Healthy
Conditions
Brief summary
To investigate the safety/tolerability and pharmacokinetic characteristics after single intravenous (IV) administration of hzVSF-v13 (humanized Virus Suppressing Factor-variant 13) in healthy male volunteers
Detailed description
Dose blocked-randomized, double-blind, placebo controlled, single dose, dose-escalation study to investigate the safety/tolerability and pharmacokinetic characteristics of hzVSF-v13 after IV administration in healthy male volunteers
Interventions
DRUGhzVSF-v13
Dosage form: 10mg / 20mg / 50mg / 100mg / 200mg / 400mg / 800mg / 1200mg of hzVSF-v13 (40 mg/mL in a 5 mL vial) Frequency: Dose at Day 1 (single administration)
DRUGPlacebo
Dosage form: 0.9% NaCl Solution Frequency: Dose at Day 1 (single administration)
Sponsors
ImmuneMed, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males aged 19 to 45 years at the time of the screening visit * Individuals with a BMI of at least 18 kg/m2 and up to 27.0 kg/m2 weighed more than 55 kg and less than 90 kg at the time of the screening visit * Individuals deemed clinically healthy based on medical history, physical examination, vital signs, electrocardiography (ECG), and appropriate clinical laboratory tests (provided that individuals outside the normal range may participate subject to investigator discretion) * Individuals who have agreed to use a medically acceptable method of dual contraception and not to donate sperm from the first day until 30 days after the last day of investigational product administration * Individuals who have voluntarily decided to participate in this clinical study and have given written consent to comply with the requirements of the study
Exclusion criteria
* Individuals with a clinically significant hepatic, renal, digestive, respiratory, musculoskeletal, endocrine, neurologic, psychological, hematologic, oncologic, cardiovascular, or other disease or history * Individuals with a clinically significant history of sensitivity to the components of hzVSF-v13, drugs containing components of the same series, or other drugs (aspirin, non-steroidal anti-inflammatory drugs, antibiotics, etc.) * Individuals testing positive in the immunogenicity test for hzVSF-v13 conducted during screening * Individuals who have a history of drug abuse, or who turns out positive in test for abuse-likely drugs in the urine drug screening test * Individuals with abnormal results for any of the following vital signs at the time of the screening visit A. Systolic blood pressure: \< 90 mmHg or \> 140 mmHg B. Diastolic blood pressure: \< 50 mmHg or \> 90 mmHg C. Heart rate: \< 50 bpm or \> 90 bpm * Individuals with abnormal results for any of the following ECG items at the time of the screening visit A. PR (Pulse rate): \> 210 msec B. QRS complex : \> 120 msec \* QRS complex is the name for the combination of three of the graphical deflections seen on a typical electrocardiogram (EKG or ECG) C. QTc (Corrected QT interval): \> 450 msec * Individuals who have participated in another clinical study or bioequivalence study in the 3 months prior to the first day of administration * Individuals who have donated whole blood within the 2 months prior to the first day of administration, or donated blood components or received blood within the 1 month prior to the first day of administration * Individuals who have taken barbitals or other drug-metabolizing enzyme inducers or inhibitors within the 1 month prior to screening * Individuals who have consumed grapefruit or caffeine-containing foods within 3 days of the first administration, and individuals who are unable to avoid consuming grapefruit-containing foods from 3 days prior to admission until the date of discharge * Individuals who have taken prescription drugs or oriental medications within 2 weeks prior to the first day of administration, or who have taken over-the-counter (OTC) drugs within the 1 week prior to the first day of administration (provided that individuals who meet other requirements may participate in the clinical study subject to investigator discretion) * Individuals who consume high amounts of caffeine or alcohol and individuals who are heavy smokers (caffeine \> 5 units/day, alcohol \> 21 units/week (1 unit = 10 mL of pure alcohol), smoking \> 10 cigarettes/day) * Individuals who are unable to eat meals provided by the institution * Individuals who have participated in the present study * Individuals who test positive (for hepatitis B, human immunodeficiency virus (HIV), hepatitis C) on serological testing * Individuals with veins that are not suitable for intravenous catheter insertion or multiple venipunctures * Individuals who do not agree to use a medically acceptable method of dual contraception from the first day until 30 days after the last day of investigational product administration * Other individuals deemed unsuitable as a subject by an investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Assessments by Vital Signs | 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose) | Systolic Blood Pressure: ≤ 90 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 140 mmHg and increase from baseline ≥ 20 mmHg Diastolic Blood Pressure: ≤ 50 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 90 mmHg and increase from baseline ≥ 10 mmHg Heart Rate: ≤ 40 beats/min and decrease from baseline ≥ 20 beats/min, ≥ 100 beats/min and increase from baseline ≥ 20 beats/min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose) | Maximum observed Concentration of hzVSF-v13 from Day1 to Day92. |
| PK - AUClast (Area Under the Curve Last) | 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose) | Area under the plasma concentration from Day1 to time of last measurable concentration. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (hzVSF-v13 10mg) Group 1 received a single 10mg dose of hzVSF-v13 on Day 1. | 3 |
| Group 2 (hzVSF-v13 20mg) Group 2 received a single 20mg dose of hzVSF-v13 on Day 1. | 3 |
| Group 3 (hzVSF-v13 50mg) Group 3 received a single 50mg dose of hzVSF-v13 on Day 1. | 6 |
| Group 4 (hzVSF-v13 100mg) Group 4 received a single 100mg dose of hzVSF-v13 on Day 1. | 6 |
| Group 5 (hzVSF-v13 200mg) Group 5 received a single 200mg dose of hzVSF-v13 on Day 1. | 6 |
| Group 6 (hzVSF-v13 400mg) Group 6 received a single 400mg dose of hzVSF-v13 on Day 1. | 6 |
| Group 7 (hzVSF-v13 800mg) Group 7 received a single 800mg dose of hzVSF-v13 on Day 1. | 6 |
| Group 8 (hzVSF-v13 1200mg) Group 8 received a single 1200mg dose of hzVSF-v13 on Day 1. | 6 |
| Placebo Placebo group received a single placebo on Day 1. | 14 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Group 3 (hzVSF-v13 50mg) | Group 4 (hzVSF-v13 100mg) | Group 2 (hzVSF-v13 20mg) | Group 5 (hzVSF-v13 200mg) | Group 6 (hzVSF-v13 400mg) | Group 7 (hzVSF-v13 800mg) | Group 8 (hzVSF-v13 1200mg) | Group 1 (hzVSF-v13 10mg) | Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 14 Participants |
| Age, Continuous | 32.3 years STANDARD_DEVIATION 5.9 | 32.8 years STANDARD_DEVIATION 5.6 | 31.8 years STANDARD_DEVIATION 4.5 | 32.0 years STANDARD_DEVIATION 6.6 | 30.3 years STANDARD_DEVIATION 7.2 | 27.8 years STANDARD_DEVIATION 4.9 | 35.5 years STANDARD_DEVIATION 5.5 | 32.3 years STANDARD_DEVIATION 5.9 | 34.7 years STANDARD_DEVIATION 6.7 | 33.4 years STANDARD_DEVIATION 6.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 56 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 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 | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Korea | 56 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 56 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 14 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 |
Outcome results
Primary
Safety and Tolerability Assessments by Vital Signs
Systolic Blood Pressure: ≤ 90 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 140 mmHg and increase from baseline ≥ 20 mmHg Diastolic Blood Pressure: ≤ 50 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 90 mmHg and increase from baseline ≥ 10 mmHg Heart Rate: ≤ 40 beats/min and decrease from baseline ≥ 20 beats/min, ≥ 100 beats/min and increase from baseline ≥ 20 beats/min
Time frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (hzVSF-v13 10mg) | Safety and Tolerability Assessments by Vital Signs | 3 Participants |
| Group 2 (hzVSF-v13 20mg) | Safety and Tolerability Assessments by Vital Signs | 3 Participants |
| Group 3 (hzVSF-v13 50mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Group 4 (hzVSF-v13 100mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Group 5 (hzVSF-v13 200mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Group 6 (hzVSF-v13 400mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Group 7 (hzVSF-v13 800mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Group 8 (hzVSF-v13 1200mg) | Safety and Tolerability Assessments by Vital Signs | 6 Participants |
| Placebo | Safety and Tolerability Assessments by Vital Signs | 13 Participants |
Secondary
Pharmacokinetic Characteristics - Cmax (Concentration Maximum)
Maximum observed Concentration of hzVSF-v13 from Day1 to Day92.
Time frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose)
Population: Placebo group were not included in pharmacokinetic analysis set as the it was below the quantification limit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (hzVSF-v13 10mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 1.77 mg/L | Standard Deviation 0.47 |
| Group 2 (hzVSF-v13 20mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 4.38 mg/L | Standard Deviation 1.31 |
| Group 3 (hzVSF-v13 50mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 14.04 mg/L | Standard Deviation 2.35 |
| Group 4 (hzVSF-v13 100mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 27.26 mg/L | Standard Deviation 5.82 |
| Group 5 (hzVSF-v13 200mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 45.39 mg/L | Standard Deviation 7.43 |
| Group 6 (hzVSF-v13 400mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 99.00 mg/L | Standard Deviation 14.07 |
| Group 7 (hzVSF-v13 800mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 174.43 mg/L | Standard Deviation 26.66 |
| Group 8 (hzVSF-v13 1200mg) | Pharmacokinetic Characteristics - Cmax (Concentration Maximum) | 268.09 mg/L | Standard Deviation 28.07 |
p-value: 0.1075Kruskal-Wallis
Secondary
PK - AUClast (Area Under the Curve Last)
Area under the plasma concentration from Day1 to time of last measurable concentration.
Time frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose)
Population: Placebo group were not included in pharmacokinetic analysis set as the it was below the quantification limit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (hzVSF-v13 10mg) | PK - AUClast (Area Under the Curve Last) | 176.74 h·mg/L | Standard Deviation 35.76 |
| Group 2 (hzVSF-v13 20mg) | PK - AUClast (Area Under the Curve Last) | 1264.31 h·mg/L | Standard Deviation 315.53 |
| Group 3 (hzVSF-v13 50mg) | PK - AUClast (Area Under the Curve Last) | 4554.13 h·mg/L | Standard Deviation 1143.05 |
| Group 4 (hzVSF-v13 100mg) | PK - AUClast (Area Under the Curve Last) | 8226.23 h·mg/L | Standard Deviation 2766.32 |
| Group 5 (hzVSF-v13 200mg) | PK - AUClast (Area Under the Curve Last) | 17386.38 h·mg/L | Standard Deviation 5362.11 |
| Group 6 (hzVSF-v13 400mg) | PK - AUClast (Area Under the Curve Last) | 39032.00 h·mg/L | Standard Deviation 7672.94 |
| Group 7 (hzVSF-v13 800mg) | PK - AUClast (Area Under the Curve Last) | 80395.46 h·mg/L | Standard Deviation 9269.87 |
| Group 8 (hzVSF-v13 1200mg) | PK - AUClast (Area Under the Curve Last) | 102677.10 h·mg/L | Standard Deviation 25759.47 |
p-value: 0.0548Kruskal-Wallis