A Phase 3 interventional study of Omalizumab and Placebo in Chronic Spontaneous Urticaria, sponsored by Novartis Pharmaceuticals. Completed at 27 sites in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-11-04.
Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment
The purpose of this study was to demonstrate the efficacy and safety of omalizumab, compared with placebo, as an add-on to H1 antihistamines (H1AH) therapy in adult patients suffering from Chronic Spontaneous Urticaria (CSU) who remained symptomatic despite H1AH therapy.
This was a randomized, multicenteric, double-blinded, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients of refractory CSU who remained symptomatic despite approved-dosed H1AH treatment.
The study consisted of three distinct epochs over 24 weeks: Screening epoch (Day -28 to Day -1), Randomized treatment epoch (Day 1 to Week 12) and Post-treatment follow-up epoch (Week 12 to Week 20). Patients were randomized into three treatment groups (omalizumab 300 mg s.c. omalizumab 150 mg s.c. and placebo) in a 2:2:1 ratio, stratified by latent tuberculosis (TB) status at Baseline (Yes/No).
On Day 1, eligible patients were randomly assigned to receive omalizumab (150 mg or 300 mg) or placebo by subcutaneous (s.c.) injection every 4 weeks (on Day 1, Week 4, and Week 8) during the 12-week double-blind randomized-treatment epoch. Patients visited the study center at 4-week intervals. Patients were instructed to stay on the same CSU H1AH treatment at stable dose that they were using during the pre-randomization period during the randomized treatment epoch. They were allowed to use diphenhydramine as rescue medication during all epochs. The last dose of the study drug during the randomized-treatment epoch was administered at Week 8 study visit, however, the last assessment was done at Week 12.
After the completion of the 12-week randomized-treatment epoch, all patients entered an 8-week post-treatment follow-up epoch.
Main Inclusion Criteria:
Main Exclusion Criteria
patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Drug: Omalizumab
patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)
Drug: Omalizumab
patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Drug: Placebo
injection of 150mg or 300 mg
Also known as: IGE025
Injection of placebo
Change From Baseline of the Itch Severity Score (ISS7) Score After 12 Weeks of Treatment
The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None 1. = Mild (minimal awareness, easily tolerated) 2. = Moderate (definite awareness, bothersome but tolerable) 3. = Severe (difficult to tolerate)
Time frame: Baseline, Week 12
Change From Baseline of Urticaria Activity Score (UAS7) After 12 Weeks of Treatment
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
Time frame: Baseline, Week 12
Change From Baseline of Number of Hives Score (NHS7) After 12 Weeks of Treatment
Hives Severity Score (HSS), defined by number of hives, were recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 - None * Mild (1-6 hives/12 hours) * Moderate (7-12 hives/12 hours) * Severe (\>12 hives/12 hours)
Time frame: Baseline, Week 12
Percentage of Patients With UAS7≤6 at Week 12
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.
Time frame: Week 12
Percentage of Complete Responders (UAS7 = 0) at Week 12
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Complete responders are defined as participants who achieved UAS7 = 0.
Time frame: Week 12
Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12
The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None 1. = Mild (minimal awareness, easily tolerated) 2. = Moderate (definite awareness, bothersome but tolerable) 3. = Severe (difficult to tolerate) The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points.
Time frame: Week 12
Change From Baseline of Dermatology Life Quality Index (DLQI) Score After 12 Weeks of Treatment
Dermatology life quality index (DLQI) is a 10-item dermatology- specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 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: Week 12
Time to ISS7 MID Response by Week 12
The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points. Time to ISS7 MID response was the time (in weeks) from the date of the first dose to the date where ISS7 MID response was first achieved during Week 1 to Week 12.
Time frame: 12 weeks
Patients were recruited from 27 sites across China.
| Milestone | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Started | 168 | 167 | 83 |
| Full analysis set (fas) | 167 | 167 | 83 |
| Completed | 152 | 162 | 81 |
| Not completed | 16 | 5 | 2 |
| Withdrew: Adverse event | 4 | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 |
| Withdrew: Pregnancy | 3 | 0 | 0 |
| Withdrew: Patient/guardian decision | 8 | 3 | 1 |
| Withdrew: Lack of efficacy | 1 | 0 | 0 |
| Milestone | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Started | 161 | 163 | 81 |
| Completed | 153 | 160 | 79 |
| Not completed | 8 | 3 | 2 |
| Withdrew: Adverse event | 4 | 0 | 1 |
| Withdrew: Lack of efficacy | 1 | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 |
| Withdrew: Patient/guardian decision | 2 | 1 | 0 |
The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None 1. = Mild (minimal awareness, easily tolerated) 2. = Moderate (definite awareness, bothersome but tolerable) 3. = Severe (difficult to tolerate)
| Score on a scale | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Change From Baseline of the Itch Severity Score (ISS7) Score After 12 Weeks of Treatment | -10.11 ± 0.430 | -9.66 ± 0.424 | -5.87 ± 0.604 |
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
| Score on a scale | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Change From Baseline of Urticaria Activity Score (UAS7) After 12 Weeks of Treatment | -21.82 ± 0.895 | -20.74 ± 0.882 | -11.62 ± 1.258 |
Hives Severity Score (HSS), defined by number of hives, were recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 - None * Mild (1-6 hives/12 hours) * Moderate (7-12 hives/12 hours) * Severe (\>12 hives/12 hours)
| Score on a scale | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Change From Baseline of Number of Hives Score (NHS7) After 12 Weeks of Treatment | -11.68 ± 0.492 | -11.11 ± 0.485 | -5.76 ± 0.690 |
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.
| Participants | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Percentage of Patients With UAS7≤6 at Week 12 | 81 | 79 | 9 |
UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Complete responders are defined as participants who achieved UAS7 = 0.
| Participants | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Percentage of Complete Responders (UAS7 = 0) at Week 12 | 62 | 39 | 4 |
The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None 1. = Mild (minimal awareness, easily tolerated) 2. = Moderate (definite awareness, bothersome but tolerable) 3. = Severe (difficult to tolerate) The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points.
| Participants | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12 | 125 | 125 | 49 |
Dermatology life quality index (DLQI) is a 10-item dermatology- specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 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.
| Score on a scale | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| Change From Baseline of Dermatology Life Quality Index (DLQI) Score After 12 Weeks of Treatment | -10.4 ± 0.50 | -9.9 ± 0.49 | -6.5 ± 0.69 |
The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points. Time to ISS7 MID response was the time (in weeks) from the date of the first dose to the date where ISS7 MID response was first achieved during Week 1 to Week 12.
| Participants | Omalizumab 300mg | Omalizumab 150mg | Placebo |
|---|---|---|---|
| First Response: >0 to <=4 weeks | 114 | 109 | 42 |
| First Response: >4 to <=8 weeks | 18 | 25 | 10 |
| First Response: >8 to <=12 weeks | 10 | 10 | 7 |
| No response | 25 | 23 | 24 |
Collected over Adverse events were collected from first dose of study treatment until end of study treatment (Day 1 to week 12) plus 8 weeks post-treatment follow-up epoch (week 12 to week 20).. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Omalizumab 300 mg | 0/167 (0%) | 5/167 (3%) | 84/167 (50.3%) |
| Omalizumab 150 mg | 0/167 (0%) | 5/167 (3%) | 79/167 (47.3%) |
| Placebo | 0/83 (0%) | 3/83 (3.6%) | 43/83 (51.8%) |
| Event | Omalizumab 300 mg | Omalizumab 150 mg | Placebo |
|---|---|---|---|
| Lumbar vertebral fractureInjury, poisoning and procedural complications | 0/167 | 0/167 | 1/83 |
| Meniscus injuryInjury, poisoning and procedural complications | 0/167 | 0/167 | 1/83 |
| Embolism venousVascular disorders | 0/167 | 0/167 | 1/83 |
| Vertigo positionalEar and labyrinth disorders | 1/167 | 0/167 | 0/83 |
| Pelvic inflammatory diseaseInfections and infestations | 0/167 | 1/167 | 0/83 |
| Upper respiratory tract infectionInfections and infestations | 1/167 | 0/167 | 0/83 |
| Ectopic pregnancyPregnancy, puerperium and perinatal conditions | 0/167 | 1/167 | 0/83 |
| PregnancyPregnancy, puerperium and perinatal conditions | 1/167 | 1/167 | 0/83 |
| Cervical dysplasiaReproductive system and breast disorders | 0/167 | 1/167 | 0/83 |
| RectoceleReproductive system and breast disorders | 0/167 | 1/167 | 0/83 |
| Event | Omalizumab 300 mg | Omalizumab 150 mg | Placebo |
|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 36/167 | 25/167 | 12/83 |
| NasopharyngitisInfections and infestations | 7/167 | 8/167 | 7/83 |
| CoughRespiratory, thoracic and mediastinal disorders | 11/167 | 3/167 | 2/83 |
| Blood uric acid increasedInvestigations | 5/167 | 5/167 | 4/83 |
| InfluenzaInfections and infestations | 7/167 | 7/167 | 1/83 |
| Hepatic function abnormalHepatobiliary disorders | 0/167 | 2/167 | 3/83 |
| PharyngitisInfections and infestations | 1/167 | 4/167 | 3/83 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 4/167 | 1/167 | 3/83 |
| DermatitisSkin and subcutaneous tissue disorders | 2/167 | 1/167 | 3/83 |
| Alanine aminotransferase increasedInvestigations | 1/167 | 6/167 | 1/83 |
| Age, Continuous(years) | Omalizumab 300mg | Omalizumab 150mg | Placebo | Total |
|---|---|---|---|---|
| Mean | 40.4 ± 12.29 | 38.8 ± 12.18 | 42.8 ± 12.32 | 40.2 ± 12.31 |
| Sex: Female, Male(Participants) | Omalizumab 300mg | Omalizumab 150mg | Placebo | Total |
|---|---|---|---|---|
| Female | 115 | 108 | 53 | 276 |
| Male | 53 | 59 | 30 | 142 |
| Race/Ethnicity, Customized(Participants) | Omalizumab 300mg | Omalizumab 150mg | Placebo | Total |
|---|---|---|---|---|
| Race — Asian | 168 | 167 | 83 | 418 |
| Race/Ethnicity, Customized(Participants) | Omalizumab 300mg | Omalizumab 150mg | Placebo | Total |
|---|---|---|---|---|
| Ethnicity — Chinese | 168 | 167 | 83 | 418 |
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