HealthyPhase 1NCT03882424
A Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®
A Phase 1 study testing TRS003, China-approved Bevacizumab and US-licensed Avastin in people with Healthy, run by Zhejiang Teruisi Pharmaceutical Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- TRS003, China-approved Bevacizumab and US-licensed Avastin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2018to 25 Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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).
- A positive hepatitis B, hepatitis C or HIV tests at screening indicative of a current or past infection.
- Current use of tobacco or nicotine-containing products. Concomitant treatment was given only if Investigator believes strictly necessary and should be documented.
- Current use of any biologic drugs.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Single-dose, Three-arm, Parallel-group, Phase 1 Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®，When Administered to Healthy Male Participants
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.
Read the detailed description
The primary assessment of PK similarity will be based upon a 90 percentage confidence interval (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. Secondary PK parameters such as but not limited to Cmax, AUClast will be analyzed using the same statistical approach. A nonparametric approach, for example, Wilcoxon signed-rank test, will be taken to evaluate parameters such as t1/2. Exploratory analyses may be performed for other PK parameters as deemed appropriate. All adverse events (AEs) will be listed and summarized using descriptive methodology. The incidence of AEs for each treatment will be presented by severity and association with the study drugs. Clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be listed and summarized using descriptive statistics. The number and percentage of participants testing positive for anti-drug antibodies (ADAs) will be summarized by treatment and time point.
- Conditions
- Healthy
- Being tested
- TRS003, China-approved Bevacizumab, US-licensed Avastin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRS003Biological
25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
China-approved BevacizumabBiological
25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
US-licensed AvastinBiological
25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes
| Study group | Role | What they receive |
|---|---|---|
| TRS003 | Experimental | Proposed biosimilar of bevacizumab，Intravenous administration Receives: Biological: TRS003 |
| China-approved Bevacizumab | Active comparator | Intravenous administration Receives: Biological: China-approved Bevacizumab |
| US-licensed Avastin | Active comparator | Intravenous administration Receives: Biological: US-licensed Avastin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
To assess other PK parameters such as Cmax, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for Cmax is within the range of 80-125 percentage, then PK similarity will be concluded.
Measured: 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
To assess other PK parameters such as AUClast, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for AUC0-last is within the range of 80-125 percentage, then PK similarity will be concluded.
Measured: 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)
To determine the number of participants with immunogenicity against TRS003, China-approved bevacizumab, and US-licensed Avastin® in healthy male participants, blood samples will be collected for ADA analyses.
Measured: Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion)
Number of Participants With Adverse Events (AEs)
Adverse events will be classified using the MedDRA classification system. The severity of the toxicities will be graded according to the NCI CTCAE version 4.03.
Measured: Within 85 days following the drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2019
- Study start12 Jun 2018
- Primary completion30 Sep 2018
- Study completion25 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhejiang Teruisi Pharmaceutical Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Smith Robina, MD, Principal investigator, WCCT Global, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03882424
- Sponsor's protocol ID
- TRS00301001
- Status last verified
- Jun 2020
- First submitted
- 18 Mar 2019
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Single-dose, Three-arm, Parallel-group, Phase 1 Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®，When Administered to Healthy Male Participants
- ClinicalTrials.gov ID
- NCT03882424
- Acronym / sponsor ID
- TRS00301001
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Zhejiang Teruisi Pharmaceutical Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Jun 2018 (actual)
- Primary completion
- 30 Sep 2018 (actual)
- Study completion
- 25 Oct 2018 (actual)
- First posted
- 20 Mar 2019 (actual)
- Results
- Posted 16 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary assessment of PK similarity will be based upon a 90 percentage confidence interval (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. Secondary PK parameters such as but not limited to Cmax, AUClast will be analyzed using the same statistical approach. A nonparametric approach, for example, Wilcoxon signed-rank test, will be taken to evaluate parameters such as t1/2. Exploratory analyses may be performed for other PK parameters as deemed appropriate. All adverse events (AEs) will be listed and summarized using descriptive methodology. The incidence of AEs for each treatment will be presented by severity and association with the study drugs. Clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be listed and summarized using descriptive statistics. The number and percentage of participants testing positive for anti-drug antibodies (ADAs) will be summarized by treatment and time point.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TRS003 | Experimental | Biological: TRS003Proposed biosimilar of bevacizumab，Intravenous administration |
| China-approved Bevacizumab | Active comparator | Biological: China-approved BevacizumabIntravenous administration |
| US-licensed Avastin | Active comparator | Biological: US-licensed AvastinIntravenous administration |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRS00325mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes | Biological | TRS003 |
| China-approved Bevacizumab25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes | Biological | China-approved Bevacizumab |
| US-licensed Avastin25mg/mL (4 mL/vial) Injection，Single dose of 3mg/kg Intravenous infusion for 90 minutes | Biological | US-licensed Avastin |
Primary outcome
AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity
Time frame: 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
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.
4 secondary outcomes
Cmax, Maximum Drug Concentration
Time frame: 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
Time frame: 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)
Time frame: Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion)
Number of Participants With Adverse Events (AEs)
Time frame: Within 85 days following the drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Smith Robina, MD principal investigator
WCCT Global, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TRS003, China-approved Bevacizumab and US-licensed Avastin in people with Healthy, run by Zhejiang Teruisi Pharmaceutical Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.