Clinical Trial: Safety and Immunogenicity of Co-Administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 in Gabonese Adults

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

Official Title: Randomized, Controlled, Phase 1 Study to Assess Safety and Immunogenicity of Co-administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 Adjuvanted With Alhydrogel® and Gluco-pyranosylphosp

Brief Summary: Na-GST-1 and Na-APR-1 are proteins expressed during the adult stage of the Necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination with recombinant GST-1 or APR-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of co-administering Na-GST-1 and Na-APR-1 to healthy Gabonese adults living in an area of endemic hookworm infection.

Detailed Summary:

Double-blind, randomized, controlled dose-escalation Phase 1 clinical trial in hookworm exposed adults.

Study site: Centre de Recherches Médicales de Lambaréné Number of participants: 32 in 2 cohorts of 16

Doses of Na-GST-1 to be tested: 30 and 100 μg Doses of Na-APR-1 to be tested: 30 and 100 μg Dose of GLA-AF: 5 μg per antigen

Cohort 1: 30 μg of each of the two antigens (Na-GST-1/Alhydrogel® and Na-APR-1 (M74)/Alhydrogel®) or hepatitis B vaccine; Cohort 2: 100 μg of each of the two antigens (Na-GST- 1/Alhydrogel® and Na-APR-1 (M74) /Alhydrogel®) or hepatitis B vaccine.

Randomization: Cohort 1: 30 μg Na-GST-1 + 30 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine/placebo (n = 4) Cohort 2: 100 μg Na-GST-1 + 100 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine + placebo (n = 4)

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-GST-1 and Na-APR-1 dose escalation from 30 to 100 µg.

Pre-treatment: Albendazole (400 mg) at least 2 weeks prior to first vaccination

Immunization schedule: Study days 0, 28 and 180 Route: Intramuscular in the deltoid muscle

Study duration: approximately 20 months; each participant will be followed for a total of 12 months.


Sponsor: Baylor College of Medicine

Current Primary Outcome: Vaccine-related Adverse Events [ Time Frame: Day 360 ]

To estimate the frequency of vaccine-related adverse events, graded by severity, for each dose of co-administered Na-GST-1 and Na-APR-1 (M74).

The frequency of immediate, systemic, and local injection site adverse events will be summarized. Adverse events will be assessed by study team members at 1 hour post-vaccination as well as 1, 3, 7, 14, and 28 days following each vaccination.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • IgG response to Na-GST-1 and Na-APR-1 (M74) [ Time Frame: Day 194 ]
    To determine the doses of Na-GST-1 and Na-APR-1 (M74) that generate the highest IgG antibody responses at Day 194, as determined by indirect enzyme-linked immunosorbent assays (ELISA)
  • Duration of antibody response to Na-GST-1 and Na-APR-1 (M74) [ Time Frame: Day 14, 28, 42, 56, 180, 194, 208, 270, 360 ]
    To assess and compare the duration of antibody responses to Na- GST-1 and Na-APR-1 (M74).
  • Exploratory studies of memory B-cell responses [ Time Frame: Days 14, 28, 42, 56, 180, 194, 208, 270, 360 ]
    Exploratory studies of memory B-cell responses against the metabolomics changes before and after Na-GST-1 and NA-APR-1 (M74) vaccine antigens.


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: April 28, 2014
Date Started: November 2014
Date Completion:
Last Updated: May 30, 2017
Last Verified: May 2017