CNJ-016 Injection
Name: CNJ-016 Injection
- CNJ-016 Injection 50 mg
- CNJ-016 Injection drug
- CNJ-016 Injection injection
- CNJ-016 Injection dosage
- CNJ-016 Injection action
Dosage Forms and Strengths
Drug Interactions
Live, Attenuated Vaccines
Immune globulin administration may impair the efficacy of live attenuated vaccines such as measles, rubella, mumps and varicella. Defer vaccination with live virus vaccines until approximately three months after administration of VIGIV. Revaccinate people who received VIGIV shortly after live virus vaccination three months after the administration of the VIGIV.
Drug/Laboratory Interactions
• VIGIV contains maltose, which can be misinterpreted as glucose by certain types of blood glucose testing systems (for example, those based on the GDH-PQQ or glucose-dye-oxidoreductase methods). Due to the potential for falsely elevated glucose readings, only testing systems that are glucose-specific should be used to test or monitor blood glucose levels in patients receiving VIGIV [see BOXED WARNING and 5.2 Interference with Blood Glucose Testing]. • Antibodies present in VIGIV may interfere with some serological tests. After administration of immune globulins like VIGIV, a transitory increase of passively transferred antibodies in the patient’s blood may result in positive results in serological testing (e.g. Coombs’ test) [see 5.5 Hemolysis].Use in specific populations
Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with VIGIV; therefore, it is not known whether VIGIV can cause fetal harm when administered to a pregnant woman or whether it can affect reproduction capacity. However, immune globulins have been widely used during pregnancy for many years without any apparent negative reproductive effects (4). The risk/benefit of VIGIV administration should be assessed for each individual case.
Nursing Mothers
It is not known whether VIGIV is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VIGIV is administered to a nursing mother.
Pediatric Use
Safety and effectiveness in the pediatric population (<16 yrs of age) has not been established for VIGIV.
Geriatric Use
Safety and effectiveness in the geriatric population (>65 yrs of age) has not been established for VIGIV.
Renal Insufficiency
Use VIGIV with caution in patients with pre-existing renal insufficiency and in patients at increased risk of developing renal insufficiency [see 5.8 Acute Renal Dysfunction/Failure].
CNJ-016 Injection - Clinical Pharmacology
Mechanism of Action
VIGIV provides passive immunity for individuals with complications to vaccinia virus vaccination. The exact mechanism of action is not known.
Pharmacodynamics
Two phase 2, double-blind pharmacodynamic studies were conducted in which 82 healthy volunteers were randomized to receive vaccinia vaccination with or without VIGIV.
In the first study, the efficacy of 9,000 Units per kg of VIGIV on the immunologic and local response to Dryvax was evaluated. A total of 32 healthy subjects were randomized to receive single IV infusions of either VIGIV (9,000 Units per kg) or Placebo (0.9% Sodium Chloride Injection USP) on Day 0, and either Placebo or VIGIV (9,000 Units per kg) concurrently with vaccinia (Dryvax) vaccination on Day 4.
In a second study, 50 healthy subjects were randomized to receive a single IV infusion of either VIGIV (9,000 Units per kg), VIGIV (24,000 Units per kg), or Placebo (0.9% Sodium Chloride Injection USP) on Day 0, and either placebo or vaccinia (Dryvax) vaccination on Day 4.
The effect of VIGIV on the immunologic response to Dryvax was determined by measuring vaccinia antibody titer (vaccinia IgG) in plasma and comparing titer levels across all three treatment arms. In addition, the effect of VIGIV on the local response (tissue) to Dryvax was assessed by evaluating the size of the pox reaction, as well as the area of erythema and induration following vaccination.
VIGIV (9,000 Units per kg and 24,000 Units per kg) reduced the local and immunological response to vaccinia vaccination when it was administered 4 days prior to vaccination compared to vaccination alone. This is consistent with the hypothesis that VIGIV can neutralize vaccinia virus in vivo [see 14 CLINICAL STUDIES]. In addition, infusions of VIGIV of up to 24,000 Units per kg were well tolerated [see 6.1 Clinical Trials Experience].
Pharmacokinetics
A phase 1, double-blind study was conducted in which 60 healthy subjects were randomized to receive either 6,000 Units per kg or 9,000 Units per kg VIGIV. After intravenous administration of 6,000 Units per kg to 31 healthy subjects, a mean peak plasma concentration of 161 Units per mL was achieved within 2 hours. The half-life of VIGIV was 30 days (range of 13 to 67 days) and the volume of distribution was 6630 mL. Pharmacokinetic parameters were calculated based on antibody levels determined by an ELISA.
The levels of vaccinia immune globulin remained in circulation for a prolonged period of time, with a mean half-life ranging from approximately 26 to 30 days. Maximum plasma concentrations (Cmax) of VIGIV reached levels ranging from approximately 160 to 232 Units per mL in 1.8 to 2.6 hours. In addition, the drug had a large volume of distribution, as demonstrated by both non-compartmental and compartmental analyses.
Non-compartmental analyses demonstrated that at the two dose levels studied, the drug exhibited dose-proportionality (AUC and Cmax values) (Table 3). The pharmacokinetic parameters estimated by compartmental analysis were similar to those calculated by non-compartmental methods.
| VIGIV (6,000 U/kg or 9,000 U/kg) from Measured Data | ||
| Parameter | 6,000 U/kg | 9,000 U/kg |
| AUC0 - ∞ (U*h/mL) | 58521 (16079) | 78401 (17502) |
| AUC0-t (U*h/mL) | 49405 (13246) | 71541 (13173) |
| CMAX (U/mL) | 161 (40.0) | 232 (40.9) |
| TMAX (h) | 1.84 (1.12) | 2.61 (2.41) |
| T½ (days) | 30.0 (10.0) | 26.2 (5.08) |
The plasma concentration of circulating VIGIV was also compared to a theoretical value obtained from a model of previously licensed Baxter Vaccinia Immune Globulin (VIG) product at day 5 after IV administration of VIGIV. Since Baxter VIG was administered IM and VIGIV is to be administered IV, the comparison was made at approximately five days to account for equilibration between the extravascular and intravascular compartments following IM injection.
The binding capacity and neutralizing antibody activity of anti-vaccinia antibody in these subjects five days after intravenous administration of VIGIV (both 6,000 Units per kg and 9,000 Units per kg dosages) were at least as high as the theoretical values that would be achieved following the intramuscular administration of the comparator VIG (see Table 4). Five days represents the approximate time of peak serum anti-vaccinia antibody concentration following intramuscular administration of other Immune Globulin (Human) products. No historical pharmacokinetic data are available for the theoretical intramuscular comparator VIG.
| * geometric mean (range) † expressed as a percentage relative to the geometric mean of the simulated concentrations at Day 5 after 6,000 U/kg intramuscular administration ‡ observed levels § simulated levels | |||
| Dose VIGIV (U/kg) | Plasma Levels, U/mL (Range*) | Ratio of Means % (97.5% Lower Confidence Interval Bound)† | |
| VIGIV‡ | VIGIM§ | ||
| 6,000 | 60.1 | 66.2 | 90.82 |
| 9,000 | 90.3 | 64.8 | 139.40 |