Clinical trial NCT03083990: Compare IBI305 and Bevacizumab on Pharmacokinetics/Safety/Immunogenicity on Healthy Male
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2017-03-20
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: AUC0 - t
timeFrame: 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
measure: AUC0 - ∞
timeFrame: 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 outcomes:
measure: Cmax
timeFrame: 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
measure: t1/2
timeFrame: 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
measure: Clearance Rate
timeFrame: 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
measure: Apparent Volume of Distribution
timeFrame: 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 outcomes:
measure: Number of Participants Positive for Nab（Neutralizing Antibody）
timeFrame: 99 days after administration
measure: Number of Participants Positive for Anti-drug Antibodies
timeFrame: 99 days after administration
measure: Systolic Blood Pressure
timeFrame: 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
measure: Diastolic Blood Pressure
timeFrame: 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
measure: Urinalysis
timeFrame: Baseline,D2,D5,D15,D29,D57,D71,D99
measure: Hemoglobin
timeFrame: Baseline,D2,D5,D15,D29,D57,D71,D99
Locations:
city: Changchun
country: China
facility: Jilin University First Hospital
state: Jilin
Study officials:
affiliation: Jilin University First Hospital
name: yanhua Ding, Doctor
role: PRINCIPAL_INVESTIGATOR
References: