Phase 1 Trial of Na-ASP-2 Hookworm Vaccine in Previously Infected Brazilian Adults

Study Overview
=================
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.

Official Title
-----------------
Double-blind, Randomized, Controlled Phase 1 Study of the Safety and Immunogenicity of Na-ASP-2 Hookworm Vaccine in Previously-Infected Brazilian Adults

Conditions
-----------------
Hookworm Infection

Intervention / Treatment
-----------------
* Biological: Na-ASP-2 Hookworm Vaccine


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mcg Na-ASP-2/Alhydrogel<br>Na-ASP-2 Hookworm Vaccine | Biological: Na-ASP-2 Hookworm Vaccine<br>* 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.<br>|
| Active Comparator: Butang hepatitis B vaccine<br>Hepatitis B Vaccine - comparator vaccine | Biological: Na-ASP-2 Hookworm Vaccine<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Hookworm, Phase 1, Na-ASP-2