Bioequivalence and Safety Study of Bevacizumab-biosimilar (RPH-001) Compared to Bevacizumab-innovator

Study Overview
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Brief Summary
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The purpose of this to assess pharmacokinetic bioequivalence between two bevacizumab products, RPH-001 (TRPHARM) and EU sourced Avastin® (Roche), after single IV administration at 5 mg/kg fixed dose.

Official Title
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Phase I, Double Blind, Randomized, Parallel-Arm, Single-Dose, Bioequivalence and Safety Study of Bevacizumab-biosimilar (RPH-001) Compared to Bevacizumab-innovator (Avastin®, Roche) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: RPH001
* Biological: Avastin®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 18 to 55 years inclusive. Adult healthy male subjects between 18.0 and 30.0 kg/m2 body mass index (inclusive) and body weight ≥ 60 kg and ≤ 100 kg (inclusive). Exclusion Criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab). Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). Positive alcohol test at screening or baseline visits

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RPH-001<br>A single dose of RPH-001 will be administered (IV) 5 mg/kg dose . | Biological: RPH001<br>* Avastin® has been approved for treatment of various cancers in many countries of the world including the USA, EU countries, and Turkey. In Turkey, Avastin® is approved with a different trade name, Altuzan®, for treatment of metastatic colorectal cancer.<br>|
| Active Comparator: EU sourced Avastin®<br>A single dose of Avastin® will be administered (IV) 5 mg/kg dose . | Biological: Avastin®<br>* R-Pharm created a biological analog of Avastin®, RPH-001. RPH-001 and Avastin® have similar physicochemical properties, pharmacokinetic profile and affinity to human vascular endothelial growth factor, similar toxicity and efficacy confirmed by preclinical study results.<br>* Other names: Bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration | Cmax | Until 100 days after administration | 
| Area under concentration-time curve from time zero to the last sampling time | Area Under the Curve - AUC(0-t) | Until 100 days after administration | 
| Area under concentration-time curve from time zero to infinity | Area Under the Curve - AUC(0-∞) | Until 100 days after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration-time profiles | RPH-001 and Avastin® | Until 100 days after administration | 
| Time to maximum concentration (Tmax) | RPH-001 and Avastin® | Until 100 days after administration | 
| Terminal elimination half-life (t½) | RPH-001 and Avastin® | Until 100 days after administration | 
| Terminal elimination rate constant (λz) | RPH-001 and Avastin® | Until 100 days after administration | 
| Apparent volume of distribution (Vz) | RPH-001 and Avastin® | Until 100 days after administration | 
| Clearance (CL) |  | Until 100 days after administration | 
| Volume of distribution at steady state (Vss) |  | Until 100 days after administration | 
| Nature, frequency, severity and relationship to study drug of recorded adverse events |  | Until 100 days after administration | 
| Physical examination |  | Until 100 days after administration | 
| Heart rate |  | Until 100 days after administration | 
| Blood Pressure |  | Until 100 days after administration | 
| Respiratory rate |  | Until 100 days after administration | 
| Oxygen saturation |  | Until 100 days after administration | 
| Body temperature |  | Until 100 days after administration | 
| ECG |  | Until 100 days after administration | 
| Clinical laboratory tests |  | Until 100 days after administration | 
| Anti-drug-antibody (ADA) |  | Until 100 days after administration | 
| Neutralizing antibody (NAb) |  | Until 100 days after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RPH101, RPH-101, Biosimilar, Bevacizumab, Safety