Safety and Immunogenicity Study of Na-GST-1 With or Without CpG

NCT02143518 | Completed Phase 1 Results DMC

• 1 other identifier: SVI-GST-03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Na-GST-1 is a protein expressed during the adult stage of the hookworm life cycle that is thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination with recombinant GST-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-GST-1 in healthy adult volunteers when co-administered with the immunostimulant CpG 10104, a Toll-like Receptor-9 agonist.

Conditions

Hookworm Infection; Hookworm Disease

Keywords

Human Hookworm; Necator americanus; Hookworm; Hookworm Disease; Iron-deficiency anemia; Soil-transmitted helminth infection; Neglected Tropical Disease; Na-GST-1; CpG

Outcome Measures

Primary Outcomes (1)

• Vaccine-related Adverse Events

  The frequency of immediate, systemic, and local injection site adverse events, graded by severity, for Na-GST-1/Alhydrogel administered alone or in combination with CpG 10104

  Up to study day 470

Secondary Outcomes (2)

• IgG Antibody Response to Na-GST-1 on Study Day 126

  14 days after final vaccination

• Exploratory Cellular Immune Response to Na-GST-1

  Up to study day 290

Study Arms (3)

100 µg Na-GST-1/Alhydrogel

EXPERIMENTAL

High Dose Na-GST-1/Alhydrogel® Only

Biological: Na-GST-1/Alhydrogel®

30 µg Na-GST-1/Alhydrogel + CpG 10104

EXPERIMENTAL

Low Dose Na-GST-1/Alhydrogel® Plus 500 µg CpG 10104

Biological: Na-GST-1/Alhydrogel®; Biological: CpG 10104

100 µg Na-GST-1/Alhydrogel + CpG 10104

EXPERIMENTAL

High Dose Na-GST-1/Alhydrogel® Plus 500 µg CpG 10104

Biological: Na-GST-1/Alhydrogel®; Biological: CpG 10104

Interventions

Na-GST-1/Alhydrogel® BIOLOGICAL

The Na-GST-1 candidate vaccine contains the recombinant Na-GST-1 protein expressed by Pichia pastoris. Purified Na-GST-1 was subsequently adsorbed onto aluminum hydroxide gel (Alhydrogel®) and suspended in a solution containing 10% glucose and 10 mM imidazole. The final concentration of Na-GST-1 in the drug product is 0.1 mg/ml whereas that of Alhydrogel® is 0.8 mg/ml. Different doses of Na-GST-1 will be delivered by injecting different volumes of the 0.1 mg/ml Na-GST-1 preparation.

Also known as: Na-GST-1, Necator americanus glutathione S-transferase-1

100 µg Na-GST-1/Alhydrogel; 100 µg Na-GST-1/Alhydrogel + CpG 10104; 30 µg Na-GST-1/Alhydrogel + CpG 10104

CpG 10104 BIOLOGICAL

Unmethylated cytosine-guanine dinucleotides (CpGs) are found in bacterial DNA in the expected frequency predicted by random usage, whereas their occurrence is suppressed 4-fold in vertebrate DNA. In vertebrate DNA CpG motifs are also usually methylated. Bacterial CpG-DNA motifs are recognized by the human innate immune system via Toll-like Receptor-9 (TLR-9), a pathogen-associated molecular pattern (PAMP) receptor that is expressed, in particular, by antigen-presenting dendritic cells. Interactions between CpG-DNA and TLR9 rapidly activate antigen-presenting dendritic cells to upregulate co-stimulatory molecules and to produce Th1-polarizing cytokines such as interleukin-12 and interferon gamma. CpG 10104 is a short synthetic oligodeoxynucleotide of the following sequence: 5'-TCG TCG TTT CGT CGT TTT GTC GTT-3'.

Also known as: Cytosine-phosphate-Guanine oligodeoxynucleotide, CpG ODN 101014, CpG ODN

100 µg Na-GST-1/Alhydrogel + CpG 10104; 30 µg Na-GST-1/Alhydrogel + CpG 10104

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females between 18 and 50 years, inclusive.
• Good general health as determined by means of the screening procedure.
• Available for the duration of the trial (68 weeks).
• 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).
• Participant unwilling to use reliable contraception up until one month following the third immunization (if female and not surgically sterile, abstinent, at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile).
• Currently lactating and breast-feeding (if female).
• 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.
• 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 with the exception of greater than 1+ blood detected in females during menses).
• 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; or platelet count \<140,000/mm3).
• Laboratory evidence of a coagulopathy (activated PTT or PT INR greater than 1.1-times the upper reference limit).
• Serum glucose greater than 1.2-times the upper reference limit.
• 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 Visit #17 (6 months after the third vaccination).
• 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 clinic visit or hospitalization within 6 months of the volunteer's expected first vaccination in the study.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• George Washington University: collaborator

Study Sites (1)

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20036, United States

Location

MeSH Terms

Conditions

Hookworm Infections; Ancylostomiasis; Anemia, Iron-Deficiency; Neglected Diseases

Interventions

CPG-oligonucleotide

Condition Hierarchy (Ancestors)

Strongylida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 21, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: October 1, 2016
• Last Updated: July 4, 2025
• Results First Posted: July 4, 2025

Record last verified: 2025-07

Locations

US (1)