Safety and Pharmacokinetics Study of Anthrax Immune Globulin Intravenous (AIGIV)

• TNA (toxin neutralizing antibody) [ Time Frame: pre-infusion, 5 minutes, 8, 24, and 48 hours following infusion and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 following infusion. ] [ Designated as safety issue: No ]
• Viral serology testing, including HBsAg, Anti-HCV, Anti-HIV-1/-2/-O, Anti-HAV Total, Anti-HBc IgM and Anti-HBc total [ Time Frame: 7-28 days before infusion and Day 90 (last visit) ] [ Designated as safety issue: Yes ]
• Complete blood count (CBC) with differential [ Time Frame: 7 - 28 days before infusion, pre-infusion day, infusion day (before infusion), 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]
• Serum Chemistry [ Time Frame: 7 - 28 days before infusion, 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]
• Direct Coombs, haptoglobin, free hemoglobin and urine hemosiderin [ Time Frame: pre-infusion, 8, 24, 48 hours and 5 days after infusion ] [ Designated as safety issue: Yes ]
• Urinalysis [ Time Frame: 7 - 28 days before infusion, 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]

• TNA (toxin neutralizing antibody) [ Time Frame: pre-infusion, 5 minutes, 8, 24, and 48 hours following infusion and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 following the last infusion. ] [ Designated as safety issue: No ]
• Viral serology testing, including HBsAg, Anti-HCV, Anti-HIV-1/-2/-O, Anti-HAV Total, Anti-HBc IgM and Anti-HBc total [ Time Frame: 7-28 days before infusion and Day 90 (last visit) ] [ Designated as safety issue: Yes ]
• Complete blood count (CBC) with differential [ Time Frame: 7 - 28 days before infusion, 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]
• Serum Chemistry [ Time Frame: 7 - 28 days before infusion, 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]
• Hematology [ Time Frame: preinfusion, 8, 24, 48 hours and 5 days after infusion ] [ Designated as safety issue: Yes ]
• Urinalysis [ Time Frame: 7 - 28 days before infusion, 8, 24, 48 hours and 5, 14, 45 days after infusion ] [ Designated as safety issue: Yes ]

The purpose of this study is to:

• evaluate the safety profile of a single intravenous administration of AIGIV (containing either 3.5 mg/kg, 7.0 mg/kg or 14.0 mg/kg anti-PA IgG) as compared with either 90 mg/kg, 180 mg/kg or 360 mg/kg total IgG, GAMUNEX(R)(immune globulin intravenous (human) 10% caprylate/chromatography purified). GAMUNEX is a trademark of Talecris Biotherapeutics.
• evaluate the pharmacokinetic (PK) profile of a single intravenous administration of AIGIV (containing either 3.5 mg/kg, 7.0 mg/kg or 14.0 mg/kg anti-PA IgG) as measured by lethal toxin neutralizing antibody (TNA).

• Biological: Anthrax Immune Globulin Intravenous (AIGIV)
  Three cohorts evaluating three dosage levels of AIGIV containing 3.5, 7.0, or 14.0 mg/kg anti-PA IgG as a single intravenous infusion.
• Biological: Gamunex
  Three cohorts evaluating three dosage levels containing Gamunex 90, 180, or 360 mg/kg total IgG as a single intravenous infusion.
  Other Name: human immune globulin intravenous

• Experimental: AIGIV
  Three cohorts evaluating three dosage levels of AIGIV containing 3.5, 7.0, or 14.0 mg/kg anti-PA IgG as a single intravenous infusion.
  Intervention: Biological: Anthrax Immune Globulin Intravenous (AIGIV)
• Gamunex
  Gamunex 90, 180, or 360 mg/kg total IgG as a single intravenous infusion.
  Intervention: Biological: Gamunex

Inclusion Criteria:

• Between 18 and 65 years of age, inclusive.
• Have a minimal weight of 110 lbs and a body mass index (BMI) between 17 and 35.
• In good health.
• For pre-menopausal female subjects, using acceptable methods of birth control.
• Willing and capable of complying with all aspects of the protocol through completion of the program period.
• No blood donation in the preceding 8 weeks; willing to not donate whole blood or plasma during the clinical trial; and willing to not donate whole blood or plasma for up to one year following the last infusion.
• Has read and signed an informed consent form.
• Adequate venous access and can receive intravenous infusion.

Exclusion Criteria:

• Previously intolerant of immune globulin or blood product preparations or known immunodeficiency.
• Previous treatment with immune globulin products or blood products within three months of study.
• Previous receipt of anthrax vaccine, known exposure to anthrax organisms, or previously enlisted in the military.
• Receipt of any live vaccine within three months or inactivated vaccine within 2 weeks prior to study; plans to receive any vaccine at any time during the study.
• Participation in any investigational clinical trial within one month prior to study.
• Positive serology for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
• Receipt of chemotherapy, radiation therapy, immunosuppressive therapy, or high-dose corticosteroid therapy within five years of study.
• Use of prohibited medications as defined in the protocol.
• History of drug or alcohol abuse within 1 year of study.
• History of IgA deficiency.
• Pregnancy.
• Positive Coombs test at screening.
• Males with a hemoglobin value less than 13.2 gm/dL and females less than 10.9 gm/dL.
• Absolute eosinophil counts greater than 600 cells/mm3 or Absolute lymphocyte counts less than 1000 cells/mm3.
• Aspartate aminotransferase (AST) >55 U/L or alanine aminotransferase (ALT) >60 U/L.
• Hyperglycemia with random blood glucose >141 mg/dL, fasting blood glucose >112 mg/dL, or urine glucose >50 mg/dL; or hypoglycemia with a blood glucose <65 mg/dL.
• BUN >25 mg/dL or creatinine, for males >1.4 mg/dL and, for females >1.2 mg/dL.
• Urine protein >15 mg/dL for males and non-menstruating females, or >30 mg/dL for menstruating females.
• Febrile illness within three days prior to study.
• History of significant medical or psychiatric condition or abnormal laboratory tests indicating possible underlying medical condition.
• An opinion of the investigator that a condition exists that would preclude compliance with protocol-specified procedures.
• Absolute neutrophil count is less than 3000 cells/mm3 as defined by the central lab (screening) or local lab (pre-infusion) for cohort B. Absolute neutrophil count is less than 2500 cells/mm3 as defined by the central lab (screening) or local lab (pre-infusion) for cohort C.
• White blood cell counts are less than 3500 cells/mm3 as defined by the central lab (screening) or local lab (pre-infusion) for cohorts B and C.
• History of a severe or anaphylactic reaction to quinolone or penicillin antibiotics.