Efficacy of Na-GST-1/Alhydrogel Hookworm Vaccine Assessed by Controlled Challenge Infection

NCT03172975 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: H-38292U01AI129789
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the efficacy, safety and immunogenicity of different formulations of the Na-GST-1 hookworm vaccine using a controlled human hookworm infection model in healthy, hookworm-naive adults.

Conditions

Hookworm Infections

Keywords

Controlled infection; Na-GST-1; Hookworm vaccine

Outcome Measures

Primary Outcomes (8)

• Detectable Hookworm Infection

  Proportion of subjects with detectable hookworm eggs, at any time point, in fecal samples, as determined by microscopy using the qualified saline flotation technique

  On Study Days 175, 182, 189, 203, 217, 231, 245, 259, 273, and 280.

• Incidence of Serious Adverse Events

  Frequency of study vaccine-related Serious Adverse Events from the time of the first study vaccination through approximately 10 months after the last study vaccination.

  Beginning on Day 0 when the first dose is received and ending on Day 380 (final study visit).

• Incidence of Solicited Injection Site and Systemic Reactogenicity

  Frequency of solicited injection site and systemic reactogenicity, graded by severity, on the day of each study vaccination through 14 days after each study vaccination.

  Dose 1: Days 0, 3, 7, 14; Dose 2: Days 56, 59, 63, 70; Dose 3: Days 112, 115, 119, 126

• Incidence of Solicited Adverse Events

  Frequency of solicited adverse events, graded by severity, on the day of CHHI through study Day 280

  Day of CHHI, Day 140, and study days: 143, 147, 154, 175, 182, 189, 196, 203, 210, 217, 224, 231, 238, 245, 252, 259, 266, 273, 280. Day 280 is the day of anti-worm treatment.

• Incidence of Clinical Safety Laboratory Abnormalities

  Frequency of clinical safety laboratory adverse events.

  Study days: 0, 14, 56, 70, 112, 126, 140, 154, 175, 189, 203, 217, 231, 259, 280.

• Incidence of Unsolicited Adverse Events

  Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination; and from the time of CHHI through treatment with albendazole (Day 280)

  From Dose 1 on Day 0 until anti-worm treatment on Day 280.

• Incidence of New-onset Chronic Medical Conditions

  Frequency of new-onset chronic medical conditions through approximately 10 months after the third study vaccination.

  Entire duration of the study. Beginning Day 0, day of first dose, until Day 380, final study visit.

• Incidence of Adverse Events of Special Interest

  Frequency of Adverse Events of Special Interest through approximately 10 months after the third study vaccination.

  Entire duration of the study. Beginning Day 0, day of first dose, until Day 380, final study visit.

Secondary Outcomes (2)

• Fecal Egg Counts

  Week 5 and Week 20 post-CHHI. Study days: 175, 182, 189, 203, 217, 231, 245, 259, 273, and 280.

• Anti-Na-GST-1 IgG Antibody Response

  Study days: 14, 70, 126, 140, 175, 189, 231, 280, 320, and 380

Study Arms (4)

Na-GST-1/Alhydrogel

EXPERIMENTAL

100 µg Na-GST-1/Alhydrogel administered intramuscularly in the deltoid on study days 0, 56 and 112 followed by controlled human hookworm infection with 50 infectious Necator americanus larvae on study day 140.

Biological: Na-GST-1/Alhydrogel; Drug: Albendazole; Other: Necator americanus Larval Inoculum

Na-GST-1/Alhydrogel + CPG 10104

EXPERIMENTAL

100 µg Na-GST-1/Alhydrogel co-administered with 500 µg CPG 10104 delivered intramuscularly in the deltoid on study days 0, 56 and 112 followed by controlled human hookworm infection with 50 infectious Necator americanus larvae on study day 140.

Biological: Na-GST-1/Alhydrogel + CPG 10104; Drug: Albendazole; Other: Necator americanus Larval Inoculum

Na-GST-1/Alhydrogel + GLA-AF

EXPERIMENTAL

100 µg Na-GST-1/Alhydrogel co-administered with 5 µg GLA-AF delivered intramuscularly in the deltoid on study days 0, 56 and 112 followed by controlled human hookworm infection with 50 infectious Necator americanus larvae on study day 140.

Biological: Na-GST-1/Alhydrogel + GLA-AF; Drug: Albendazole; Other: Necator americanus Larval Inoculum

Saline Placebo

PLACEBO COMPARATOR

Sterile saline placebo delivered intramuscularly in the deltoid on study days 0, 56 and 112 followed by controlled human hookworm infection with 50 infectious Necator americanus larvae on study day 140.

Biological: Placebo; Drug: Albendazole; Other: Necator americanus Larval Inoculum

Interventions

Necator americanus Larval Inoculum OTHER

50 infectious Necator americanus larvae applied via dermal application (challenge infection).

Na-GST-1/Alhydrogel; Na-GST-1/Alhydrogel + CPG 10104; Na-GST-1/Alhydrogel + GLA-AF; Saline Placebo

Na-GST-1/Alhydrogel BIOLOGICAL

Recombinant Necator americanus Glutathione-S Transferase adjuvanted with Alhydrogel

Also known as: Necator americanus Glutathione-S Transferase

Na-GST-1/Alhydrogel

Na-GST-1/Alhydrogel + CPG 10104 BIOLOGICAL

Recombinant Necator americanus Glutathione-S Transferase adjuvanted with Alhydrogel and co-administered with CPG 10104, a synthetic oligodeoxynucleotide

Na-GST-1/Alhydrogel + CPG 10104

Na-GST-1/Alhydrogel + GLA-AF BIOLOGICAL

Recombinant Necator americanus Glutathione-S Transferase adjuvanted with Alhydrogel and co-administered with an aqueous formulation of Glucopyranosyl-Lipid A (GLA-AF)

Na-GST-1/Alhydrogel + GLA-AF

Placebo BIOLOGICAL

Physiological sterile saline solution

Saline Placebo

Albendazole DRUG

Treatment with 3 daily oral doses of 400 mg albendazole at end of study.

Na-GST-1/Alhydrogel; Na-GST-1/Alhydrogel + CPG 10104; Na-GST-1/Alhydrogel + GLA-AF; Saline Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and non-pregnant females between 18 and 45 years, inclusive.
• Good general health as determined by means of the screening procedures1.
• Available for the duration of individual subject study participation (14 months).
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Able to understand and comply with planned study procedures.

You may not qualify if:

• Pregnancy as determined by a positive urine human choriogonadotropin (hCG) test (if female).
• Subject unwilling to use effective contraception for a minimum of 30 days prior to vaccination and up until documentation of clearance of hookworm infection post-CHHI (if female and not surgically sterile, abstinent from intercourse with a male partner, in a monogamous relationship with a vasectomized partner, at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile).
• Currently lactating and breast-feeding or plans to breastfeed at any given time from the first study vaccination until clearance of hookworm infection post-CHHI (if female).
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, gastrointestinal, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
• Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric condition that would make compliance with study visits/procedures difficult (e.g., subject with psychoses or history of suicide attempt or gesture in the 3 years before study entry, ongoing risk for suicide).
• Known or suspected immunodeficiency or immunosuppression as a result of an underlying illness or treatment (causes for immunosuppression may include, but are not limited to, poorly-controlled diabetes mellitus, chronic liver disease, renal insufficiency, active neoplastic disease or a history of hematologic malignancy, connective tissue disease, organ transplant).
• 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 urine dipstick testing positive for glucose or more than trace protein).
• Laboratory evidence of hematologic disease (hemoglobin \<11.1 g/dl \[females\] or \<12.5 g/dl \[males\]; absolute leukocyte count \<3400/mm3 or \>10.8 x 103/mm3; absolute eosinophil count \<500/mm3; 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.
• Planned participation in another investigational vaccine or drug trial within 30 days of starting this study or until the last study visit (this may include other licensed or unlicensed vaccines, drugs, biologics, devices, blood products, or medications).
• Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 24 months.
• Positive fecal occult blood test at screening.
• Infection with a pathogenic intestinal helminth as determined by stool examination for ova and parasites at screening.
• History of iron deficiency anemia or laboratory evidence of iron deficiency (serum ferritin concentration below the lower reference limit).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• George Washington University: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Related Publications (1)

• DiRosato CK, Malkin EM, Lee SM, Erwin G, Hoeweler L, Scholte L, Bottazzi ME, Pritchard DI, Hotez PJ, Bethony JM, Diemert DJ. Na-GST-1 adsorbed on Alhydrogel co-administered with different Toll-like receptor agonists in hookworm-naive adults using a controlled human infection model in the USA: a phase 2, double-blind, randomised controlled trial. Lancet Infect Dis. 2026 Mar 17:S1473-3099(26)00018-6. doi: 10.1016/S1473-3099(26)00018-6. Online ahead of print.

  PMID: 41861834 DERIVED

MeSH Terms

Conditions

Hookworm Infections

Interventions

Albendazole

Condition Hierarchy (Ancestors)

Strongylida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David J. Diemert, MD
• Organization: George Washington University

ddiemert@gwu.edu

202-994-2909

Study Officials

• David Diemert, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and investigators will be blinded to study product allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 1, 2017
• Study Start: March 1, 2018
• Primary Completion: December 31, 2024
• Study Completion: January 30, 2025
• Last Updated: March 12, 2026
• Results First Posted: December 5, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Within 12 months of final study visit.
• Access Criteria: To be determined.

Locations

US (1)