A Phase 1 interventional study of 10 μg Na-GST-1/Alhydrogel and 30 μg Na-GST-1/Alhydrogel in Hookworm Infection and Hookworm Disease, sponsored by Baylor College of Medicine. Completed at 2 sites in Brazil. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-05-31.
Sponsored by Baylor College of Medicine · Phase 1, Interventional, and Prevention
This two part study will evaluate the safety and immunogenicity of two formulations of Na-GST-1, first in hookworm-naïve individuals using an open-label design, and then in adults living in an area of endemic hookworm infection using a randomized, double-blind design. The two formulations to be evaluated are Na-GST-1 adsorbed to an adjuvant, Alhydrogel®, and Na-GST-1 adsorbed to Alhydrogel® and administered with GLA-AF.
Human hookworm infection is a soil-transmitted helminth infection caused by the nematode parasites Necator americanus and Ancylostoma duodenale. It is one of the most common chronic infections of humans, afflicting up to 740 million people in the developing nations of the tropics. The largest number of cases occurs in impoverished rural areas of sub-Saharan Africa, Southeast Asia, China, and the tropical regions of the Americas. Approximately 3.2 billion people are at risk for hookworm infection in these areas. N. americanus is the most common hookworm worldwide, whereas A. duodenale is more geographically restricted.
The primary approach to hookworm control worldwide has been the frequent and periodic mass administration of benzimidazole anthelminthics to school-aged children living in high-prevalence areas. In 2001, the World Health Assembly adopted Resolution 54.19 which urges member states to provide regular anthelminthic treatment to high-risk groups with the target of regular treatment of at least 75% of all at-risk school-aged children. However, the cure rates for a single dose of a benzimidazole varies with rates as low as 61% (400 mg) and 67% (800 mg) for albendazole and 19% (single dose) and 45% (repeated dose) for mebendazole being reported. These concerns have prompted interest in developing alternative tools for hookworm control. Vaccination to prevent the anemia associated with moderate and heavy intensity hookworm infection would alleviate the public health deficiencies of drug treatment alone.
The current strategy for development of Human Hookworm candidate vaccines is focused on antigens expressed during the adult stage of the hookworm life cycle which play a role in digesting the host hemoglobin, used by the worm as an energy source. These antigens are relatively hidden from the human immune system during natural infection, and hence have a low likelihood of inducing antigen-specific IgE in exposed/infected individuals, reducing the potential for allergic reaction upon vaccination.
The nutritional and metabolic requirements of the adult hookworm living in the human intestine are dependent upon degradation of host hemoglobin that has been ingested by the worm. N. americanus hookworms depend on host hemoglobin for survival. Following hemolysis, adult hookworms use an ordered cascade of hemoglobinases to cleave hemoglobin into smaller molecules. Following hemoglobin digestion, the freed heme generates toxic oxygen radicals that can be bound and detoxified by molecules such as glutathione S-transferase-1 (GST-1). GST-1 of N. americanus (Na-GST-1) is a critical enzyme that plays a role in parasite blood feeding; when used as a vaccine, the investigators hypothesize that the antigen will induce anti-enzyme neutralizing antibodies that will interfere with parasite blood-feeding and cause parasite death or reduce worm fecundity.
Following its selection as a candidate antigen Na-GST-1 has been successfully manufactured and tested in the laboratory and in animals with both Alhydrogel® (aluminum hydroxide suspension)and Alhydrogel® plus Gluco-Pyranosylphospho-Lipid A Aqueous Formulation (GLA-AF). Na-GST-1 has been shown to be pure, potent, and stable when administered as either of these two formulations.
The Na-GST-1 vaccine formulations to be tested in this study consist of the 24 kDa recombinant protein Na-GST-1 adsorbed to Alhydrogel® either with or without the addition of GLA-AF. For the Na-GST-1/GLA-AF formulation, the GLA-AF will be added to the Alhydrogel® formulation immediately prior to immunization. The active ingredient in both vaccine formulations is the recombinant Na-GST-1 protein that is derived by fermentation of Pichia pastoris yeast cells genetically engineered to express Na-GST-1.
In this first-in-human study, the evaluation of the safety and immunogenicity of the Na-GST-1 and Na-GST-1/GLA-AF formulations will be conducted in two parts. First, healthy adults who have not been infected with or exposed to hookworm will be enrolled in the urban center of Belo Horizonte, Brazil. Hookworm in Brazil is primarily a rural disease and is uncommon in developed urban areas such as Belo Horizonte. If no significant safety concerns are observed in these volunteers, the study will proceed to enroll and vaccinate healthy adults in a hookworm-endemic region of the state of Minas Gerais, Brazil. The vaccine formulations will be tested in both populations (i.e., non-endemic and endemic areas), given the possibility that the safety profile of the vaccine formulations may be different in a population that has been chronically exposed to the antigen contained in these vaccines.
In Part I of the study, 36 volunteers will be enrolled into one of six cohorts. In the first cohort, 6 individuals will receive the 10 µg dose of Na-GST-1/Alhydrogel®; in the second cohort, 6 individuals will receive the 10 µg dose of Na-GST-1/Alhydrogel®/GLA-AF; in the third and fourth cohorts, 6 volunteers each will receive 30 µg Na-GST-1/Alhydrogel® and Na-GST-1/Alhydrogel®/GLA-AF, respectively; while in the fifth and sixth cohorts, 6 volunteers each will receive 100 µg Na-GST-1/Alhydrogel® and Na-GST-1/Alhydrogel®/GLA-AF, respectively. Enrollment of these cohorts will be staggered by one-week intervals: Cohorts 2 and 3 will be enrolled and begin vaccinations 1 week after Cohort 1, Cohorts 4 and 5 will be vaccinated 1 week after Cohorts 2 and 3, and Cohort 6 will be vaccinated 1 week after Cohorts 4 and 5.
In Part II of the study, 66 volunteers will be progressively enrolled into one of six dose cohorts. In the first, third and fifth cohorts, volunteers will be randomized to receive either Na-GST-1/Alhydrogel® (n=8) or Butang® (n=2), while in the second, fourth and sixth cohorts, volunteers will be randomized to receive either Na-GST-1/Alhydrogel® (n=2) or Na-GST-1/Alhydrogel®/GLA-AF (n=10). Volunteers randomized to receive Na-GST-1 will receive either the 10 µg, 30 µg or 100 µg dose. In order to ensure that the vaccine formulations will be evaluated in individuals recently infected with hookworm, at least 4 individuals will be enrolled into each of the Part II chohorts who were infected with hookworm based on the fecal exam conducted during the screening for the study, or who had a documented infection within 3 months of the date planned for the first vaccination for the participant.
The investigators have chosen the Butang® hepatitis B vaccine (Instituto Butantan, Sao Paulo, Brazil) as the comparator vaccine for five principal reasons: (1) it is likely to confer some benefit to the participants receiving it, (2) it has an established safety record, (3) it is a yeast-derived recombinant protein adsorbed to an aluminum-containing immunostimulant, (4) it has the same physical appearance as Na-GST-1 immunostimulanted with Alhydrogel, and (5) its dosing schedule permits easy incorporation into the study design. Furthermore, Butang® is the most widely-used hepatitis B vaccine in Brazil, with over 15 million doses distributed annually.
Each participant will recieve 3 doses of the assigned study agent given in 56 day intervals (i.e. Day 0, Day 56 and Day 112). The trial is expected to last for a total of 24 months. Each participant will be followed for 16 months from the time of the first injection.
Safety parameters will be monitored throughout both parts of the study. The primary immunological endpoint for both parts will be the measurement of the antigen-specific antibody response.
39 studies on the registry are indexed under Hookworm Infections; 5 are open to participants now.
This study's enrollment of 102 is below the median of 182 across 36 interventional studies indexed under Hookworm Infections.
Browse Hookworm Infections studies →Baylor College of Medicine is the lead sponsor of 747 studies on the registry; 110 are open to participants now.
Of its 84 completed or terminated interventional studies of FDA-regulated products, 45 (54%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Part I (non-endemic area), Formulation A
Biological: 10 μg Na-GST-1/Alhydrogel
Part I (non-endemic area), Formulation B
Biological: 30 μg Na-GST-1/Alhydrogel
Part I (non-endemic area), Formulation C
Biological: 100 μg Na-GST-1/Alhydrogel
Part I (non-endemic area), Formulation D
Biological: 10 μg Na-GST-1/ Alhydrogel/GLA-AF
Part I (non-endemic area), Formulation E
Biological: 30 μg Na-GST-1/Alhydrogel/GLA-AF
Part I (non-endemic area), Formulation F
Biological: 100 μg Na-GST-1/Alhydrogel/GLA-AF
Part II (endemic area), Formulation A
Biological: 10 μg Na-GST-1/Alhydrogel
Part II (endemic area), Formulation B
Biological: 30 μg Na-GST-1/Alhydrogel
Part II (endemic), Formulation C
Biological: 100 μg Na-GST-1/Alhydrogel
Part II (endemic area), Formulation D
Biological: 10 μg Na-GST-1/ Alhydrogel/GLA-AF
Part II (endemic area), Formulation E
Biological: 30 μg Na-GST-1/Alhydrogel/GLA-AF
Part II (endemic area), Formulation F
Biological: 100 μg Na-GST-1/Alhydrogel/GLA-AF
Part II (endemic), HepB comparator
Biological: Butang® hepatitis B vaccine
3 doses 10 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Also known as: Formulation A
3 doses 30 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Also known as: Formulation B
3 doses 100 μg Na-GST-1/Alhydrogel administered at 56 day intervals
Also known as: Formulation C
3 doses 10 μg Na-GST-1/ Alhydrogel/GLA-AF administered at 56 day intervals
Also known as: Formulation D
3 doses 30 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Also known as: Formulation E
3 doses 100 μg Na-GST-1/Alhydrogel/GLA-AF administered at 56 day intervals
Also known as: Formulation F
3 doses Butang® hepatitis B vaccine administered at 56 day intervals
Immediate vaccine related adverse events
Frequency of vaccine-related AEs, graded by severity, for each dose and formulation of Na-GST-1
Time frame: 2 hours post vaccination
IgG antibody response to Na-GST-1
Dose and formulation of Na-GST-1 that generates the highest IgG antibody response at Day 126, as determined by an indirect enzyme-linked immunosorbent assay (ELISA)
Time frame: 126 days post dose 1
Duration of antibody response to Na-GST-1
Duration of anti-GST-1 antibody, up to Day 290, as determined by an indirect enzyme-linked immunosorbent assay (ELISA)
Time frame: 290 days post dose 1
Exploratory cellular immune response to Na-GST-1
Cellular immune responses to the Na-GST-1 antigen both before and after immunization
Time frame: Up to 290 days post dose 1
The record gives a start of Nov 2011, a primary completion of Aug 2014 and a completion of Dec 2014. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
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