The Study of Omalizumab (CMAB007 and Xolair) in Healthy Subjects to Compare the PK, PD, Safety and Immunogenicity

Study Overview
=================
Brief Summary
-----------------
A phase 1, randomized, double-blind, parallel group, single-dose study to compare the pharmacokinetics, pharmacodynamics, safety and immunogenicity of two formulations of Omalizumab (CMAB007 and Xolair) in healthy subjects.

Detailed Description
-----------------
This is a randomized, double-blind, parallel-controlled, single-dose phase I clinical study in healthy Chinese male subjects. A total of 114 subjects were planned to be enrolled and randomly assigned to the test group or the control group in a 1:1 ratio. Subjects in both groups received a single subcutaneous injection of CMAB007 or Xolair#Omalizumab# 150 mg, respectively. Subjects in both groups were observed for 106 days after administration to evaluate similarities in PK, PD, safety, and immunogenicity.

Official Title
-----------------
Phase I Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of CMAB007 and Xolair in a Randomized, Double-blind, Parallel Controlled, Single-dose Study in Healthy Chinese Male Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Biological: CMAB007
* Biological: Xolair


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male volunteers, age ranged 18 to 45 years (both inclusive) when sign the informed consent form. Subjects with body weight of ≥50 kg and ≤ 75 kg and BMI ≥20.0 and ≤ 26.0 kg/m2 (both inclusive). Subjects have the ability to understand the full characteristics and objectives of the study, including the possible risks and side effects of the study; moreover, subjects can communicate well with researchers and complete the research according to the regulations. Subjects must be informed consent of the study and voluntarily sign informed consent form (name and time) prior to the study. Exclusion Criteria: After medical examination (vital signs, physical examination, electrocardiogram, positive chest X-radiography, abdominal B-ultrasound, and various laboratory examinations including blood routine, urine routine, blood biochemistry and total IgE, etc.), any examination item was judged abnormal by the investigator and had clinical significance. Those who have a history of drug or food allergy, or who have special allergy history (asthma, urticaria, dermatitis eczema, etc.); those who have allergic rhinitis, or are known to be allergic to any component of the test drug or latex (contained in the syringe needle cover). Those who have a history of serious diseases including but not limited to cardiovascular system, respiratory system, digestive system, urogenital system, endocrine system, immune system, mental or nervous system (eg, epilepsy, etc), or currently have any of the above diseases or active infected diseases, or any other disease or medical condition that may interfere with the results of the trial, such as hereditary bleeding tendency, coagulation disorders or history of blood clots or bleeding. History of malignant neoplasms within the last 5 years (other than completely resected basal cell or squamous cell carcinoma of the skin in situ). Any one of HBV surface antigen, HIV antibody, HCV antibody and treponema pallidum antibody is positive. Anti-nuclear antibody is positive. Fecal parasite test is positive. Those who smoke more than 10 cigarettes per day on average in the 6 months before screening. Alcoholics or regular drinkers within 3 months before the test, i.e. those who drink more than 14 unites of alcohol per week (14 bottles of 360 ml beer or 45 ml spirits with 40% alcohol or 150 ml wine), or whose alcohol breath test is positive. Drug abusers, or use of soft drugs within 3 months prior to screening or hard drugs within 1 year prior the trial, or excessive daily consumption of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250mL) in the 3 months prior to screening, or positive urine drug screening. Surgery within 4 weeks prior to screening; Or plan to have surgery during the study period. Use of any prescription drug, over-the-counter drug or health product or vaccine within 4 weeks prior to screening, or who plan to receive live vaccine during the study period, or prior use of drug within 5 half-lives, whichever is longer. Those who had lost blood or donated at least 400 mL in the 3 months prior to the screening, or had lost blood or donated at least 200 mL in the 1 month prior to screening, or planned to donate blood during the trial. Those who have been enrolled in other clinical studies or less than 3 months since the end of the most recent clinical study. Subjects and their partners were not willing to use medically approved contraceptive methods within 6 months of study administration, or partners plan to become pregnant, or subjects plan to donate sperm. Use of anti-IgE mab within 12 months, or any biological agent within 3 months prior to screening. The investigator judges the subject inappropriate to be included in this study or other reasons not eligible to complete the study. Employees or related personnel of the research unit, sponsor or contract research organization.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Biological: CMAB007 Biological: Xolair #Omalizumab#
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMAB007<br>150 mg Subcutaneous injection | Biological: CMAB007<br>* for subcutaneous injection only<br>|
| Active Comparator: Xolair<br>150 mg Subcutaneous injection | Biological: Xolair<br>* for subcutaneous injection only<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Zero (0) Hours Extrapolated to infinite time | Area Under the Plasma Concentration-time Curve From Zero (0) Hours Extrapolated to infinite time After the Single injection of Omalizumab | up to 2520 hours | 
| Maximum Concentration of Omalizumab | Maximum Concentration of Omalizumab After the Single Injection of Omalizumab | up to 2520 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 2520 Hours | Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 2520 Hours After the Single Injection of Omalizumab | up to 2520 hours | 
| Time to Maximum Concentration of Omalizumab | Time to Maximum Concentration of Omalizumab after the Single Injection of Omalizumab | up to 2520 hours | 
| Half time | Half-time after the Single Injection of Omalizumab | up to 2520 hours | 
| Terminal elimination rate constant (λz) | Terminal elimination rate constant (λz) after the Single Injection of Omalizumab | up to 2520 hours | 
| Apparent total body clearance (CL/F) | Apparent total body clearance (CL/F) after the Single Injection of Omalizumab | up to 2520 hours | 
| Apparent total distribution (Vd/F) | Apparent total distribution (Vd/F) after the Single Injection of Omalizumab | up to 2520 hours | 
| Immunoglobulin E levels | Free IgE in the serum samples from subjects | up to 2520 hours | 
| anti-drug antibodies (ADA) | ADA Positive Rate after the Single Injection of Omalizumab | up to 2520 hours | 
| Neutralization antibodies (Nab) | Neutralizing Antibody Positive Rate after the Single Injection of Omalizumab | up to 2520 hours | 
| Percentage and Severity of Participants with Adverse Events | Total Frequency and Severity of Adverse Events/Serious Adverse Events Within the Whole Time of the Study | up to 2520 hours |