Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults
Condition: Hookworm Infection; Hookworm Disease
MeSH terms: Hookworm Infections; Ancylostomiasis
Study type: Interventional
Phase: Phase 1

Summary: 
      Hookworms digest hemoglobin from erythrocytes for use as an energy source via a proteolytic
      cascade that begins with the aspartic protease, APR-1. Vaccination with recombinant APR-1 has
      protected animals from infection in challenge studies. This study will evaluate the safety
      and immunogenicity of two formulations of Na-APR-1 (M74) in healthy adult volunteers when
      co-administered with different concentrations of the immunostimulant GLA-AF.
    

Detailed description: 
      Open-label, dose-escalation phase 1 clinical trial in healthy, hookworm-naïve adults:

        -  Study site: George Washington Medical Faculty Associates, Washington, DC

        -  Number of participants: 40 in 2 cohorts of 20.

      In Cohort 1 five (5) volunteers will receive 30 µg Na-APR-1 (M74) /Alhydrogel®, five (5) will
      receive 30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 30 µg
      Na-APR-1 (M74) /Alhydrogel® plus 5 µg GLA-AF. In Cohort 2 five (5) volunteers will receive
      100 µg Na-APR-1 (M74)/Alhydrogel®, five (5) will receive 100 µg Na-APR-1 (M74) /Alhydrogel®
      plus 2.5 µg GLA-AF, and ten (10) will receive 100 µg Na-APR-1 (M74)/Alhydrogel® plus 5 µg
      GLA-AF.

      The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the
      Na-APR-1 dose escalation from 30 to 100 µg. In addition, within each cohort, vaccinations
      will be staggered such that formulations containing 0, 2.5, and 5 µg GLA-AF will be tested
      sequentially: for example, those receiving Na-APR-1 (M74)/Alhydrogel® in combination with 2.5
      µg GLA-AF will be vaccinated no sooner than 3 days after the last volunteer is vaccinated
      with the formulation containing no GLA-AF, whereas those vaccinated with Na-APR-1
      (M74)/Alhydrogel® plus 5 µg GLA-AF will be vaccinated no sooner than 7 days after the last
      one receives the 2.5 µg GLA-AF formulation.

        -  Immunization schedule: Study days 0, 56 and 112.

        -  Route: IM in the deltoid muscle.

        -  Doses of Na-APR-1 (M74) to be tested: 30 and 100 µg.

        -  Doses of Alhydrogel®: 240 and 800 µg for the 30 and 100 µg doses of Na-APR-1 (M74),
           respectively.

        -  Doses of GLA-AF to be tested: 2.5 µg and 5 µg.

        -  Study duration: 44 weeks (10 months) per study participant; total duration of the study
           estimated at approximately 13 months.
    

Intervention name(s): Na-APR-1 (M74)/Alhydrogel®; Gluco-Pyranosylphospho-Lipid A Aqueous Formulation
Intervention type(s): Biological; Biological
Intervention description(s): The Na-APR-1 (M74) candidate vaccine contains the recombinant Na-APR-1 (M74) protein expressed by Nicotiana plants. Purified Na-APR-1 (M74) was subsequently adsorbed onto aluminum hydroxide gel (Alhydrogel®) and suspended in a solution containing 10 mM imidazole, 150 mM sodium chloride and 0.3% Empigen BB, with pH 7.4 ± 0.1. The final concentration of Na-APR-1 (M74) in the drug product is 0.1 mg/ml, whereas that of Alhydrogel® is 0.8 mg/ml. Different doses of Na-APR-1 (M74) will be delivered by injecting different volumes of the 0.1 mg/ml Na-APR-1 (M74) preparation.; GLA-AF contains a synthetic monophosphoryl lipid A (MPL) molecule that has Toll-Like Receptor-4 agonist activity. MPL is itself derived from the lipopolysaccharide (LPS) of Salmonella minnesota, a natural TLR4 agonist that is pyrogenic and can induce toxic shock. LPS, and more specifically, its lipid A component, has long been known for its strong adjuvant effects; however, its high toxicity has precluded its use in a vaccine formulation.
Other intervention name(s): Na-APR-1; Necator americanus Aspartic Protease-1; GLA-AF
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Human Hookworm; Necator americanus; Hookworm; Hookworm Disease; Iron-deficiency anemia; Soil-transmitted helminth infection; Neglected Tropical Disease; Na-APR-1