Compare IBI305 and Bevacizumab on Pharmacokinetics/Safety/Immunogenicity on Healthy Male

Compare IBI305 to Avastin on the Pharmacokinetics, Safety, Tolerance and Immunogenicity of a Single Dose In Healthy Male Subjects: a Randomized Double-blind Parallel Controlled Phase I Clinical Study

To confirm the PK similarity of IBI305 and bevacizumab in healthy volunteers .

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: IBI305(Bevacizumab Biosimilar); Drug: Avastin(Bevacizumab)

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China
      • Jilin University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• To be eligible for the study, patients should fulfill all the following criteria:

  1. Fully understand the study purpose, and understand the pharmacological effects and potential adverse reactions of the drug, voluntarily signed written informed consent according to the declaration of Helsinki.
  2. Age ≥18 and ≤ 50, healthy male subjects
  3. Weigh ≥ 50 kg and ≤ 100 kg， BMI≥ 19 and ≤ 28 kg/m2
  4. All the system test result within the normal range, or abnormal test results without clinical significance judged by the investigator.
  5. The subjects must agree to use effective contraceptive measures during the study treatment and for 6 months after receiving last does of study drug (e.g. abstinence, sterilization surgery, oral contraceptives, contraception by progesterone injection or subcutaneous)

Exclusion Criteria:

• Patients should not enter the study if any of the following exclusion criteria are fulfilled:

  1. Medical history of high blood pressure or abnormal blood pressure at screening/baseline(Double confirmed systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg within one day)
  2. Proteinuria with clinical significance judged by the investigator (routine urine examination, urine protein 2 + and above) or a history of proteinuria.
  3. Any prior VEGF(vascular endothelial growth factor) and VEGFR(Vascular Endothelial Growth Factor Receptor) antibody or protein treatment within one year.
  4. Any biological products or a live virus vaccine treatment within 3 months , or any monoclonal antibodies within 12 months before the first dose of study drug.
  5. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus.
  6. History of digestive tract perforation or digestive tract fistula.
  7. Serious, non-healing wound, active ulcer, or untreated bone fracture, or major surgical procedure within 2 months prior to randomization or anticipation of need for major surgery during the course of the study or 2 months after last dose of the study drug.
  8. Use Rx or OTC drugs or nutritional health products within 5 half-lives or within 2 weeks before the first dose of study drug (According to the longer time).Herbal supplements need to stop at 28 days before the first dose of study drug.
  9. Positive hepatitis b surface antigen (HBsAg), hepatitis c virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody or syphilis
  10. Known hypersensitivity to Bevacizumab or any excipients
  11. Known allergic disease or allergic constitution
  12. History of blood donation within 3 months before the first dose of study drug
  13. Treatment with any other investigational agent or participation in another clinical trial within 3 months prior to screening
  14. History of alcoholism or drug abuse within 12 months prior to screening; Subjects cannot temperance within 72 hours before study drug infusion and during the whole study
  15. History of mental illness
  16. Anticipated of partner pregnancy during the study.
  17. Incompliance to the clinical study protocol during the study.
  18. Other conditions that the investigator thinks unsuitable in this study

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: Group A; IBI 305 ,3mg/kg, infusion in 90 minutes	Biological: IBI305(Bevacizumab Biosimilar); 3mg/kg, infusion in 90minutes
Active Comparator: Group B; Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes	Drug: Avastin(Bevacizumab); 3mg/kg, infusion in 90minutes; Other Names: avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0 - t	the area under the blood drug concentration time curve form 0 to t (AUC0 - t)	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days
AUC0 - ∞	the area under the blood drug concentration time curve form 0 to ∞AUC0 - ∞)	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum serum concentration	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days
t1/2	elimination half life	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days
Clearance Rate	apparent clearance	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days
Apparent Volume of Distribution	apparent volume of distribution(V）	60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Positive for Nab（Neutralizing Antibody）	The analysis of NAb was done by Covance Pharmaceutical R&D (Shanghai) Co., Ltd. using methodologically validated ECL immunoassay.	99 days after administration
Number of Participants Positive for Anti-drug Antibodies	The analysis of ADA was done by Wuxi AppTec (Shanghai) Co., Ltd. using methodologically validated electrochemiluminescence (ECL) immunoassay.	99 days after administration
Systolic Blood Pressure	Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.	0, D1( immediately after the end of infusion), D1 (4 hrs after the start of infusion), D1, 8 hrs after the start of infusion, D1 (12 hrs after the start of infusion), D2, D3, D5, D8, D15, D22, D29, D43, D57, D64, D71, D85, D99
Diastolic Blood Pressure	Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.	0, D1( immediately after the end of infusion), D1 (4 hrs after the start of infusion), D1, 8 hrs after the start of infusion, D1 (12 hrs after the start of infusion), D2, D3, D5, D8, D15, D22, D29, D43, D57, D64, D71, D85, D99
Urinalysis	Urine specific gravity as assessed by laboratory tests up to 99 days post-treatment	Baseline,D2,D5,D15,D29,D57,D71,D99
Hemoglobin	Hemoglobin as assessed by laboratory tests up to 99 days post-treatment.	Baseline,D2,D5,D15,D29,D57,D71,D99

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Principal Investigator: yanhua Ding, Doctor, Jilin University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Actual): August 17, 2017
• Study Completion (Actual): August 17, 2017

Study Registration Dates

• First Submitted: November 12, 2016
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 20, 2017

Study Record Updates

• Last Update Posted (Actual): November 27, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CIBI305A201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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