Hookworm Infection
Conditions
Keywords
Vaccine, Hookworm, Phase 1, Na-ASP-2
Brief summary
Na-ASP-2 is a protein expressed during the larval stage of the N. americanus hookworm life cycle. Vaccination with recombinant ASP-2 has protected dogs and hamsters from infection in challenge studies. In a clinical study in hookworm-uninfected adults in the USA, Na-ASP-2 Hookworm Vaccine was safe and immunogenic. This study will evaluate its safety and immunogenicity in individuals living in an area of endemic hookworm infection.
Detailed description
* Double-blind, randomized, controlled Phase 1 clinical trial. * Study site: Americaninhas, Minas Gerais, Brazil. * Number of participants: 48 in three groups of 16, randomized to receive either Na-ASP-2 Hookworm Vaccine (n=36) or Butang® hepatitis B vaccine (n=12). * Study duration: 48 weeks; each participant will be followed for a total of 42 weeks. * Immunization schedule: Study days 0, 56 and 112. * Route: IM in the deltoid muscle. * Dose of Na-ASP-2: 10, 50 and 100 µg for the first, second and third dose cohort, respectively. * Dose of Alhydrogel®: 800 µg for each dose of Na-ASP-2.
Interventions
BIOLOGICALNa-ASP-2 Hookworm Vaccine
Injections of one of three different dose concentrations of the Na-ASP-2 vaccine (10, 50, or 100 mcg) vs. the hepatitis B vaccine, delivered at 0, 2, and 4 months by intramuscular injection.
Sponsors
Oswaldo Cruz Foundation
George Washington University
London School of Hygiene and Tropical Medicine
Albert B. Sabin Vaccine Institute
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females between 18 and 45 years, inclusive. * Known residents of the Municipality of Novo Oriente de Minas, Minas Gerais, Brazil. * Good general health as determined by means of the screening procedure. * Completed a 3-dose albendazole treatment for documented hookworm infection during the previous 3 months. * Available for the duration of the trial (42 weeks). * 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). * Inability to correctly answer all questions on the informed consent comprehension questionnaire. * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies. * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol. * Laboratory evidence of liver disease (alanine aminotransferase \[ALT\] greater than 64 U/l \[females\] or greater than 58 U/l \[males\]). * Laboratory evidence of renal disease (serum creatinine greater than 1.1 mg/dl \[females\] or greater than 1.3 mg/dl \[males\], 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 \[females\] or \<11.0 g/dl \[males\]; absolute lymphocyte count \<900/mm3; or platelet count \<120,000/mm3). * 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. * Known immunodeficiency syndrome. * 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. * Previous receipt of a primary series of any hepatitis B vaccine. * History of allergy to yeast.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the frequency of vaccine-related adverse events, graded by severity, for each dose of the Na-ASP-2 Hookworm Vaccine | For the duration of the study |
Secondary
| Measure | Time frame |
|---|---|
| To determine the dose of Na-ASP-2 that generates the highest antibody response as determined by an indirect enzyme-linked immunosorbent assay (ELISA) | 2 weeks after the third injection |
| To assess and compare the duration of antibody response to Na-ASP-2 | For the duration of the study |
| To perform exploratory studies of the cellular immune responses to the Na-ASP-2 antigen both before and after immunization | For the duration of the study |
Countries
Brazil
Outcome results
None listed