NCT01717950

Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults

Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® in Healthy Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

Conditions

• Hookworm Infection
• Hookworm Disease

Interventions

Type	Name	Description
BIOLOGICAL	Na-APR-1 (M74)/Alhydrogel®	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.
BIOLOGICAL	Gluco-Pyranosylphospho-Lipid A Aqueous Formulation	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.

Timeline

• Start date: 2013-09-01
• Primary completion: 2015-06-01
• Completion: 2015-09-01
• First posted: 2012-10-31
• Last updated: 2019-07-31

Locations

1 site across 1 country: United States