Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults

NCT01717950 | Completed Phase 1 DMC

• 1 other identifier: SVI-12-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hookworm Infection; Hookworm Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Vaccine-related Adverse Events

  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.

  Day 290

Secondary Outcomes (3)

• IgG antibody response to Na-APR-1

  14 days after final vaccination

• B cell response to Na-APR-1

  Study Days 14, 70, 126, 140 and 290

• Exploratory cellular immune response to Na-APR-1

  Study Days 14, 70, 126, 140 and 290

Study Arms (6)

30 µg Na-APR-1 (M74)/Alhydrogel®

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®

30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®; Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation

30 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®; Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation

100 µg Na-APR-1 (M74)/Alhydrogel®

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®

100 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®; Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation

100 µg Na-APR-1 (M74)/Alhydrogel® plus 5.0 µg GLA-AF

EXPERIMENTAL

Biological: Na-APR-1 (M74)/Alhydrogel®; Biological: Gluco-Pyranosylphospho-Lipid A Aqueous Formulation

Interventions

Na-APR-1 (M74)/Alhydrogel® BIOLOGICAL

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.

Also known as: Na-APR-1, Necator americanus Aspartic Protease-1

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

Gluco-Pyranosylphospho-Lipid A Aqueous Formulation BIOLOGICAL

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.

Also known as: GLA-AF

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

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 (44 weeks).
• Willingness to participate in the study as evidenced by signing the informed consent document.

You may not qualify if:

• Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female).
• 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).
• Currently lactating and breast-feeding (if female).
• 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 (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).
• Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).
• Serum glucose (random) 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.
• Participation in another investigational vaccine or drug trial within 30 days of starting this 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 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

GLA-AF adjuvant

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

Study Officials

• David J Diemert, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 31, 2012
• Study Start: September 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 31, 2019

Record last verified: 2019-07

Locations

US (1)