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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Emergent BioSolutions
ClinicalTrials.gov Identifier:
NCT00845650
First received: February 13, 2009
Last updated: November 21, 2012
Last verified: November 2012

February 13, 2009
November 21, 2012
February 2009
October 2010   (final data collection date for primary outcome measure)
Adverse events [ Time Frame: pre-infusion, infusion, 5 minutes, 30 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: Yes ]
Adverse events [ 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: Yes ]
Complete list of historical versions of study NCT00845650 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
 
Safety and Pharmacokinetics Study of Anthrax Immune Globulin Intravenous (AIGIV)
A Randomized, Double-Blind, Dose-Escalation Study Evaluating Pharmacokinetics and Safety of Anthrax Immune Globulin Intravenous (AIGIV)

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).
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Anthrax
  • 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
Mytle N, Hopkins RJ, Malkevich NV, Basu S, Meister GT, Sanford DC, Comer JE, Van Zandt KE, Al-Ibrahim M, Kramer WG, Howard C, Daczkowski N, Chakrabarti AC, Ionin B, Nabors GS, Skiadopoulos MH. Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax. Antimicrob Agents Chemother. 2013 Nov;57(11):5684-92. doi: 10.1128/AAC.00458-13. Epub 2013 Aug 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
129
October 2010
October 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00845650
EBS.AIG.001, DMID 07-0067
Yes
Emergent BioSolutions
Emergent BioSolutions
National Institutes of Health (NIH)
Principal Investigator: Mohamed Al-Ibrahim, MD SNBL Clinical Pharmacology Center Inc, Baltimore, MD
Study Director: Robert J Hopkins, MD, MPH & TM Emergent Product Development Gaithersburg
Emergent BioSolutions
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP