Ascites Hepatic
Conditions
Keywords
OsrHSA
Brief summary
A Phase 1 randomized, double blinded, placebo-controlled single dose escalation study of OsrHSA in adult healthy male and female volunteers
Detailed description
This is a Phase 1 randomized, double blinded, placebo-controlled, single dose escalation study to evaluate safety, tolerability, PK, and immunogenicity of OsrHSA in healthy volunteers.
Interventions
DRUGOsrHSA 20 mg/kg IV
A single dose of OsrHSA 20 mg/kg IV infusion at a rate lower than 2 ml/min
DRUGOsrHSA 40 mg/kg IV
A single dose of OsrHSA 40 mg/kg IV infusion at a rate lower than 2 ml/min
DRUGOsrHSA 80 mg/kg IV
A single dose of OsrHSA 80 mg/kg IV infusion at a rate lower than 2 ml/min
DRUGOsrHSA 140 mg/kg IV
A single dose of OsrHSA 140 mg/kg IV infusion at a rate lower than 2 ml/min
DRUGOsrHSA 200 mg/kg IV
A single dose of OsrHSA 200 mg/kg IV infusion at a rate lower than 2 ml/min
OTHERPlacebo
Normal Saline (0.9% Sodium Chloride)
Sponsors
Healthgen Biotechnology Corp.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a Phase 1 randomized, double blinded, placebo-controlled, single dose escalation study in healthy volunteers to evaluate safety, tolerability, PK, PD and immunogenicity of OsrHSA.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all the following criteria to be enrolled in the trial 1. Able to understand and willing to sign the ICF 2. Healthy male and female subjects, 18-55 years of age, non-smokers, or subjects must have been non-smoking for at least 3 months prior to their screening visit. 3. Has adequate venous access 4. With no significant medical history, and in good health as determined by detailed medical history (neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease), full physical examination,vital signs, 12-lead electrocardiogram (ECG), urinalysis and laboratory tests at screening. For eligibility purposes, abnormal laboratory or vital signs results may be repeated once if abnormal result is observed at the initial reading. Moreover, abnormalities found in the ECG may need to be confirmed by repeated measurements. 5. Subjects must have adequate organ function according to the following laboratory values: * Bone marrow function (absolute neutrophil count ≥1500/mm3 and platelet count ≥100,000/mm3) * Adequate liver function \[alanine aminotransferase (ALT) to ≤1.5× upper limit normal (ULN) and alkaline phosphatase to ≤1.5× ULN, total bilirubin ≤1.5 mg/dL\] * Adequate renal function creatinine clearance ≥60 mL/min based on Cockcroft- Gault equation, or serum creatinine level ≤1.5 times the ULN. 6. Be a female of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal and have an FSH \> 40mIU/mL, or surgically sterile \[defined as having a bilateral oophorectomy, hysterectomy or tubal ligation\]) or agree to one of the following to prevent pregnancy and, if a woman of childbearing potential, have a negative urine pregnancy test at screening: * Practicing abstinence * If a sexually active woman of childbearing potential (sexually active with a non-sterile male partner) agrees to prevent pregnancy by using double methods of contraception as follow until at least 30 days after the administration of the investigational product: 1. simultaneous use of intra-uterine contraceptive device, placed at least 4 weeks prior to study drug administration, and condom for the male partner; 2. simultaneous use of hormonal contraceptives, starting at least 4 weeks prior to study drug administration and must agree to use the same hormonal contraceptive throughout the study, and condom for the male partner; 3. simultaneous use of diaphragm with intravaginally applied spermicide and male condom for the male partner, starting at least 21 days prior to study drug administration. * Male subjects who are not vasectomized for at least 6 months and who are sexually active with a non-sterile female partner must agree to use double methods of contraception below from the first dose of randomized study drug until 90 days after their dose and must not donate sperm during their study participation period: 1. Simultaneous use of a male condom and, for the female partner, hormonal contraceptives (used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 4 weeks); 2. Simultaneous use of a male condom and, for the female partner, a diaphragm with intravaginally applied spermicide. 7. Body mass index (BMI) 18-30 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females. 8. Blood pressure ≤ 139/89 mm Hg. 9. Subjects are able to follow the study protocol and complete the trial. 10. At least 25% of the enrolled subjects will be of Asian descent, defined as Chinese, Japanese, Korean, Vietnamese, Hmong, and their offspring.
Exclusion criteria
Subjects who meet any of the following criteria cannot be enrolled: 1. History of severe infection within 4 weeks to dosing. 2. Signs and symptoms of any active infection regardless of severity within 2 weeks prior to dosing. 3. Meals & Dietary Restrictions: No seafood or high-fat food will be served during confinement in the clinical center 4. Subjects who have any history of allergy to food or drug will be excluded ( Including allergies, hypersensitivity, or intolerance to rice or rice products ) 5. Use of any prescription drugs, herbal supplements, or nonprescription drugs including oral anti-histamines (for seasonal allergies) within 1 month or 5 half-lives (whichever is longer) prior to study drug administration, or dietary supplements within 1 week prior to study drug administration, unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with the study. Over-the-counter multivitamins will be permitted. If needed, paracetamol/acetaminophen may be used, but must be documented in the Concomitant medications/Significant non-drug therapies page of the source data. Any questions of concomitant medications should be directed to the Sponsor. 6. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration. 7. Donation of blood 12 week prior to dosing. 8. Pregnant, or nursing females. 9. A history of substance abuse, psychiatric and psychological condition that, in the judgment of the investigator, may interfere with the planned treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications 10. A history of severe allergic reaction to any HpHSA component. 11. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval \>450 milliseconds \[ms\]) 12. History of or active obstructive disease in biliary tract, liver, kidney and spleen defined by ultrasound. 13. Subjects who test positive for hepatitis B or C. (no matter carriers or active will be excluded from the study 14. Subjects who test positive for Syphilis, Human immunodeficiency virus (HIV) positive will also be excluded from the study. 15. Immunization with a live or attenuated vaccine is prohibited within 4 weeks prior to study drug administration. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed) 16. Positive Ig E and Ig G against rice at screening 17. History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit (more than fourteen units of alcohol per week \[1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]) or positive alcohol breath test at screening 18. History of significant drug abuse within one year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening 19. Positive urine drug screen, cotinine test, or alcohol breath test at screening 20. Any reason which, in the opinion of the Qualified Investigator, would prevent the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-Emergent Adverse Events | from date of Informed Consent through Day 30 (Study Completion) |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration [Cmax] | pre-dose, 0.5 hours after dose initiating, EOI (End of Infusion), and 0.5 hours, 4 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), Day 5, Day 8, Day 15, Day 22, and Day 30 post End of Infusion. |
| Number of Participants With ADA Incident Events | pre-dose, Day 8, Day 15, Day 22, and Day 30 post End of Infusion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Normal Saline (0.9% Sodium Chloride) | 10 |
| OsrHSA 20 mg/kg IV OsrHSA 20 mg/kg IV: A single dose of OsrHSA 20 mg/kg IV infusion at a rate lower than 2 ml/min | 6 |
| OsrHSA 40 mg/kg IV OsrHSA 40 mg/kg IV: A single dose of OsrHSA 40 mg/kg IV infusion at a rate lower than 2 ml/min | 6 |
| OsrHSA 80 mg/kg IV OsrHSA 80 mg/kg IV: A single dose of OsrHSA 80 mg/kg IV infusion at a rate lower than 2 ml/min | 6 |
| OsrHSA 140 mg/kg IV OsrHSA 140 mg/kg IV: A single dose of OsrHSA 140 mg/kg IV infusion at a rate lower than 2 ml/min | 7 |
| OsrHSA 200 mg/kg IV OsrHSA 200 mg/kg IV: A single dose of OsrHSA 200 mg/kg IV infusion at a rate lower than 2 ml/min | 6 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | OsrHSA 20 mg/kg IV | OsrHSA 40 mg/kg IV | OsrHSA 80 mg/kg IV | OsrHSA 140 mg/kg IV | OsrHSA 200 mg/kg IV | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.0 years | 34.5 years | 33.5 years | 34.0 years | 37.0 years | 35.5 years | 35.0 years |
| BMI | 22.0 kg/m2 STANDARD_DEVIATION 3.16 | 24.4 kg/m2 STANDARD_DEVIATION 2.91 | 25.8 kg/m2 STANDARD_DEVIATION 2.46 | 24.0 kg/m2 STANDARD_DEVIATION 2.5 | 25.4 kg/m2 STANDARD_DEVIATION 4.58 | 23.9 kg/m2 STANDARD_DEVIATION 3.32 | 24.1 kg/m2 STANDARD_DEVIATION 3.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 3 Participants | 3 Participants | 5 Participants | 7 Participants | 4 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.5 Centimeter | 169.0 Centimeter | 161.4 Centimeter | 173.4 Centimeter STANDARD_DEVIATION 8.06 | 171.1 Centimeter | 165.8 Centimeter | 169.1 Centimeter |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 4 Participants | 1 Participants | 5 Participants | 4 Participants | 23 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 2 Participants | 18 Participants |
| Weight | 61.8 Kilograms STANDARD_DEVIATION 10.78 | 67.6 Kilograms STANDARD_DEVIATION 13.51 | 68.2 Kilograms STANDARD_DEVIATION 4.35 | 72.2 Kilograms STANDARD_DEVIATION 10.36 | 76.0 Kilograms STANDARD_DEVIATION 23.21 | 68.7 Kilograms STANDARD_DEVIATION 17.56 | 67.3 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 1 / 10 | 0 / 6 | 2 / 6 | 1 / 6 | 2 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events
Time frame: from date of Informed Consent through Day 30 (Study Completion)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Incidence of Treatment-Emergent Adverse Events | 1 Participants |
| OsrHSA 20 mg/kg IV | Incidence of Treatment-Emergent Adverse Events | 0 Participants |
| OsrHSA 40 mg/kg IV | Incidence of Treatment-Emergent Adverse Events | 2 Participants |
| OsrHSA 80 mg/kg IV | Incidence of Treatment-Emergent Adverse Events | 1 Participants |
| OsrHSA 140 mg/kg IV | Incidence of Treatment-Emergent Adverse Events | 2 Participants |
| OsrHSA 200 mg/kg IV | Incidence of Treatment-Emergent Adverse Events | 0 Participants |
Secondary
Maximum Plasma Concentration [Cmax]
Time frame: pre-dose, 0.5 hours after dose initiating, EOI (End of Infusion), and 0.5 hours, 4 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), Day 5, Day 8, Day 15, Day 22, and Day 30 post End of Infusion.
Secondary
Number of Participants With ADA Incident Events
Time frame: pre-dose, Day 8, Day 15, Day 22, and Day 30 post End of Infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With ADA Incident Events | 0 participants |
| OsrHSA 20 mg/kg IV | Number of Participants With ADA Incident Events | 0 participants |
| OsrHSA 40 mg/kg IV | Number of Participants With ADA Incident Events | 0 participants |
| OsrHSA 80 mg/kg IV | Number of Participants With ADA Incident Events | 0 participants |
| OsrHSA 140 mg/kg IV | Number of Participants With ADA Incident Events | 0 participants |
| OsrHSA 200 mg/kg IV | Number of Participants With ADA Incident Events | 0 participants |