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To confirm the PK similarity of IBI305 and bevacizumab in healthy volunteers .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | IBI 305 ,3mg/kg, infusion in 90 minutes |
|
| Group B | Active Comparator | Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IBI305(Bevacizumab Biosimilar) | Biological | 3mg/kg, infusion in 90minutes |
| |
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
To be eligible for the study, patients should fulfill all the following criteria:
Exclusion Criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
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| Name | Affiliation | Role |
|---|---|---|
| yanhua Ding, Doctor | Jilin University First Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jilin University First Hospital | Changchun | Jilin | China |
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| ID | Title | Description |
|---|---|---|
| FG000 | IBI305 | IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes |
| FG001 | Bevacizumab | Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The baseline demographics of the subjects were analyzed based on the Pharmacokinetics analysis set.A total of 98 (98.0%) subjects were included , and 2 (4%) subjects in the IBI305 arm were excluded in the due to positive anti-drug antibody at baseline.
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| ID | Title | Description |
|---|---|---|
| BG000 | IBI305 | IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes |
| BG001 | Bevacizumab | Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC0 - t | the area under the blood drug concentration time curve form 0 to t (AUC0 - t) | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Geometric Mean | Standard Deviation | h*ug/mL | 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 |
|
from participants are enrolled to 99 days after infusion
The analysis population consisted of all participants.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IBI305 | IBI 305 ,3mg/kg, infusion in 90 minutes IBI305(Bevacizumab Biosimilar): 3mg/kg, infusion in 90minutes |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hand injury | Musculoskeletal and connective tissue disorders | MedDRA(19.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertriglyceridemia | Metabolism and nutrition disorders | MedDRA(19.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yi Bo | Innovent Biologics (Suzhou) Co., Ltd. (seal) | +86 13382419112 | jessica.yi@innoventbio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 3, 2016 | Jul 6, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 30, 2017 | Jul 6, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Avastin(Bevacizumab) |
| Drug |
3mg/kg, infusion in 90minutes |
|
|
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 |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeter |
|
| Weight | Mean | Standard Deviation | kilogram |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
|
|
|
|
| Primary | AUC0 - ∞ | the area under the blood drug concentration time curve form 0 to ∞AUC0 - ∞) | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Geometric Mean | Standard Deviation | h*ug/mL | 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 | Cmax | Maximum serum concentration | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Geometric Mean | Standard Deviation | ug/mL | 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 | t1/2 | elimination half life | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Mean | Standard Deviation | hour | 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 | Clearance Rate | apparent clearance | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Mean | Standard Deviation | ml/h/kg | 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 | Apparent Volume of Distribution | apparent volume of distribution(V) | 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline | Posted | Mean | Standard Deviation | ml/kg | 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 Pre-specified | 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. | All 100 (100%) subjects were included in the NAb-AS (Neutralizing anti-body analysis set) | Posted | Number | Participants | 99 days after administration |
|
|
|
| Other Pre-specified | 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. | All 100 (100%) subjects were included in the ADA-AS(Anti-drug Antibody Analysis set) | Posted | Number | Participants | 99 days after administration |
|
|
|
| Other Pre-specified | Systolic Blood Pressure | Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded. | All 100 (100%) subjects were included in the safety analysis set. Blood pressure of certain timepoint was not collected because of serve adverse event. | Posted | Mean | Standard Deviation | mmHg | 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 |
|
|
|
| Other Pre-specified | Diastolic Blood Pressure | Systolic blood pressure and diastolic blood pressure on certain timepoints are measured and recorded. | All 100 (100%) subjects were included in the safety analysis set. Blood pressure of certain timepoint was not collected because of serve adverse event. | Posted | Mean | Standard Deviation | mmHg | 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 |
|
|
|
| Other Pre-specified | Urinalysis | Urine specific gravity as assessed by laboratory tests up to 99 days post-treatment | All 100 (100%) subjects were included in the analysis set | Posted | Mean | Standard Deviation | Urine specific gravity | Baseline,D2,D5,D15,D29,D57,D71,D99 |
|
|
|
| Other Pre-specified | Hemoglobin | Hemoglobin as assessed by laboratory tests up to 99 days post-treatment. | All 100 (100%) subjects were included in the safety analysis set (SS) | Posted | Mean | Standard Deviation | Hemoglobin (g/L) | Baseline,D2,D5,D15,D29,D57,D71,D99 |
|
|
|
| 0 |
| 50 |
| 1 |
| 50 |
| 40 |
| 50 |
| EG001 | Bevacizumab | Bevacizumab (Avastin) 3mg/kg, infusion in 90 minutes Avastin(Bevacizumab): 3mg/kg, infusion in 90minutes | 0 | 50 | 0 | 50 | 40 | 50 |
| ALT increased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA(19.1) | Systematic Assessment |
|
| AST increased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA(19.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Red blood cells urine positive | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA(19.1) | Systematic Assessment |
|
| Intermediate insomnia | Psychiatric disorders | MedDRA(19.1) | Systematic Assessment |
|
| Bilirubin increased | Investigations | MedDRA(19.1) | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA(19.1) | Systematic Assessment |
|
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| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D43 |
|
| D71 |
|
| D99 |
|
| D43 |
|
| D71 |
|
| D99 |
|
| D1, immediately after the end of infusion |
|
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| D1, 4 hrs after the start of infusion |
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| D1, 8 hrs after the start of infusion |
|
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| D1, 12 hrs after the start of infusion |
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| D2 |
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| D3 |
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| D5 |
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| D8 |
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| D15 |
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| D22 |
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| D29 |
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| D43 |
|
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| D57 |
|
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| D64 |
|
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| D71 |
|
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| D85 |
|
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| D99 |
|
|
| D1, immediately after the end of infusion |
|
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| D1, 4 hrs after the start of infusion |
|
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| D1, 8 hrs after the start of infusion |
|
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| D1, 12 hrs after the start of infusion |
|
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| D2 |
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| D3 |
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| D5 |
|
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| D8 |
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| D15 |
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| D22 |
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| D29 |
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| D43 |
|
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| D57 |
|
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| D64 |
|
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| D71 |
|
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| D85 |
|
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| D99 |
|
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| D5 |
|
| D15 |
|
| D29 |
|
| D57 |
|
| D71 |
|
| D99 |
|
| D5 |
|
| D15 |
|
| D29 |
|
| D57 |
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| D71 |
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| D99 |
|