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

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03083990
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.3
• Patients Per Site Per Month: 18.9

Study Details

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
• 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: Mar 9, 2017
• Actual Primary Completion Date: Aug 17, 2017
• Actual Study Completion Date: Aug 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 Names: avastin

Outcome Measures

Primary Outcome Measures

1. 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]

   the area under the blood drug concentration time curve form 0 to t (AUC0 - t)

2. 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]

   the area under the blood drug concentration time curve form 0 to ∞AUC0 - ∞)

Secondary Outcome Measures

1. Cmax [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 [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 [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 [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） [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 [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 [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 [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 [Baseline,D2,D5,D15,D29,D57,D71,D99]

   Urine specific gravity as assessed by laboratory tests up to 99 days post-treatment

6. Hemoglobin [Baseline,D2,D5,D15,D29,D57,D71,D99]

   Hemoglobin as assessed by laboratory tests up to 99 days post-treatment.

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol - Aug 3, 2016
• Statistical Analysis Plan - Sep 30, 2017

More Information

Publications

None provided.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03083990
• Other Study ID Numbers: CIBI305A201
• First Posted: Mar 20, 2017
• Last Update Posted: Nov 27, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Period Title: Overall Study
STARTED	50	50
COMPLETED	49	50
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	IBI305	Bevacizumab	Total
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes	Total of all reporting groups
Overall Participants	48	50	98
Age (years) [Mean (Standard Deviation) ]
Mean (SD)	36.5 (8.92)	34.0 (8.87)	35.2 (8.94)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	48 100%	50 100%	98 100%
Race/Ethnicity, Customized (Count of Participants)
Han	43 89.6%	45 90%	88 89.8%
Others	5 10.4%	5 10%	10 10.2%
Region of Enrollment (Count of Participants)
China	48 100%	50 100%	98 100%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	169.7 (5.69)	169.0 (5.12)	169.3 (5.39)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	67.32 (7.763)	68.42 (6.629)	67.88 (7.191)
Body mass index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	23.414 (2.739)	23.962 (2.040)	23.694 (2.412)

Outcome Measures

1. Primary Outcome

Title	AUC0 - t
Description	the area under the blood drug concentration time curve form 0 to t (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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Geometric Mean (Standard Deviation) [h*ug/mL]	19704.2 (18.8)	20736.9 (19.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IBI305, Bevacizumab
	Comments
	Type of Statistical Test	Equivalence
	Comments	Geometric mean ratio and its 90%CI are obtained after anti-logarithmic transformation.If 90% CI for the geometric mean ratio of AUC 0-t and AUC 0-∞ (trial/control) ranges between 0.8-1.25, then it is considered that IBI305 and Bevacizumab are bioequivalent.
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9502
	Confidence Interval	(2-Sided) 90%; 0.8921 to 1.0120
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC0 - ∞
Description	the area under the blood drug concentration time curve form 0 to ∞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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Geometric Mean (Standard Deviation) [h*ug/mL]	20180.2 (18.6)	21281.4 (19.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IBI305, Bevacizumab
	Comments
	Type of Statistical Test	Equivalence
	Comments	Geometric mean ratio and its 90%CI are obtained after anti-logarithmic transformation.If 90% CI for the geometric mean ratio of AUC 0-t and AUC 0-∞ (trial/control) ranges between 0.8-1.25, then it is considered that IBI305 and Bevacizumab are bioequivalent.
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9483
	Confidence Interval	(2-Sided) 90%; 0.8896 to 1.0108
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Cmax
Description	Maximum serum concentration
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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Geometric Mean (Standard Deviation) [ug/mL]	65.3 (21.0)	67.0 (18.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IBI305, Bevacizumab
	Comments
	Type of Statistical Test	Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9749
	Confidence Interval	(2-Sided) 90%; 0.9123 to 1.0418
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	t1/2
Description	elimination half life
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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Mean (Standard Deviation) [hour]	340.2 (51.1)	356.5 (69.6)

5. Secondary Outcome

Title	Clearance Rate
Description	apparent clearance
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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Mean (Standard Deviation) [ml/h/kg]	0.151 (0.0296)	0.144 (0.0281)

6. Secondary Outcome

Title	Apparent Volume of Distribution
Description	apparent volume of distribution(V）
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

Outcome Measure Data

Analysis Population Description

2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	48	50
Mean (Standard Deviation) [ml/kg]	73.8 (15.9)	72.3 (12.8)

7. Other Pre-specified Outcome

Title	Number of Participants Positive for Nab（Neutralizing Antibody）
Description	The analysis of NAb was done by Covance Pharmaceutical R&D (Shanghai) Co., Ltd. using methodologically validated ECL immunoassay.
Time Frame	99 days after administration

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the NAb-AS (Neutralizing anti-body analysis set)

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	2 4.2%	0 0%
D15	4 8.3%	0 0%
D43	2 4.2%	0 0%
D71	2 4.2%	0 0%
D99	1 2.1%	0 0%

8. Other Pre-specified Outcome

Title	Number of Participants Positive for Anti-drug Antibodies
Description	The analysis of ADA was done by Wuxi AppTec (Shanghai) Co., Ltd. using methodologically validated electrochemiluminescence (ECL) immunoassay.
Time Frame	99 days after administration

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the ADA-AS(Anti-drug Antibody Analysis set)

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	2 4.2%	0 0%
D15	4 8.3%	0 0%
D43	2 4.2%	0 0%
D71	2 4.2%	0 0%
D99	1 2.1%	0 0%

9. Other Pre-specified Outcome

Title	Systolic Blood Pressure
Description	Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.
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

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the safety analysis set. Blood pressure of certain timepoint was not collected because of serve adverse event.

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	119.6 (8.73)	121.4 (8.02)
D1, immediately after the end of infusion	113.3 (10.23)	114.5 (8.7)
D1, 4 hrs after the start of infusion	118.0 (9.60)	119.6 (7.87)
D1, 8 hrs after the start of infusion	120.4 (9.48)	120.3 (8.30)
D1, 12 hrs after the start of infusion	119.8 (8.67)	123.4 (9.63)
D2	119.8 (9.72)	121.9 (8.81)
D3	120.2 (8.37)	123.2 (9.52)
D5	120.7 (7.97)	121.4 (8.34)
D8	118.4 (7.69)	122.6 (9.22)
D15	118.6 (9.70)	118.5 (10.19)
D22	121.8 (8.73)	122.5 (8.88)
D29	121.6 (9.20)	123.1 (8.91)
D43	119.7 (9.12)	121.3 (9.03)
D57	118.4 (10.30)	122.1 (8.12)
D64	119.4 (8.78)	120.2 (10.00)
D71	118.3 (10.01)	119.8 (10.10)
D85	115.8 (9.04)	120.6 (9.59)
D99	118.2 (7.61)	118.2 (10.66)

10. Other Pre-specified Outcome

Title	Diastolic Blood Pressure
Description	Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded.
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

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the safety analysis set. Blood pressure of certain timepoint was not collected because of serve adverse event.

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	79.2 (8.02)	81.4 (5.94)
D1, immediately after the end of infusion	71.8 (7.82)	73.7 (6.64)
D1, 4 hrs after the start of infusion	75.5 (6.68)	77.4 (7.13)
D1, 8 hrs after the start of infusion	77.8 (5.94)	79.3 (6.95)
D1, 12 hrs after the start of infusion	77.0 (6.96)	81.3 (7.37)
D2	79.8 (6.57)	81.6 (6.46)
D3	80.5 (6.45)	82.8 (6.17)
D5	80.4 (8.30)	82.1 (4.71)
D8	78.2 (6.23)	81.4 (6.62)
D15	78.2 (7.67)	79.2 (6.50)
D22	80.5 (6.04)	82.3 (7.47)
D29	79.6 (6.43)	81.6 (7.02)
D43	79.5 (7.34)	80.0 (6.96)
D57	78.6 (7.87)	82.2 (6.18)
D64	78.7 (7.33)	80.5 (6.18)
D71	77.1 (8.01)	80.2 (6.32)
D85	79.2 (6.96)	80.0 (6.42)
D99	76.8 (6.91)	77.9 (6.83)

11. Other Pre-specified Outcome

Title	Urinalysis
Description	Urine specific gravity as assessed by laboratory tests up to 99 days post-treatment
Time Frame	Baseline,D2,D5,D15,D29,D57,D71,D99

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the analysis set

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	1.017 (0.006)	1.017 (0.006)
D2	1.017 (0.006)	1.017 (0.005)
D5	1.017 (0.005)	1.018 (0.005)
D15	1.016 (0.006)	1.017 (0.006)
D29	1.017 (0.005)	1.017 (0.005)
D57	1.016 (0.005)	1.018 (0.006)
D71	1.017 (0.004)	1.016 (0.005)
D99	1.017 (0.006)	1.019 (0.006)

12. Other Pre-specified Outcome

Title	Hemoglobin
Description	Hemoglobin as assessed by laboratory tests up to 99 days post-treatment.
Time Frame	Baseline,D2,D5,D15,D29,D57,D71,D99

Outcome Measure Data

Analysis Population Description

All 100 (100%) subjects were included in the safety analysis set (SS)

Arm/Group Title	IBI305	Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes	Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
Measure Participants	50	50
Baseline	161.0 (9.42)	163.5 (9.52)
D2	158.8 (11.53)	160.4 (9.21)
D5	165.4 (10.93)	167.7 (10.02)
D15	160.9 (10.67)	164.5 (9.21)
D29	161.1 (10.01)	164.5 (11.03)
D57	160.4 (12.45)	165.5 (10.42)
D71	159.8 (12.19)	163.9 (9.12)
D99	154.6 (11.01)	159.9 (10.22)

Adverse Events

Time Frame	from participants are enrolled to 99 days after infusion
Adverse Event Reporting Description	The analysis population consisted of all participants.
Arm/Group Title	IBI305		Bevacizumab
Arm/Group Description	IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes		Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes
All Cause Mortality
	IBI305		Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Serious Adverse Events
	IBI305		Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/50 (2%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
hand injury	1/50 (2%)	1	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	IBI305		Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/50 (80%)		40/50 (80%)
Cardiac disorders
Sinus bradycardia	4/50 (8%)	6	3/50 (6%)	4
Investigations
ALT increased	10/50 (20%)	12	12/50 (24%)	17
AST increased	6/50 (12%)	8	10/50 (20%)	12
White blood cell count increased	6/50 (12%)	9	8/50 (16%)	9
Neutrophil count increased	5/50 (10%)	7	8/50 (16%)	9
White blood cell count decreased	4/50 (8%)	7	2/50 (4%)	5
Red blood cells urine positive	4/50 (8%)	4	1/50 (2%)	1
Neutrophil count decreased	3/50 (6%)	5	3/50 (6%)	8
Bilirubin increased	2/50 (4%)	3	6/50 (12%)	8
White blood cells urine positive	2/50 (4%)	3	5/50 (10%)	7
Metabolism and nutrition disorders
Hypertriglyceridemia	11/50 (22%)	25	13/50 (26%)	24
Hyperglycemia	7/50 (14%)	8	9/50 (18%)	11
Nervous system disorders
Headache	3/50 (6%)	4	0/50 (0%)	0
Psychiatric disorders
Intermediate insomnia	3/50 (6%)	3	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.