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

• ClinicalTrials.gov Identifier: NCT03083990
• Recruitment Status: Completed
• First Posted: March 20, 2017
• Results First Posted: November 4, 2020
• Last Update Posted: November 27, 2020
• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Information provided by (Responsible Party): Innovent Biologics (Suzhou) Co. Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Biological: IBI305(Bevacizumab Biosimilar); Drug: Avastin(Bevacizumab)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 9, 2017
• Actual Primary Completion Date: August 17, 2017
• Actual Study Completion Date: August 17, 2017

Arms and Interventions

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 Name: avastin

Outcome Measures

Primary Outcome Measures :

1. AUC0 - t [ Time Frame: 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 ]
   the area under the blood drug concentration time curve form 0 to t (AUC0 - t)
2. AUC0 - ∞ [ Time Frame: 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 ]
   the area under the blood drug concentration time curve form 0 to ∞AUC0 - ∞)

Secondary Outcome Measures :

1. Cmax [ Time Frame: 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 ]
   Maximum serum concentration
2. t1/2 [ Time Frame: 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 ]
   elimination half life
3. Clearance Rate [ Time Frame: 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 clearance
4. Apparent Volume of Distribution [ Time Frame: 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(V）

Other Outcome Measures:

1. Number of Participants Positive for Nab（Neutralizing Antibody） [ Time Frame: 99 days after administration ]
   The analysis of NAb was done by Covance Pharmaceutical R&D (Shanghai) Co., Ltd. using methodologically validated ECL immunoassay.
2. Number of Participants Positive for Anti-drug Antibodies [ Time Frame: 99 days after administration ]
   The analysis of ADA was done by Wuxi AppTec (Shanghai) Co., Ltd. using methodologically validated electrochemiluminescence (ECL) immunoassay.
3. Systolic Blood Pressure [ Time Frame: 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 ]
   Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.
4. Diastolic Blood Pressure [ Time Frame: 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 ]
   Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.
5. Urinalysis [ Time Frame: Baseline,D2,D5,D15,D29,D57,D71,D99 ]
   Urine specific gravity as assessed by laboratory tests up to 99 days post-treatment
6. Hemoglobin [ Time Frame: Baseline,D2,D5,D15,D29,D57,D71,D99 ]
   Hemoglobin as assessed by laboratory tests up to 99 days post-treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

China, Jilin

Jilin University First Hospital

Changchun, Jilin, China

Sponsors and Collaborators

Innovent Biologics (Suzhou) Co. Ltd.

Investigators

• Principal Investigator: yanhua Ding, Doctor; Jilin University First Hospital

  Study Documents (Full-Text)

Documents provided by Innovent Biologics (Suzhou) Co. Ltd.:

Study Protocol  [PDF] August 3, 2016

Statistical Analysis Plan  [PDF] September 30, 2017

More Information

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03083990
• Other Study ID Numbers: CIBI305A201
• First Posted: March 20, 2017
• Results First Posted: November 4, 2020
• Last Update Posted: November 27, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors