Safety and Immunogenicity of Co-Administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 in Gabonese Adults

Phase 1

Completed

• Conditions: Hookworm Disease; Hookworm Infection
• Interventions: Biological: Hepatitis B vaccine; Biological: Na-APR-1 (M74)/Alhydrogel®; Biological: Na-GST-1/Alhydrogel®

• Registration Number: NCT02126462
• Lead Sponsor: Baylor College of Medicine

Brief Summary

Na-GST-1 and Na-APR-1 are proteins expressed during the adult stage of the Necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination with recombinant GST-1 or APR-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of co-administering Na-GST-1 and Na-APR-1 to healthy Gabonese adults living in an area of endemic hookworm infection.

Detailed Description

Double-blind, randomized, controlled dose-escalation Phase 1 clinical trial in hookworm exposed adults.

Study site: Centre de Recherches Médicales de Lambaréné Number of participants: 32 in 2 cohorts of 16

Doses of Na-GST-1 to be tested: 30 and 100 μg Doses of Na-APR-1 to be tested: 30 and 100 μg Dose of GLA-AF: 5 μg per antigen

Cohort 1: 30 μg of each of the two antigens (Na-GST-1/Alhydrogel® and Na-APR-1 (M74)/Alhydrogel®) or hepatitis B vaccine; Cohort 2: 100 μg of each of the two antigens (Na-GST- 1/Alhydrogel® and Na-APR-1 (M74) /Alhydrogel®) or hepatitis B vaccine.

Randomization: Cohort 1: 30 μg Na-GST-1 + 30 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine/placebo (n = 4) Cohort 2: 100 μg Na-GST-1 + 100 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine + placebo (n = 4)

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-GST-1 and Na-APR-1 dose escalation from 30 to 100 µg.

Pre-treatment: Albendazole (400 mg) at least 2 weeks prior to first vaccination

Immunization schedule: Study days 0, 28 and 180 Route: Intramuscular in the deltoid muscle

Study duration: approximately 20 months; each participant will be followed for a total of 12 months.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-04-28
• Study First Submitted QC: 2014-04-29
• Study First Posted: 2014-04-30
• Study Start: 2014-11
• Primary Completion: 2016-02
• Study Completion: 2016-06
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-30
• Last Update Posted: 2017-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Males or females between 18 and 50 years, inclusive, who are long-term residents of Gabon.
• Good general health as determined by means of the screening procedure.
• Assumed availability for the duration of the trial (12 months).
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole.

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Exclusion Criteria

• Pregnancy as determined by a positive urine hCG (if female).
• Participant unwilling to use reliable contraception up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal).
• 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, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
• Known or suspected immunodeficiency.
• Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
• Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing).
• Laboratory evidence of hematologic disease (absolute leukocyte count <3500/mm3; absolute leukocyte count >11.0 x 103/mm3; hemoglobin <10.000 g/dl [females] or <12.0 g/dl [males]; or, platelet count <140,000/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 or for the duration of the 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 daily use of inhalers or emergency room/clinic visit or hospitalization within 6 months of the volunteer's planned first vaccination in the study.
• Positive for HCV
• Positive ELISA for HBsAg.
• Positive for HIV infection
• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or expect to use for the duration of the 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 6 months prior to entry into the study.
• Previous receipt of a primary series of any hepatitis B vaccine.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
30 µg Na-GST-1 + 30 µg Na-APR-1 (M74)	Na-GST-1/Alhydrogel®	30 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 30 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF
Hepatitis B vaccine	Hepatitis B vaccine	Hepatitis B vaccine co-administered with saline
100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74)	Na-GST-1/Alhydrogel®	100 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 100 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF
30 µg Na-GST-1 + 30 µg Na-APR-1 (M74)	Na-APR-1 (M74)/Alhydrogel®	30 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 30 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF
100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74)	Na-APR-1 (M74)/Alhydrogel®	100 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 100 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF

Primary Outcome Measures

Name	Time	Method
Vaccine-related Adverse Events	Day 360	To estimate the frequency of vaccine-related adverse events, graded by severity, for each dose of co-administered Na-GST-1 and Na-APR-1 (M74).; The frequency of immediate, systemic, and local injection site adverse events will be summarized. Adverse events will be assessed by study team members at 1 hour post-vaccination as well as 1, 3, 7, 14, and 28 days following each vaccination.

Secondary Outcome Measures

Name	Time	Method
IgG response to Na-GST-1 and Na-APR-1 (M74)	Day 194	To determine the doses of Na-GST-1 and Na-APR-1 (M74) that generate the highest IgG antibody responses at Day 194, as determined by indirect enzyme-linked immunosorbent assays (ELISA)
Duration of antibody response to Na-GST-1 and Na-APR-1 (M74)	Day 14, 28, 42, 56, 180, 194, 208, 270, 360	To assess and compare the duration of antibody responses to Na- GST-1 and Na-APR-1 (M74).
Exploratory studies of memory B-cell responses	Days 14, 28, 42, 56, 180, 194, 208, 270, 360	Exploratory studies of memory B-cell responses against the metabolomics changes before and after Na-GST-1 and NA-APR-1 (M74) vaccine antigens.

Trial Locations

Locations (1)

Centre de Recherches Médicales de Lambaréné Albert Schweitzer Hospital; 🇬🇦 Lambaréné, Gabon