Safety and Pharmacokinetic Study of Anthrax Immune Globulin Derived From Human Serum
Condition: Symptoms of Inhalational Anthrax
MeSH terms: Anthrax
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to assess the pharmacokinetics of three doses of NP-015 (210, 420
      or 840 units TNA) in healthy volunteers. To evaluate the safety of NP-015 based on adverse
      events and laboratory assessments. To determine the dose proportionality relation of three
      different doses of NP-015.
    

Detailed description: 
      -  The test product is Anthrax Immune Globulin Intravenous (Human), NP-015.

        -  The product is supplied as a sterile liquid suitable for IV administration.

        -  Product potency is expressed in units of anthrax toxin neutralization assays(TNA) per
           vial.

        -  This study is a phase 1, placebo controlled, dose-ranging study in healthy volunteers.
           Subjects will receive one of three NP-015 doses (210, 420 or 840 units TNA) or equal
           volumes of saline placebo.

        -  Enrolment will be sequential, starting at the lowest NP-015 dose with accrual into the
           next higher dose after all patients at the lower dose have been treated.

        -  The first 3 Cohorts: The Subjects will be recruited in cohorts of 24, with placebo
           controls included in each dosing group. In each cohort, subjects will be randomized to
           receive either NP-015 (N = 18/dosing group) or placebo (N = 6/dosing group). For Cohort
           4: 20 Subjects will be recruited and dosed at the highest dose with 2 additional product
           lots (10 subjects per lot).

      Plasma samples will be drawn over 84 days. Plasma will be tested for anti-anthrax antibodies
      by a protective antigen (anti-PA) ELISA and toxin neutralization assay (TNA).

        -  Serological testing for HIV, HBV and HCV will be conducted at screening to determine
           eligibility. Nucleic acid amplification testing (NAT) and serological testing for HIV,
           HBV and HCV will be conducted at baseline (day -1) and at the final visit (day 84 or
           early withdrawal). NAT for parvovirus B19 will be conducted at baseline (day -1), day
           14, and the final visit (day 84 or early withdrawal).

        -  Safety data will be collected throughout the 84-day study.

      Screening (within 28 days prior to Baseline):

        -  Informed consent

        -  Review of admission criteria

        -  Medical history, general physical examination, vital signs, electrocardiogram and
           concomitant medications will be recorded

        -  Hematology, blood chemistry, urinalysis, viral serology (anti-HIV-1/2, Anti-HCV, HBsAg,
           anti-HBc)

        -  Serum pregnancy test for all female subjects

        -  Drug screen (urine)

        -  Blood collection for anti-PA antibody and toxin neutralization assay (TNA) assessment

      Baseline (Day -1, within 24 hours prior to Day 0)

        -  Review of admission criteria

        -  Assessment of brief physical exam, vital signs, weight, hematology, blood chemistry,
           urinalysis, and concomitant medications

        -  Assessment of haptoglobin and free hemoglobin levels

        -  Update of medical history

        -  NAT testing for HIV, HBV, HCV and parvovirus B19, and serological testing for HIV, HBV
           and HCV

        -  Serum pregnancy test for all female subjects

        -  Alcohol (urine) and drug screen (urine)

        -  Blood collection for baseline anti-PA antibody and TNA assessment

        -  Subjects will be required to stay overnight following their baseline assessment

      NP-015 Administration (day 0)

        -  Following baseline assessment, NP-015 will be administered intravenously

        -  Urinalysis will be performed at the end of the infusion period (appearance and color,
           specific gravity, protein, glucose, pH, occult blood, ketones, microscopic examination)

      Assessments following the completion of NP-015 administration (1, 3 and 8 hrs; days 1, 3, 5,
      7, 9, 11, 14, 21, 28, 42, 56 and 84 or early withdrawal)

        -  Following NP-015 administration, blood will be collected for anti-PA antibody ELISA
           analysis and TNA assessment at each of the respective times.

        -  Assessment of vital signs, adverse events and concomitant medications.

      Additional Assessments:

        -  Days 1, 3, 7, 14, 28 and 84 or early withdrawal: Assessment of hematology, blood
           chemistry and urinalysis.

        -  Day 1: Assessment of haptoglobin and free hemoglobin levels.

        -  Day 14: NAT for parvovirus B19.

        -  Day 28: serum pregnancy test for female subjects.

        -  Final (day 84 or early withdrawal) visit: a general physical exam, serum pregnancy test
           for female subjects, and viral marker testing (NAT for HBV, HCV, HIV and parvovirus B19,
           and serology for HIV, HBV and HCV) will be performed.

      For Cohort 4 there will be no anti anthrax antibody testing and the subjects will be assessed
      for safety only, up to day 28.
    

Intervention name(s): NP-015
Intervention type(s): Biological
Intervention description(s): Three Cohorts evaluating three dosage levels: 210, 420 or 840 units TNA, or placebo.
And a Fourth Cohort at 840 units TNA with 2 additional product lots.
Other intervention name(s): Anthrax Immune Globulin (AIG)
Intervention MeSH terms: Immunoglobulins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Inhalational Anthrax; Human Immune globulin