Efficacy of Na-GST-1/Alhydrogel Hookworm Vaccine Assessed by Controlled Challenge Infection

Hookworm Infections Clinical Trial

Official title: Phase 2 Study to Assess the Safety, Efficacy and Immunogenicity of Na-GST-1/Alhydrogel Co-administered With Different Toll-Like Receptor Agonists in Hookworm- Naïve Adults

Status Completed

Clinical Trial Summary

This study evaluates the efficacy, safety and immunogenicity of different formulations of the Na-GST-1 hookworm vaccine using a controlled human hookworm infection model in healthy, hookworm-naive adults.

Clinical Trial Description

Double blind, randomized, controlled, Phase 2 clinical trial in hookworm-unexposed adults living in the metropolitan area of Washington, DC. Subjects will receive three doses of the assigned vaccine formulation, or saline placebo, delivered intramuscularly on approximately Days 0, 56, and 112.

Subjects will be challenged with 50 infectious N. americanus larvae 4 weeks after 3rd vaccination. Fecal samples will be collected weekly starting 4 weeks post-challenge. Albendazole will be administered 20 weeks post-challenge to cure infections. Subjects will be followed until 10 months after their final vaccination.

Safety of vaccination will be measured from the time of each study vaccination (Day 0) through 14 days after each study vaccination by the occurrence of solicited injection site and systemic reactogenicity events. Safety of CHHI will be measure from the time of larval application (Day 140) through the first day of treatment with albendazole (Day 280).

Unsolicited non-serious adverse events (AEs) will be collected until approximately 1 month following each study vaccination and from study Day 140 (day of CHHI) through Day 280.

New-onset chronic medical conditions and Serious Adverse Events (SAEs) will be collected from the time of the first study vaccination through approximately 10 months after the third study vaccination (final visit). Clinical laboratory evaluations for safety will be performed on venous blood collected approximately 14 days after each vaccination and CHHI.

Immunogenicity testing will include IgG antibody responses to Na-GST-1, by a qualified indirect enzyme-linked immunosorbent assay (ELISA), on serum obtained prior to each study vaccination and CHHI, and at time points after each vaccination and after CHHI (see Appendix A); the affinity of vaccine-induced antibodies against Na-GST-1 using Surface Plasmon Resonance; the functional activity of vaccine-induced antibodies via in vitro enzyme neutralization assay; antigen-specific memory B cell responses; and, the innate immune responses to each of the TLR receptor immunostimulants.

Parasitological testing will include microscopic fecal egg detection by a qualified saline flotation technique, fecal egg counts by the McMaster method, fecal PCR for hookworm DNA, and peripheral eosinophil counts.

Recruitment and enrollment into the study will occur on an ongoing basis, with each group being recruited and vaccinated in sequence.

48 subjects will be enrolled into 4 groups of 12. Subjects will be enrolled sequentially and upon enrollment will be randomized to one of the following IP assignments in a double-blind fashion:

• Group 1 IP allocation (n=12 subjects): 12 subjects will receive 100µg Na-GST-1/Alhydrogel® delivered by IM injection in the deltoid muscle.

• Group 2 IP allocation (n=12): 12 subjects will receive Na-GST-1/Alhydrogel® plus 500µg CpG 10104 delivered by IM injection in the deltoid muscle.

• Group 3 IP allocation (n=12): 12 subjects will receive Na-GST-1/Alhydrogel® plus 5µg GLA-AF delivered by IM injection in the deltoid muscle.

• Group 4 IP allocation (n=12): 12 subjects will receive sterile saline delivered by IM injection in the deltoid muscle. ;

Related Conditions & MeSH terms

• Hookworm Infections
• Infections

• NCT number: NCT03172975
• Study type: Interventional
• Source: Baylor College of Medicine
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2018
• Completion date: September 30, 2023