participants | 34 Participants | 3 Participants | 12 Participants | 9 Participants |
| Race/Ethnicity, Customized Adult Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Adult Race Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Adult White | 220 Participants | 747 Participants | 80 Participants | 226 Participants | 221 Participants |
| Sex: Female, Male Adolescent Female | 9 Participants | 24 Participants | 1 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Adolescent Male | 3 Participants | 14 Participants | 2 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Adult Female | 226 Participants | 737 Participants | 76 Participants | 217 Participants | 218 Participants |
| Sex: Female, Male Adult Male | 86 Participants | 297 Participants | 30 Participants | 90 Participants | 91 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 316 | 0 / 324 | 0 / 319 | 0 / 109 | 0 / 102 |
| other Total, other adverse events | 178 / 316 | 182 / 324 | 206 / 319 | 38 / 109 | 43 / 102 |
| serious Total, serious adverse events | 22 / 316 | 32 / 324 | 23 / 319 | 3 / 109 | 4 / 102 |
Outcome results
Primary
Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement
Time frame: Baseline, Week 12
Population: Full analysis set (FAS) included all randomized Adult subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment to which they were assigned at randomization. FAS was used for all efficacy variables, unless otherwise stated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects | -19.368 Score | Standard Error 0.668 |
| Ligelizumab 120 mg | Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects | -19.330 Score | Standard Error 0.66 |
| Omalizumab 300 mg | Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects | -20.040 Score | Standard Error 0.663 |
| Placebo | Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects | -11.366 Score | Standard Error 1.129 |
Comparison: Treatment contrast in LS mean (change), Adultsp-value: <0.000195% CI: [-10.576, -5.428]Mixed Models Analysis
Comparison: Treatment contrast in LS mean (change), Adultsp-value: 0.762895% CI: [-1.169, 2.513]Mixed Models Analysis
Comparison: Treatment contrast in LS mean (change), Adultsp-value: <0.000195% CI: [-10.522, -5.047]Mixed Models Analysis
Comparison: Treatment contrast in LS mean (change), Adultsp-value: 0.776895% CI: [-1.118, 2.538]Mixed Models Analysis
Primary
Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS)
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement
Time frame: Baseline, Week 12
Population: Full analysis set (FAS) included all randomized adolescent subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment to which they were assigned at randomization. FAS was used for all efficacy variables, unless otherwise stated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) | -17.39 Score | Standard Deviation 13.07 |
| Ligelizumab 120 mg | Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) | -14.64 Score | Standard Deviation 14.662 |
| Omalizumab 300 mg | Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) | -13.84 Score | Standard Deviation 15.343 |
| Placebo | Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) | -12.75 Score | Standard Deviation 18.738 |
Secondary
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS)
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Time frame: Baseline, Week 12
Population: FAS: Adults
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) | 8.568 Weeks | Standard Error 0.235 |
| Ligelizumab 120 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) | 8.912 Weeks | Standard Error 0.239 |
| Omalizumab 300 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) | 8.790 Weeks | Standard Error 0.239 |
| Placebo | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) | 6.475 Weeks | Standard Error 0.327 |
Comparison: Adultsp-value: <0.000195% CI: [1.183, 1.48]Negative binomial regression model
Comparison: Adultsp-value: 0.746995% CI: [0.904, 1.051]Negative binomial regression model
Comparison: Adultsp-value: <0.000195% CI: [1.23, 1.54]Negative binomial regression model
Comparison: Adultsp-value: 0.358695% CI: [0.941, 1.092]Negative binomial regression model
Secondary
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS)
Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. No Statistical Analysis was planned.
Time frame: Baseline, Week 12
Population: FAS: Adolescents
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) | 6.0 Weeks | Standard Error 4.94 |
| Ligelizumab 120 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) | 7.3 Weeks | Standard Error 5.44 |
| Omalizumab 300 mg | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) | 9.0 Weeks | Standard Error 3.5 |
| Placebo | Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) | 11.0 Weeks | Standard Error 0 |
Secondary
Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS)
Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: FAS: Adults
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) | -8.502 score | Standard Error 0.305 |
| Ligelizumab 120 mg | Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) | -8.532 score | Standard Error 0.301 |
| Omalizumab 300 mg | Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) | -8.921 score | Standard Error 0.302 |
| Placebo | Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) | -5.402 score | Standard Error 0.514 |
Comparison: Adultsp-value: <0.000195% CI: [-4.271, -1.929]Mixed Models Analysis
Comparison: Adultsp-value: 0.836695% CI: [-0.419, 1.258]Mixed Models Analysis
p-value: <0.000195% CI: [-4.295, -1.966]Mixed Models Analysis
Comparison: Adultsp-value: 0.820195% CI: [-0.444, 1.222]Mixed Models Analysis
Secondary
Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS)
Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) Negative change from baseline indicates improvement.. No Statistical Analysis was planned for adolescent population.
Time frame: Baseline, Week 12
Population: FAS: Adolescents
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ligelizumab 72 mg | Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) | -8.40 score | Standard Deviation 6.779 |
| Ligelizumab 120 mg | Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) | -6.82 score | Standard Deviation 7.404 |
| Omalizumab 300 mg | Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) | -5.10 score | Standard Deviation 7.153 |
| Placebo | Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) | -7.00 score | Standard Deviation 9.899 |
Secondary
Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
Assessed as percentage of subjects achieving DLQI = 0-1, meaning, no impact on subjects quality of life at Week 12 The Dermatology life Quality Index (DLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). No statistical anaylsis was planned for adolescent group.
Time frame: Baseline, Week 12
Population: FAS: Adults + Adolescents (observed) = Total
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ligelizumab 72 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 133 Participants |
| Ligelizumab 72 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 3 Participants |
| Ligelizumab 120 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 6 Participants |
| Ligelizumab 120 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 150 Participants |
| Omalizumab 300 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 147 Participants |
| Omalizumab 300 mg | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 2 Participants |
| Placebo | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 22 Participants |
| Placebo | Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 1 Participants |
Comparison: Adultsp-value: <0.000195% CI: [1.621, 4.656]Regression, Logistic
Comparison: Adultsp-value: 0.858695% CI: [0.603, 1.159]Regression, Logistic
Comparison: Adultsp-value: <0.000195% CI: [1.929, 5.513]Regression, Logistic
Comparison: Adultsp-value: 0.51995% CI: [0.717, 1.373]Regression, Logistic
Secondary
Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. No Statistical analysis was planned for adolescent group.
Time frame: Week 12
Population: FAS: Adults + Adolescents (observed data) = Total
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ligelizumab 72 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 102 Participants |
| Ligelizumab 72 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 3 Participants |
| Ligelizumab 120 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 3 Participants |
| Ligelizumab 120 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 104 Participants |
| Omalizumab 300 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 116 Participants |
| Omalizumab 300 mg | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 0 Participants |
| Placebo | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adults | 8 Participants |
| Placebo | Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) | Adolescents | 1 Participants |
Comparison: Adultsp-value: <0.000195% CI: [2.667, 12.095]Regression, Logistic
Comparison: Adultsp-value: 0.84395% CI: [0.598, 1.18]Regression, Logistic
Comparison: Adultsp-value: <0.000195% CI: [2.694, 12.207]Regression, Logistic
Comparison: Adultsp-value: 0.831295% CI: [0.605, 1.188]Regression, Logistic