Pharmacokinetic, Safety and Immunogenicity Study of CMAB015 and Cosentyx in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blinded, controlled Phase I study of CMAB015 administered by subcutaneous injection. This study will characterize the pharmacokinetic, safety and immunogenicity of CMAB015 versus Cosentyx（Secukinumab ） in healthy male subjects after a single dose.

Detailed Description
-----------------
This is a randomized, double-blind, parallel-controlled, single-dose phase I clinical study in healthy Chinese male subjects. A total of 130 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 upper arm subcutaneous injection of CMAB015 or Cosentyx（Secukinumab） 150 mg, respectively. Subjects in both groups were observed for 112 days after administration to evaluate similarities in pharmacokinetics, safety, and immunogenicity.

Official Title
-----------------
Phase I Comparison of Pharmacokinetics, Safety, and Immunogenicity of CMAB015 Injection and Cosentyx in a Randomized, Double-blind, Parallel Controlled, Single-dose Study in Healthy Chinese Male Subjects

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Biological: Secukinumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male volunteers, age ranged 18 to 45 years (both inclusive)； Subjects with body weight of ≥50 kg and ≤ 75 kg and BMI ≥18 and <28 kg/m2 ; Subjects and their partners were willing to use medically approved contraceptive methods within 6 months of study administration, partners did not plan to become pregnant, subjects did not plan to donate sperm； The 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, the subjects can communicate well with researchers and complete the research according to the regulations； Subjects voluntarily sign ICF prior to the study. Exclusion Criteria: After comprehensive examination (vital signs, physical examination, electrocardiogram, chest radiography, abdominal B-ultrasound, blood routine, urine routine, blood biochemistry, etc.), any examination item was judged abnormal by the investigator and had clinical significance; Patients with serious diseases such as cardiovascular system, endocrine system, nervous system, digestive system, respiratory system, genitourinary system, hematopoietic system, immune system, or any of the above diseases； Patients with currently active infected diseases； Subjects with past or current inflammatory bowel disease; 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, HCV antibody, HIV antibody, treponema pallidum antibody positive； Subjects with T-SPOT test positive； Those who smoked more than 5 cigarettes per day in the 6 months before screening and did not cooperate with smoking bans during the study period； Alcoholics，or participants who consumed more than 14 units of alcohol per week (1 unit = 17.7mL ethanol, i.e., 1 unit = 357mL 5% beer or 43mL 40% liquor or 147mL 12% wine) during the preceding 3 months were screened，or who have positive result in blood-test of alcohol or not willing to ban alcohol； Drug abusers, or drug users in the 3 months prior to screening, 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 within 4 weeks prior to screening, or prior use of such drug or health product within 5 half-lives, whichever is longer； Those who have used any biological agent, including live vaccine, in the 3 months prior to screening, or who plan to receive live vaccine during the study period； Anti-il-17 antibody active ingredient, excipients or latex allergy； Those with anti-IL-17 antibody and anti-drug antibody positive； Those who have been enrolled in other clinical studies or less than 3 months since the end of the most recent clinical study； Those who had lost blood or donated at least 400 mL in the 3 months prior to the trial, 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 Can not tolerate venipunction, has a history of dizziness of needle and blood； Those who have special dietary requirements, or can not accept uniform diet； Other conditions considered inappropriate to be included in this study.

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: CMAB015 Biological: Cosentyx（Secukinumab ）
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biosimilar Product<br>CMAB015 150 mg Subcutaneous injection in upper arm | Biological: Secukinumab<br>* for subcutaneous injection only<br>|
| Active Comparator: Reference Product<br>Cosentyx（Secukinumab ） 150 mg Subcutaneous injection in upper arm | Biological: Secukinumab<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 CMAB015/Cosentyx | up to 2688 hours | 
| Maximum Concentration of Secukinumab | Maximum Concentration of Secukinumab After the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Concentration of Secukinumab | Time to Maximum Concentration of Secukinumab after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 2688 Hours | Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 2688 Hours After the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Half time | Half-time after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Clearance Rate | Clearance Rate after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Apparent Volume of Distribution | Apparent Volume of Distribution after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Terminal phase elimination rate constant | Terminal phase elimination rate constant after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| anti-drug antibodies(ADA) | ADA Positive Rate after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Neutralization antibodies(Nab) | Neutralizing Antibody Positive Rate after the Single Injection of CMAB015/Cosentyx | up to 2688 hours | 
| Percentage of participants with Adverse Events | Total Frequency of Adverse Events/Serious Adverse Events Within the Whole Time of the Study | up to 2688 hours |