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

Emergent BioSolutions

Status and phase: Completed; Phase 2; Phase 1

Conditions: Anthrax

Treatments: Biological: AIGIV 14.0 mg/kg; Biological: AIGIV 3.5 mg/kg; Biological: Gamunex 90 mg/kg; Biological: Gamunex 360 mg/kg; Biological: Gamunex 180 mg/kg; Biological: AIGIV 7.0 mg/kg

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00845650

DMID 07-0067 (Other Identifier)

EBS.AIG.001

HHSN272200700034C (Other Grant/Funding Number)

Details and patient eligibility

About

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).

Enrollment: 129 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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129 participants in 6 patient groups

AIGIV 3.5 mg/kg (Cohort A)

Experimental group

Description:

AIGIV containing 3.5 mg/kg anti-PA IgG as a single intravenous infusion.

Treatment:

Biological: AIGIV 3.5 mg/kg

Gamunex 90 mg/kg (Cohort A)

Other group

Description:

Gamunex 90 mg/kg total IgG as a single intravenous infusion.

Treatment:

Biological: Gamunex 90 mg/kg

AIGIV 7.0 mg/kg (Cohort B)

Experimental group

Description:

AIGIV containing 7.0 mg/kg anti-PA IgG as a single intravenous infusion.

Treatment:

Biological: AIGIV 7.0 mg/kg

Gamunex 180 mg/kg (Cohort B)

Other group

Description:

Gamunex 180 mg/kg total IgG as a single intravenous infusion.

Treatment:

Biological: Gamunex 180 mg/kg

AIGIV 14.0 mg/kg (Cohort C)

Experimental group

Description:

AIGIV containing 14.0 mg/kg anti-PA IgG as a single intravenous infusion.

Treatment:

Biological: AIGIV 14.0 mg/kg

Gamunex 360 mg/kg (Cohort C)

Other group

Description:

Gamunex 360 mg/kg total IgG as a single intravenous infusion.

Treatment:

Biological: Gamunex 360 mg/kg