Clinical Trial: Safety and Immunogenicity of a Human Hookworm Candidate Vaccine With or Without Additional Adjuvant in Brazilian Adults

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

Official Title: Phase 1 Study of the Safety and Immunogenicity of Na-GST-1/Alhydrogel® With or Without GLA-AF in Brazilian Adults

Brief Summary: This two part study will evaluate the safety and immunogenicity of two formulations of Na-GST-1, first in hookworm-naïve individuals using an open-label design, and then in adults living in an area of endemic hookworm infection using a randomized, double-blind design. The two formulations to be evaluated are Na-GST-1 adsorbed to an adjuvant, Alhydrogel®, and Na-GST-1 adsorbed to Alhydrogel® and administered with GLA-AF.

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: Baylor College of Medicine

Current Primary Outcome: Immediate vaccine related adverse events [ Time Frame: 2 hours post vaccination ]

Frequency of vaccine-related AEs, graded by severity, for each dose and formulation of Na-GST-1


Original Primary Outcome: Immediate vaccine related adverse events [ Time Frame: 60 minutes post vaccination ]

Frequency of vaccine-related AEs, graded by severity, for each dose and formulation of Na-GST-1


Current 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 (ELISA)
  • Duration of antibody response to Na-GST-1 [ Time Frame: 290 days post dose 1 ]
    Duration of anti-GST-1 antibody, up to Day 290, as determined by an indirect enzyme-linked immunosorbent assay (ELISA)
  • 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


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: December 14, 2010
Date Started: November 2011
Date Completion:
Last Updated: May 30, 2017
Last Verified: May 2017