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Study of Co-administered Na-APR-1 (M74) and Na-GST-1 in Gabonese Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02839161
Recruitment Status : Completed
First Posted : July 20, 2016
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Maria Elena Bottazzi PhD, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE July 18, 2016
First Posted Date  ICMJE July 20, 2016
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE January 2017
Actual Primary Completion Date December 13, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2016)		 Vaccine-related Adverse Events [ Time Frame: Day 380 ]
To evaluate the safety and reactogenicity of three different dose concentrations of Na-APR-1 (M74)/Alhydrogel® co-administered with Na-GST-1/Alhydrogel® in healthy Gabonese children.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2016)		 IgG response to Na-GST-1 and Na-APR-1 (M74) [ Time Frame: 14 days after the third vaccination ]
To determine the doses of co-administered Na-APR-1 (M74) and Na-GST-1 that result in the highest levels of IgG antibody approximately 14 days after the third vaccination.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 19, 2016)
  • Duration of antibody response to Na-GST-1 and Na-APR-1 (M74) [ Time Frame: Day 380 ]
    To assess and compare the duration of the antibody responses of Na-GST-1 and Na-APR-1 (M74).
  • IgG subclass response to Na-GST-1 and Na-APR-1 (M74) [ Time Frame: Day 380 ]
    To assess the distribution of IgG subclass responses to Na-GST-1 and Na-APR-1 (M74).
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of Co-administered Na-APR-1 (M74) and Na-GST-1 in Gabonese Children
Official Title  ICMJE Randomized, Controlled, Phase 1 Study to Assess Safety and Immunogenicity of Co-administered Hookworm Vaccine Candidates Na-APR-1 (M74)/Alhydrogel® and Na-GST-1/ Alhydrogel® in Gabonese Children
Brief Summary Double blind, randomized, controlled, dose-escalation Phase 1 clinical trial in hookworm-exposed children aged 6 to 10 years living in the area of Lambaréné, Gabon. Children will receive three doses of the Na-GST-1/Alhydrogel hookworm vaccine co-administered with the Na-APR-1 (M74)/Alhydrogel hookworm vaccine or the hepatitis B vaccine co-administered with sterile saline. All injections will be delivered intramuscularly (deltoid) on approximately Days 0, 56, and 112 or 180.
Detailed Description

Double blind, randomized, controlled, dose-escalation Phase 1 clinical trial in hookworm-exposed children aged 6 to 10 years living in the area of Lambaréné, Gabon. Children will receive three doses of the assigned vaccine(s) delivered intramuscularly (deltoid) on approximately Days 0, 56, and 112 or 180.

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 third 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 (see Appendix A); the functional activity of vaccine-induced antibodies will be assessed by in vitro enzyme neutralization assays; the induction of B cell memory will be measured by antigen-specific memory B cell responses.

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

60 subjects will be enrolled into 3 groups of 20. The first 20 subjects will be assembled and enrolled into Group 1:

  1. Group 1 double-blind IP allocation (n=20):

    • 16 subjects will receive 10 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 10 µg Na-GST-1 administered IM in the alternate arm.

      • 8 will be vaccinated according to a 0,2,4-month schedule
      • 8 will be vaccinated according to a 0,2,6-month schedule

    • 4 subjects will receive hepatitis B vaccine comparator:

      • 2 will be vaccinated according to a 0,2,4-month schedule
      • 2 will be vaccinated according to a 0,2,6-month schedule

  2. Group 2 double-blind IP allocation (n=20):

    • 16 subjects will receive 30 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 30µg Na-GST-1 administered IM in the alternate arm.

      • 8 will be vaccinated according to a 0,2,4-month schedule
      • 8 will be vaccinated according to a 0,2,6-month schedule

    • 4 subjects will receive hepatitis B vaccine comparator:

      • 2 will be vaccinated according to a 0,2,4-month schedule
      • 2 will be vaccinated according to a 0,2,6-month schedule

  3. Group 3 double-blind IP allocation (n=20):

    • 16 subjects will receive 100 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 100 µg Na-GST-1 administered IM in the alternate arm.

      • 8 will be vaccinated according to a 0,2,4-month schedule
      • 8 will be vaccinated according to a 0,2,6-month schedule

    • 4 subjects will receive hepatitis B vaccine comparator:

      • 2 will be vaccinated according to a 0,2,4-month schedule
      • 2 will be vaccinated according to a 0,2,6-month schedule
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Hookworm Disease
  • Hookworm Infection
Intervention  ICMJE
  • Biological: Na-GST-1/Alhydrogel
  • Biological: Na-APR-1 (M74)/Alhydrogel
  • Biological: Hepatitis B Vaccine
Study Arms  ICMJE
  • Experimental: Low-dose (0,2,4 months)
    10 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 10 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 4 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Experimental: Low-dose (0,2,6 months)
    10 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 10 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 6 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Experimental: Medium-dose (0,2,4 months)
    30 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 30 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 4 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Experimental: Medium-dose (0,2,6 months)
    30 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 30 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 6 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Experimental: High-dose (0,2,4 months)
    100 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 100 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 4 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Experimental: High-dose (0,2,6 months)
    100 µg Na-APR-1 (M74) plus 5 µg GLA-AF delivered by IM injection in the deltoid muscle, with 100 µg Na-GST-1 administered IM in the alternate arm. Injections at 0, 2, and 6 months.
    Interventions:
    • Biological: Na-GST-1/Alhydrogel
    • Biological: Na-APR-1 (M74)/Alhydrogel
  • Active Comparator: Comparator (0,2,4 months)
    Hepatitis B vaccine delivered by IM injection in the deltoid muscle, with sterile saline solution administered IM in the alternate arm. Injections at 0, 2, and 4 months.
    Intervention: Biological: Hepatitis B Vaccine
  • Active Comparator: Comparator (0,2,6 months)
    Hepatitis B vaccine delivered by IM injection in the deltoid muscle, with sterile saline solution administered IM in the alternate arm. Injections at 0, 2, and 6 months.
    Intervention: Biological: Hepatitis B Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 19, 2016)		 60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 28, 2019
Actual Primary Completion Date December 13, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males or females between 6 and 10 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 (up to 15 months).
  4. Willingness of parent or legal guardian for child to participate in the study as evidenced by signing the informed consent document in combination with the child assent form.
  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. Inability of parent/legal guardian to correctly answer all questions on the informed consent comprehension questionnaire.
  2. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
  3. Known or suspected immunodeficiency.
  4. Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
  5. Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than 1+ protein, or more than trace blood on urine dipstick testing with the exception of greater than trace blood detected in females during menses).
  6. Laboratory evidence of hematologic disease (absolute leukocyte count <4500/mm3; absolute leukocyte count >13.0 x 103/mm3; hemoglobin <9.5 g/dl; or, platelet count <140,000/mm3).
  7. Other condition that in the opinion of the investigator could jeopardize the safety or rights of a child participating in the trial or would render the child unable to comply with the protocol.
  8. Participation in another investigational vaccine or drug trial within 30 days of starting this study or for the duration of the study.
  9. History of a severe allergic reaction or anaphylaxis.
  10. Severe asthma as defined by the need for daily use of inhalers or emergency room/clinic visit or hospitalization within 6 months of the child's planned first vaccination in the study.
  11. Positive for HCV.
  12. Positive for HBsAg.
  13. Positive for HIV infection.
  14. Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or expect to use for the duration of the study.
  15. Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
  16. History of a surgical splenectomy.
  17. Receipt of blood products within the 6 months prior to entry into the study.
  18. Previous receipt of a primary series (three doses according to a 0, 1, and 6 -12 month schedule) of the hepatitis B vaccine.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Gabon
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02839161
Other Study ID Numbers  ICMJE HV-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Maria Elena Bottazzi PhD, Baylor College of Medicine
Original Responsible Party Albert B. Sabin Vaccine Institute
Current Study Sponsor  ICMJE Baylor College of Medicine
Original Study Sponsor  ICMJE Albert B. Sabin Vaccine Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ayola Adegnika, MD Centre de Recherches Medicales de Lambaréné
PRS Account Baylor College of Medicine
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP