Ignite Creation Date:
2025-12-24 @ 5:24 PM
Ignite Modification Date:
2026-01-01 @ 6:48 PM
Study NCT ID:
NCT01717950
Status:
COMPLETED
Last Update Posted:
2019-07-31
First Post:
2012-10-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006725', 'term': 'Hookworm Infections'}, {'id': 'D000724', 'term': 'Ancylostomiasis'}, {'id': 'D018798', 'term': 'Anemia, Iron-Deficiency'}, {'id': 'D058069', 'term': 'Neglected Diseases'}], 'ancestors': [{'id': 'D017206', 'term': 'Strongylida Infections'}, {'id': 'D017190', 'term': 'Secernentea Infections'}, {'id': 'D009349', 'term': 'Nematode Infections'}, {'id': 'D006373', 'term': 'Helminthiasis'}, {'id': 'D010272', 'term': 'Parasitic Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000747', 'term': 'Anemia, Hypochromic'}, {'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D000090463', 'term': 'Iron Deficiencies'}, {'id': 'D019189', 'term': 'Iron Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000592475', 'term': 'GLA-AF adjuvant'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-07', 'completionDateStruct': {'date': '2015-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-07-29', 'studyFirstSubmitDate': '2012-10-25', 'studyFirstSubmitQcDate': '2012-10-29', 'lastUpdatePostDateStruct': {'date': '2019-07-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2012-10-31', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Vaccine-related Adverse Events', 'timeFrame': 'Day 290', 'description': '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 3, 7, 14, and 28 days following each vaccination. In addition, study participants will be asked to complete symptom diaries for the 7 days after each vaccination.'}], 'secondaryOutcomes': [{'measure': 'IgG antibody response to Na-APR-1', 'timeFrame': '14 days after final vaccination', 'description': 'Dose and formulation of Na-APR-1 that generates the highest IgG antibody response at Day 126 (14 days after final vaccination), as determined by an indirect enzyme-linked immunosorbent assay (ELISA).'}, {'measure': 'B cell response to Na-APR-1', 'timeFrame': 'Study Days 14, 70, 126, 140 and 290', 'description': 'Dose and formulation of the Na-APR-1 (M74) vaccine that results in the highest production of Na-APR-1 (M74) specific B cells and subtypes (memory or plasma).'}, {'measure': 'Exploratory cellular immune response to Na-APR-1', 'timeFrame': 'Study Days 14, 70, 126, 140 and 290', 'description': 'Exploratory studies of the cellular immune responses to the Na APR-1 (M74) antigen both before and after immunization.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Human Hookworm', 'Necator americanus', 'Hookworm', 'Hookworm Disease', 'Iron-deficiency anemia', 'Soil-transmitted helminth infection', 'Neglected Tropical Disease', 'Na-APR-1'], 'conditions': ['Hookworm Infection', 'Hookworm Disease']}, 'referencesModule': {'availIpds': [{'url': 'https://smhs.gwu.edu/mitm-crg/', 'type': 'Clinical Study Report'}]}, 'descriptionModule': {'briefSummary': 'Hookworms digest hemoglobin from erythrocytes for use as an energy source via a proteolytic cascade that begins with the aspartic protease, APR-1. Vaccination with recombinant APR-1 has protected animals from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-APR-1 (M74) in healthy adult volunteers when co-administered with different concentrations of the immunostimulant GLA-AF.', 'detailedDescription': 'Open-label, dose-escalation phase 1 clinical trial in healthy, hookworm-naïve adults:\n\n* Study site: George Washington Medical Faculty Associates, Washington, DC\n* Number of participants: 40 in 2 cohorts of 20.\n\nIn Cohort 1 five (5) volunteers will receive 30 µg Na-APR-1 (M74) /Alhydrogel®, five (5) will receive 30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 30 µg Na-APR-1 (M74) /Alhydrogel® plus 5 µg GLA-AF. In Cohort 2 five (5) volunteers will receive 100 µg Na-APR-1 (M74)/Alhydrogel®, five (5) will receive 100 µg Na-APR-1 (M74) /Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 100 µg Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF.\n\nThe cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-APR-1 dose escalation from 30 to 100 µg. In addition, within each cohort, vaccinations will be staggered such that formulations containing 0, 2.5, and 5 µg GLA-AF will be tested sequentially: for example, those receiving Na-APR-1 (M74)/Alhydrogel® in combination with 2.5 µg GLA-AF will be vaccinated no sooner than 3 days after the last volunteer is vaccinated with the formulation containing no GLA-AF, whereas those vaccinated with Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF will be vaccinated no sooner than 7 days after the last one receives the 2.5 µg GLA-AF formulation.\n\n* Immunization schedule: Study days 0, 56 and 112.\n* Route: IM in the deltoid muscle.\n* Doses of Na-APR-1 (M74) to be tested: 30 and 100 µg.\n* Doses of Alhydrogel®: 240 and 800 µg for the 30 and 100 µg doses of Na-APR-1 (M74), respectively.\n* Doses of GLA-AF to be tested: 2.5 µg and 5 µg.\n* Study duration: 44 weeks (10 months) per study participant; total duration of the study estimated at approximately 13 months.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Males or females between 18 and 50 years, inclusive.\n* Good general health as determined by means of the screening procedure.\n* Available for the duration of the trial (44 weeks).\n* Willingness to participate in the study as evidenced by signing the informed consent document.\n\nExclusion Criteria:\n\n* Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female).\n* Participant unwilling to use reliable contraception methods up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal).\n* Currently lactating and breast-feeding (if female).\n* Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.\n* Known or suspected immunodeficiency.\n* Laboratory evidence of liver disease (alanine aminotransferase \\[ALT\\] greater than 1.25-times the upper reference limit).\n* 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).\n* Laboratory evidence of hematologic disease (hemoglobin \\<11.5 g/dl \\[females\\] or \\<12.5 g/dl \\[males\\]; absolute leukocyte count \\<3600/mm3 or \\>10.7 x 103/mm3; absolute neutrophil count \\[ANC\\] \\<1700/ mm3; absolute lymphocyte count \\<700/mm3; or platelet count \\<140,000/mm3).\n* Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).\n* Serum glucose (random) greater than 1.2-times the upper reference limit.\n* 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.\n* Participation in another investigational vaccine or drug trial within 30 days of starting this study.\n* Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.\n* History of a severe allergic reaction or anaphylaxis.\n* Severe asthma as defined by the need for daily use of inhalers or emergency clinic visit or hospitalization within 6 months of the volunteer's expected first vaccination in the study.\n* Positive ELISA for hepatitis B surface antigen (HBsAg).\n* Positive confirmatory test for HIV infection.\n* Positive confirmatory test for hepatitis C virus (HCV) infection.\n* Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of the volunteer's expected first vaccination in this study.\n* Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to the volunteer's expected first vaccination in the study.\n* History of a surgical splenectomy.\n* Receipt of blood products within the past 6 months.\n* History of previous infection with hookworm or residence for more than 6 months in a hookworm-endemic area."}, 'identificationModule': {'nctId': 'NCT01717950', 'briefTitle': 'Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults', 'organization': {'class': 'OTHER', 'fullName': 'Baylor College of Medicine'}, 'officialTitle': 'Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® in Healthy Adults', 'orgStudyIdInfo': {'id': 'SVI-12-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '30 µg Na-APR-1 (M74)/Alhydrogel®', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®']}, {'type': 'EXPERIMENTAL', 'label': '30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®', 'Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation']}, {'type': 'EXPERIMENTAL', 'label': '30 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®', 'Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation']}, {'type': 'EXPERIMENTAL', 'label': '100 µg Na-APR-1 (M74)/Alhydrogel®', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®']}, {'type': 'EXPERIMENTAL', 'label': '100 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®', 'Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation']}, {'type': 'EXPERIMENTAL', 'label': '100 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF', 'interventionNames': ['Biological: Na-APR-1 (M74)/Alhydrogel®', 'Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation']}], 'interventions': [{'name': 'Na-APR-1 (M74)/Alhydrogel®', 'type': 'BIOLOGICAL', 'otherNames': ['Na-APR-1', 'Necator americanus Aspartic Protease-1'], 'description': 'The Na-APR-1 (M74) candidate vaccine contains the recombinant Na-APR-1 (M74) protein expressed by Nicotiana plants. Purified Na-APR-1 (M74) was subsequently adsorbed onto aluminum hydroxide gel (Alhydrogel®) and suspended in a solution containing 10 mM imidazole, 150 mM sodium chloride and 0.3% Empigen BB, with pH 7.4 ± 0.1. The final concentration of Na-APR-1 (M74) in the drug product is 0.1 mg/ml, whereas that of Alhydrogel® is 0.8 mg/ml. Different doses of Na-APR-1 (M74) will be delivered by injecting different volumes of the 0.1 mg/ml Na-APR-1 (M74) preparation.', 'armGroupLabels': ['100 µg Na-APR-1 (M74)/Alhydrogel®', '100 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', '100 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF', '30 µg Na-APR-1 (M74)/Alhydrogel®', '30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', '30 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF']}, {'name': 'Gluco-Pyranosylphospho-Lipid A Aqueous Formulation', 'type': 'BIOLOGICAL', 'otherNames': ['GLA-AF'], 'description': 'GLA-AF contains a synthetic monophosphoryl lipid A (MPL) molecule that has Toll-Like Receptor-4 agonist activity. MPL is itself derived from the lipopolysaccharide (LPS) of Salmonella minnesota, a natural TLR4 agonist that is pyrogenic and can induce toxic shock. LPS, and more specifically, its lipid A component, has long been known for its strong adjuvant effects; however, its high toxicity has precluded its use in a vaccine formulation.', 'armGroupLabels': ['100 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', '100 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF', '30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF', '30 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20036', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'George Washington University Medical Faculty Associates', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}], 'overallOfficials': [{'name': 'David J Diemert, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'George Washington University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Baylor College of Medicine', 'class': 'OTHER'}, 'collaborators': [{'name': 'George Washington University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Sponsor', 'investigatorFullName': 'Maria Elena Bottazzi PhD', 'investigatorAffiliation': 'Baylor College of Medicine'}}}}