LEISH-F3 + GLA-SE and the LEISH-F3 + MPL-SE Vaccine
Condition: Leishmaniasis
MeSH terms: Leishmaniasis
Study type: Interventional
Phase: Phase 1

Summary: 
      Investigational products: LEISH-F3 (recombinant protein antigen) + GLA-SE (adjuvant)
      leishmaniasis vaccine and LEISH-F3 (recombinant protein antigen) + MPL-SE (adjuvant)
      leishmaniasis vaccine. Stage of development: Phase 1 clinical development. Healthy adult
      subjects, 18 to 49 will be recruited through a U.S. site. Primary objective: To evaluate the
      safety and tolerability of the LEISH-F3 + GLA-SE vaccine and the LEISH-F3 + MPL-SE vaccine
      following intramuscular (IM) administration of 20 µg of LEISH-F3 together with 2 or 5 µg of
      GLA-SE or 10 µg of MPL-SE on Days 0, 28, and 168. Secondary objective: To assess the
      immunogenicity of LEISH-F3 formulated with GLA-SE, MPL-SE, or SE by evaluating IgG antibody
      responses to LEISH-F3 at Days 0, 28, 56, 168, 196, and 365, and T cell responses to LEISH-F3
      at Days 0, 14, 42, 168, 182, and 365. Each subject's duration of participation will be about
      18 months.
    

Detailed description: 
      Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. The
      parasites are transmitted from an animal or human reservoir through the bite of infected
      female phlebotomine sand flies. This study is a randomized, open-label clinical trial
      designed to evaluate the safety, tolerability, and immunogenicity of the LEISH-F3 recombinant
      protein antigen formulated with GLA-SE, MPL-SE, or SE adjuvant in healthy adults 18 to 49
      years of age. Each subject's duration of participation will be about 18 months. Subjects will
      receive a total of 3 doses of vaccine, which will be given by intramuscular injection on Days
      0, 28, and 168. The volume of each vaccine dose will be 0.5 mL. A computerized system will be
      used to acquire any data regarding halting criteria throughout the study. Primary objective
      is to evaluate the safety and tolerability of LEISH-F3 formulated with GLA-SE, MPL-SE, or SE
      following intramuscular administration of 20 µg of LEISH-F3 together with 5 µg of GLA-SE, 10
      µg of MPL-SE, or SE alone. Secondary objective is to assess the immunogenicity of LEISH-F3
      formulated with GLA-SE, MPL-SE, or SE by evaluating IgG antibody responses to LEISH-F3 at
      Days 0, 28, 56, 168, 196, and 365, and T cell responses to LEISH-F3 at Days 0, 14, 42, 168,
      182, and 365. A substudy will be performed using up to 12 subjects from each Study Group
      (Groups 1, 2 and 3) and an additional 12 subjects to serve as controls. This substudy will
      investigate whether, as in murine cells, cell surface markers (CD11a, CD49d) can be used as a
      surrogate to identify protective immune CD4+ T cells in human subjects receiving a vaccine
      antigen.
    

Intervention name(s): GLA-SE; LEISH-F3; MPL-SE; SE
Intervention type(s): Biological; Biological; Biological; Drug
Intervention description(s): Glucopyranosyl Lipid A- Stable oil-in-water emulsion (GLA-SE) is formulated in a stable oil-in-water emulsion (SE) to yield the adjuvant formulation GLA-SE. The combination of GLA-SE with a recombinant protein antigen (LEISH-F3) results in a Th1-type T cell response. GLA-SE appears as a milky- white liquid. 16 subjects receive vaccine on day 0, 28, and 168 of 0.5 ml of 20 mcg of LEISH-F3 + 5 mcg GLA-SE.; LEISH-F3 is a lyophilized formulation containing 50 mcg LEISH-F3 and excipients (mannitol, sucrose, and polysorbate 80). All subjects receive vaccine on day 0, 28, and 168 of 0.5 ml of 20 mcg of LEISH-F3.; Monophosphoryl Lipid A-Stable oil-in-water emulsion (MPL-SE) is an oil-in-water emulsion that contains Monophosphoryl Lipid A, an attenuated form of Lipid A from Salmonella Minnesota R595 in a emulsion (SE). The combination of MPL-SE with a recombinant protein antigen (LEISH-F3) results in a TH1-type T cell response. MPL-SE appears as a milky-white liquid. 16 subjects receive vaccine on day 0, 28, and 168 of 0.5 ml of 20 mcg of LEISH-F3+10 mcg MPL-SE.; Stable oil-in-water Emulsion (SE) is a squalene oil-in-water emulsion that has adjuvant properties of its own, but in a Th2-dependent manner. SE appears as milky-white liquid. 16 subjects receive vaccine on day 0, 28, and 168 of 0.5 ml of 20 mcg LEISH-F3 + SE.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: GLA-SE,LEISH-F3,leishmaniasis,MPL-SE,parent protocol,vaccine