Efficacy, Safety, and Pharmacokinetics of a New 10 % Liquid Intravenous Immunoglobulin Containing High Titer Neutralizing Antibody to RSV and Other Respiratory Viruses in Subjects with Primary Immunodeficiency Disease

Wasserman, Richard L.; Lumry, William; Harris, James; Levy, Robyn; Stein, Mark; Forbes, Lisa; Cunningham-Rundles, Charlotte; Melamed, Isaac; Kobayashi, Ai Lan; Du, Wei; Kobayashi, Roger

Thirty subjects, 20 subjects on a 4-week infusion cycle and 10 subjects on a 3-week infusion cycle, participated in the PK portion of the study. Administration of RI-002 with either regimen resulted in increases in IgG and in CMV, tetanus, Hib, measles, RSV, and S. pneumoniae serotype antibodies with the greatest increase in C max observed in antibodies to RSV. There was a 5.47-fold increase in the titer of anti-RSV neutralizing antibody immediately after infusion of the IVIG and a 6.79-fold increase in those subjects who received greater than 500 mg/kg (Table 3 ). In this calculation, baseline was that value of anti-RSV measured immediately prior to entry into the trial. Figure 1 shows the pharmacokinetics of anti-RSV antibodies, and in this situation, baseline was the value of anti-RSV that was measured in the subjects enrolled in the PK portion of the study immediately prior to infusion of the seventh or ninth dose of IVIG. RI-002 is manufactured to contain standardized, elevated levels of neutralizing antibodies to RSV, and all lots are tested for release potency for RSV antibody levels. There was no apparent difference between groups in the mean plasma concentrations of IgG and the mean values for C max despite a slightly larger AUC over the dosing interval due to the 7-day longer period. Although the mean values for t½ should be considered as qualitative because of the period of time over which λz was measured, they are consistent with literature values for the t½ of IgG. Although there was a range of RI-002 doses within each group, there was no apparent relationship between AUC over the dosing interval and either total dose or weight adjusted dose for either cohort (Table 4 ). Taken as a whole, the increases in the RSV, CMV, tetanus, Hib, measles, and S. pneumoniae antibodies were not affected by the treatment intervals used in this study. The mean values for all antibodies measured at baseline were comparable to the pre-infusion titers for both cohorts, and the maximum titers were higher than the baseline and pre-infusion titers. There did not appear to be a difference in exposure to IgG as a function of sex or age group. Analysis of baseline corrected plasma IgG concentrations resulted in comparisons between the 3 and 4-week cycle cohorts that were comparable to those using plasma concentrations without baseline correction.