Clinical trial NCT03373214: Na-GST-1/Alhydrogel With or Without CpG 10104 in Gabonese Adults
Official title: Randomized, Controlled, Phase 1 Study to Assess Safety and Immunogenicity of Na-GST-1/Alhydrogel®, With or Without a CPG ODN Adjuvant, in Gabonese Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Centre de Recherche Médicale de Lambaréné
name: George Washington University
name: Leiden University Medical Center
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Amsterdam Institute for Global Health and Development
First posted: 2017-12-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Na-GST-1 is a protein expressed during the adult stage of the Necator americanus 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 Na-GST-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of administering Na-GST-1 with or without the CpG 10104 immunostimulant to healthy Gabonese adults living in an area of endemic hookworm infection.

Detailed description: Double blind, randomized, controlled, dose-escalation Phase 1 clinical trial in hookworm-exposed adults aged 18 to 50 years living in the area of Lambaréné, Gabon. Participants will receive three doses of the assigned vaccine(s) delivered intramuscularly (deltoid) on approximately Days 0, 56, and 112.

Safety will be measured from the time of each study vaccination (Day 0) through 14 days after each study vaccination by the occurrence of solicited injection site and systemic reactogenicity events.

Unsolicited non-serious adverse events (AEs) will be collected from the time of the first study vaccination through approximately 1 month after each study vaccination. New-onset chronic medical conditions and Serious Adverse Events (SAEs) will be collected from the time of the first study vaccination through approximately 9 months after the final study vaccination (final visit). Clinical laboratory evaluations for safety will be performed on venous blood collected approximately 14 days after each vaccination.

Immunogenicity testing will include IgG antibody responses to each vaccine antigen, by a qualified indirect enzyme-linked immunosorbent assay (ELISA), on serum or plasma obtained prior to each study vaccination and at time points after each vaccination; the functional activity of vaccine-induced antibodies will be assessed by in vitro enzyme neutralization assays.

Recruitment and enrollment into the study will occur on an ongoing basis, with each group being recruited and vaccinated in sequence.

24 subjects will be enrolled into 2 groups:

* Group 1 (n=12):

  * 8 subjects will receive 30 µg Na-GST-1 plus 500 µg CPG 10104 delivered by IM injection in the deltoid muscle
  * 4 subjects will receive 100 µg Na-GST-1 delivered by IM injection in the deltoid muscle
* Group 2 (n=12):

  * 8 subjects will receive 100 µg Na-GST-1 plus 500 µg CPG 10104 delivered by IM injection in the deltoid muscle
  * 4 subjects will receive 100 µg Na-GST-1 delivered by IM injection in the deltoid muscle

Eligibility criteria: Inclusion Criteria:

1. Males or females between 18 and 50 years, inclusive, who are long-term residents of the study area.
2. Good general health as determined by means of the screening procedure.
3. Assumed availability for the duration of the trial (13 months).
4. Willingness to participate in the study as evidenced by signing the informed consent document.
5. Negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole.

Exclusion Criteria:

1. Pregnancy as determined by a positive urine human choriogonadotropin (hCG) test (if female).
2. Participant unwilling to use reliable contraception up until one month following the final immunization (if female and not surgically sterile, abstinent, at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile).
3. Currently lactating and breast-feeding (if female).
4. Inability to correctly answer all questions on the informed consent comprehension questionnaire.
5. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
6. 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).
7. Known or suspected immunodeficiency.
8. Laboratory evidence of liver disease (alanine aminotransferase \[ALT\] greater than 1.25-times the upper reference limit).
9. Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than 1+ protein, or glucose on urine dipstick testing).
10. Laboratory evidence of hematologic disease (absolute leukocyte count \<3500/mm3; absolute leukocyte count \>11.0 x 103/mm3; hemoglobin \<10.0 g/dl \[females\] or \<12.0 g/dl \[males\]; or, platelet count \<140,000/mm3).
11. Other condition that in the opinion of the investigator could jeopardize the safety or rights of a volunteer participating in the trial or would render them unable to comply with the protocol.
12. Participation in another investigational vaccine or drug trial within 30 days of starting this study or for the duration of the study.
13. History of a severe allergic reaction or anaphylaxis.
14. 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.
15. Positive for HCV.
16. Positive for HBsAg.
17. Positive for HIV infection.
18. Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or planned use up to one month after the volunteer's final vaccination.
19. Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
20. History of a surgical splenectomy.
21. Receipt of blood products within the 6 months prior to entry into the study.
22. Previous receipt of the Na-GST-1/Alhydrogel® vaccine.
23. Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia; or laboratory evidence of possible autoimmune disease determined by a positive anti-dsDNA titer, positive rheumatoid factor, proteinuria (greater than trace protein on urine dipstick testing) and/or a positive ANA.

Primary outcomes:
measure: Vaccine-related Adverse Events
timeFrame: Day 380
Secondary outcomes:
measure: Anti-Na-GST-1 IgG Antibody Level on Day 126
timeFrame: Day 126
Other outcomes:
measure: Duration of antibody response to Na-GST-1
timeFrame: Day 14, 28, 42, 56, 180, 194, 208, 270, 380
measure: IgG Subclass Distribution to Na-GST-1
timeFrame: Day 14, 28, 42, 56, 180, 194, 208, 270, 380
Locations:
city: Lambaréné
country: Gabon
facility: Centre de Récherches Médicales de Lambaréné
Study officials:
affiliation: Centre de Recherches Medicales de Lambarené
name: Ayola Adegnika, MD
role: PRINCIPAL_INVESTIGATOR
References: