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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Children's Research Institute
George Washington University
Information provided by (Responsible Party):
Albert B. Sabin Vaccine Institute
ClinicalTrials.gov Identifier:
NCT01385189
First received: June 28, 2011
Last updated: September 13, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Hookworm Infection
Hookworm Disease
Biological: 10 μg Na-GST-1/Alhydrogel
Biological: 30 μg Na-GST-1/Alhydrogel
Biological: 100 μg Na-GST-1/Alhydrogel
Biological: 10 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
Biological: 30 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
Biological: 100 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
Biological: 10 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
Biological: 30 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
Biological: 100 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Albert B. Sabin Vaccine Institute:

Primary Outcome Measures:
  • Immediate vaccine related adverse events [ Time Frame: 2 hours post vaccination ] [ Designated as safety issue: Yes ]
    Frequency of vaccine-related AEs, graded by severity, for each dose and formulation of Na-GST-1


Secondary Outcome Measures:
  • IgG antibody response to Na-GST-1 [ Time Frame: 126 days post dose 1 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Cellular immune responses to the Na-GST-1 antigen both before and after immunization


Estimated Enrollment: 90
Study Start Date: May 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Formulation A
A: 10 μg Na-GST-1/Alhydrogel
Biological: 10 μg Na-GST-1/Alhydrogel
3 doses 10 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Experimental: Formulation B
B: 30 μg Na-GST-1/Alhydrogel
Biological: 30 μg Na-GST-1/Alhydrogel
3 doses 30 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Experimental: Formulation C
C: 100 μg Na-GST-1/Alhydrogel
Biological: 100 μg Na-GST-1/Alhydrogel
3 doses 100 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Experimental: Formulation D
D: 10 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg)
Biological: 10 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
3 doses 10 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg) administered at 56 day intervals
Experimental: Formulation E
E: 30 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg)
Biological: 30 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
3 doses of 30 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg) administered at 56 day intervals
Experimental: Formulation F
F: 100 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg)
Biological: 100 μg Na-GST-1/Alhydrogel with 1 μg GLA-AF
3 doses 100 μg Na-GST-1/Alhydrogel/GLA-AF (1 μg) administered at 56 day intervals
Experimental: Formulation G
G: 10 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg)
Biological: 10 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
3 doses 10 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg) administered at 56 day intervals
Experimental: Formulation H
H: 30 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg)
Biological: 30 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
3 doses 30 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg) administered at 56 day intervals
Experimental: Formulation I
I: 100 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg)
Biological: 100 μg Na-GST-1/Alhydrogel with 5 μg GLA-AF
3 doses 100 μg Na-GST-1/Alhydrogel/GLA-AF (5 μg) administered at 56 day intervals

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males or females between 18 and 45 years, inclusive.
  • Good general health as determined by means of the screening procedure.
  • Available for the duration of the trial (16 months).
  • Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

  • Pregnancy as determined by a positive urine β-hCG (if female).
  • Participant unwilling to use reliable contraception methods up until one month following the third immunization (if female).
  • Currently lactating and breast-feeding (if female).
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
  • Known or suspected immunodeficiency.
  • Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
  • Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing).
  • Laboratory evidence of hematologic disease (hemoglobin <12.5 g/dl [females] or <13.5 g/dl [males]; absolute leukocyte count <3500/mm-cubed or >10.5 x 103/mm-cubed; absolute neutrophil count [ANC] <2000/ mm-cubed; absolute lymphocyte count <1100/mm-cubed; or platelet count <140,000/mm-cubed).
  • Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).
  • Serum glucose (random) greater than 1.2-times the upper reference limit.
  • Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
  • Participation in another investigational vaccine or drug trial within 30 days of starting this study.
  • Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
  • History of a severe allergic reaction or anaphylaxis.
  • Severe asthma as defined by the need for regular use of inhalers or emergency clinic visit or hospitalization within the last 6 months.
  • Positive ELISA for HBsAg.
  • Positive ELISA and confirmatory Western blot tests for HIV-1.
  • Positive ELISA and confirmatory immunoblot tests for HCV.
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
  • Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
  • History of a surgical splenectomy.
  • Receipt of blood products within the past 6 months.
  • History of allergy to yeast.
  • History of previous infection with hookworm or residence for more than 6 months in a hookworm-endemic area.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01385189

Locations
United States, District of Columbia
Children's National Medical Center
Washington, DC, District of Columbia, United States, 20010
Sponsors and Collaborators
Albert B. Sabin Vaccine Institute
Children's Research Institute
George Washington University
Investigators
Study Director: David Diemert, MD Albert B. Sabin Vaccine Institute
  More Information

No publications provided

Responsible Party: Albert B. Sabin Vaccine Institute
ClinicalTrials.gov Identifier: NCT01385189     History of Changes
Other Study ID Numbers: SVI-11-01
Study First Received: June 28, 2011
Last Updated: September 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Albert B. Sabin Vaccine Institute:
Human Hookworm Vaccine Initiative
HHVI
Human Hookworm
Hookworm
Hookworm Disease
N. americanus
Soil-transmitted helminth infection
Intestinal blood loss
Iron deficiency anemia

Additional relevant MeSH terms:
Hookworm Infections
Ancylostomiasis
Strongylida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014