NCT02143518

Safety and Immunogenicity Study of Na-GST-1 With or Without CpG

Phase 1 Study of the Safety and Immunogenicity of Na-GST-1/Alhydrogel, With or Without a CpG ODN Adjuvant, in Healthy Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Na-GST-1 is a protein expressed during the adult stage of the hookworm life cycle that is thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination with recombinant GST-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-GST-1 in healthy adult volunteers when co-administered with the immunostimulant CpG 10104, a Toll-like Receptor-9 agonist.

Detailed description

This is a Phase 1 randomized double-blind dose-escalation clinical trial in healthy hookworm-naïve adults conducted at the George Washington Medical Faculty Associates, Washington, DC, and the George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, Washington, DC. In total, 24 subjects will be progressively enrolled into 2 cohorts of 12 subjects each. In the first cohort 8 subjects will receive 30µg Na-GST-1/Alhydrogel co-administered with 500µg CpG 10104 and 4 subjects will receive 100µg Na-GST-1/Alhydrogel® only, in a randomized, double-blinded fashion. In the second cohort 8 subjects will receive 100µg Na-GST-1/Alhydrogel co-administered with 500µg CpG 10104 and 4 volunteers will receive 100µg Na-GST-1/Alhydrogel only, in a randomized, double-blinded fashion. Vaccinations will be administered intramuscularly in the deltoid muscle according to a 0, 2, 4-month schedule. Each subject will participate in the study for 68 weeks (16 months) and the total duration of the study is estimated at approximately 19 months.

Conditions

• Hookworm Infection
• Hookworm Disease

Interventions

Type	Name	Description
BIOLOGICAL	Na-GST-1/Alhydrogel®	The Na-GST-1 candidate vaccine contains the recombinant Na-GST-1 protein expressed by Pichia pastoris. Purified Na-GST-1 was subsequently adsorbed onto aluminum hydroxide gel (Alhydrogel®) and suspended in a solution containing 10% glucose and 10 mM imidazole. The final concentration of Na-GST-1 in the drug product is 0.1 mg/ml whereas that of Alhydrogel® is 0.8 mg/ml. Different doses of Na-GST-1 will be delivered by injecting different volumes of the 0.1 mg/ml Na-GST-1 preparation.
BIOLOGICAL	CpG 10104	Unmethylated cytosine-guanine dinucleotides (CpGs) are found in bacterial DNA in the expected frequency predicted by random usage, whereas their occurrence is suppressed 4-fold in vertebrate DNA. In vertebrate DNA CpG motifs are also usually methylated. Bacterial CpG-DNA motifs are recognized by the human innate immune system via Toll-like Receptor-9 (TLR-9), a pathogen-associated molecular pattern (PAMP) receptor that is expressed, in particular, by antigen-presenting dendritic cells. Interactions between CpG-DNA and TLR9 rapidly activate antigen-presenting dendritic cells to upregulate co-stimulatory molecules and to produce Th1-polarizing cytokines such as interleukin-12 and interferon gamma. CpG 10104 is a short synthetic oligodeoxynucleotide of the following sequence: 5'-TCG TCG TTT CGT CGT TTT GTC GTT-3'.

Timeline

• Start date: 2014-10-01
• Primary completion: 2016-06-01
• Completion: 2016-10-01
• First posted: 2014-05-21
• Last updated: 2025-07-04
• Results posted: 2025-07-04

Locations

1 site across 1 country: United States