Clinical Trial: Safety and Immunogenicity of a Human Hookworm Candidate Vaccine With Different Doses of a Novel Adjuvant

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Study of the Safety and Immunogenicity of Na-GST-1/Alhydrogel® With Different Doses of the Novel Immunostimulant GLA-AF in Healthy Adults

Brief Summary: This study is designed to evaluate the safety, reactogenicity, and immunogenicity of Na-GST-1 adsorbed to Alhydrogel® with or without two different dose concentrations of a novel adjuvant, GLA-AF (1 µg or 5 μg) among healthy adult volunteers.

Detailed Summary:

Human hookworm infection is a soil-transmitted helminth infection caused by the nematode parasites Necator americanus and Ancylostoma duodenale. It is one of the most common chronic infections of humans, afflicting up to 740 million people in the developing nations of the tropics. The largest number of cases occurs in impoverished rural areas of sub-Saharan Africa, Southeast Asia, China, and the tropical regions of the Americas. Approximately 3.2 billion people are at risk for hookworm infection in these areas. N. americanus is the most common hookworm worldwide, whereas A. duodenale is more geographically restricted.

The primary approach to hookworm control worldwide has been the frequent and periodic mass administration of benzimidazole anthelminthics to school-aged children living in high-prevalence areas. In 2001, the World Health Assembly adopted Resolution 54.19 which urges member states to provide regular anthelminthic treatment to high-risk groups with the target of regular treatment of at least 75% of all at-risk school-aged children. However, the cure rates for a single dose of a benzimidazole varies with rates as low as 61% (400 mg) and 67% (800 mg) for albendazole and 19% (single dose) and 45% (repeated dose) for mebendazole being reported. These concerns have prompted interest in developing alternative tools for hookworm control. Vaccination to prevent the anemia associated with moderate and heavy intensity hookworm infection would alleviate the public health deficiencies of drug treatment alone.

The current strategy for development of Human Hookworm candidate vaccines is focused on antigens expressed during the adult stage of the hookworm life cycle which play a role in digesting the host hemoglobin, used by the worm as an energy source. These antigens are relatively hidden from the human immune system during
Sponsor: Albert B. Sabin Vaccine Institute

Current Primary Outcome: Immediate Vaccine Related Adverse Events [ Time Frame: 2 hours post vaccination ]

Original Primary Outcome: Same as current

Current Secondary Outcome: IgG Antibody Response to Na-GST-1 [ Time Frame: 126 days post dose 1 ]

Original Secondary Outcome:

• IgG Antibody Response to Na-GST-1 [ Time Frame: 126 days post dose 1 ]
  Dose and formulation of Na-GST-1 that generates the highest IgG antibody response at Day 126, as determined by an indirect enzyme-linked immunosorbent assay (ELIZA)
• Antibody response to Na-GST-1 with greatest affinity [ Time Frame: 290 days post dose 1 ]
  To determine the dose, formulation, and number of injections of Na-GST-1 that generates the antibody response of greatest affinity
• Most robust Na-GST-1 antibody response [ Time Frame: 126 days post dose 1 ]
  To determine the dose and formulation of the Na-GST-1 vaccine that results in the most robust production of Na-GST-1 specific B cells and subtypes (memory or plasma)
• Exploratory cellular immune response to Na-GST-1 [ Time Frame: Up to 290 days post dose 1 ]
  Cellular immune responses to the Na-GST-1 antigen both before and after immunization

Information By: Albert B. Sabin Vaccine Institute

Dates:
Date Received: June 28, 2011
Date Started: May 2012
Date Completion:
Last Updated: March 10, 2017
Last Verified: March 2017