Safety and Immunogenicity of Co-Administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 in Gabonese Adults

NCT02126462 | Completed Phase 1 DMC

• 2 other identifiers: HV-001602843-2
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Na-GST-1 and Na-APR-1 are proteins expressed during the adult stage of the Necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination with recombinant GST-1 or APR-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of co-administering Na-GST-1 and Na-APR-1 to healthy Gabonese adults living in an area of endemic hookworm infection.

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; Na-GST-1

Outcome Measures

Primary Outcomes (1)

• Vaccine-related Adverse Events

  To estimate the frequency of vaccine-related adverse events, graded by severity, for each dose of co-administered Na-GST-1 and Na-APR-1 (M74). 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 1, 3, 7, 14, and 28 days following each vaccination.

  Day 360

Secondary Outcomes (3)

• IgG response to Na-GST-1 and Na-APR-1 (M74)

  Day 194

• Duration of antibody response to Na-GST-1 and Na-APR-1 (M74)

  Day 14, 28, 42, 56, 180, 194, 208, 270, 360

• Exploratory studies of memory B-cell responses

  Days 14, 28, 42, 56, 180, 194, 208, 270, 360

Study Arms (3)

30 µg Na-GST-1 + 30 µg Na-APR-1 (M74)

EXPERIMENTAL

30 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 30 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF

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

Hepatitis B vaccine

ACTIVE COMPARATOR

Hepatitis B vaccine co-administered with saline

Biological: Hepatitis B vaccine

100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74)

EXPERIMENTAL

100 µg Na-GST-1/Alhydrogel plus 5 µg GLA-AF co-administered with 100 µg Na-APR-1 (M74)/Alhydrogel plus 5 µg GLA-AF

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

Interventions

Na-APR-1 (M74)/Alhydrogel® BIOLOGICAL

100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74); 30 µg Na-GST-1 + 30 µg Na-APR-1 (M74)

Na-GST-1/Alhydrogel® BIOLOGICAL

100 µg Na-GST-1 plus 100 µg Na-APR-1 (M74); 30 µg Na-GST-1 + 30 µg Na-APR-1 (M74)

Hepatitis B vaccine BIOLOGICAL

Hepatitis B vaccine co-administered with saline

Hepatitis B vaccine

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, who are long-term residents of Gabon.
• Good general health as determined by means of the screening procedure.
• Assumed availability for the duration of the trial (12 months).
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole.

You may not qualify if:

• Pregnancy as determined by a positive urine hCG (if female).
• Participant unwilling to use reliable contraception 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).
• Inability to correctly answer all questions on the informed consent comprehension questionnaire.
• 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 (absolute leukocyte count \<3500/mm3; absolute leukocyte count \>11.0 x 103/mm3; hemoglobin \<10.000 g/dl \[females\] or \<12.0 g/dl \[males\]; 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.
• Participation in another investigational vaccine or drug trial within 30 days of starting this study or for the duration of the 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 room/clinic visit or hospitalization within 6 months of the volunteer's planned first vaccination in the study.
• Positive for HCV

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Centre de Recherches Médicales de Lambaréné Albert Schweitzer Hospital

Lambaréné, BP: 118, Gabon

Location

Related Publications (2)

• Mouwenda YD, Betouke Ongwe ME, Sonnet F, Stam KA, Labuda LA, De Vries S, Grobusch MP, Zinsou FJ, Honkpehedji YJ, Dejon Agobe JC, Diemert DJ, van Leeuwen R, Bottazzi ME, Hotez PJ, Kremsner PG, Bethony JM, Jochems SP, Adegnika AA, Massinga Loembe M, Yazdanbakhsh M. Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. PLoS Negl Trop Dis. 2021 Oct 1;15(10):e0009732. doi: 10.1371/journal.pntd.0009732. eCollection 2021 Oct.

  PMID: 34597297 DERIVED

• Adegnika AA, de Vries SG, Zinsou FJ, Honkepehedji YJ, Dejon Agobe JC, Vodonou KG, Bikangui R, Bouyoukou Hounkpatin A, Bache EB, Massinga Loembe M, van Leeuwen R, Molemans M, Kremsner PG, Yazdanbakhsh M, Hotez PJ, Bottazzi ME, Li G, Bethony JM, Diemert DJ, Grobusch MP; HookVac Consortium. Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial. Lancet Infect Dis. 2021 Feb;21(2):275-285. doi: 10.1016/S1473-3099(20)30288-7. Epub 2020 Sep 11.

  PMID: 32926834 DERIVED

MeSH Terms

Conditions

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

Interventions

Hepatitis B Vaccines

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

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Ayola Adegnika, MD

  Centre de Recherches Medicales de Lambarené

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor

Study Record Dates

• First Submitted: April 28, 2014
• First Posted: April 30, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: June 1, 2016
• Last Updated: May 31, 2017

Record last verified: 2017-05

Locations

GA (1)