Phase 1 Trial of Na-ASP-2 Hookworm Vaccine in Previously Infected Brazilian Adults
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 10 mcg Na-ASP-2/Alhydrogel Na-ASP-2 Hookworm Vaccine |
Biological: Na-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.
|
Active Comparator: Butang hepatitis B vaccine Hepatitis B Vaccine - comparator vaccine |
Biological: Na-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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Centro de Pesquisas Rene Rachou | Belo Horizonte | Brazil |
Sponsors and Collaborators
- Albert B. Sabin Vaccine Institute
- Oswaldo Cruz Foundation
- George Washington University
- London School of Hygiene and Tropical Medicine
Investigators
- Principal Investigator: David J Diemert, MD, Albert B. Sabin Vaccine Institute
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- SVI-06-02