Chronic Spontaneous Uriticaria
Conditions
Keywords
Chronic spontaneous uriticaria, Omalizumab
Brief summary
This was a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult participants 12 - 75 years who received the diagnosis of refractory chronic spontaneous uriticaria and who remained symptomatic despite standard-dosed non-sedating H1 antihistamine treatment.
Interventions
BIOLOGICALOmalizumab
Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.
OTHERPlacebo
Placebo was supplied as a lyophilized, sterile powder in a single-use vial without study drug.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamine at the time of randomization * Chronic spontaneous urticaria diagnosis for 6 months Key
Exclusion criteria
* Weight less than 20 kg * Clearly defined underlying etiology for chronic urticaria other than chronic spontaneous urticaria * Evidence of parasitic infection * Any other skin diseases than chronic spontaneous urticaria with chronic itching * Previous treatment with omalizumab * Contraindications to diphenhydramine * History of anaphylactic shock * History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study * History of hypersensitivity to omalizumab or to drugs of similar chemical classes * Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly Itch Severity Score at Week 12 | Baseline to Week 12 | The weekly itch severity score is a component of the Urticaria Activity Score 7 (UAS7) composite score. The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly Number of Hives Score at Week 12 | Baseline to Week 12 | The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement. |
| Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 | Week 12 | The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms. |
| Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 | Baseline to Week 12 | The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score from baseline indicates a reduction in hive size. |
| Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12 | Baseline to Week 12 | The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. |
| Percentage of Complete Responders (UAS7 = 0) at Week 12 | Week 12 | Complete responders are defined as participants who achieved UAS7 = 0. |
| Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 | Baseline to Week 12 | The DLQI is a 10-item dermatology-specific health-related quality of life measure. Participants rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score from baseline indicates improvement. |
| Percentage of Participants With Production of Anti-omalizumab Antibody | Week 24 | Serum samples were collected for anti-omalizumab antibody testing. |
| Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12 | Week 12 | Weekly itch severity score MID response is defined as a reduction from baseline in weekly itch severity score of ≥ 5 points. |
Countries
Japan, South Korea
Participant flow
Pre-assignment details
Participants were randomly assigned to the 3 treatment groups in a 1:1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab 300 mg Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period. | 73 |
| Omalizumab 150 mg Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period. | 71 |
| Placebo Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period. | 74 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 5 |
Baseline characteristics
| Characteristic | Omalizumab 300 mg | Omalizumab 150 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.6 Years STANDARD_DEVIATION 14.86 | 43.6 Years STANDARD_DEVIATION 12.24 | 42.5 Years STANDARD_DEVIATION 14.26 | 43.5 Years STANDARD_DEVIATION 13.81 |
| Sex: Female, Male Female | 40 Participants | 43 Participants | 48 Participants | 131 Participants |
| Sex: Female, Male Male | 33 Participants | 28 Participants | 26 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 73 | 25 / 71 | 29 / 74 |
| serious Total, serious adverse events | 3 / 73 | 3 / 71 | 0 / 74 |
Outcome results
Primary
Change From Baseline in the Weekly Itch Severity Score at Week 12
The weekly itch severity score is a component of the Urticaria Activity Score 7 (UAS7) composite score. The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score from baseline indicates improvement.
Time frame: Baseline to Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria(CSU) and received the assigned study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 300 mg | Change From Baseline in the Weekly Itch Severity Score at Week 12 | -10.22 Units on a scale | Standard Error 0.571 |
| Omalizumab 150 mg | Change From Baseline in the Weekly Itch Severity Score at Week 12 | -8.80 Units on a scale | Standard Error 0.591 |
| Placebo | Change From Baseline in the Weekly Itch Severity Score at Week 12 | -6.51 Units on a scale | Standard Error 0.581 |
p-value: <0.00195% CI: [-5.31, -2.098]Mixed Model with repeated measures(MMRM)
p-value: 0.00695% CI: [-3.921, -0.654]Mixed Model with repeated measures(MMRM)
Secondary
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12
The DLQI is a 10-item dermatology-specific health-related quality of life measure. Participants rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score from baseline indicates improvement.
Time frame: Baseline to Week 12
Population: Only participants from the FAS, who were greater than age 16, were analyzed. The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 300 mg | Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 | -8.4 Units on a scale | Standard Error 0.52 |
| Omalizumab 150 mg | Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 | -7.2 Units on a scale | Standard Error 0.53 |
| Placebo | Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 | -5.3 Units on a scale | Standard Error 0.52 |
Secondary
Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12
The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
Time frame: Baseline to Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 300 mg | Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12 | -22.44 Units on a scale | Standard Error 1.243 |
| Omalizumab 150 mg | Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12 | -18.79 Units on a scale | Standard Error 1.288 |
| Placebo | Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12 | -13.90 Units on a scale | Standard Error 1.265 |
Secondary
Change From Baseline in the Weekly Number of Hives Score at Week 12
The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.
Time frame: Baseline to Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 300 mg | Change From Baseline in the Weekly Number of Hives Score at Week 12 | -12.17 Units on a scale | Standard Error 0.742 |
| Omalizumab 150 mg | Change From Baseline in the Weekly Number of Hives Score at Week 12 | -10.04 Units on a scale | Standard Error 0.769 |
| Placebo | Change From Baseline in the Weekly Number of Hives Score at Week 12 | -7.41 Units on a scale | Standard Error 0.756 |
Secondary
Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12
The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score from baseline indicates a reduction in hive size.
Time frame: Baseline to Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 300 mg | Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 | -10.71 Units on a scale | Standard Error 0.684 |
| Omalizumab 150 mg | Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 | -9.30 Units on a scale | Standard Error 0.709 |
| Placebo | Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 | -6.27 Units on a scale | Standard Error 0.696 |
Secondary
Percentage of Complete Responders (UAS7 = 0) at Week 12
Complete responders are defined as participants who achieved UAS7 = 0.
Time frame: Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab 300 mg | Percentage of Complete Responders (UAS7 = 0) at Week 12 | 35.6 Percentage of participants |
| Omalizumab 150 mg | Percentage of Complete Responders (UAS7 = 0) at Week 12 | 18.6 Percentage of participants |
| Placebo | Percentage of Complete Responders (UAS7 = 0) at Week 12 | 4.1 Percentage of participants |
Secondary
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12
The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms.
Time frame: Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab 300 mg | Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 | 57.5 Percentage of participants |
| Omalizumab 150 mg | Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 | 42.9 Percentage of participants |
| Placebo | Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 | 18.9 Percentage of participants |
Secondary
Percentage of Participants With Production of Anti-omalizumab Antibody
Serum samples were collected for anti-omalizumab antibody testing.
Time frame: Week 24
Population: The safety analysis set, which included all participants who received their assigned study treatment, were considered for the analysis. Only participants, who had antibody results (conclusive or inconclusive), were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omalizumab 300 mg | Percentage of Participants With Production of Anti-omalizumab Antibody | Conclusive results (n=64,63) | 0.0 Percentage of participants |
| Omalizumab 300 mg | Percentage of Participants With Production of Anti-omalizumab Antibody | Inconclusive results (n=4,1) | NA Percentage of participants |
| Omalizumab 150 mg | Percentage of Participants With Production of Anti-omalizumab Antibody | Conclusive results (n=64,63) | 0.0 Percentage of participants |
| Omalizumab 150 mg | Percentage of Participants With Production of Anti-omalizumab Antibody | Inconclusive results (n=4,1) | NA Percentage of participants |
Secondary
Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12
Weekly itch severity score MID response is defined as a reduction from baseline in weekly itch severity score of ≥ 5 points.
Time frame: Week 12
Population: The Full Analysis Set (FAS) was analyzed. The FAS included all participants who were diagnosed with chronic spontaneous urticaria (CSU) and received the assigned study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab 300 mg | Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12 | 87.7 Percentage of participants |
| Omalizumab 150 mg | Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12 | 68.6 Percentage of participants |
| Placebo | Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12 | 55.4 Percentage of participants |