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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hookworm Infection
• Intervention / Treatment: Biological: Na-ASP-2 Hookworm Vaccine

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Centro de Pesquisas Rene Rachou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Albert B. Sabin Vaccine Institute
• Collaborators: London School of Hygiene and Tropical Medicine; George Washington University; Oswaldo Cruz Foundation
• Investigators: Principal Investigator: David J Diemert, MD, Albert B. Sabin Vaccine Institute

Publications and helpful links

General Publications

• 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.

Helpful Links

• Sponsor's Web page
• Trial site website

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ACTUAL): March 1, 2008
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: May 14, 2007
• First Submitted That Met QC Criteria: May 14, 2007
• First Posted (ESTIMATE): May 16, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): July 9, 2012
• Last Update Submitted That Met QC Criteria: July 6, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Vaccine; Phase 1; Hookworm; Na-ASP-2
• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Strongylida Infections; Hookworm Infections; Ancylostomiasis
• Other Study ID Numbers: SVI-06-02