Chronic spontaneous urticaria (Allergic asthma, Chronic rhinosinusitis with nasal polyps) MedDRA version: 20.0 Level: PT Classification code 10072757 Term: Chronic spontaneous urticaria System Organ Class: 10040785 - Skin and subcutaneous tissue disorders MedDRA version: 21.1 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.1 Level: PT Classification code 10080060 Term: Chronic rhino
Conditions
Interventions
Product Name: Omalizumab
Product Code: SYN008
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: OMALIZUMAB
CAS Number: 242138-07-4
Current Sponsor code: SYN008 Om
Sponsors
Synermore Biologics Co., Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be included in the study: 1. Have read, understood, and signed the informed consent form (ICF) before any protocol-specific procedure including screening procedures. 2. Male or female aged = 18 years with a clinical diagnosis of CSU for at least 6 months prior to first administration of study drug. 3. Have a diagnosis with CSU refractory to H1 antihistamines defined as: a. Presence of hives associated with itch for > 6 consecutive weeks at any time prior to screening despite concomitant H1 antihistamines treatment. b. UAS7 = 16 and ISS7 = 8 during the 7 days (without any missing day in the completion of the symptom e-diary) prior to first administration of study drug. c. Use of H1 antihistamines at a stable dose up to 4-fold the approved dose for = 3 consecutive days immediately prior to Screening Visit and throughout the study (list of permitted antihistamines in APPENDIX 2). 4. Must be willing to continue H1 antihistamines at stable dose throughout the study. 5. Must be willing and able to complete a symptom diary twice daily for 7 days prior to first administration of study drug and throughout the study. 6. Females of childbearing potential (FOCBP) and male patients with a female partner of childbearing potential must be willing to take reliable contraceptive precautions throughout the study (until Week 32). If an FOCBP, patient should have a negative pregnancy test result at Screening and Baseline visits Must be willing to comply with precautions to reduce the risk of COVID-19 infection in accordance with recommendations from the applicable medical associations and the investigator for the duration of the study and to undergo COVID-19 polymerase chain reaction (PCR) test as required based on the investigator judgment and/or local requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 480 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria at screening or baseline are ineligible to participate in this study: 1. Known hypersensitivity to omalizumab, study treatment excipients, or components of injecting devices. 2. Previous exposure to omalizumab (either Xolair or a biosimilar product). 3. Previous exposure to ligelizumab or any IgE antagonists. 4. Having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria. 5. Conditions that may have urticarial or angioedema symptoms (eg, urticaria pigmentosa, urticarial vasculitis, hereditary or acquired angioedema, erythema multiforme, mastocytosis, lymphoma). 6. Has the evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. Stool testing will be conducted only in patients presenting at screening with a risk factor for parasitic infection (living in endemic region, chronic gastrointestinal symptoms, and/or chronic immunosuppression) and an eosinophil count > 2 × upper limit of normal (ULN). 7. Positive serology results of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), hepatitis C antibody, or human immunodeficiency virus (HIV) antibody) at screening. 8. Any other skin disease associated with chronic itching that might influence in the investigator’s opinion the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus). 9. Any current active infection requiring treatment. 10. Body temperature of 37.5 °C or above at screening or baseline visits, and/or signs or symptoms that in the opinion of the investigator may be suggestive of COVID-19 infection. The patient may be allowed to enter the study if a COVID-19 PCR test performed during the Screening Period results in a negative outcome or had received an approved COVID-19 vaccine (if available), based on investigator’s clinical judgment. 11. Has received H2 antihistamines and/ or LTRAs within 7 days prior to Screening Visit. 12. Routine doses (ie, daily or every other day for = 5 consecutive days) of systemic or cutaneous (topical) corticosteroids (prescription or over-the-counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide within 30 days prior to Screening Visit. 13. Intravenous immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to Screening Visit. 14. Regular (daily/every other day) use of oral doxepin = 2 weeks prior to Screening Visit. 15. Treatment with an investigational agent = 30 days or = 5 × half-life, whichever is longer, prior to Screening Visit. 16. Has a current or history of malignancy, except non-melanoma skin cancer that has been treated or excised and is considered resolved. 17. History of anaphylactic reaction. 18. Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions including abnormal blood/urine test results that could, in the investigator’s opinion, interfere with the interpretation of the study results and or compromise the safety of the patients. 19. History of and/or concomitant immune complex disease (including Type III hypersensitivity), hyperimmunoglobulin E syndrome, autoimmune disease or bronchopulmonary aspergil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate equivalent efficacy of SYN008 and Xolair in patients with chronic spontaneous urticaria (CSU) and inadequate response to H1 antihistamine treatment;Secondary Objective: • Evaluate the efficacy profile of SYN008 compared with Xolair over time based on secondary efficacy end points • Evaluate the safety and tolerability profile of SYN008 compared with Xolair over the entire study period • Evaluate the immunogenicity profile of SYN008 compared with Xolair in terms of anti-drug antibody (ADAs) production • Evaluate trough serum omalizumab (Ctrough) of both treatment groups over the study • Evaluate the pharmacodynamic (PD) effects of SYN008 compared with Xolair • Assess safety and immunogenicity following transition from Xolair to SYN008;Primary end point(s): Change from baseline to Week 12 in weekly itch-severity score (ISS7) ;Timepoint(s) of evaluation of this end point: Change from baseline to Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Change of ISS7 from Baseline to Week 4 • Change of ISS7 from Baseline to each study visit other than Week 4 or Week 12 • Changes of weekly hive severity score (HSS7) from Baseline to each study visit • Change of weekly urticaria activity score (UAS7) from Baseline to each study visit o Proportion of patients with UAS7 = 6 at Week 12 and Week 32 visits o Proportion of patients with UAS7 = 0 at Week 12 and Week 32 visits o Change in Dermatology Life Quality Index (DLQI) from Baseline to Week 12, Week 20, and Week 32. Safety: • Adverse events (AEs), including treatment-emergent adverse events (TEAEs), Serious AEs (SAEs), treatment-related AEs, treatment-related SAEs, and adverse events of special interest (AESIs) • Injection site reactions • Laboratory parameters, hematology, chemistry, and urinalysis • Vital signs • Physical examination • 12-lead Electrocardiogram (ECG) Imunogenicity: • Proportion of patients developing ADA and Neutralizing Antibody (NAb) to omalizumab over the course of the study. Pharmacokinetics • Trough serum concentration (Ctrough) of omalizumab at predose over the course of the study for both treatment groups Pharmacodynamics • Change in serum concentration of total and free anti-immunoglobulin E (IgE) from baseline over the course of the study for both treatment groups ;Timepoint(s) of evaluation of this end point: -Change of ISS7 from Baseline to Week 4 - Change of ISS7 from Baseline to each study visit other than Week 4 or Week 12 - Change of weekly hive severity score (HSS7) from Baseline to each study visit - Change of urticarial activity score (UAS7) from Baseline to each study visit - Proportion of patients with UAS7 = 6 and UAS7 = 0 Week 12 and Week 32 visits - Change in Dermatology of Life Quality Index (DLQI) from Baseline to Week 12, Week 20, and Week 32. - AEs, SAEs, AESIs and Injection site reactions trough all study -Imunogenicity, Pharmacokinetics and Pharmacodyna | — |
Countries
Bulgaria, Czechia, Hungary, Poland, Romania, Russian Federation, Slovakia
Contacts
Public ContactEric I Tsao
Synermore Biologics Co., Ltd
Outcome results
None listed