NCT01540474

Trial of a Falciparum Malaria Protein (FMP012), E. Coli-expressed PfCelTOS, in Healthy Malaria-Naive Adults

Phase 1 Study With the Vaccine Candidate Plasmodium Falciparum Malaria Protein (FMP012), an E.Coli-expressed Cell-Traversal Protein, Administered Intramuscularly in Healthy Malaria-Naive Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: U.S. Army Medical Research and Development Command · Federal
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Malaria has remained a major concern for the US military. During World War II, malaria was the leading cause of disease and non-battle injury with 500-700 men infected per day, resulting in 24,000 malaria-related casualties.(10) Currently, the methods used for protecting troops against malaria are insecticidal nets, clothing, and antimalarial treatment. To be effective, these methods must be self-administered and be used consistently, often unattainable in field or combat situations. The United States Army Medical Research and Development Command (USAMRMC), through the United States Army Medical Materiel Development Activity (USAMMDA) and the Walter Reed Army Institute of Research (WRAIR) are actively pursuing the development of an effective vaccine against P. falciparum malaria; development of such a vaccine is a high priority for the US military and other individuals who travel to endemic regions, and is equally important to populations residing in those areas. A Phase 1 study using FMP012, a recombinant E.coli expressed malaria protein (CelTOS) vaccine will 1. assess the safety and reactogenicity of candidate P. falciparum malaria vaccine FMP012/GLA-SE Secondary: 2. measure the humoral immune response to FMP012/GLA-SE using enzyme-linked immunosorbent assay (ELISA) 3. assess the protective efficacy of FMP012/GLA-SE against a P. falciparum sporozoite challenge.

Detailed description

Single center, non-randomized, open label, dose escalation Phase 1study with sporozoite challenge. The antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant produced by the Infectious Disease Research Institute (IDRI). This is a first-in-human study of FMP012. Thirty subjects, divided into 3 groups (10 subjects per group), will receive 3 doses of the FMP012/GLA-SE vaccine. Group 1 will receive 10 µg of FMP012 formulated with 2 µg GLA-SE adjuvant and Group 2 will receive 10 µg of FMP012 formulated with 5 µg GLA-SE adjuvant. Group 3 will receive 50 µg of FMP012 formulated with either 5 µg GLA-SE adjuvant (Group 3a) or 2 µg GLA-SE adjuvant (Group 3b). Determination of whether to proceed with Group 3a or Group 3b will be made by the principal investigator (PI) and the independent medical monitor after the second vaccination dose in Group 2 has been completed, based on predefined safety and group hold criteria in this protocol. There will be a staggered start for Group 1 and Group 2 separated by a minimum of 14 days. Group 3a or Group 3b will start vaccinations 2 weeks after the second vaccination for Group 2. The first and second vaccination doses in each group will be separated by 28 days and all groups will receive the third vaccination dose on the same day. The second and third vaccination doses in Group 1 will be separated by 84 days, Group 2 by 70 days, and Group 3 by 28 days. Six non-immunized infectivity control subjects will be enrolled prior to the challenge phase. All subjects from the Vaccination Group and Infectivity Control Group will participate in the primary malaria sporozoite challenge and will be required to stay at a hotel for evaluation for a maximum of 10 nights starting 9 days after the challenge. A directly monitored, sequentially allocated, open-label oral regimen of chloroquine or artemether/lumefantrine will be administered to all parasitemic subjects.

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	Group 1: 10 ug FMP012 with 2 ug GLA-SE	Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
BIOLOGICAL	Group 2: 10 ug FMP012 with 5 ug GLA-SE	E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant
BIOLOGICAL	50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE	E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant
OTHER	Controlled group-Challenged Only: no vaccination	The control group participated in the primary malaria sporozoite challenge.E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant

Timeline

• Start date: 2012-02-01
• Primary completion: 2012-10-01
• Completion: 2012-12-01
• First posted: 2012-02-28
• Last updated: 2021-06-08
• Results posted: 2021-06-08

Locations

1 site across 1 country: United States