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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 RL, Lumry W, Harris J, Levy R, Stein M, Forbes L, Cunningham-Rundles C, Melamed I, Kobayashi AL, Du W, Kobayashi R - J. Clin. Immunol. (2016)

Bottom Line: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002).Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections.While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD.

View Article: PubMed Central - PubMed

Affiliation: Allergy Partners of North Texas Research, 7777 Forest Lane, Building B, Suite 332, Dallas, TX, 75230, USA. drrichwasserman@gmail.com.

ABSTRACT

Purpose: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV).

Methods: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD.

Results: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year.

Conclusions: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.

No MeSH data available.


Related in: MedlinePlus

Neutralizing antibodies to RSV before and post-infusion by dose and nominal time point post infusion – PK evaluable set (N = 30)
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Related In: Results  -  Collection


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Fig1: Neutralizing antibodies to RSV before and post-infusion by dose and nominal time point post infusion – PK evaluable set (N = 30)

Mentions: 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 Cmax 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 Cmax 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.Table 3


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 RL, Lumry W, Harris J, Levy R, Stein M, Forbes L, Cunningham-Rundles C, Melamed I, Kobayashi AL, Du W, Kobayashi R - J. Clin. Immunol. (2016)

Neutralizing antibodies to RSV before and post-infusion by dose and nominal time point post infusion – PK evaluable set (N = 30)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940435&req=5

Fig1: Neutralizing antibodies to RSV before and post-infusion by dose and nominal time point post infusion – PK evaluable set (N = 30)
Mentions: 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 Cmax 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 Cmax 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.Table 3

Bottom Line: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002).Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections.While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD.

View Article: PubMed Central - PubMed

Affiliation: Allergy Partners of North Texas Research, 7777 Forest Lane, Building B, Suite 332, Dallas, TX, 75230, USA. drrichwasserman@gmail.com.

ABSTRACT

Purpose: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV).

Methods: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD.

Results: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year.

Conclusions: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.

No MeSH data available.


Related in: MedlinePlus