Healthy
Conditions
Brief summary
Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Bevacizumab
Detailed description
A Randomised, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Bevacizumab (SB8, EU Sourced Avastin®, and US Sourced Avastin®) in Healthy Male Subjects
Interventions
BIOLOGICALSB8
SB8, proposed bevacizumab biosimilar
BIOLOGICALEU sourced Avastin®
EU sourced Avastin® (bevacizumab, Roche Registration Ltd.)
BIOLOGICALUS Sourced Avastin®
US Sourced Avastin® (bevacizumab, Roche Registration Ltd.)
Sponsors
Samsung Bioepis Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects * Have body weight between 65.0-90.0 kg (inclusive) and body mass index between 20.0-29.9 kg/m2 (inclusive)
Exclusion criteria
* Have a history of hypersensitivity or allergic reactions to bevacizumab or to any of the excipients * Have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric, or allergic disease excluding mild asymptomatic seasonal allergies * Have a history of arterial thromboembolic events including cerebrovascular accidents, transient ischaemic attacks, and myocardial infarction * Have a history of and/or current cardiac disease * Have previously been exposed to vascular endothelial growth factor (VEGF) antibody, any other antibody, or protein targeting the VEGF receptor * Have a history of cancer including lymphoma, leukaemia, and skin cancer. * Have received live vaccine(s) within 30 days prior to Screening visit or who will require a vaccine(s) between Screening and the end of study visit * Have taken medication with a half-life of \> 24 hours within 30 days or 10 half-lives of the medication prior to the IP administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) | 0 to 2016 hours after start of infusion | 0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 0 to 2016 hours after start of infusion | 0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion. |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 0 to 2016 hours after start of infusion | 0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Cmax (Tmax) | 0 to 2016 hours after start of infusion | 0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB8 (Proposed Bevacizumab Biosimilar) SB8, single dose of 3 mg/kg, IV infusion
SB8: SB8, proposed bevacizumab biosimilar | 40 |
| EU Sourced Avastin® EU Sourced Avastin®, single dose of 3 mg/kg, IV infusion
EU sourced Avastin®: EU sourced Avastin® (bevacizumab, Roche Registration Ltd.) | 40 |
| US Sourced Avastin® US Sourced Avastin®, single dose of 3 mg/kg, IV infusion
US Sourced Avastin®: US Sourced Avastin® (bevacizumab, Roche Registration Ltd.) | 39 |
| Total | 119 |
Baseline characteristics
| Characteristic | SB8 (Proposed Bevacizumab Biosimilar) | EU Sourced Avastin® | US Sourced Avastin® | Total |
|---|---|---|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 9.24 | 39.5 years STANDARD_DEVIATION 10.45 | 38.9 years STANDARD_DEVIATION 9.32 | 40.9 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 40 Participants | 39 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 20 / 40 | 15 / 40 | 21 / 39 |
| serious Total, serious adverse events | 1 / 40 | 0 / 40 | 0 / 39 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Time frame: 0 to 2016 hours after start of infusion
Population: Among the subjects discountinued, subjects with major protocol deviations were excluded from the PK population for the PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB8 (Proposed Bevacizumab Biosimilar) | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 25354.4 h·μg/mL | Standard Deviation 4833.1 |
| EU Sourced Avastin® | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 28896.8 h·μg/mL | Standard Deviation 6221.62 |
| US Sourced Avastin® | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 28684.8 h·μg/mL | Standard Deviation 5425.14 |
Primary
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Time frame: 0 to 2016 hours after start of infusion
Population: Among the subjects discountinued, subjects with major protocol deviations were excluded from the PK population for the PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB8 (Proposed Bevacizumab Biosimilar) | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 24199.2 h·μg/mL | Standard Deviation 4367.53 |
| EU Sourced Avastin® | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 27342.2 h·μg/mL | Standard Deviation 5374.53 |
| US Sourced Avastin® | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 27177.9 h·μg/mL | Standard Deviation 4770.93 |
Primary
Maximum Serum Concentration (Cmax)
0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Time frame: 0 to 2016 hours after start of infusion
Population: Among the subjects discountinued, subjects with major protocol deviations were excluded from the PK population for the PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB8 (Proposed Bevacizumab Biosimilar) | Maximum Serum Concentration (Cmax) | 76.259 μg/mL | Standard Deviation 14.6999 |
| EU Sourced Avastin® | Maximum Serum Concentration (Cmax) | 76.059 μg/mL | Standard Deviation 11.7053 |
| US Sourced Avastin® | Maximum Serum Concentration (Cmax) | 76.485 μg/mL | Standard Deviation 16.9916 |
Secondary
Time to Reach Cmax (Tmax)
0 (pre-dose), 0.75, 1.5 (end of infusion), 3, 6, 12, 24, 48, and 96 hours, then at Day 8 (168 h), 15 (336 h), 22 (504 h), 29 (672 h), 43 (1008 h), 57 (1344 h), 71 (1680 h), and 85 (2016 h) after start of infusion.
Time frame: 0 to 2016 hours after start of infusion
Population: Among the subjects discountinued, subjects with major protocol deviations were excluded from the PK population for the PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB8 (Proposed Bevacizumab Biosimilar) | Time to Reach Cmax (Tmax) | 3.639 h | Standard Deviation 2.1885 |
| EU Sourced Avastin® | Time to Reach Cmax (Tmax) | 3.638 h | Standard Deviation 2.4261 |
| US Sourced Avastin® | Time to Reach Cmax (Tmax) | 5.646 h | Standard Deviation 15.6665 |