Trial Outcomes & Findings for Study of Efficacy and Safety of Omalizumab in Refractory Chronic Spontaneous Urticaria Patients (NCT NCT02329223)
NCT ID: NCT02329223
Last Updated: 2016-09-21
Results Overview
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.
COMPLETED
PHASE3
218 participants
Baseline to Week 12
2016-09-21
Participant Flow
Participants were randomly assigned to the 3 treatment groups in a 1:1:1 ratio.
Participant milestones
| Measure |
Omalizumab 300 mg
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Overall Study
STARTED
|
73
|
71
|
74
|
|
Overall Study
Full Analysis Set
|
73
|
70
|
74
|
|
Overall Study
Safety Set
|
73
|
71
|
74
|
|
Overall Study
COMPLETED
|
72
|
68
|
68
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
6
|
Reasons for withdrawal
| Measure |
Omalizumab 300 mg
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
5
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
Study of Efficacy and Safety of Omalizumab in Refractory Chronic Spontaneous Urticaria Patients
Baseline characteristics by cohort
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=71 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
Total
n=218 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.6 Years
STANDARD_DEVIATION 14.86 • n=5 Participants
|
43.6 Years
STANDARD_DEVIATION 12.24 • n=7 Participants
|
42.5 Years
STANDARD_DEVIATION 14.26 • n=5 Participants
|
43.5 Years
STANDARD_DEVIATION 13.81 • n=4 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
131 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Change From Baseline in the Weekly Itch Severity Score at Week 12
|
-10.22 Units on a scale
Standard Error 0.571
|
-8.80 Units on a scale
Standard Error 0.591
|
-6.51 Units on a scale
Standard Error 0.581
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
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
|
-18.79 Units on a scale
Standard Error 1.288
|
-13.90 Units on a scale
Standard Error 1.265
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Change From Baseline in the Weekly Number of Hives Score at Week 12
|
-12.17 Units on a scale
Standard Error 0.742
|
-10.04 Units on a scale
Standard Error 0.769
|
-7.41 Units on a scale
Standard Error 0.756
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12
|
57.5 Percentage of participants
|
42.9 Percentage of participants
|
18.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
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
|
-9.30 Units on a scale
Standard Error 0.709
|
-6.27 Units on a scale
Standard Error 0.696
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
Weekly itch severity score MID response is defined as a reduction from baseline in weekly itch severity score of ≥ 5 points.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12
|
87.7 Percentage of participants
|
68.6 Percentage of participants
|
55.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
Complete responders are defined as participants who achieved UAS7 = 0.
Outcome measures
| Measure |
Omalizumab 300 mg
n=73 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=70 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Percentage of Complete Responders (UAS7 = 0) at Week 12
|
35.6 Percentage of participants
|
18.6 Percentage of participants
|
4.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Omalizumab 300 mg
n=71 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=69 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
n=74 Participants
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
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
|
-7.2 Units on a scale
Standard Error 0.53
|
-5.3 Units on a scale
Standard Error 0.52
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
Serum samples were collected for anti-omalizumab antibody testing.
Outcome measures
| Measure |
Omalizumab 300 mg
n=68 Participants
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Omalizumab 150 mg
n=64 Participants
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.
|
Placebo
Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Production of Anti-omalizumab Antibody
Conclusive results (n=64,63)
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
—
|
|
Percentage of Participants With Production of Anti-omalizumab Antibody
Inconclusive results (n=4,1)
|
NA Percentage of participants
Results were inconclusive.
|
NA Percentage of participants
Results were inconclusive.
|
—
|
Adverse Events
IGE025 300 mg
IGE025 150 mg
Placebo
Serious adverse events
| Measure |
IGE025 300 mg
n=73 participants at risk
IGE025 300 mg
|
IGE025 150 mg
n=71 participants at risk
IGE025 150 mg
|
Placebo
n=74 participants at risk
Placebo
|
|---|---|---|---|
|
Hepatobiliary disorders
CHOLECYSTITIS CHRONIC
|
1.4%
1/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
PNEUMONIA
|
1.4%
1/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Injury, poisoning and procedural complications
LIMB TRAUMATIC AMPUTATION
|
0.00%
0/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Injury, poisoning and procedural complications
SPINAL CORD INJURY
|
0.00%
0/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
1.4%
1/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.00%
0/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
Other adverse events
| Measure |
IGE025 300 mg
n=73 participants at risk
IGE025 300 mg
|
IGE025 150 mg
n=71 participants at risk
IGE025 150 mg
|
Placebo
n=74 participants at risk
Placebo
|
|---|---|---|---|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/73 • over 24 weeks following randomization
|
2.8%
2/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
0.00%
0/73 • over 24 weeks following randomization
|
2.8%
2/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
BRONCHITIS
|
2.7%
2/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
CONJUNCTIVITIS
|
0.00%
0/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
2.7%
2/74 • over 24 weeks following randomization
|
|
Infections and infestations
CYSTITIS
|
0.00%
0/73 • over 24 weeks following randomization
|
2.8%
2/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
FOLLICULITIS
|
1.4%
1/73 • over 24 weeks following randomization
|
2.8%
2/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
NASOPHARYNGITIS
|
12.3%
9/73 • over 24 weeks following randomization
|
9.9%
7/71 • over 24 weeks following randomization
|
16.2%
12/74 • over 24 weeks following randomization
|
|
Infections and infestations
OTITIS EXTERNA
|
0.00%
0/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
2.7%
2/74 • over 24 weeks following randomization
|
|
Infections and infestations
PHARYNGITIS
|
4.1%
3/73 • over 24 weeks following randomization
|
4.2%
3/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/73 • over 24 weeks following randomization
|
4.2%
3/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.7%
2/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Nervous system disorders
HEADACHE
|
4.1%
3/73 • over 24 weeks following randomization
|
4.2%
3/71 • over 24 weeks following randomization
|
6.8%
5/74 • over 24 weeks following randomization
|
|
Nervous system disorders
MIGRAINE
|
2.7%
2/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Nervous system disorders
SOMNOLENCE
|
2.7%
2/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
1.4%
1/74 • over 24 weeks following randomization
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
2.7%
2/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
ACNE
|
2.7%
2/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
CHRONIC SPONTANEOUS URTICARIA
|
4.1%
3/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
1.4%
1/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
DERMATITIS CONTACT
|
1.4%
1/73 • over 24 weeks following randomization
|
0.00%
0/71 • over 24 weeks following randomization
|
4.1%
3/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
ECZEMA
|
6.8%
5/73 • over 24 weeks following randomization
|
4.2%
3/71 • over 24 weeks following randomization
|
2.7%
2/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
MILIARIA
|
2.7%
2/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
1.4%
1/74 • over 24 weeks following randomization
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
2.7%
2/73 • over 24 weeks following randomization
|
5.6%
4/71 • over 24 weeks following randomization
|
2.7%
2/74 • over 24 weeks following randomization
|
|
Vascular disorders
HYPERTENSION
|
2.7%
2/73 • over 24 weeks following randomization
|
1.4%
1/71 • over 24 weeks following randomization
|
0.00%
0/74 • over 24 weeks following randomization
|
Additional Information
Study Director
Novartis
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER