Hookworm Disease, Hookworm Infection
Conditions
Keywords
Human Hookworm, Necator americanus, Hookworm, Hookworm Disease, Iron-deficiency anemia, Soil-transmitted helminth infection, Neglected Tropical Disease, Na-APR-1, Na-GST-1
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.
Interventions
BIOLOGICALNa-APR-1 (M74)/Alhydrogel®
BIOLOGICALNa-GST-1/Alhydrogel®
BIOLOGICALHepatitis B vaccine
Hepatitis B vaccine co-administered with saline
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Gabon
Outcome results
None listed