Healthy Volunteers
Conditions
Keywords
randomized, double-blind
Brief summary
The purpose of this study is to compare the pharmacokinetics, as well as to evaluate the safety, tolerability and immunogenicity of HD204, US-Avastin and EU-Avastin in healthy male subjects after intravenous administration of a single dose..
Detailed description
This is a double-blind, randomized, three-arm, parallel-group, single-dose study. A total of 120 evaluable subjects are required.
Interventions
DRUGHD204
Single-Dose 1mg/kg body weight by 90 minute intravenous infusion
DRUGAvastin
Single-Dose 1mg/kg body weight by 90 minute intravenous infusion
Sponsors
Prestige Biopharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-smoking healthy male subjects, 18-50 years old inclusive * Body Mass index is between 19 to 30 kg/m2, inclusive * NO history of hypersensitivity or allergic reaction to the active ingredient, murine proteins, or excipients, spontaneous or following drug administration. * For subjects with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the end of study. Adequate contraception is defined as the usage by the female partner of any form of hormonal contraception or intra-uterine device (which should be established prior to the start of study) plus usage by one of the partners of an additional spermicide-containing barrier method of contraception. The use of a barrier method alone or reliance on abstinence is not considered adequate. * Subjects must agree not to donate sperm during the study and for 4 months following treatment with the study medication or until scheduled End Of Study (EOS), whichever is longer. * Subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent.
Exclusion criteria
* Clinically significant abnormalities in physical examination, laboratory test results or electrocardiogram (ECG) * Systolic blood pressure \> 140 mmHg or \< 90 mmHg , or diastolic blood pressure \> 90 mmHg or \<50 mmHg * Proteinuria (with a urine dipstick value of 2+ or above) * Coagulation abnormalities ( i.e., INR \> 2x ULN) * Bleeding diathesis, history of duodenal ulcers, concomitant use of anticoagulants, or any hemorrhage within 6 months prior to study enrollment. * Surgical procedure within 2 months of screening, or planned surgical procedure within 2 months of EOS * Positive test result for drugs of abuse or alcohol breathing test. * Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 or 2. * Donated or lost \> 500ml of blood in the previous 3 months * Taken an investigational drug within 3 months (or 5 half-lives), whichever is longer. * Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug or non-prescription drugs (with the exception of paracetamol, which is allowed). * Previously received bevacizumab or any product considered to be biosimilar to bevacizumab, or any other antibody or protein targeting VEGF or VEGFR. * Unwillingness or inability to comply with the study protocol for any reason. * Male subject whose partner is pregnant. * History or evidence of a clinically significant disorder (including cardiovascular, cerebrovascular, endocrine or psychiatric), or immunocompromised condition, or disease that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * History of alcohol and/or drug abuse within 12 months of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bevacizumab PK Parameter (AUC0-inf) | 71 Days | PK blood samples were collected from subjects to determine the AUC0-inf of bevacizumab. Samples were collected from 0 (pre-dose) to 1680 (post-dose) on days 1-74. |
| Serum Concentration of Bevacizumab (AUC0-last) | 71 days | PK blood samples were collected from subjects to determine the serum concentration of bevacizumab to evaluate the PK similarity across the three study drugs. |
| Serum Concentration of Bevacizumab (Cmax) | 71 days | PK blood samples were collected from subjects to determine the serum concentration of bevacizumab to evaluate the PK similarity across the three study drugs. |
Countries
New Zealand
Participant flow
Recruitment details
Healthy subjects, recruited from the IQVIA panel of volunteers, were included in this study.
Pre-assignment details
Each subject was randomly assigned to 1 of 3 treatment groups in a 1:1:1 ratio to receive a single IV infusion of 1 mg/kg of either HD204, EU-Avastin, or US-Avastin.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 25.0 Years |
| Race/Ethnicity, Customized Asian | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific | 0 Participants |
| Race/Ethnicity, Customized Other | 10 Participants |
| Race/Ethnicity, Customized White | 26 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 31 / 40 | 31 / 40 | 34 / 39 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 39 |
Outcome results
None listed