Pharmacokinetic, Safety and Immunogenicity Study of CMAB809 and Herceptin in Healthy Volunteers

A Randomized, Double-blinded, Controlled, Single Dosing Phase I Study to Investigate The Pharmacokinetic, Safety and Immunogenicity Characteristics of CMAB809 and Herceptin in Healthy Male Subjects

This is a randomized, double-blinded, controlled Phase I study of CMAB809 administered by intravenous infusion. This study will characterize the pharmacokinetic, safety and immunogenicity of CMAB809 versus Trastuzumab(Herceptin) in healthy male subjects after a single dose.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: CMAB809; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Shanghai Xuhui Central Hospital

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:

• Healthy male volunteers, age ranged 18 to 45 years (both inclusive)
• A subject with body weight be equal or greater than 50 kg (inclusive) and body mass index (BMI) between 19 and 26 kg/m2 (both inclusive)
• Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the laboratory reference ranges for the relevant laboratory tests (unless the investigator considers the deviation to be irrelevant for the purpose of the study)
• Left ventricular ejection fraction (LVEF) within the normal range by echocardiogram (ECHO) at 2 weeks prior to randomization
• 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 must voluntarily sign ICF prior to the study

Exclusion Criteria:

• Any clinical signs and symptoms (including blood pressure, pulse, and electrocardiogram) found during medical examination; And those who underwent surgery within 4 weeks before screening; Or plans to operate during the trial period
• Diagnosed with any clinical history of serious illness or any other disease or physiological conditions which can interfere with the test results
• Prescription or over-the-counter drugs with a long half-life (greater than 24h) within 1 month prior to administration. Take any other medication that the investigator considers may affect the subject's enrollment within 2 weeks prior to administration. A subject who has participated in any other clinical trial within 3 months before the study drug administration
• Have used or are using biological products such as monoclonal antibodies or fusion proteins
• Patients who have or have had chronic hepatitis b, c, syphilis or HIV infection, or who have tested positive for the above infection were deemed unsuitable to participate in this study
• Those who had been vaccinated within 30 days prior to screening or who needed to be vaccinated between screening and the end of the trial
• Drug abusers, or those who used soft drugs (e.g., marijuana) 3 months before screening, or took hard drugs (e.g., cocaine, phenyclohexidine, etc.) 1 year before the test, or drank excessive amounts of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250ml) every day, or those who showed positive urine drug screening
• Blood donation (containing component blood) or lost more than 400 mL of blood within 3 months before screening, or blood transfusion; Blood donation (containing component blood) or blood loss of more than 200 mL within 1 month before screening
• Related allergies (including allergy to any mouse\human protein or immunoglobulin products, rubber or latex)
• Those who smoked more than 10 cigarettes per day within 6 months before screening; And those who could not quit during the study period
• Alcoholics (who drink more than 14 standard units per week), or who have positive result in breath-test of alcohol
• Vigorous activity for 72h before drug administration; and cannot be avoided within 7 days after drug administration
• Unable to accept clinical trial center diet
• Fertile men who were unwilling to use highly effective contraceptives during the trial and for five months after administration
• The investigator judges the subject not eligible for the study after reviewing clinical laboratory results or other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMAB809	Drug: CMAB809; CMAB809 will be administered by IV infusion at a single dose of 6mg/kg.
Active Comparator: Trastuzumab	Drug: Trastuzumab; Trastuzumab will be administered by IV infusion at a single dose of 6mg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve [AUC]	Area under the concentration-time curve [AUC] from 0 to the last time point selected of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Serum Concentration(Cmax) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose
AUC0-∞	Area under the concentration-time curve from 0 to inf(AUC0-∞) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose
Tmax	The time of maximum blood concentration after administration(Tmax) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose
CL	Total clearance after bioavailability correction(CL) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose
T1/2	Half-life(T1/2) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose
Vd	Apparent volume of distribution corrected for bioavailability(Vd) of CMAB809	pre-dose, hour1.5, hour3, hour8, hour24, hour48, hour96, hour168, hour336, hour504, hour672, hour1008, hour1344, hour1680 post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with Adverse Events	Percentage of participants with Adverse Events (AEs) according to National Cancer Institute Common Terminology Criteria for AEs, Version 5.0(NCI CTCAE V5.0) Common Terminology Criteria for AEs, Version 5.0 (NCI CTCAE V5.0)	Up to 71 days after administration
anti-drug antibodies(ADA)	The number of subjects will be summarized	pre-dose, week3, week5 and week11 post-dose
anti-drug antibodies(ADA)	The percentage of subjects will be summarized	pre-dose, week3, week5 and week11 post-dose
Neutralization antibodies(Nab)	The number of subjects will be summarized	pre-dose, week3, week5 and week11 post-dose
Neutralization antibodies(Nab)	The percentage of subjects will be summarized	pre-dose, week3, week5 and week11 post-dose

Collaborators and Investigators

• Sponsor: Taizhou Mabtech Pharmaceutical Co.,Ltd
• Investigators: Principal Investigator: Jingying Jia, MSC, Shanghai Xuhui Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): November 20, 2019

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: CMAB809HV-I

Drug and device information, study documents

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