A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®

NCT03882424 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TRS00301001
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 12-week, randomized, double-blind, single-dose pharmacokinetic (PK) study. Approximately 114 healthy male participants (screening occurred within 28 days prior to dosing) will be randomized 1:1:1 to either TRS003, China-approved bevacizumab, and US-licensed Avastin® groups. Study drug will be dispensed as a single 3 mg/kg dose for intravenous infusion within 90 minutes. PK and immunogenicity samples will be collected and safety will be assessed. The primary objective of this study was to demonstrate pharmacokinetic similarity between TRS003, China-approved bevacizumab and US-licensed Avastin®, as measured by AUC0-inf in healthy male participants after a single 3 mg/kg dose.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity

  The primary assessment of PK similarity will be based upon a 90 percentage CI for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded.

  Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI

Secondary Outcomes (4)

• Cmax, Maximum Drug Concentration

  Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI

• AUC0-last, Area Under the Serum Concentration-time Curve，Time 0 to Last

  Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI

• Number of Participants Who Develop Detectable Anti-drug Antibody (ADA)

  Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion)

• Number of Participants With Adverse Events (AEs)

  Within 85 days following the drug administration

Study Arms (3)

TRS003

EXPERIMENTAL

Proposed biosimilar of bevacizumab，Intravenous administration

Biological: TRS003

China-approved Bevacizumab

ACTIVE COMPARATOR

Intravenous administration

Biological: China-approved Bevacizumab

US-licensed Avastin

ACTIVE COMPARATOR

Intravenous administration

Biological: US-licensed Avastin

Interventions

TRS003 BIOLOGICAL

25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes

TRS003

China-approved Bevacizumab BIOLOGICAL

25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes

China-approved Bevacizumab

US-licensed Avastin BIOLOGICAL

25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes

US-licensed Avastin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, male participants, 18-55 years old with no significant medical history, and in good health as determined by detailed medical history, full physical examination, vital signs, 12-lead electrocardiogram (ECG), urinalysis and laboratory tests at screening.
• Body mass index of 17.5-30.5 kg/m\^2 and body weight of 50-95 kg.
• Protocol-specified hematology, coagulation, blood chemistry and urinalysis within the laboratory normal range at screening, unless deemed not clinically significant by the Investigator.
• Participants must have adequate organ function according to the following laboratory values:
• Bone marrow function (absolute neutrophil count ≥1500/mm\^3 and platelet count ≥100,000/mm\^3)
• Adequate liver function \[alanine aminotransferase (ALT) ≤3 × upper limit normal (ULN) and alkaline phosphatase ≤2 × ULN, total bilirubin ≤1.5 mg/dL\]
• Adequate renal function creatinine clearance ≥60 mL/min based on Cockcroft-Gault equation
• Participants must agree to use an acceptable form of birth control throughout the study and for at least 18 weeks after the study is over.

You may not qualify if:

• Participants unable to give voluntary informed consent.
• Evidence or history of clinically significant disease, cancer other than adequately treated basal cell or squamous cell carcinoma of the skin.
• Participants on anticoagulant drugs, anemic or with known bleeding diatheses.
• Participants with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents, gastrointestinal bleeding, hemoptysis, frequent epistaxis or gingival bleeding.
• History clinically significant orthostatic hypotension, fainting spells, vasovagal syncope.
• Uncontrolled severe hypertension (140/90 mm Hg).
• Previous treatment with an anti-VEGF antibody or any other antibody or protein targeting the VEGF receptor.
• Use of any prescription, investigational drugs, herbal supplements or nonprescription drugs within 1 month or 5 half-lives (whichever is longer) prior to the first dose, or dietary supplements within 1 week prior to the first dose. If needed, paracetamol/acetaminophen may be used, but must be documented in the Concomitant medications/Significant non-drug therapies page of the case report form (CRF).
• Serious unhealed wound, cutaneous ulcer or bone fracture at the time of screening.
• Major surgery or major dental procedure or significant traumatic injury within 2 months prior to screening, or any planned surgery or procedure within 3 months after investigational treatment administration. Participants must have recovered from all acute surgery- or trauma-related complications.
• Participant's medical and family history of recent or recurrent thromboembolism or other clotting and coagulation disorders.
• Donated blood over 400 mL within 3 months.
• History of relevant and clinically significant intra-abdominal inflammation, gastrointestinal perforation or gall bladder perforation.
• History of severe allergic or anaphylactic reaction to a therapeutic drug or severe seasonal allergies.
• Recent (within the last three \[3\] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).

Sponsors & Collaborators

• Zhejiang Teruisi Pharmaceutical Inc.: lead

Study Sites (1)

WCCT Global, Inc.

Cypress, California, 90630, United States

Location

Results Point of Contact

• Title: Yilin Li, Medical Director
• Organization: Zhejiang Teruisi Pharmaceutical Inc.

yilin.li@teruisipharm.com

13601247168

Study Officials

• Smith Robina, MD

  WCCT Global, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 20, 2019
• Study Start: June 12, 2018
• Primary Completion: September 30, 2018
• Study Completion: October 25, 2018
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-06

Locations

US (1)