NCT01751048

LEISH-F3 + GLA-SE and the LEISH-F3 + MPL-SE Vaccine

A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of the Vaccine Candidates LEISH-F3 + GLA-SE, LEISH-F3 + MPL-SE, and LEISH-F3 + SE in Healthy Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

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.

Conditions

• Leishmaniasis

Interventions

Type	Name	Description
BIOLOGICAL	GLA-SE	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.
BIOLOGICAL	LEISH-F3	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.
BIOLOGICAL	MPL-SE	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.
DRUG	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.

Timeline

• Start date: 2013-03-01
• Primary completion: 2015-01-01
• Completion: 2015-01-01
• First posted: 2012-12-17
• Last updated: 2017-01-02

Locations

1 site across 1 country: United States