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

Study Overview
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Brief Summary
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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® (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).

Official Title
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A Randomized, Double-Blind, Dose-Escalation Study Evaluating Pharmacokinetics and Safety of Anthrax Immune Globulin Intravenous (AIGIV)

Conditions
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Anthrax

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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. Creatinine clearance <80 mL/min. 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 infusion. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIGIV 3.5 mg/kg (Cohort A)<br>AIGIV containing 3.5 mg/kg anti-PA IgG as a single intravenous infusion. | Biological: AIGIV 3.5 mg/kg<br>* AIGIV containing 3.5 mg/kg anti-PA IgG as a single intravenous infusion.<br>|
| Other: Gamunex 90 mg/kg (Cohort A)<br>Gamunex 90 mg/kg total IgG as a single intravenous infusion. | Biological: Gamunex 90 mg/kg<br>* Gamunex 90 mg/kg total IgG as a single intravenous infusion.<br>* Other names: human immune globulin intravenous;|
| Experimental: AIGIV 7.0 mg/kg (Cohort B)<br>AIGIV containing 7.0 mg/kg anti-PA IgG as a single intravenous infusion. | Biological: AIGIV 7.0 mg/kg<br>* AIGIV containing 7.0 mg/kg anti-PA IgG as a single intravenous infusion.<br>|
| Other: Gamunex 180 mg/kg (Cohort B)<br>Gamunex 180 mg/kg total IgG as a single intravenous infusion. | Biological: Gamunex 180 mg/kg<br>* Gamunex 180 mg/kg total IgG as a single intravenous infusion.<br>|
| Experimental: AIGIV 14.0 mg/kg (Cohort C)<br>AIGIV containing 14.0 mg/kg anti-PA IgG as a single intravenous infusion. | Biological: AIGIV 14.0 mg/kg<br>* AIGIV containing 14.0 mg/kg anti-PA IgG as a single intravenous infusion.<br>|
| Other: Gamunex 360 mg/kg (Cohort C)<br>Gamunex 360 mg/kg total IgG as a single intravenous infusion. | Biological: Gamunex 360 mg/kg<br>* Gamunex 360 mg/kg total IgG as a single intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Adverse Events (AEs) | Any untoward medical occurrence reported to or observed by the principal investigator (PI), including as identified from other safety assessments (eg, vital signs, clinical laboratory testing, electrocardiogram). | From the time of infusion through Day 90. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Titer/Concentration of TNA (Toxin Neutralizing Antibody) (Cmax) | 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. Assay results are reported as the 50% neutralization factor, TNA NF50: the ED50 of the test sample (ie, effective dilution of test sample that neutralized 50% of toxin) divided by the ED50 of the reference standard. | From the time of infusion through Day 90 postinfusion. | 
| Time of Cmax | 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. | From the time of infusion through Day 90 postinfusion. | 
| Area Under the Curve to the Last Time With a Measurable TNA Titer (AUC[0-t]) | 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. | From the time of infusion through Day 90 postinfusion. | 
| Area Under the Curve to Infinity (AUC[0-inf]) | 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. | From the time of infusion through Day 90 postinfusion. | 
| Elimination Rate Constant | 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. | From the time of infusion through Day 90 postinfusion. | 
| Elimination Half-life (t½) | 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. | From the time of infusion through Day 90 postinfusion. | 
| Mean Residence Time (MRT) | 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. | From the time of infusion through Day 90 postinfusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anthrax, Human Anthrax Immune Globulin Intravenous, Safety, Pharmacokinetics