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

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ClinicalTrials.gov Identifier: NCT00845650
Recruitment Status : Completed
First Posted : February 18, 2009
Last Update Posted : February 8, 2018
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Emergent BioSolutions

Brief Summary:

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).

Condition or disease Intervention/treatment Phase
Anthrax Biological: AIGIV 3.5 mg/kg Biological: Gamunex 90 mg/kg Biological: AIGIV 7.0 mg/kg Biological: Gamunex 180 mg/kg Biological: AIGIV 14.0 mg/kg Biological: Gamunex 360 mg/kg Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Dose-Escalation Study Evaluating Pharmacokinetics and Safety of Anthrax Immune Globulin Intravenous (AIGIV)
Study Start Date : February 2009
Actual Primary Completion Date : October 2010
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anthrax
U.S. FDA Resources

Arm Intervention/treatment
Experimental: AIGIV 3.5 mg/kg (Cohort A)
AIGIV containing 3.5 mg/kg anti-PA IgG as a single intravenous infusion.
Biological: AIGIV 3.5 mg/kg
AIGIV containing 3.5 mg/kg anti-PA IgG as a single intravenous infusion.
Gamunex 90 mg/kg (Cohort A)
Gamunex 90 mg/kg total IgG as a single intravenous infusion.
Biological: Gamunex 90 mg/kg
Gamunex 90 mg/kg total IgG as a single intravenous infusion.
Other Name: human immune globulin intravenous
Experimental: AIGIV 7.0 mg/kg (Cohort B)
AIGIV containing 7.0 mg/kg anti-PA IgG as a single intravenous infusion.
Biological: AIGIV 7.0 mg/kg
AIGIV containing 7.0 mg/kg anti-PA IgG as a single intravenous infusion.
Gamunex 180 mg/kg (Cohort B)
Gamunex 180 mg/kg total IgG as a single intravenous infusion.
Biological: Gamunex 180 mg/kg
Gamunex 180 mg/kg total IgG as a single intravenous infusion.
Experimental: AIGIV 14.0 mg/kg (Cohort C)
AIGIV containing 14.0 mg/kg anti-PA IgG as a single intravenous infusion.
Biological: AIGIV 14.0 mg/kg
AIGIV containing 14.0 mg/kg anti-PA IgG as a single intravenous infusion.
Gamunex 360 mg/kg (Cohort C)
Gamunex 360 mg/kg total IgG as a single intravenous infusion.
Biological: Gamunex 360 mg/kg
Gamunex 360 mg/kg total IgG as a single intravenous infusion.



Primary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: From the time of infusion through Day 90. ]
    Signs and symptoms reported to or observed by the principal investigator (PI).


Secondary Outcome Measures :
  1. Maximum plasma titer/concentration of TNA (toxin neutralizing antibody) (Cmax) [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  2. Time of Cmax [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  3. Area under the curve to the last time with a measurable TNA titer (AUC[0-t]) [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  4. Area under the curve to infinity (AUC[0-inf]) [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  5. Elimination rate constant [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  6. Elimination half-life (t½) [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.

  7. Mean residence time (MRT) [ Time Frame: From the time of infusion through Day 90 postinfusion. ]
    Blood samples for TNA analysis collected at pre-infusion; 5 minutes postinfusion; 8, 24, and 48 hours postinfusion; and Days 3, 5, 10, 14, 21, 30, 45, 60, and 90 postinfusion.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00845650


Locations
United States, Maryland
SNBL Clinical Pharmacology Center Inc.
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Emergent BioSolutions
National Institutes of Health (NIH)
Investigators
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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Emergent BioSolutions
ClinicalTrials.gov Identifier: NCT00845650     History of Changes
Other Study ID Numbers: EBS.AIG.001
DMID 07-0067 ( Other Identifier: NIAID )
HHSN272200700034C ( Other Grant/Funding Number: NIAID )
First Posted: February 18, 2009    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: January 2018

Keywords provided by Emergent BioSolutions:
Anthrax
Human Anthrax Immune Globulin Intravenous
Safety
Pharmacokinetics

Additional relevant MeSH terms:
Anthrax
Bacillaceae Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Antitoxins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs