EFFICACY OF KEDRAB

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.

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 8430
(100)
RVNA titer
No. of participants with RVNA titer ≥0.5 IU/mL at day 1428
(93.3)
Mean ± SD18.89 ± 31.61
Median8.81
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 

  
ParameterUnitsKEDRAB
(Test)
HRIG Comparator
(Reference)
Test/Reference
(%)
90% CI
(%)
Cmax IU/mL44.8736.02124.5990.62-171.28
AUC0-lastDay•IU/mL1741.401686.03103.2879.03-134.98
AUC0-infDay•IU/mL2045.871916.90106.7380.48-141.54

*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*

TreatmentCmax
(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*

 

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
  • 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*

TreatmentCmax
(IU/mL)
Tmax
(days)
AUCT
(days•IU/mL)
KEDRAB 20 IU/kg9.4
(10.72)
42
(42-42)
85.2
(92.2)
Saline Placebo24.0
(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*

Mean AUC1 for KEDRAB plus vaccination was significantly lower compared to placebo plus vaccine

*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

FDA-approval for use in children

KEDRAB–the Only HRIG With Established Safety and Effectiveness in Pediatric Patients1

All trademarks are property of their respective owners.

 

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.