Angioedema, Chronic Spontaneous Urticaria
Conditions
Keywords
Chronic spontanous urticaria, refractory CSU, Angioedema
Brief summary
This study will assess the impact of omalizumab on the quality of life improvement when added to the standard therapy in refractory patients suffering from chronic spontaneous urticaria and angioedema.
Detailed description
This study will be conducted using a double-blind, placebo-controlled, randomized, multicenter design to investigate the impact of omalizumab on Quality of Life (QoL) in Chronic Spontaneous Urticaria (CSU) and will assess its effectiveness in reducing and/or inhibiting the occurrence, time-course and severity of angioedema episodes. Omalizumab is administered subcutaneously every 4 weeks as an add-on therapy to the current approved treatment of adult CSU patients. The treatment period is 28 weeks which is followed by an 8-week follow-up. The study aims to enroll approximately 70 patients. The study is divided into a 2-week screening period, a 28-week double-blind treatment phase with omalizumab or placebo-omalizumab, and an 8-week follow-up phase.
Interventions
BIOLOGICALOmalizumab
Humanized monoclonal antibody against human IgE
DRUGPlacebo
Placebo to omalizumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1-antihistamine treatment * Presence of itch an hives for more than 6 weeks * UAS7 score of more than 14 (range 0-42) * Patient has history of insufficient response to 4x of the approved dose of H1-antihistamines * CSU diagnosis for more than 6 months * Angioedema at least 4x in the last 6 months
Exclusion criteria
* Patients with non urticaria associated angioedema * History of hypersensitivity to omalizumab or the rescue medication or to drugs of similar chemical structure * Evidence of parasitic infection * Previous treatment with omalizumab within the last 6 months prior to screening * History of anaphylactic shock * Woman who are pregnant or breast feeding * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | Baseline, 4, 12, 20, 28 and 36 weeks | The CU-Q2oL is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Participants are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1= not at all to 5= very much). An overall score is calculated and normalized to a scale of 1 to 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | Baseline to week 28 | — |
| Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Baseline to week 28; and follow-up period (to week 36) | A cumulative activity score, evaluated in the screening period and throughout the study. The records each evening on a daily basis symptoms of itch and hives into a patient diary. min. score = 0 ; max. score= 100 |
| Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | week -2 to -1 | data points per group |
| Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | weeks 25 to 28 | data points per group |
| Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | weeks 33 to 36 | data points per group |
| Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | weeks -2 to -1 | data points per group |
| Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | weeks 25 to 28 | data points per group |
| Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Baseline, week 28; and the follow-up period (weeks 29-36) | — |
| Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | baseline to week 28; and then follow-up to week 36 | The AE-Q2oL is a questionnaire for patients suffering from angioedema. It consists of 29 questions relevant to angioedema and its specific impact on quality of life. Patients are asked to respond how much they are troubled be each problem on a 5-point Likert scale (1= does not apply to 5= very much). An overall score is calculated and a higher score indicates lower quality of life. A negative change score (week 28 score minus baseline score) indicates improvement. Each AE-QoL question has 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. The total score is calculated, which is then transformed into a linear scale that ranges from 0 to 100, with a score of 100 indicating the worst possible impairment of HRQoL |
| Rescue Medication During the Treatment Period | baseline to 28 weeks | — |
| Days of Rescue Medication During the Treatment Period | baseline to 28 weeks | data points per group |
| Days of Rescue Medication During the Follow-up Period | weeks 33 to 36 | data points per group |
| Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | baseline to week 28; and then follow-up to week 36 | The UAS7 is the sum of urticaria activity scores over a seven day period. The possible range of the weekly UAS7 score is 0-42. 0 means complete response and a better outcome and 42 means no response and a worse outcome. Complete UAS7 response is defined as UAS7=0. The UAS7 is the sum of the Hive Severity Score over seven days (HSS7) and the Itch Severity Score over seven days (ISS7) . The Hive Severity Score has a scale of 0 (none) to 3 (intense/severe). Complete hives response is defined as HSS7=0. The Itch Severity Score has a scale of 0 (None) to 3 (Severe (difficult to tolerate)). Complete itch response is defined as ISS7=0 |
| Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | baseline to week 28; and follow-up to week 36 | change in Dermatology Quality of Life Index scores The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. |
| Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | weeks 33 to 36 | data points per group |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Omalizumab once a month via subcutaneous injection. | 44 |
| Placebo Placebo of omalizumab once a month via subcutaneous injection | 47 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discon for rescue medication after wk 24 | 0 | 5 |
| Overall Study | Other | 4 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 13 |
Baseline characteristics
| Characteristic | Total | Placebo | Omalizumab |
|---|---|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 12.3 | 41.1 years STANDARD_DEVIATION 10.6 | 44.9 years STANDARD_DEVIATION 13.7 |
| Age, Customized <65 years | 88 Participants | 47 Participants | 41 Participants |
| Age, Customized >=65 years | 3 Participants | 0 Participants | 3 Participants |
| BMI | 28.2 kg/m^2 STANDARD_DEVIATION 6.1 | 29.0 kg/m^2 STANDARD_DEVIATION 5.9 | 27.3 kg/m^2 STANDARD_DEVIATION 6.3 |
| BMI group <18.5 | 0 Participants | 0 Participants | 0 Participants |
| BMI group 18.5-25 | 32 Participants | 12 Participants | 20 Participants |
| BMI group >25 | 59 Participants | 35 Participants | 24 Participants |
| Disease history and baseline charactaristics >10 years | 20 Participants | 7 Participants | 13 Participants |
| Disease history and baseline charactaristics 2-10 years | 45 Participants | 27 Participants | 18 Participants |
| Disease history and baseline charactaristics <=2 years | 82 Participants | 40 Participants | 42 Participants |
| Disease history and baseline charactaristics <2 years | 26 Participants | 13 Participants | 13 Participants |
| Disease history and baseline charactaristics 3-5 years | 9 Participants | 7 Participants | 2 Participants |
| Disease history and baseline charactaristics >5 years | 0 Participants | 0 Participants | 0 Participants |
| Disease history and baseline charactaristics No | 65 Participants | 32 Participants | 33 Participants |
| Disease history and baseline charactaristics Yes | 26 Participants | 15 Participants | 11 Participants |
| Disease history and baseline charactaristics | 7.9 years STANDARD_DEVIATION 9 | 7.4 years STANDARD_DEVIATION 8.8 | 8.4 years STANDARD_DEVIATION 9.3 |
| [Disease history and baseline characteristics of angioedema (FAS)] <24 hours | 50 Participants | 25 Participants | 25 Participants |
| [Disease history and baseline characteristics of angioedema (FAS)] >24 hours | 41 Participants | 22 Participants | 19 Participants |
| Disease history and baseline characteristics of angioedema (FAS) Arms/legs | 52 participants | 28 participants | 24 participants |
| Disease history and baseline characteristics of angioedema (FAS) Eyes/lids/periorbital | 77 participants | 41 participants | 36 participants |
| Disease history and baseline characteristics of angioedema (FAS) Hands | 61 participants | 34 participants | 27 participants |
| Disease history and baseline characteristics of angioedema (FAS) Lips/perioral | 78 participants | 41 participants | 37 participants |
| Disease history and baseline characteristics of angioedema (FAS) Mouth/laryngeal | 50 participants | 28 participants | 22 participants |
| Disease history and baseline characteristics of angioedema (FAS) Trunk | 30 participants | 20 participants | 10 participants |
| Disease history and baseline characteristics of angioedema (FAS) <6 episodes a year | 4 Participants | 3 Participants | 1 Participants |
| Disease history and baseline characteristics of angioedema (FAS) >6 episodes per year | 33 Participants | 14 Participants | 19 Participants |
| Disease history and baseline characteristics of angioedema (FAS) Daily | 9 Participants | 6 Participants | 3 Participants |
| Disease history and baseline characteristics of angioedema (FAS) Weekly | 45 Participants | 24 Participants | 21 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 88 Participants | 46 Participants | 42 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 63 Participants | 33 Participants | 30 Participants |
| Sex: Female, Male Male | 28 Participants | 14 Participants | 14 Participants |
| Smoking status Current smoker | 37 Participants | 18 Participants | 19 Participants |
| Smoking status Ex-smoker | 23 Participants | 16 Participants | 7 Participants |
| Smoking status Never smoked | 31 Participants | 13 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 44 | 29 / 47 |
| serious Total, serious adverse events | 4 / 44 | 2 / 47 |
Outcome results
Primary
Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS)
The CU-Q2oL is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Participants are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1= not at all to 5= very much). An overall score is calculated and normalized to a scale of 1 to 100.
Time frame: Baseline, 4, 12, 20, 28 and 36 weeks
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V5 (week 12) | -32.1 score | Standard Deviation 21.8 |
| Omalizumab | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V9 (week 28) | -35.1 score | Standard Deviation 24.2 |
| Omalizumab | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V7 (week 20) | -31.4 score | Standard Deviation 23.7 |
| Omalizumab | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | Follow-up (week 36) | -23.9 score | Standard Deviation 23 |
| Omalizumab | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V3 (week 4) | -25.5 score | Standard Deviation 21.3 |
| Placebo | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | Follow-up (week 36) | -14.7 score | Standard Deviation 19.2 |
| Placebo | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V3 (week 4) | -6.4 score | Standard Deviation 15.9 |
| Placebo | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V5 (week 12) | -12.1 score | Standard Deviation 20.3 |
| Placebo | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V7 (week 20) | -16.2 score | Standard Deviation 18.8 |
| Placebo | Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | V9 (week 28) | -13.9 score | Standard Deviation 17.7 |
Secondary
Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)
The AE-Q2oL is a questionnaire for patients suffering from angioedema. It consists of 29 questions relevant to angioedema and its specific impact on quality of life. Patients are asked to respond how much they are troubled be each problem on a 5-point Likert scale (1= does not apply to 5= very much). An overall score is calculated and a higher score indicates lower quality of life. A negative change score (week 28 score minus baseline score) indicates improvement. Each AE-QoL question has 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. The total score is calculated, which is then transformed into a linear scale that ranges from 0 to 100, with a score of 100 indicating the worst possible impairment of HRQoL
Time frame: baseline to week 28; and then follow-up to week 36
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 (n= 35, 29) | -37.4 AE-QoL Score | Standard Deviation 23.8 |
| Omalizumab | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 (n=34, 25) | -41.4 AE-QoL Score | Standard Deviation 25.7 |
| Omalizumab | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 (n=34,27) | -37.1 AE-QoL Score | Standard Deviation 26.5 |
| Omalizumab | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 (n=33,23) | -27.2 AE-QoL Score | Standard Deviation 26.4 |
| Omalizumab | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 (n=38,36) | -26.5 AE-QoL Score | Standard Deviation 20.4 |
| Placebo | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 (n=33,23) | -24.6 AE-QoL Score | Standard Deviation 23.3 |
| Placebo | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 (n=38,36) | -10.3 AE-QoL Score | Standard Deviation 21 |
| Placebo | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 (n= 35, 29) | -20.4 AE-QoL Score | Standard Deviation 27.4 |
| Placebo | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 (n=34,27) | -28.8 AE-QoL Score | Standard Deviation 22 |
| Placebo | Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 (n=34, 25) | -24.2 AE-QoL Score | Standard Deviation 24.3 |
Secondary
Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation)
A cumulative activity score, evaluated in the screening period and throughout the study. The records each evening on a daily basis symptoms of itch and hives into a patient diary. min. score = 0 ; max. score= 100
Time frame: Baseline to week 28; and follow-up period (to week 36)
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 12 | -19.0 AAS (Angioedema Activity Score) | Standard Deviation 22.4 |
| Omalizumab | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 28 | -20.6 AAS (Angioedema Activity Score) | Standard Deviation 21.5 |
| Omalizumab | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 20 | -21.3 AAS (Angioedema Activity Score) | Standard Deviation 21.6 |
| Omalizumab | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 36 | -9.6 AAS (Angioedema Activity Score) | Standard Deviation 18.4 |
| Omalizumab | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 4 | -17.7 AAS (Angioedema Activity Score) | Standard Deviation 20 |
| Placebo | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 36 | -15.3 AAS (Angioedema Activity Score) | Standard Deviation 20.8 |
| Placebo | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 4 | -5.0 AAS (Angioedema Activity Score) | Standard Deviation 18.2 |
| Placebo | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 12 | -9.0 AAS (Angioedema Activity Score) | Standard Deviation 22.8 |
| Placebo | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 20 | -16.9 AAS (Angioedema Activity Score) | Standard Deviation 21 |
| Placebo | Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | Diary week 28 | -10.8 AAS (Angioedema Activity Score) | Standard Deviation 21.3 |
Secondary
Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)
change in Dermatology Quality of Life Index scores The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.
Time frame: baseline to week 28; and follow-up to week 36
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 | -10.1 DLQI Score | Standard Deviation 7.5 |
| Omalizumab | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 | -10.5 DLQI Score | Standard Deviation 8.3 |
| Omalizumab | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 | -9.5 DLQI Score | Standard Deviation 8.4 |
| Omalizumab | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 | -6.8 DLQI Score | Standard Deviation 8.6 |
| Omalizumab | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 | -8.3 DLQI Score | Standard Deviation 7.3 |
| Placebo | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 | -5.4 DLQI Score | Standard Deviation 8.3 |
| Placebo | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 | -2.4 DLQI Score | Standard Deviation 6.9 |
| Placebo | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 | -3.9 DLQI Score | Standard Deviation 7.6 |
| Placebo | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 | -5.1 DLQI Score | Standard Deviation 8.3 |
| Placebo | Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 | -5.6 DLQI Score | Standard Deviation 8 |
Secondary
Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)
The UAS7 is the sum of urticaria activity scores over a seven day period. The possible range of the weekly UAS7 score is 0-42. 0 means complete response and a better outcome and 42 means no response and a worse outcome. Complete UAS7 response is defined as UAS7=0. The UAS7 is the sum of the Hive Severity Score over seven days (HSS7) and the Itch Severity Score over seven days (ISS7) . The Hive Severity Score has a scale of 0 (none) to 3 (intense/severe). Complete hives response is defined as HSS7=0. The Itch Severity Score has a scale of 0 (None) to 3 (Severe (difficult to tolerate)). Complete itch response is defined as ISS7=0
Time frame: baseline to week 28; and then follow-up to week 36
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 | -16.4 scores on a scale | Standard Deviation 14.3 |
| Omalizumab | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 | -16.8 scores on a scale | Standard Deviation 14.8 |
| Omalizumab | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 | -15.0 scores on a scale | Standard Deviation 15 |
| Omalizumab | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 | -8.3 scores on a scale | Standard Deviation 15.3 |
| Omalizumab | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 | -12.6 scores on a scale | Standard Deviation 13.3 |
| Placebo | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | follow-up, week 36 | -6.2 scores on a scale | Standard Deviation 13.3 |
| Placebo | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 4 | -3.0 scores on a scale | Standard Deviation 9.4 |
| Placebo | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 12 | -4.4 scores on a scale | Standard Deviation 13.3 |
| Placebo | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 20 | -7.2 scores on a scale | Standard Deviation 14.7 |
| Placebo | Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | week 28 | -6.5 scores on a scale | Standard Deviation 13.4 |
Secondary
Days of Rescue Medication During the Follow-up Period
data points per group
Time frame: weeks 33 to 36
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Days of Rescue Medication During the Follow-up Period | Any rescue medication | 165 days |
| Omalizumab | Days of Rescue Medication During the Follow-up Period | Any nsH1 - antihistamine rescue medication | 158 days |
| Omalizumab | Days of Rescue Medication During the Follow-up Period | Any clemastine rescue medication | 15 days |
| Omalizumab | Days of Rescue Medication During the Follow-up Period | Any corticosteroid rescue medication | 0 days |
| Placebo | Days of Rescue Medication During the Follow-up Period | Any corticosteroid rescue medication | 17 days |
| Placebo | Days of Rescue Medication During the Follow-up Period | Any rescue medication | 118 days |
| Placebo | Days of Rescue Medication During the Follow-up Period | Any clemastine rescue medication | 19 days |
| Placebo | Days of Rescue Medication During the Follow-up Period | Any nsH1 - antihistamine rescue medication | 85 days |
Secondary
Days of Rescue Medication During the Treatment Period
data points per group
Time frame: baseline to 28 weeks
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Days of Rescue Medication During the Treatment Period | Any rescue medication | 507 days |
| Omalizumab | Days of Rescue Medication During the Treatment Period | Any nsH1 - antihistamine rescue medication | 403 days |
| Omalizumab | Days of Rescue Medication During the Treatment Period | Any clemastine rescue medication | 92 days |
| Omalizumab | Days of Rescue Medication During the Treatment Period | Any corticosteroid rescue medication | 25 days |
| Placebo | Days of Rescue Medication During the Treatment Period | Any corticosteroid rescue medication | 113 days |
| Placebo | Days of Rescue Medication During the Treatment Period | Any rescue medication | 787 days |
| Placebo | Days of Rescue Medication During the Treatment Period | Any clemastine rescue medication | 236 days |
| Placebo | Days of Rescue Medication During the Treatment Period | Any nsH1 - antihistamine rescue medication | 524 days |
Secondary
Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36)
data points per group
Time frame: weeks 33 to 36
Population: full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter <10cm | 92 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter 10-20cm | 28 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter >20cm | 8 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | unknown | 17 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | unknown | 18 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter <10cm | 90 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter >20cm | 19 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | Acute swelling episode, Diameter 10-20cm | 58 Number of episodes |
Secondary
Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28)
data points per group
Time frame: weeks 25 to 28
Population: actual patient numbers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter <10cm | 31 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter 10-20cm | 0 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter 20cm | 0 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | unknown | 0 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | unknown | 12 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter <10cm | 76 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter 20cm | 24 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | Acute swelling episode, Diameter 10-20cm | 94 Number of episodes |
Secondary
Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1)
data points per group
Time frame: week -2 to -1
Population: full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter <10cm | 146 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter >20cm | 19 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter 10-20cm | 54 Number of episodes |
| Omalizumab | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | unknown | 12 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | unknown | 15 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter <10cm | 165 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter 10-20cm | 99 Number of episodes |
| Placebo | Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | Acute swelling episode, Diameter >20cm | 46 Number of episodes |
Secondary
Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes
Time frame: Baseline to week 28
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 1st to 2nd episode | 20 days | Standard Deviation 41.63 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 2nd to 3rd episode | 11.0 days | Standard Deviation 19.52 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 3rd to 4th episode | 26.4 days | Standard Deviation 50.73 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 4th to 5th episode | 14.9 days | Standard Deviation 23.87 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 5th to 6th episode | 14.2 days | Standard Deviation 20.54 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 6th to 7th episode | 11.2 days | Standard Deviation 22.11 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 7th to 8th episode | 18.1 days | Standard Deviation 29.41 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 8th to 9th episode | 10.7 days | Standard Deviation 15.05 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 9th to 10th episode | 11.4 days | Standard Deviation 20.16 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 10th to 11th episode | 11.5 days | Standard Deviation 13.02 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 11th to 12th episode | 8.9 days | Standard Deviation 9.42 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 12th to 13th episode | 6.0 days | Standard Deviation 4.47 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 13th to 14th episode | 3.6 days | Standard Deviation 3.02 |
| Omalizumab | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 14th to 15th episode | 6.9 days | Standard Deviation 9.96 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 11th to 12th episode | 9.4 days | Standard Deviation 13.89 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 1st to 2nd episode | 7.8 days | Standard Deviation 14.29 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 8th to 9th episode | 8.0 days | Standard Deviation 12.26 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 2nd to 3rd episode | 7.2 days | Standard Deviation 10.16 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 13th to 14th episode | 7.3 days | Standard Deviation 4.56 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 3rd to 4th episode | 8.3 days | Standard Deviation 13.24 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 9th to 10th episode | 8.7 days | Standard Deviation 12.26 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 4th to 5th episode | 8.6 days | Standard Deviation 20.44 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 12th to 13th episode | 4.3 days | Standard Deviation 4.43 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 5th to 6th episode | 13.6 days | Standard Deviation 30.09 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 10th to 11th episode | 8.5 days | Standard Deviation 10.41 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 6th to 7th episode | 7.5 days | Standard Deviation 11.32 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 14th to 15th episode | 10.1 days | Standard Deviation 11.86 |
| Placebo | Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes | 7th to 8th episode | 9.1 days | Standard Deviation 17.58 |
Secondary
Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation)
Time frame: Baseline, week 28; and the follow-up period (weeks 29-36)
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omalizumab | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Screening (Week -2 to -1) | 5.2 days | Standard Deviation 3.9 |
| Omalizumab | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Treatment (Week 1 to 28) | 14.6 days | Standard Deviation 19.5 |
| Omalizumab | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Follow-up (Week 29 to 36) | 5.8 days | Standard Deviation 9.1 |
| Placebo | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Screening (Week -2 to -1) | 6.8 days | Standard Deviation 4.3 |
| Placebo | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Treatment (Week 1 to 28) | 49.5 days | Standard Deviation 50.8 |
| Placebo | Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) | Follow-up (Week 29 to 36) | 12.8 days | Standard Deviation 16.2 |
Secondary
Rescue Medication During the Treatment Period
Time frame: baseline to 28 weeks
Population: safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Rescue Medication During the Treatment Period | Any clemastine rescue medication | 12 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Betamethasone | 2 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Any nsH1 - antihistamine rescue medication | 19 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Prednisolone | 3 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Any corticosteroid rescue medication | 5 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Prednisolone succinate | 2 participants |
| Omalizumab | Rescue Medication During the Treatment Period | Any rescue medication | 25 participants |
| Placebo | Rescue Medication During the Treatment Period | Prednisolone succinate | 0 participants |
| Placebo | Rescue Medication During the Treatment Period | Any rescue medication | 35 participants |
| Placebo | Rescue Medication During the Treatment Period | Any nsH1 - antihistamine rescue medication | 27 participants |
| Placebo | Rescue Medication During the Treatment Period | Any clemastine rescue medication | 26 participants |
| Placebo | Rescue Medication During the Treatment Period | Any corticosteroid rescue medication | 13 participants |
| Placebo | Rescue Medication During the Treatment Period | Betamethasone | 12 participants |
| Placebo | Rescue Medication During the Treatment Period | Prednisolone | 3 participants |
Secondary
Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36)
data points per group
Time frame: weeks 33 to 36
Population: full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: No | 127 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Severely | 0 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Slightly | 14 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Unknown | 3 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Moderately | 1 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Unknown | 4 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Moderately | 3 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: No | 172 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Slightly | 5 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | Shortness of breath: Severely | 1 Number of episodes |
Secondary
Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28)
data points per group
Time frame: weeks 25 to 28
Population: full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Slightly | 3 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Severely | 0 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Moderately | 0 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Unknown | 0 Number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: No | 28 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Unknown | 1 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: No | 195 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Slightly | 5 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Moderately | 5 Number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | Shortness of breath: Severely | 0 Number of episodes |
Secondary
Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1)
data points per group
Time frame: weeks -2 to -1
Population: full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Slightly | 13 number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Severely | 1 number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Moderately | 7 number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Unknown | 7 number of episodes |
| Omalizumab | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: No | 203 number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Unknown | 4 number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: No | 264 number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Slightly | 25 number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Moderately | 25 number of episodes |
| Placebo | Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | Shortness of breath: Severely | 7 number of episodes |