Pharmacokinetic, Safety, Tolerability, and Immunogenicity Study of SB8 in Healthy Male Subjects

Study Overview
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Brief Summary
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Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Bevacizumab

Detailed Description
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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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: SB8
* Biological: EU sourced Avastin®
* Biological: US Sourced Avastin®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SB8<br>SB8, single dose of 3 mg/kg, IV infusion | Biological: SB8<br>* SB8, proposed bevacizumab biosimilar<br>|
| Active Comparator: EU Sourced Avastin®<br>EU Sourced Avastin®, single dose of 3 mg/kg, IV infusion | Biological: EU sourced Avastin®<br>* EU sourced Avastin® (bevacizumab, Roche Registration Ltd.)<br>|
| Active Comparator: US Sourced Avastin®<br>US Sourced Avastin®, single dose of 3 mg/kg, IV infusion | Biological: US Sourced Avastin®<br>* US Sourced Avastin® (bevacizumab, Roche Registration Ltd.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 to 2016 hours after start of infusion | 
| 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. | 0 to 2016 hours after start of infusion | 
| 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. | 0 to 2016 hours after start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 to 2016 hours after start of infusion |