Healthy Male SubjectsPhase 1NCT03483649
Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX04 Versus Avastin® in Healthy Male Subjects
A Phase 1 study testing HLX04, US-Avastin® and EU-Avastin® in people with Healthy Male Subjects, run by Shanghai Henlius Biotech at 1 site in China.
Trial summary
This is a Phase I, randomized, double blind, IV, single dose, 4-arm parallel study to compare the PK, and to evaluate the safety, tolerability and immunogenicity of HLX04, US Avastin®, EU Avastin®, and CN Avastin® in healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Male Subjects
- What is being tested?
- HLX04, US-Avastin® and EU-Avastin®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 1 siteChina
- Study dates
- 21 Apr 2017to 29 Oct 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects who are willing to comply with the contraception restrictions for this study (see Section 4.3.3).
- Subjects who are able and willing to give written informed consent.
- Subjects who are willing to comply with the study restrictions from screening until end of study.
- Adult males aged 18 to 50 years inclusive and between 19 and 26 kg/m2 body mass index and body weight ≥ 50 kg and ≤ 80 kg.
- Subjects who are non smokers or have not used tobacco or nicotine containing products for at least 3 months preceding screening and have less than 5 cigarettes per day smoking history. Subjects must agree to refrain from smoking during days of confinement at the study center.
- Subjects negative for Hepatitis B surface antigen, Hepatitis C virus antibody, Treponema pallidum antibody, and human immunodeficiency virus antibody tests.
- Subjects negative for urine drug screen and alcohol tests.
- Subjects determined healthy by medical history, physical examination, laboratory tests, 12 lead electrocardiogram (ECG), and chest X ray, without any clinically significant abnormality judged by the Investigator.
Who cannot join
- History of gastrointestinal, endocrine, pulmonary, hepatic, renal, psychiatric, neurological, cardiovascular, hematological, and metabolic (including known diabetes mellitus) disease or disorder considered as significant by the Investigator.
- History of any cancer, lymphoma, or leukemia, except basal cell carcinoma of skin after localized cancer is removed.
- History or current clinically significant atopic allergy, hypersensitivity or allergic reactions including known or suspected clinically relevant drug hypersensitivity to any component of the study drug formulations or comparable drugs.
- Any disorder that, in the Investigator's opinion, may interfere with the safety of the subject and the study procedures and evaluations.
- Blood loss or blood donation (including blood components donation) ≥ 400 mL or blood transfusion within 3 months before screening; blood loss or blood donation (including blood components donation) ≥ 200 mL within 1 months before screening.
- Surgery within the past 8 weeks or surgery planned during the study duration.
Show all 28Show fewer
- Poor oral hygiene that may require surgical intervention during the study or any planned dental interventions during the study duration.
- Live virus vaccination within 4 weeks prior to screening or intention to receive live virus vaccination during the study until the final follow up visit.
- History of prior exposure to bevacizumab or any anti VEGF or anti VEGF receptor (VEGFR) monoclonal antibodies or proteins (e.g., aflibercept, ramucirumab, lapatinib, and sunitinib).
- Prior exposure to any other investigational monoclonal antibody within 12 months of study drug administration.
- Use of any investigational drug in any clinical study within the 3 months prior to first dose administration in this study; or remains on follow up of any clinical study.
- Any intake of a non steroidal anti inflammatory drug (NSAID) including any dose of aspirin in the last 14 days. NSAIDs are not allowed for the duration of the study. Paracetamol is allowed for pain control if required.
- Intake of prescribed or over the counter drugs within 28 days of study drug administration or herbal drugs or dietary supplements within 28 days prior to study drug administration.
- Any persons who are:
- An employee of the Principal Investigators, study centers, contract research organization (CRO) or the Sponsor.
- A relative of an employee of the study centers, the Investigators, CRO or the Sponsor.
- Abnormal ECG with clinical significance judged by the Investigator.
- Abnormal serum Immunoglobulin G with clinical significance judged by the Investigator.
- Confirmed positive ADA at screening.
- Occurrence of acute disease during screening or predose, e.g., acute hepatitis, acute diarrhea.
- Intake of any product containing alcohol within 24 hours of study drug administration.
- Subjects with relevant family history of hypertension or abnormal blood pressure at screening or admission to the study center (Day 1):
- Systolic blood pressure > 140 mmHg
- Diastolic blood pressure > 90 mmHg.
- Any inherited predisposition to bleeding or to thrombosis or history of non traumatic hemorrhage (i.e., requiring medical intervention), thromboembolic event or any condition which may increase bleeding risk including clotting disorders, thrombocytopenia (platelet count < 100000/µL) or an international normalized ratio (INR) higher than 1.5.
- Any clinically significant infection ongoing at screening or admission to the Phase I clinical trial unit.
- Total cholesterol > 1.5×upper limit of normal or fasting glucose abnormality with clinical significance at screening or admission.
- History of alcohol abuse or a positive alcohol breath test, history of drug abuse or positive urine drug screen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Double Blind, Intravenous, Single Dose, Parallel, 4-arm Comparative Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX04 Versus US-sourced Avastin®, EU-sourced Avastin®, and CN-sourced Avastin® in Healthy Male Subjects
This is a Phase I, randomized, double blind, IV, single dose, 4-arm parallel study to compare the PK, and to evaluate the safety, tolerability and immunogenicity of HLX04, US Avastin®, EU Avastin®, and CN Avastin® in healthy male subjects.
Read the detailed description
A total of 188 evaluable male subjects are required. Taking into account a dropout rate of approximately 10%, a total of 208 healthy male subjects who meet the required entry criteria will be randomly assigned to one of four treatment groups in a 1:1:1:1 ratio to receive a single IV infusion of HLX04, EU Avastin® or US Avastin®. The first 8 subjects (with at least 2 subjects receiving HLX04) will be dosed as a maximum of 1 subject per day. Prior to administration of study drug to the next subject, the safety findings of the preceding subject must be reviewed by the Principal Investigator. Each subject will be required to remain in the study center for 96 hours after dosing (overnight) for safety evaluation. After the first 8 subjects are evaluated and the experimental drug deemed safe, the Principal Investigator will decide the continuous enrollment in the four parallels according to the Phase I clinical trial unit capability.
The duration of participation for each subject is expected to be approximately120 days starting with a 21 day screening period, followed by administration of study drug and a 99 day follow up period.
After the follow up visit on Day 99, subjects who are confirmed positive for anti drug antibody (ADA) will be followed for 12 months after study drug administration or until 2 consecutive samples are tested negative for ADA.
The start of study is considered the date of the first subject providing informed consent and the end of study will be the last subject's last scheduled visit (Day 99 or early termination). Additional follow up visits for subjects who are positive for ADAs or have ongoing/resolving adverse events (AEs) will be conducted and recorded separately.
Subjects who meet all eligibility criteria and have signed the informed consent form (ICF) will be admitted to the Phase I clinical trial unit the day prior to dosing (Day 1) and will be discharged 96 hours postdose on Day 5. Then after, subjects will be followed up and continue participation in the study on an outpatient basis for further safety assessments, for blood sampling for PK and to test for ADA and neutralizing ADA (NADA) at selected visits.
- Conditions
- Healthy Male Subjects
- Being tested
- HLX04, US-Avastin®, EU-Avastin®, CN-Avastin®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLX04Drug
HLX04: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.
US-Avastin®Drug
US Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.
EU-Avastin®Drug
EU-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.
CN-Avastin®Drug
CN-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes.
| Study group | Role | What they receive |
|---|---|---|
| HLX04 | Experimental | Not described Receives: Drug: HLX04 |
| United States (US) Avastin® | Active comparator | Not described Receives: Drug: US-Avastin® |
| European Union (EU) Avastin® | Active comparator | Not described Receives: Drug: EU-Avastin® |
| China (CN) Avastin® | Active comparator | Not described Receives: Drug: CN-Avastin® |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC(0-t)
Area under the concentration time curve of the analyte in serum over the time interval from 0 to the last quantifiable concentration at time "t" [AUC(0-t)]
Measured: from 0 to day 99
AUC(0-∞)
Area under the concentration time curve of the analyte in serum over the time interval from 0 extrapolated to infinity [AUC(0-∞)]
Measured: from 0 to day 99
Secondary outcomes (9)
Cmax
Maximum measured concentration of the analyte in serum (Cmax)
Measured: from 0 to day 99
TEAE and SAE
Treatment emergent adverse events and serious adverse events
Measured: from 0 to day 99
tmax
- Time from dosing to maximum measured concentration (tmax)
Measured: from 0 to day 99
t1/2
- Terminal half life of the analyte in serum (t1/2)
Measured: from 0 to day 99
λz
- Terminal elimination rate constant (λz)
Measured: from 0 to day 99
CL
- Total clearance of the analyte in serum following IV infusion (CL)
Measured: from 0 to day 99
Vss
- Volume of distribution at steady state (Vss)
Measured: from 0 to day 99
Vz
- Volume of distribution during the terminal phase λz following an intravascular dose (Vz)
Measured: from 0 to day 99
Immunogenicity
Incidence of anti drug antibodies (ADAs), including neutralizing ADAs (NADAs)
Measured: from 0 to day 99
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2018
- Study start21 Apr 2017
- Primary completion29 Oct 2017
- Study completion29 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy Male SubjectsStudies of the same condition, open and under way.
- More trials run by Shanghai Henlius BiotechThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Henlius Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yanhua Ding, M.D., Principal investigator, The First Hospital of Jilin UniversityChen Yu, M.D., Principal investigator, Xuhui Central Hospital, Shanghai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03483649
- Sponsor's protocol ID
- HLX04 HV01
- Status last verified
- May 2022
- First submitted
- 30 Nov 2017
- Last updated
- 11 May 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zhu X, Qian H, Sun J, Wu M, Yu C, Ding Y, Zhang X, Chai K, Li X. A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers. Cancer Chemother Pharmacol. 2021 Sep;88(3):465-474. doi: 10.1007/s00280-021-04297-z. Epub 2021 Jun 4.
PubMed 34086067
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind, Intravenous, Single Dose, Parallel, 4-arm Comparative Pharmacokinetic, Safety and Immunogenicity Phase I Study of HLX04 Versus US-sourced Avastin®, EU-sourced Avastin®, and CN-sourced Avastin® in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03483649
- Acronym / sponsor ID
- HLX04 HV01
- Conditions
- Healthy Male Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- Shanghai Henlius BiotechIndustry (pharma, biotech, devices)
- Study start
- 21 Apr 2017 (actual)
- Primary completion
- 29 Oct 2017 (actual)
- Study completion
- 29 Oct 2017 (actual)
- First posted
- 30 Mar 2018 (actual)
- Results
- Not posted in the source record
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 Phase I, randomized, double blind, IV, single dose, 4-arm parallel study to compare the PK, and to evaluate the safety, tolerability and immunogenicity of HLX04, US Avastin®, EU Avastin®, and CN Avastin® in healthy male subjects.
Detailed description
A total of 188 evaluable male subjects are required. Taking into account a dropout rate of approximately 10%, a total of 208 healthy male subjects who meet the required entry criteria will be randomly assigned to one of four treatment groups in a 1:1:1:1 ratio to receive a single IV infusion of HLX04, EU Avastin® or US Avastin®. The first 8 subjects (with at least 2 subjects receiving HLX04) will be dosed as a maximum of 1 subject per day. Prior to administration of study drug to the next subject, the safety findings of the preceding subject must be reviewed by the Principal Investigator. Each subject will be required to remain in the study center for 96 hours after dosing (overnight) for safety evaluation. After the first 8 subjects are evaluated and the experimental drug deemed safe, the Principal Investigator will decide the continuous enrollment in the four parallels according to the Phase I clinical trial unit capability.
The duration of participation for each subject is expected to be approximately120 days starting with a 21 day screening period, followed by administration of study drug and a 99 day follow up period.
After the follow up visit on Day 99, subjects who are confirmed positive for anti drug antibody (ADA) will be followed for 12 months after study drug administration or until 2 consecutive samples are tested negative for ADA.
The start of study is considered the date of the first subject providing informed consent and the end of study will be the last subject's last scheduled visit (Day 99 or early termination). Additional follow up visits for subjects who are positive for ADAs or have ongoing/resolving adverse events (AEs) will be conducted and recorded separately.
Subjects who meet all eligibility criteria and have signed the informed consent form (ICF) will be admitted to the Phase I clinical trial unit the day prior to dosing (Day 1) and will be discharged 96 hours postdose on Day 5. Then after, subjects will be followed up and continue participation in the study on an outpatient basis for further safety assessments, for blood sampling for PK and to test for ADA and neutralizing ADA (NADA) at selected visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HLX04 | Experimental | Drug: HLX04 |
| United States (US) Avastin® | Active comparator | Drug: US-Avastin® |
| European Union (EU) Avastin® | Active comparator | Drug: EU-Avastin® |
| China (CN) Avastin® | Active comparator | Drug: CN-Avastin® |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subjects who are willing to comply with the contraception restrictions for this study (see Section 4.3.3).
- Subjects who are able and willing to give written informed consent.
- Subjects who are willing to comply with the study restrictions from screening until end of study.
- Adult males aged 18 to 50 years inclusive and between 19 and 26 kg/m2 body mass index and body weight ≥ 50 kg and ≤ 80 kg.
- Subjects who are non smokers or have not used tobacco or nicotine containing products for at least 3 months preceding screening and have less than 5 cigarettes per day smoking history. Subjects must agree to refrain from smoking during days of confinement at the study center.
Key exclusion criteria (28 listed)
- History of gastrointestinal, endocrine, pulmonary, hepatic, renal, psychiatric, neurological, cardiovascular, hematological, and metabolic (including known diabetes mellitus) disease or disorder considered as significant by the Investigator.
- History of any cancer, lymphoma, or leukemia, except basal cell carcinoma of skin after localized cancer is removed.
- History or current clinically significant atopic allergy, hypersensitivity or allergic reactions including known or suspected clinically relevant drug hypersensitivity to any component of the study drug formulations or comparable drugs.
- Any disorder that, in the Investigator's opinion, may interfere with the safety of the subject and the study procedures and evaluations.
- Blood loss or blood donation (including blood components donation) ≥ 400 mL or blood transfusion within 3 months before screening; blood loss or blood donation (including blood components donation) ≥ 200 mL within 1 months before screening.
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 |
|---|---|---|
| HLX04HLX04: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes. | Drug | HLX04 |
| US-Avastin®US Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes. | Drug | United States (US) Avastin® |
| EU-Avastin®EU-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes. | Drug | European Union (EU) Avastin® |
| CN-Avastin®CN-Avastin®: Supplied as 100 mg/4 mL solution; reconstituted to 100 mL with 0.9% sodium chloride; a single dose of 3 mg/kg will be administered intravenously for 90 minutes. | Drug | China (CN) Avastin® |
Primary outcome
AUC(0-t)
Time frame: from 0 to day 99
Area under the concentration time curve of the analyte in serum over the time interval from 0 to the last quantifiable concentration at time "t" [AUC(0-t)]
AUC(0-∞)
Time frame: from 0 to day 99
Area under the concentration time curve of the analyte in serum over the time interval from 0 extrapolated to infinity [AUC(0-∞)]
9 secondary outcomes
Cmax
Time frame: from 0 to day 99
TEAE and SAE
Time frame: from 0 to day 99
tmax
Time frame: from 0 to day 99
t1/2
Time frame: from 0 to day 99
λz
Time frame: from 0 to day 99
CL
Time frame: from 0 to day 99
Vss
Time frame: from 0 to day 99
Vz
Time frame: from 0 to day 99
Immunogenicity
Time frame: from 0 to day 99
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Derived from this study: PubMed 34086067Zhu X, Qian H, Sun J, Wu M, Yu C, Ding Y, Zhang X, Chai K, Li X. A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers. Cancer Chemother Pharmacol. 2021 Sep;88(3):465-474. doi: 10.1007/s00280-021-04297-z. Epub 2021 Jun 4.
- Related InfoLink provided by the sponsor.
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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.
Yanhua Ding, M.D. principal investigator
The First Hospital of Jilin University
Chen Yu, M.D. principal investigator
Xuhui Central Hospital, Shanghai
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 HLX04, US-Avastin® and EU-Avastin® in people with Healthy Male Subjects, run by Shanghai Henlius Biotech at 1 site in China.
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 28 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 11 May 2022. 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 China. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
AUC(0-t) (time frame: from 0 to day 99). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03483649, which also lists 1 linked publication.
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 11 May 2022.