Results of a Phase 1, Double-Blind, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of ISIS 333611 Administered Intrathecally to Patients with Familial ALS Due to SOD1 Gene Mutations (S25.001)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. S25.001-S25.001
Author(s):  
T. Miller ◽  
R. Smith ◽  
A. Pestronk ◽  
W. David ◽  
J. Rothstein ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Gene Mutations ◽  
Sod1 Gene ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Familial Als

scholarly journals Phase 1/2 Double-Blind, Placebo-Controlled, Dose Escalation, Safety, and Pharmacokinetic Study of Pagibaximab (BSYX-A110), an Antistaphylococcal Monoclonal Antibody for the Prevention of Staphylococcal Bloodstream Infections, in Very-Low-Birth-Weight Neonates

2009 ◽  
Vol 53 (7) ◽  
pp. 2879-2886 ◽  
Author(s):  
Leonard E. Weisman ◽  
Helen M. Thackray ◽  
Joseph A. Garcia-Prats ◽  
Mirjana Nesin ◽  
Joseph H. Schneider ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Birth Weight ◽  
High Risk ◽  
Adverse Events ◽  
Dose Escalation ◽  
Very Low Birth Weight ◽  
Phase 1 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Vlbw Infants

ABSTRACT Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2, randomized, double-blind, placebo-controlled, dose escalation study was conducted in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14 days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or placebo in a 2:1 ratio. Blood and urine samples were obtained pre- and postinfusion for analysis of safety and pharmacokinetics, and data on adverse events were gathered. Staphylococcal organisms causing sepsis were collected and evaluated. Fifty-three patients received at least one dose of pagibaximab or placebo. The average gestational age was 27.6 weeks; the average birth weight was 1,003 g. All serious adverse events were deemed unrelated or probably not drug related. Morbidity and mortality were similar across treatment groups. No evidence of immunogenicity of pagibaximab was detected. Pagibaximab pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and elimination half-life of pagibaximab were independent of dose. The serum half-life was 20.5 ± 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity. All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe and tolerable, and pharmacokinetics were linear. Evaluation of more frequent doses, at the highest doses tested, in neonates at high-risk of staphylococcal sepsis, is warranted.

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