92791
document
Evaluation of the safety , immunogenicity , and pharmacokinetic profile of a new , highly purified , heat-treated equine rabies immunoglobulin , administered either alone or in association with a purified , Vero-cell rabies vaccine . A clinical evaluation of a new , purified , heat-treated equine rabies immunoglobulin ( PHT-Erig ) , F ( ab ' ) 2 preparation , was carried out in Thailand and in the Philippines-two countries where rabies is endemic . An initial prospective , randomised , controlled trial ( Study 1 ) , compared the safety and pharmacokinetics ( serum concentrations of rabies antibodies ) after administration either of PHT-Erig or of a commercially-available , equine rabies immune globulin ( Erig PMC ) . A second trial ( Study 2 ) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine , the purified Vero-cell rabies vaccine ( PVRV ) , administered in association with either Erig PMC or PHT-Erig . In Study 1 , 27 healthy , Thai adults received a 40 IU kg ( -1 ) dose of either Erig PMC ( n = 12 ) or PHT-Erig ( n = 15 ) via the intramuscular ( i.m . ) route ; half of the dose was injected into the deltoid area and the other half into the buttocks . Serum for rabies antibody determination and F ( ab ' ) 2 concentration was collected at hours ( H ) 0 , 6 and 12 , and on day ( D ) 2 , 3 , 4 , 6 , 8 , 10 , 12 and 15 . Both products were safe , with no serious adverse events , and in particular , no anaphylactic reactions or serum sickness was reported . A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products . Nonetheless , the relative bioavailability of 93 % and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar . The antibody level in either group were low throughout the 15-day study period . The geometric mean titer ( GMT ) values ranged from group 0.027-0.117 IU ml ( -1 ) in the Erig group and from 0.029 to 0.072 IU ml ( -1 ) in the PHT-Erig . There was no significant difference between the evolution of GMT values for the two groups . In Study 2 , 71 healthy volunteers received 40 IU kg ( -1 ) via the intramuscular route of either Erig PMC ( n = 36 ) or PHT-Erig ( n = 35 ) on D0 , in association with five doses of PVRV on D0 , D3 , D7 , D14 and D28 . The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 ( before injection ) D3 , D7 , D14 and D28 . No serious reactions were reported in either group . In particular , no immediate ( anaphylactic type ) or delayed ( serum sickness ) allergic reactions were observed . Over the 28-day follow-up period , GMT profiles of the two groups were statistically equivalent . On D14 , 100 % of the subjects had protective antibody titers ( anti-rabies antibodies > or = 0.5 IU ml ( -1 ) , which is the WHO-recommended level of seroconversion ) , and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen . On D28 , the GMT values were 33.2 IU ml ( -1 ) ( 95 % CI , 23.8-46.1 IU ml ( -1 ) ) in the Erig PMC/PVRV group and 31.4 IU ml ( -1 ) ( 95 % confidence interval , CI , 23.4-42.2 IU ml ( -1 ) ) in the PHT-Erig/PVRV group , showing evidence of adequate vaccine-induced antibody responses in both groups . The increased purity , the heat-treatment step introduced in the manufacturing process of PHT-Erig , and the good clinical results substantiate the use of this new generation , purified equine F ( ab ' ) 2 preparation in the post-exposure prophylaxis of rabies .
92792
Intervention_Pharmacological
highly purified , heat-treated equine rabies immunoglobulin
92793
Intervention_Pharmacological
Vero-cell rabies vaccine .
92794
Intervention_Pharmacological
purified , heat-treated equine rabies immunoglobulin ( PHT-Erig )
92795
Intervention_Pharmacological
F ( ab ' ) 2 preparation
92796
Intervention_Pharmacological
PHT-Erig
92797
Intervention_Pharmacological
equine rabies immune globulin ( Erig PMC )
92798
Intervention_Pharmacological
purified Vero-cell rabies vaccine ( PVRV )
92799
Intervention_Pharmacological
Erig PMC
92800
Intervention_Pharmacological
PHT-Erig
92801
Intervention_Pharmacological
Erig PMC
92802
Intervention_Pharmacological
PHT-Erig
92803
Outcome_Physical
safety
92804
Outcome_Physical
immunogenicity
92805
Outcome_Physical
pharmacokinetic profile
92806
Outcome_Other
safety
92807
Outcome_Other
pharmacokinetics
92808
Outcome_Other
serum concentrations of rabies antibodies
92809
Outcome_Physical
pharmacokinetic parameters
92810
Outcome_Other
relative bioavailability
92811
Outcome_Physical
absorption rates
92812
Outcome_Physical
antibody level
92813
Outcome_Physical
geometric mean titer ( GMT ) values
92814
Outcome_Physical
evolution of GMT values
92815
Outcome_Other
safety evaluation
92816
Outcome_Other
serum samples for anti-rabies antibody titration
92817
Outcome_Adverse-effects
serious reactions
92818
Outcome_Adverse-effects
immediate ( anaphylactic type ) or delayed ( serum sickness ) allergic reactions
92819
Outcome_Physical
GMT profiles
92820
Outcome_Physical
protective antibody titers
92821
Outcome_Physical
GMT values
92822
Outcome_Other
antibody responses
92823
Participant_Sample-size
27
92824
Participant_Age
adults
92825
Participant_Sample-size
71