KEDRAB® (Rabies Immune Globulin [Human]) Has Been Evaluated in 4 Clinical Studies. KEDRAB Is the Only Human Rabies Immune Globulin (HRIG) Option Studied for Use in Pediatric Patients.1
Click on the tabs below to view findings from each study.
- Study 004
(Pediatric patients) - Study 003
(Safety/Tolerability) - Study 23630
(PK of rabies antibodies) - Study 24061
(Interference of active antibodies)
A multi-center, open-label post-marketing study measured the safety and efficacy of KEDRAB in 30 pediatric patients (0.5-14.9 years of age) exposed or possibly exposed to rabies virus (patients were indicated for post-exposure prophylaxis and administered KEDRAB concurrently with a full course of active rabies vaccine). Subjects received KEDRAB 20 IU/kg, and as much of the dose as anatomically feasible was infiltrated into and around the wound site when detectable. The remaining amount was injected intramuscularly.1
Efficacy Results
93.3% of subjects had Day 14 RVNA titers ≥0.5 IU/mL1,2 |
|
|---|---|
| Participants free of active rabies infection, no. (%) | |
| At day 14 | 30 (100) |
| At day 84 | 30 (100) |
| RVNA titer | |
| No. of participants with RVNA titer ≥0.5 IU/mL at day 14 | 28 (93.3) |
| Mean ± SD | 18.89 ± 31.61 |
| Median | 8.81 |
| Range (min – max) | 0.21–153.62 |
Percentages are based on the number of participants in the as-treated population. RVNA titers denote the geometric mean of the results per participant per visit.
min – max, minimum to maximum; RVNA, rabies virus neutralizing antibody; SD, standard deviation.
- No subject developed rabies infection through Day 841
REAL-WORLD EVIDENCE IN THE US1
Between 2018-2021, no rabies cases in children treated with KEDRAB*
*Based on the Centers for Disease Control and Prevention data, no children in the US treated with KEDRAB as part of PEP have been reported to have had rabies.
A phase 2/3, single-center, prospective, randomized, double-blind, parallel-group study evaluating the safety and effectiveness of KEDRAB vs HRIG Comparator when coadministered with rabies vaccine (RabAvert®) in 118 adult subjects.1
Study subjects were healthy adults 18 to 72 years of age who were without significant acute or chronic illness. Participants were predominantly white (93%) and 64% were women.
Study objectives3:
- Evaluate the safety and tolerability of KEDRAB vs HRIG Comparator
- Determine whether KEDRAB interferes with the development of active anti-rabies antibodies when given simultaneously with active rabies vaccine, as compared to HRIG Comparator, also given simultaneously with the active rabies vaccine
Efficacy Results
Subjects With Mean Anti-Rabies Antibody Titer ≥0.5 IU/mL on Day 141* |
||
|---|---|---|
| KEDRAB With Rabies Vaccine (N=57) | HRIG Comparator With Rabies Vaccine (N=59) |
|
| Rabies virus neutralizing antibody titer ≥0.5 IU/mL, n (%) | 56 (98.2) | 59 (100) |
| 95% CI for proportion (%) | (90.6, 100) | (93.9, 100) |
| Difference (KEDRAB – HRIG Comparator) (%) | -1.8 |
|
| 90% CI for difference† (%) | (-8.1, 3.0) |
|
*Adapted from KEDRAB Prescribing Information.1
†Based on Farrington-Manning score statistic.
CI, confidence interval.
- 98.2% of subjects in the KEDRAB group and all subjects in the HRIG Comparator group had an anti-rabies antibody titer by rapid fluorescent focus inhibition test of ≥0.5 IU/mL on day 141
Mean (+SD) Plasma HRIG Concentrations for KEDRAB and HRIG Comparator1*
- No statistically significant differences in plasma antibody titer pharmacokinetic (PK) parameters (Cmax, AUC0-last, or AUC0-inf) between treatment groups3
- However, the geometric mean RVNA titer on the Day 3 visit was statistically significantly lower with KEDRAB than with HRIG Comparator (P=0.0003)3
PK Comparison of Rabies Virus Neutralizing Antibody Between KEDRAB and HRIG Comparator Administered With Rabies Vaccine1
Geometric LS Mean Values | |||||
|---|---|---|---|---|---|
| Parameter | Units | KEDRAB (Test) | HRIG Comparator (Reference) | Test/Reference (%) | 90% CI (%) |
| Cmax | IU/mL | 44.87 | 36.02 | 124.59 | 90.62-171.28 |
| AUC0-last | Day•IU/mL | 1741.40 | 1686.03 | 103.28 | 79.03-134.98 |
| AUC0-inf | Day•IU/mL | 2045.87 | 1916.90 | 106.73 | 80.48-141.54 |
*Adapted from KEDRAB Prescribing Information.1
AUC, area under the concentration-time curve; CI, confidence interval; Cmax, maximum concentration; inf, infinity.
KEDRAB is non-inferior to HRIG Comparator when administered in combination with a rabies vaccine for post-exposure prophylaxis1
A phase 1, randomized, single-dose, double-blind, 2-period, crossover pharmacokinetic (PK) study compared KEDRAB with HRIG Comparator in 26 subjects between 18 and 45 years of age4
Study objectives4:
- Evaluate the PK of rabies antibodies in subjects receiving KEDRAB (who have not previously received rabies vaccination)
- Monitor any adverse events following administration of a single intramuscular (IM) injection of KEDRAB
- No clinically meaningful conclusions to be made with regard to AEs, laboratory values, or vital signs
PK Results
Median Anti-Rabies Antibody Titer PK Findings for Each Dose Administered4* |
|||||
|---|---|---|---|---|---|
| Treatment | Cmax† (IU/mL) | Tmax (days) | AUCT (days•IU/mL) | AUCI (days•IU/mL) | t1/2 (days) |
| KEDRAB
20 IU/kg | 0.249 (0.063) | 7.0
(3 – 14) | 5.2 (1.3) | 6.7 (1.27) | 17.9 (6.37) |
| HRIG Comparator
20 IU/kg | 0.302 (0.068) | 3.0
(3 – 14) | 6.3 (1.24) | 8.0 (1.36) | 17.8 (6.74) |
*Adapted from Data on file, Kamada Ltd.4
†Represents the average of Cmax and t1/2 obtained during the entire study.
All values in parentheses are mean and standard deviation except Tmax which is median (range).
AUC, area under the concentration-time curve; Cmax, maximum concentration; IM, intramuscular; t1/2, terminal elimination half-life; Tmax, time to maximum concentration.
Mean Plasma Anti-Rabies Antibody Titer vs Time Profile (Log Scale Following Administration of IM KEDRAB 20 IU/kg or IM HRIG Comparator 20 IU/kg)4*
*Adapted from Data on file, Kamada Ltd.4
IM, intramuscular
IM, intramuscular
- The point estimate for the ratio of anti-rabies antibody titer AUCI values of KEDRAB and HRIG Comparator was 84.4 (90% CI, 78.6%-90.7%)4
- There was no statistically significant difference (P=0.4491) in anti-rabies antibody titer Tmax values between KEDRAB and HRIG Comparator4
- There was a marginally statistically significant sequence effect seen for Cmax (P=0.042) and AUCT (P=0.033). While the latter point indicates a slight difference between the 2 products, it is apparently due to a treatment-by-period interaction.4
Overall, plasma anti-rabies antibody titers achieved with KEDRAB were comparable with HRIG Comparator4
A phase 1, double-blind, one-period, single-dose pharmacokinetic (PK) study evaluated KEDRAB when administered with 3 doses of rabies vaccine (Rabipur®) in 16 subjects between 18 and 45 years of age4
Study objectives4:
- Assess whether KEDRAB interfered with the development of antibodies when given simultaneously with rabies vaccine (Rabipur®)
- Monitor any adverse events following coadministration of a single IM injection of KEDRAB and repeated injections of an active rabies vaccine
PK Results
Median Anti-Rabies Antibody Titer PK Findings for Each Dose Administered4* |
|||
|---|---|---|---|
| Treatment | Cmax (IU/mL) | Tmax (days) | AUCT (days•IU/mL) |
| KEDRAB 20 IU/kg | 9.4 (10.72) | 42 (42-42) | 85.2 (92.2) |
| Saline Placebo | 24.0 (21.1) | 42 (14-42) | 276.3 (204.7) |
*Adapted from Data on file, Kamada Ltd.4
All values in parentheses are mean and standard deviation except Tmax which is median (range).
AUCT, area under the concentration-time curve; Cmax, maximum concentration; Tmax, time to maximum concentration.
- The Cmax for rabies antibodies for KEDRAB plus vaccine appeared to be substantially lower compared to placebo plus vaccine (42.9%)4
- No statistically significant difference could be determined between Cmax from the test and placebo formulation due to a high degree of variability in the data4
Mean Plasma Anti-Rabies Antibody Titer vs Time Profile (Semi-Log Scale) Following Administration of IM KEDRAB 20 IU/kg or Saline With 3 Doses of Rabipur®4*
*Adapted from Data on file, Kamada Ltd.4
- The mean AUC1 for KEDRAB plus vaccination was statistically significantly lower compared to placebo plus vaccine4
KEDRAB inhibited rabies antibody production following immunization with a rabies vaccine (Rabipur®)4
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References: 1. KEDRAB [package insert]. Fort Lee, NJ: Kedrion Biopharma Inc.; 2021. 2. Hobart-Porter N, Stein M, et al. Safety and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure [published online ahead of print, 2021 Feb 9]. Hum Vaccin Immunother. 2021;1-7. doi:10.1080/21645515.2020.1854000. 3. Matson MA, Schenker E, Stein M, Zamfirova V, Nguyen H, Bergman GE. Safety and efficacy results of simulated post-exposure prophylaxis with human immune globulin (HRIG; KEDRAB) co-administered with active vaccine in healthy subjects: a comparative phase 2/3 trial. Hum Vaccin Immunother. 2020;16(2);452-459. doi:10.1080/21645515.2019.1656967. 4. Data on file. Kamada Ltd.