Clinical Trial to Evaluate Pharmacokinetics,Safety and Immunogenicity of Single Injection of CDP1 to Healthy Volunteers Compared to Erbitux

Study Overview
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Brief Summary
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Background Colorectal cancer (CRC) is one of the most common human malignant tumors. The incidence and mortality of colorectal cancer in our country are on the rise. Surgery-based, combined with chemotherapy, radiotherapy comprehensive treatment, is the main treatment of colorectal cancer. Surgical resection has been recognized as the primary treatment of colorectal cancer. However, due to the majority of patients already advanced at the time of diagnosis, some difficulties are brought to radical surgery. Therefore, the importance of chemotherapy for colorectal cancer gradually been clinically recognized, But rarely survive more than 18 months. In addition to chemotherapy, there is now a more ideal model of cancer treatment- molecular targeted therapies, including monoclonal antibody drugs such as cetuximab, as well as small molecule tyrosine kinases Inhibitors gefitinib and so on. Molecular targeted drugs make use of the difference in molecular biology between tumor cells and normal cells. Targeting drugs to tumor cells and inhibiting the growth and proliferation of the cells can achieve the therapeutic effect, which has the advantages of high specificity and low adverse reaction. The bio-targeted drug cetuximab is the first drug approved to marketed as an epidermal growth factor receptor (EGFR)-targeting immunoglobulin 1（IgG1）monoclonal antibody. Cetuximab, either monotherapy or combined radiotherapy and chemotherapy, can exert excellent anti-tumor activity in EGFR-positive malignant tumors and can significantly enhance the efficacy of radiotherapy and chemotherapy. Reference to cetuximab injection, guilin sanjin Co., Ltd. and dragonboat Co., Ltd. jointly developed a recombinant anti-EGFR human mouse chimeric monoclonal antibody (R & D code: CDP1).The primary structure of CDP1 is exactly the same with cetuximab, the higher structure and Physical and chemical properties and cetuximab are highly similar. Pharmacodynamic activity in vivo and in vitro, pharmacokinetic characteristics and toxicological reactions are also similar to cetuximab. CDP1 selected with cetuximab consistent formulations, prescriptions, specifications. CDP1 was approved by China Food and Drug Administration (No. 2016L06884) in August 2016 for clinical studies. According to the contents of the document and guidelines for biological analogs, the clinical pharmacokinetic and clinical effectiveness comparison tests of CDP1 and the safety and immunogenicity assessment are planned.

Detailed Description
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OBJECTIVES: Primary: To compare the pharmacokinetic characteristics of a single dose between CDP1 and the original drug Erbitux in healthy volunteers. Secondary : To compare the safety and immunogenic characteristics of the single dose between CDP1 and the original drug Erbitux in healthy volunteers.

Official Title
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Clinical Trial to Evaluate Pharmacokinetics,Safety and Immunogenicity of Single Injection of Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) to Healthy Volunteers Compared to Erbitux

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: anti-EGFR monoclonal antibody
* Drug: Cetuximab injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult volunteers participate in clinical trials voluntarily and sign informed consent. Age 18   45 (inclusive) years , male. The body weight is not less than 50 kg, and the body mass index is between 18.5 and 26 (including both ends). Good health, no heart, liver, kidney or other acute or chronic digestive tract diseases, respiratory diseases, blood, endocrine, nervous, mental and other systemic diseases. Physical examination, vital signs, blood routine, urine routine, blood biochemistry, electrocardiogram and chest X-ray examination are all normal, or the abnormal results of the examination are not clinically meaningful by the investigator. Agree to avoid spouse pregnancy during the trial period and within 6 months after the end of the administration. Exclusion Criteria: Allergic constitution, those who are allergic to the test drug ingredients or have a history of allergies to any drug or food or a history of pollen allergy; those with abnormal serum immunoglobulin E (IgE) (more than 3 times higher than the upper limit of normal). Anti-drug antibody (ADA) positive. Infections currently in need of clinical treatment. HBsAg, HBeAg, HCV-Ab, HIV-Ab or TP-Ab positive. Upon inquiry, there is a clear current medical history of the central nervous system, cardiovascular system, kidney, liver, digestive system, respiratory system, metabolic system or other significant diseases. Upon inquiry, a person with a history of mental illness. Upon inquiry, there is a history of cancer and it is judged by the investigator that it is not suitable for participation. According to the investigator's judgment, the investigator believes that it is not suitable for the participants in this clinical trial for various reasons.

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-EGFR monoclonal antibody<br>Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection 250mg/m2 single administration | Drug: anti-EGFR monoclonal antibody<br>* Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection<br>* Other names: CDP1;|
| Active Comparator: Cetuximab<br>Cetuximab,Erbitux 250mg/m2 single administration | Drug: Cetuximab injection<br>* Cetuximab injection<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Infusion | AUC(0-t) for CDP1 | Up to 22 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-00) After Infusion | Pharmacokinetic parameters: AUC(0-00) for CDP1 | Up to 22 Days | 
| Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of CDP1 After Infusion | Pharmacokinetic parameters Cmax for CDP1 | Up to 22 Days | 
| Pharmacokinetic parameters: Mean Residence Time of Drug in the Body (MRT) of CDP1 After Infusion | Pharmacokinetic parameters MRT for CDP1 | Up to 22 Days | 
| Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of CDP1 After Infusion | Pharmacokinetic parameters T1/2 for CDP1 | Up to 22 Days | 
| Pharmacokinetic parameters: Total Body Clearance of Drug From Serum (CL) After Infusion | Pharmacokinetic parameters CL for CDP1 | Up to 22 Days | 
| Vital signs: Blood pressure | Vital signs: Blood pressure | Up to 29 Days | 
| Vital signs: Pulse rate | Vital signs: Pulse rate | Up to 29 Days | 
| Vital signs: Respiratory rate | Vital signs: Respiratory rate | Up to 29 Days | 
| Physical examination: Weigh | Physical examination: Weigh | Up to 29 Days | 
| Frequency of adverse events (AE) | Frequency of adverse events (AE) | Up to 29 Days | 
| Immunogenicity indicators: Anti-drug antibodies (ADA) | Immunogenicity indicators: Anti-drug antibodies (ADA) | Up to 29 Days | 
| Immunogenicity indicators: neutralizing antibodies | Immunogenicity indicators: neutralizing antibodies | Up to 29 Days |