title: Multicenter study to determine antibody concentrations and assess the safety of administration of INH-A21, a donor-selected human Staphylococcal immune globulin, in low-birth-weight infants.
abstract: Nosocomial or late-onset sepsis is a common complication among premature infants, with a frequency inversely correlated with birth weight. Increased susceptibility to infection is due in part to an immature humoral (antibody-mediated) immune response. This study investigated the pharmacokinetics (PKs) and safety of a donor-selected specific intravenous immune globulin (IVIG) preparation, INH-A21 (Veronate), for prevention of sepsis in premature infants. Thirty-six infants weighing between 500 and 1,250 g during the first postnatal week were eligible to begin a series of up to four intravenous infusions of 500 or 750 mg/kg of body weight INH-A21. Blood samples were analyzed for antibodies against the Ser-Asp dipeptide repeat G (SdrG) and clumping factor A (ClfA) surface proteins of staphylococci. Sparse sampling and population PK analyses were performed to derive PK parameters. Following administration of the 500- and 750-mg/kg doses, the estimated average steady-state levels of anti-ClfA were 6.1 U/ml and 9.2 U/ml, respectively, and those of anti-SdrG were 5.2 U/ml and 7.7 U/ml, respectively. The elimination half-lives for anti-ClfA and anti-SdrG were 719 h and 701 h, respectively, and the clearances were 0.18 ml/h and 0.21 ml/h, respectively. In the final model, the values of the PK parameters were independent of gestational age. Both doses of INH-A21 were well tolerated, and the safety profile was similar to those of other IVIG preparations. These results suggest that a shorter dosing interval should be utilized between the first and second doses to achieve and maintain higher titers of anti-ClfA and anti-SdrG antibodies. Further studies examining INH-A21 for the prevention of late-onset sepsis in infants within the weight range studied are warranted.
authors.affiliation: Trials-by-Design LLC, San Diego, California, USA.
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Barry T
authors.initials: BT
authors.lastname: Bloom
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Kueser
authors.forename: David G
authors.initials: DG
authors.lastname: Oelberg
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Bifano
authors.forename: Robert D
authors.initials: RD
authors.lastname: White
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelonka
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Pearlman
authors.forename: Joseph
authors.initials: J
authors.lastname: Patti
authors.forename: Seth V
authors.initials: SV
authors.lastname: Hetherington
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D001499:Bayes Theorem; D006207:Half-Life; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007700:Kinetics; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000517:prevention & control; D014481:United States
chemical_list: D000907:Antibodies, Bacterial; D016756:Immunoglobulins, Intravenous; C511124:Veronate