Effect of Raxibacumab on Immunogenicity of Anthrax Vaccine Adsorbed
Condition: Infections, Bacterial
MeSH terms: Anthrax; Bacterial Infections
Intervention: AVA; Raxibacumab; Diphenhydramine
Intervention description: Sterile, milky-white suspension with dosage level of 0.5 mL for SC administration; Sterile, liquid formulation with unit dose strength of 40 mg/ kg for IV administration; Depending upon the labelling of the specific product chosen, 25 - 50 mg will be administered orally or IV
Intervention MeSH terms: Diphenhydramine; Promethazine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 573.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Anthrax Vaccine Adsorbed; Raxibacumab; Immunogenicity

Summary:

      This study, as a post-marketing commitment to the Food and Drug Administration, is designed
      to detect the effect of raxibacumab on anthrax vaccine adsorbed (AVA) immunogenicity in a
      healthy volunteer population. This is a randomized, open-label, parallel group, two arm study
      to compare the immunogenicity of AVA at 4 weeks after the first AVA dose, when AVA is
      administered alone or concomitantly with raxibacumab. The study is planned to enroll
      approximately 30 to 534 subjects in up to 3 cohorts. The total duration of the study will be
      approximately 26 weeks. The dates reflect cohort 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy as determined by the Investigator or medically qualified designee based on a
             medical evaluation including medical history, physical examination and laboratory
             tests

          -  Men and women between 18 to 65 years of age

          -  Willing and able to adhere to the procedures stated in the protocol.

          -  Female subject is eligible to participate if she is not pregnant (as confirmed by a
             negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and
             at least one of the following conditions applies:

        Non-reproductive potential defined as:

        Pre-menopausal females with one of the following: Documented tubal ligation, Documented
        hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal
        occlusion, Hysterectomy, Documented Bilateral Oophorectomy Postmenopausal defined as 12
        months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose
        menopausal status is in doubt will be required to use one of the highly effective
        contraception methods if they wish to continue their HRT during the study. Otherwise, they
        must discontinue HRT to allow confirmation of post-menopausal status prior to study
        enrollment.

        Reproductive potential and agrees to follow one of the options listed in the GSK Modified
        List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
        Potential (FRP), from 30 days prior to the first dose of study medication and until after
        the last dose of study medication and completion of the follow-up visit at Day 183 (at
        least five terminal half-lives for raxibacumab).

        Exclusion Criteria:

          -  Concurrently participating in another clinical study, at any time during the study
             period, in which the subject has been or will be exposed to an investigational or
             non-investigational study vaccine/product (pharmaceutical product or device).

          -  Be a member of the military, a laboratory worker, first responder, health care worker,
             or otherwise be at higher risk of exposure to anthrax.

          -  History of regular alcohol consumption within 1 month of the study defined as:

        An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
        equivalent to 12 g of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL)
        of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

          -  Female planning to become pregnant or planning to discontinue contraceptive
             precautions before the Day 183 study visit.

          -  Pregnant (confirmed by a serum or urine hCG test) or lactating female.

          -  Alanine aminotransferase (ALT) and bilirubin >1.5 x upper limit of normal (ULN)
             (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition resulting
             from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or
             immunosuppressive/cytotoxic therapy (e.g., medications used during cancer
             chemotherapy, organ transplantation or to treat autoimmune disorders).

          -  Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
             results at screening or within 3 months prior to first dose of study treatment.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for HIV antibody.

          -  History of sensitivity to any of the study medications, or components thereof
             (especially latex and aluminium) or a history of other known drug allergies that, in
             the opinion of the Investigator or GSK Medical Monitor, contraindicates their
             participation.

          -  Have previously been vaccinated against PA.

          -  Have an anti-PA Ab concentration >2 times the lower limit of quantitation at
             screening.

          -  Administration of immunoglobulins not included in this trial and/or any blood products
             within the 3 months preceding the first dose of study vaccine or planned
             administration during the study period.

          -  Administration of long-acting immune-modifying drugs (e.g. infliximab) within six
             months prior to the first vaccine dose or expected administration at any time during
             the study period.

          -  Chronic administration (defined as more than 14 consecutive days) of systemic
             immunosupressants or other immune-modifying drugs within six months prior to the first
             vaccine dose. Inhaled, topical and intra-articular corticosteroids are allowed.

          -  Administration or planned administration of a vaccine not foreseen by the study
             protocol within the period starting 35 days before the first dose of study vaccine(s)
             and ending 30 days after the last dose of study vaccine. This includes any type of
             vaccine such as (but not limited to) live, inactivated, and subunit vaccines.
             Influenza vaccines are permitted after Week 8.

          -  Subjects must abstain from taking prescription or non-prescription drugs (including
             vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is
             a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
             dose of study medication until completion of the follow-up visit, unless in the
             opinion of the Investigator and sponsor the medication will not interfere with the
             study.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Any condition which, in the opinion of the investigator, prevents the subject from
             participating in the study.