To Demonstrate Similarity of Pharmacokinetics and Evaluate Safety of CT-P16, EU-Approved Avastin and US-licensed Avastin

A Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics and Safety of Three Formulations of Bevacizumab (CT-P16, EU-approved Avastin and US-licensed Avastin) in Healthy Male Subjects

This study is a Phase 1 Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to compare the PK, safety and immunogenicity of the proposed biosimilar test product CT-P16 with EU-approved Avastin and US-licensed Avastin after a single IV infusion of 5mg/kg of each product to healthy male subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CT-P16; Drug: EU-approved Avastin; Drug: US-licensed Avastin

Detailed Description

This study is a double-blind, three-arm, parallel group, single-dose study. A total of 141 subjects will be enrolled; 47 subjects in each of the 3 arms of the clinical study. In each arm, all subjects will receive a single dose (5 mg/kg) of either CT-P16, EU-approved Avastin, or US-licensed Avastin by intravenous (IV) infusion for 90 min (±5 min) on Day 1 followed by 15 weeks during which the PK, safety, and immunogenicity measurements will be made. The randomization will be stratified by body weight and site.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of
    • Seoul St.Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between the ages of 19 and 55 years, both inclusive
• Body Mass Index (BMI) between 18.0 and 29.9 kg/m2 (both inclusive) and a body weight ≥ 50 kg

Exclusion Criteria:

• Subject is a female.
• Clinically significant allergic reactions, hypersensitivity
• A disease classed as significant by the Investigator
• Non-healing wound, ulcer, bone fracture, a major surgical procedure, significant traumatic injury
• Any malignancy
• Undergone treatment with an investigational drug or participated in another clinical trial
• Plans to father a child or donates sperms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT-P16; CT-P16 will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: CT-P16; CT-P16 is a biosimilar product for Avastin; Other Names: bevacizumab
Active Comparator: EU-approved Avastin; EU-approved Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: EU-approved Avastin; EU-approved Avastin; Other Names: bevacizumab
Active Comparator: US-licensed Avastin; US-licensed Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects	Drug: US-licensed Avastin; US-licensed Avastin; Other Names: bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf	Area under the concentration-time curve from time zero to infinity	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Cmax	Maximum Serum Concentration (Cmax)	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
AUC0-last	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional Pharmacokinetics (Time to Cmax)	To assess the additional PK of study drugs (Time to Cmax)	pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
Number of Participants With Anti-Drug Antibody Positive	number of participants with anti-drug antibody positive at post-dose	up to 15 weeks

Collaborators and Investigators

• Sponsor: Celltrion
• Investigators: Study Director: Sung Young Lee, Celltrion

Publications and helpful links

General Publications

• Cho SH, Han S, Ghim JL, Nam MS, Yu S, Park T, Kim S, Bae J, Shin JG. A Randomized, Double-Blind Trial Comparing the Pharmacokinetics of CT-P16, a Candidate Bevacizumab Biosimilar, with its Reference Product in Healthy Adult Males. BioDrugs. 2019 Apr;33(2):173-181. doi: 10.1007/s40259-019-00340-x.

Helpful Links

• Celltrion, Inc. homepage

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2017
• Primary Completion (Actual): December 22, 2017
• Study Completion (Actual): January 17, 2018

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 14, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: safety; Pharmacokinetics; Immunogenicity
• 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: CT-P16 1.1

Drug and device information, study documents

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