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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Albert B. Sabin Vaccine Institute
ClinicalTrials.gov Identifier:
NCT01261130
First received: December 14, 2010
Last updated: September 13, 2013
Last verified: September 2013
  Purpose

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.


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/GLA-AF
Biological: 30 μg Na-GST-1/Alhydrogel/GLA-AF
Biological: 100 μg Na-GST-1/Alhydrogel/GLA-AF
Biological: Butang® hepatitis B vaccine
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 1 Study of the Safety and Immunogenicity of Na-GST-1/Alhydrogel® With or Without GLA-AF in Brazilian 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 (ELISA)

  • Duration of antibody response to Na-GST-1 [ Time Frame: 290 days post dose 1 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Cellular immune responses to the Na-GST-1 antigen both before and after immunization


Estimated Enrollment: 102
Study Start Date: November 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I-A: 10μgNaGST1/Alhydrogel
Part I (non-endemic area), Formulation A
Biological: 10 μg Na-GST-1/Alhydrogel
3 doses 10 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation A
Experimental: Part I-B: 30μgNaGST1/Alhydrogel
Part I (non-endemic area), Formulation B
Biological: 30 μg Na-GST-1/Alhydrogel
3 doses 30 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation B
Experimental: Part I-C: 100μgNaGST1/Alhydrogel
Part I (non-endemic area), Formulation C
Biological: 100 μg Na-GST-1/Alhydrogel
3 doses 100 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation C
Experimental: Part I-D: 10μgNaGST1/Alhydrogel/GLA
Part I (non-endemic area), Formulation D
Biological: 10 μg Na-GST-1/ Alhydrogel/GLA-AF
3 doses 10 μg Na-GST-1/ Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation D
Experimental: Part I-E: 30μgNaGST1/Alhydrogel/GLA
Part I (non-endemic area), Formulation E
Biological: 30 μg Na-GST-1/Alhydrogel/GLA-AF
3 doses 30 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation E
Experimental: Part I-F: 100μgNaGST1/Alhydrogel/GLA
Part I (non-endemic area), Formulation F
Biological: 100 μg Na-GST-1/Alhydrogel/GLA-AF
3 doses 100 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation F
Experimental: Part II-A: 10μgNaGST1/Alhydrogel
Part II (endemic area), Formulation A
Biological: 10 μg Na-GST-1/Alhydrogel
3 doses 10 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation A
Experimental: Part II-B: 30μgNaGST1/Alhydrogel
Part II (endemic area), Formulation B
Biological: 30 μg Na-GST-1/Alhydrogel
3 doses 30 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation B
Experimental: Part II-C: 100μgNaGST1/Alhydrogel
Part II (endemic), Formulation C
Biological: 100 μg Na-GST-1/Alhydrogel
3 doses 100 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Other Name: Formulation C
Experimental: Part II-D: 10μgNaGST1/Alhydrogel/GLA
Part II (endemic area), Formulation D
Biological: 10 μg Na-GST-1/ Alhydrogel/GLA-AF
3 doses 10 μg Na-GST-1/ Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation D
Experimental: Part II-E: 30μgNaGST1/Alhydrogel/GLA
Part II (endemic area), Formulation E
Biological: 30 μg Na-GST-1/Alhydrogel/GLA-AF
3 doses 30 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation E
Experimental: Part II-F: 100μgNaGST1/Alhydrogel/GLA
Part II (endemic area), Formulation F
Biological: 100 μg Na-GST-1/Alhydrogel/GLA-AF
3 doses 100 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Other Name: Formulation F
Active Comparator: Part II-G: Butang® hepatitis B vaccine
Part II (endemic), HepB comparator
Biological: Butang® hepatitis B vaccine
3 doses Butang® hepatitis B vaccine administered at 56 day intervals
Other Name: Butang® hepatitis B vaccine

  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 (42 weeks).
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • If found to be infected with hookworm during screening, has completed a course of three doses of albendazole.

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).
  • Inability to correctly answer all questions on the informed consent comprehension questionnaire.
  • 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 (absolute leukocyte count <3000/mm3 or >12.5 x 103/mm3; hemoglobin <10.3 g/dl or <11.0 g/dl [females in Americaninhas and Belo Horizonte, respectively] or <11.0 g/dl or <12.0 [males in Americaninhas and Belo Horizonte, respectively); absolute lymphocyte count <900/mm3; or platelet count <120,000/mm3).
  • Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit [in Belo Horizonte] or PT INR greater than 1.3 [Americaninhas]).
  • 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 HCV.
  • Positive ELISA for HBsAg.
  • Positive ELISA for HIV.
  • 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.
  • Anti-Na-GST-1 IgE antibody level above 0.35 kUA/L by the ImmunoCAP method.
  • For Part I only: history of previous infection with hookworm; residence for more than 6 months in a hookworm-endemic area; or, positive for hookworm infection on screening microscopic fecal examination.
  • For Part II only: previous receipt of a primary series of any hepatitis B vaccine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01261130

Locations
Brazil
Americaninhas Vaccine Center
Americaninhas, Minas Gerais, Brazil
Centro de Pesquisas René Rachou - FIOCRUZ
Belo Horizonte, Minas Gerais, Brazil
Sponsors and Collaborators
Albert B. Sabin Vaccine Institute
Investigators
Principal Investigator: David Diemert, MD Albert B. Sabin Vaccine Institute
  More Information

No publications provided

Responsible Party: Albert B. Sabin Vaccine Institute
ClinicalTrials.gov Identifier: NCT01261130     History of Changes
Other Study ID Numbers: SVI-10-01
Study First Received: December 14, 2010
Last Updated: September 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency

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 August 19, 2014