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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Biological: RPH001; Biological: Avastin®

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RPH-001; A single dose of RPH-001 will be administered (IV) 5 mg/kg dose .	Biological: RPH001; 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.
Active Comparator: EU sourced Avastin®; A single dose of Avastin® will be administered (IV) 5 mg/kg dose .	Biological: Avastin®; 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.; Other Names: Bevacizumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TRPHARM
• Investigators: Principal Investigator: Zafer Sezer, PHD, IKUM

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Bevacizumab; Biosimilar; RPH101; RPH-101
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: RPH001BEV01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No