This study is a multicenter, randomized, double-blind, positive parallel controlled phase III clinical trial to compare efficacy, immunogenicity, pharmacokinetics, pharmacodynamics and safety of omalizumab α(CMAB007) and Xolair® in patients with refractory chronic spontaneous urticaria
The study will consist of three periods: a screening period (up to 2 weeks), a 12-week treatment period and a 8-week follow-up period. The total duration of the study is up to 22 weeks. After signing informed consent, subjects who meet the inclusion criteria and do not meet the exclusion criteria will be assigned to the CMAB007 or Xolair® in a 1:1 ratio. The subjects will treated with three doses of CMAB007 or Xolair®, subcutaneous injection every four weeks in the treatment period. After the end of the treatment period, an 8-week safety follow-up was conducted. The type and dosage of H1 antihistamines remained stable in the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
392
Huashan Hospital
Shanghai, China
Change From Baseline of the Itch Severity Score (ISS7) Score At Week 12
The severity of the itch was recorded by the patient twice daily in their Diary, 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: Week 12
Change From Baseline of Urticaria Activity Score (UAS7) 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.
Time frame: Week 12
Change From Baseline of Number of Hives Score (NHS7) At Week 12
Hives Severity Score (HSS), defined by number of hives, were recorded by the patient once daily in their Diary, 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 * 1=Mild (\< 20 hives/24 hours) * 2=Moderate (20-50 hives/24 hours) * 3=Severe (\>50 hives/24 hours)
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.
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Time frame: 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.
Time frame: Week 12
Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12
The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points.
Time frame: Week 12
Change From Baseline of Urticaria Control Test (UCT) at Week 12
The urticaria control score (UCT) was a retrospective assessment of disease control over the past 4 weeks. The assessment contents four-items: physical symptoms of the urticaria (itch, hives\[welts\], and or swelling), quality of life, treatment control and overall disease control. The score range for each item is 0 to 4, and the total score is the sum of the four questions.The possible score range of the UCT is 0 to 16. A score of 16 indicates complete disease control. A score of \<12 on identifies patients with poorly controlled chronic urticaria (CU), and a score of ≥12 identifies those with well-controlled symptoms.
Time frame: Week 12
Percentage of Patients With UCT≥12 at Week 12
The possible range of the UCT is 0 to 16. A higher UCT indicates better control. The total score ≥12 indicates that urticaria is well controlled.
Time frame: Week 12
Percentage of Complete Controls (UCT=16) at Week 12
The possible range of the UCT is 0 to 16. A higher UCT indicates better control. The total score=16 indicates that urticaria is complete controlled.
Time frame: Week 12
Change From Baseline of Dermatology Life Quality Index (DLQI) Score at Week 12
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
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 Angioedema-free Days From Week 4 to Week 12
The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days for which a patient responded "No" to the angioedema question in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.
Time frame: Week 4 to Week 12
Incidence of adverse events
Number of patients reporting at least one adverse event in the study. An adverse event is defined as any untoward medical occurrence in a clinical trial participant graded according to the common terminology criteria for adverse events (CTCAE) v.5.0 criteria,including clinically-significant changes in physical examinations, laboratory safety tests, ECG and vital signs
Time frame: Week 20
Immunogenicity
Percentage of anti-drug antibody and neutralizing antibody in the study. Subjects with a positive antibody response to Omalizumab were determined to test neutralizing antibody.
Time frame: Week 20
AUC0-t
AUC0-t, the area under the concentration-time curve from time zero to the time of the last quantifiable concentration, will be analyzed using a non-atrioventricular model.
Time frame: Week 20
AUC0-inf
AUC0-inf, the area under the concentration-time curve from time zero to infinity, will be analyzed using a non-atrioventricular model.
Time frame: Week 20
Half time
Half time will be analyzed using a non-atrioventricular model.
Time frame: Week 20
Cmax
Cmax is the maximum concentration.
Time frame: Week 20
Tmax
Tmax is the time of the maximum concentration.
Time frame: Week 20
Clearance Rate
Clearance rate will be analyzed using a non-atrioventricular model.
Time frame: Week 20
Apparent Volume of Distribution
Apparent Volume of Distribution will be analyzed using a non-atrioventricular model.
Time frame: Week 20
Level of Total IgE and Free IgE
Pharmacodynamics
Time frame: Week 20