To Compare Efficacy and Safety of CMAB007 and Xolair® in Patients With Chronic Spontaneous Urticaria

A Multicenter, Randomized, Double-Blind, Positive Parallel Controlled Phase III Clinical Trial to Compare Omalizumab α(CMAB007) and Xolair® in Patients With Chronic Spontaneous Urticaria

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.

Inclusion Criteria:

1. Male or female patients 15 to 75 years old (both inclusive).

2. Diagnosis of CSU refractory to H1AH, as defined by all of the following:

   • Diagnosis of CSU at the time of screening, urticaria history ≥ 6 months at the time of randomization
   • The presence of itch and hives for ≥ 6 consecutive weeks within half year prior to randomization despite use of H1AH treatment during this time period;
   • UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1);
   • In-clinic UAS ≥ 4 on at least one of the screening visit days;
   • Patients must have been on an approved dose of an H1AH for CSU for at least the 3 consecutive days immediately prior to the screening visit and must have documented current use on the day of the initial screening visit.

3. Voluntarily sign the informed consent form. Willing and able to complete a daily symptom diary for the duration of the study, and comply with the protocol requirements.

4. Patients must not have had any missing diary entries in the 7 days prior to randomization.

5. Women of childbearing age have negative pregnancy tests and are not in the lactation period at the time of screening. Both male and female patients must agree to practice contraception from the signing of informed consent to 6 months after the last dose of study drugs.

Exclusion Criteria:

1. Chronic inducible urticaria. This includes but is not limited to: dermatographism (factitious urticaria), cold, heat, solar, delayed pressure, aquagenic, cholinergic or contact urticarias. Any of the following diseases, which may have symptoms of urticaria and/or angioedema: urticarial vasculitis, erythema multiforme, mastocytosis, hereditary or acquired angioedema, etc.

2. Suffer from other chronic pruritic dermatosis that may confound the results: atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, psoriasis, etc.

3. CSU patients who had difficulty breathing episodes due to angioedema in the past six months.

4. Previous treatment with omalizumab within one year prior to signing the informed consent.

5. Hypersensitivity to omalizumab, study drug excipients or other biosimilars, or have a history of severe drug allergy or anaphylactic shock.

6. Use systemic or local corticosteroids, hydroxychloroquine, methotrexate, cyclosporin or cyclophosphamide, and tripterygium within 30 days prior to screening; Use compound glycyrrhizin, total glucosides of paeony and other traditional Chinese medicine within 14 days before screening; Use H2 antihistamines and leukotriene modulators within 7 days before screening; Use H1 antihistamines exceeding protocol requirements within 3 days prior to screening; Use other CSU drugs (including but not limited to biologics, small molecule drugs) within 3 months or 5 drug half-lives (whichever is longer) prior to screening.

7. Patients with a stool examination positive for ova or parasites at screening.

8. Active infections requiring treatment at screening, include but not limited to pulmonary infection, tuberculosis and acute bronchial asthma.

9. Have received live attenuated vaccine or intravenous immunoglobulin within 30 days before screening; Live attenuated vaccines are planned or received at any time during the study period.

10. History of malignancy of any organ or system within 5 years prior to screening (except for basal cell carcinoma, Cervical carcinoma in situ)

11. Evidence of cardiovascular disease (e.g., myocardial infarction, unstable angina, acute coronary syndrome, NYHA Grade III/VI left ventricular failure, arrhythmias and uncontrolled hypertension within 6 months prior to screening), neurological, psychiatric, pulmonary, renal, liver, endocrine, metabolic, hematological, gastrointestinal, or immune deficiencies that the investigators believe may compromise subjects' safety or interfere study results.

12. Presence of clinically significant examination, include but not limited:

    • Abnormal liver function [AST or ALT ≥ 2 x ULN, or total bilirubin ≥ 2 x ULN];
    • Abnormal renal function [elevated serum creatinine > 1.5 x ULN] or estimated glomerular filtration rate (eGFR) < 45 mL/min (using Cockcroft-Gault equation);
    • Abnormal ECG, e.g.,corrected QTcF interval (using Fridericia's correction formula) ≥470ms (female) or 450ms (male), II-III degree atrioventricular block, tachyarrhythmia requiring treatment.
    • Hematological abnormalities: hemoglobin<100g/L, platelets<100*10^9/L, white blood cells<3.0*10^9/L, neutrophils<1.5*10^9/L.

13. Patients with serological results positive for human immunodeficiency virus, treponema pallidum, hepatitis B or hepatitis C. (1) Hepatitis B surface antigen positive patients will be excluded; (2) Hepatitis B core antibody positive: 1) Hepatitis B surface antibody positive patients can be included in this study; 2) Patients with negative hepatitis B surface antibodies need to be tested for HBV-DNA (if HBV DNA is negative, patients can be included in this study; If the HBV DNA is positive, the patient will be excluded).

14. Participated in clinical trials of other drugs within 3 months or 5 drug half-lives (whichever is longer) prior to screening.

15. History of alcohol or drug abuse, or failure to take medication as prescribed.

16. Pregnant or nursing (lactating) women.

17. Currently taking or plan to take medications prohibited by the protocol at screening.

18. Other conditions deemed by investigator as unsuitable for this trial.