Clinical trial NCT00473967: Phase 1 Trial of Na-ASP-2 Hookworm Vaccine in Previously Infected Brazilian Adults
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hookworm Infection
Keywords: Vaccine
Hookworm
Phase 1
Na-ASP-2
Lead sponsor: Albert B. Sabin Vaccine Institute
Sponsor class: OTHER
Collaborators: name: Oswaldo Cruz Foundation
name: George Washington University
name: London School of Hygiene and Tropical Medicine
First posted: 2007-05-16
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: To determine the frequency of vaccine-related adverse events, graded by severity, for each dose of the Na-ASP-2 Hookworm Vaccine
timeFrame: For the duration of the study
Secondary outcomes:
measure: To determine the dose of Na-ASP-2 that generates the highest antibody response as determined by an indirect enzyme-linked immunosorbent assay (ELISA)
timeFrame: 2 weeks after the third injection
measure: To assess and compare the duration of antibody response to Na-ASP-2
timeFrame: For the duration of the study
measure: To perform exploratory studies of the cellular immune responses to the Na-ASP-2 antigen both before and after immunization
timeFrame: For the duration of the study
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Centro de Pesquisas Rene Rachou
Study officials:
affiliation: Albert B. Sabin Vaccine Institute
name: David J Diemert, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diemert DJ, Pinto AG, Freire J, Jariwala A, Santiago H, Hamilton RG, Periago MV, Loukas A, Tribolet L, Mulvenna J, Correa-Oliveira R, Hotez PJ, Bethony JM. Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths. J Allergy Clin Immunol. 2012 Jul;130(1):169-76.e6. doi: 10.1016/j.jaci.2012.04.027. Epub 2012 May 26.