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

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

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.

Study Overview

• Status: Unknown
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: anti-EGFR monoclonal antibody; Drug: Cetuximab injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhang Xiaolei, doctor; Phone Number: （86）021-50276381-637; Email: zhangxiaolei@dragonboatbio.com
• Study Contact Backup: Name: Wang Qihui, doctor; Phone Number: (86)021-50276381-301; Email: Qihui.Wang@dragonboatbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Public Health Clinical Center
      • Contact: meng xian min, dr; Phone Number: 021-37990333
  • Sichuang
    • Chengdu, Sichuang, China
      • Recruiting
      • West China Hospital
      • Contact: qian ying, Dr; Phone Number: 028-85422707

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy adult volunteers participate in clinical trials voluntarily and sign informed consent.
2. Age 18 ~ 45 (inclusive) years , male.
3. The body weight is not less than 50 kg, and the body mass index is between 18.5 and 26 (including both ends).
4. Good health, no heart, liver, kidney or other acute or chronic digestive tract diseases, respiratory diseases, blood, endocrine, nervous, mental and other systemic diseases.
5. 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.
6. Agree to avoid spouse pregnancy during the trial period and within 6 months after the end of the administration.

Exclusion Criteria:

1. 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).
2. Anti-drug antibody (ADA) positive.
3. Infections currently in need of clinical treatment.
4. HBsAg, HBeAg, HCV-Ab, HIV-Ab or TP-Ab positive.
5. 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.
6. Upon inquiry, a person with a history of mental illness.
7. Upon inquiry, there is a history of cancer and it is judged by the investigator that it is not suitable for participation.
8. According to the investigator's judgment, the investigator believes that it is not suitable for the participants in this clinical trial for various reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dragonboat Biopharmaceutical Company Limited
• Collaborators: West China Hospital; Shanghai Public Health Clinical Center
• Investigators: Principal Investigator: Zheng Li, doctor, West China Hospital; Study Director: zhu tongyu, doctor, Shanghai Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2019
• Primary Completion (Anticipated): October 30, 2019
• Study Completion (Anticipated): December 30, 2019

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Antibodies, Monoclonal; Cetuximab
• Other Study ID Numbers: CDP100002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No