Safety and Immunogenicity of Co-Administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 in Gabonese Adults
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 30 µg Na-GST-1 + 30 µg Na-APR-1 (M74) 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 |
Biological: Na-APR-1 (M74)/Alhydrogel®
Biological: Na-GST-1/Alhydrogel®
|
Active Comparator: Hepatitis B vaccine Hepatitis B vaccine co-administered with saline |
Biological: Hepatitis B vaccine
Hepatitis B vaccine co-administered with saline
|
Experimental: 100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74) 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 |
Biological: Na-APR-1 (M74)/Alhydrogel®
Biological: Na-GST-1/Alhydrogel®
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males or females between 18 and 50 years, inclusive, who are long-term residents of Gabon.
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Good general health as determined by means of the screening procedure.
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Assumed availability for the duration of the trial (12 months).
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Willingness to participate in the study as evidenced by signing the informed consent document.
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Negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole.
Exclusion Criteria:
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Pregnancy as determined by a positive urine hCG (if female).
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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).
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Currently lactating and breast-feeding (if female).
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Inability to correctly answer all questions on the informed consent comprehension questionnaire.
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Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
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Known or suspected immunodeficiency.
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Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
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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).
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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).
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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.
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Participation in another investigational vaccine or drug trial within 30 days of starting this study or for the duration of the study.
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Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
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History of a severe allergic reaction or anaphylaxis.
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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.
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Positive for HCV
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Positive ELISA for HBsAg.
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Positive for HIV infection
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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.
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Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
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History of a surgical splenectomy.
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Receipt of blood products within the 6 months prior to entry into the study.
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Previous receipt of a primary series of any hepatitis B vaccine.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Centre de Recherches Médicales de Lambaréné Albert Schweitzer Hospital | Lambaréné | Gabon | BP: 118 |
Sponsors and Collaborators
- Baylor College of Medicine
Investigators
- Principal Investigator: Ayola Adegnika, MD, Centre de Recherches Medicales de Lambarené
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HV-001
- 602843-2