Clinical trial NCT00845650: Safety and Pharmacokinetics Study of Anthrax Immune Globulin Intravenous (AIGIV)
Official title: A Randomized, Double-Blind, Dose-Escalation Study Evaluating Pharmacokinetics and Safety of Anthrax Immune Globulin Intravenous (AIGIV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anthrax
Keywords: Anthrax
Human Anthrax Immune Globulin Intravenous
Safety
Pharmacokinetics
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2009-02-18
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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® (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).


Eligibility 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.
* 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.

Primary outcomes:
measure: Number of Participants Reporting Adverse Events (AEs)
timeFrame: From the time of infusion through Day 90.
Secondary outcomes:
measure: Maximum Plasma Titer/Concentration of TNA (Toxin Neutralizing Antibody) (Cmax)
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Time of Cmax
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Area Under the Curve to the Last Time With a Measurable TNA Titer (AUC[0-t])
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Area Under the Curve to Infinity (AUC[0-inf])
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Elimination Rate Constant
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Elimination Half-life (t½)
timeFrame: From the time of infusion through Day 90 postinfusion.
measure: Mean Residence Time (MRT)
timeFrame: From the time of infusion through Day 90 postinfusion.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: SNBL Clinical Pharmacology Center Inc.
state: Maryland
Study officials:
affiliation: SNBL Clinical Pharmacology Center Inc, Baltimore, MD
name: Mohamed Al-Ibrahim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emergent Product Development Gaithersburg
name: Robert J Hopkins, MD, MPH & TM
role: STUDY_DIRECTOR
References:
citation: 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.