Study of Na-APR-1 (M74)/Alhydrogel® Co-administered With Na-GST-1/Alhydrogel in Brazilian Adults

• ClinicalTrials.gov Identifier: NCT02476773
• Recruitment Status: Completed
• First Posted: June 19, 2015
• Last Update Posted: December 3, 2019
• Sponsor: Baylor College of Medicine
• Collaborators: Centro de Pesquisas René Rachou; Johns Hopkins University; University of California, San Francisco; George Washington University
• Information provided by (Responsible Party): Maria Elena Bottazzi PhD, Baylor College of Medicine

Tracking Information

• First Submitted Date: June 17, 2015
• First Posted Date: June 19, 2015
• Last Update Posted Date: December 3, 2019
• Actual Study Start Date: January 2016
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 18, 2015)

• Frequency of solicited injection site and systemic reactogenicity, graded by severity, on the day of each study vaccination through 14 days after each study vaccination. [ Time Frame: 14 days post-vaccination ]
• Frequency of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 9 months after the last study vaccination. [ Time Frame: Day 380 ]
• Frequency of clinical safety laboratory adverse events. [ Time Frame: Day 380 ]
• Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination. [ Time Frame: 30 days post-vaccination ]
• Frequency of new-onset chronic medical conditions through approximately 9 months after the third study vaccination. [ Time Frame: Day 380 ]
• Frequency of Adverse Events of Special Interest through approximately 9 months after the third study vaccination. [ Time Frame: Day 380 ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: June 18, 2015): The IgG level by an indirect enzyme-linked immunosorbent assay (ELISA) on approximately Day 126. [ Time Frame: Day 126 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures (submitted: June 18, 2015): The IgG antibody response, by an indirect enzyme-linked immunosorbent assay (ELISA) at approximately 7, 14, and 28 days after each vaccination, and approximately 3, 6, and 9 months after the third dose. [ Time Frame: 7, 14, and 28 days after each vaccination, and approximately 3, 6, and 9 months after the third dose ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study of Na-APR-1 (M74)/Alhydrogel® Co-administered With Na-GST-1/Alhydrogel in Brazilian Adults
• Official Title: Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® Co-administered With Na-GST-1/Alhydrogel® in Brazilian Adults
• 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 wtih 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 Brazilian 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 living in the area of Americaninhas, Minas Gerais, Brazil. Subjects will receive three doses of the assigned vaccine delivered intramuscularly 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 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 an indirect enzyme-linked immunosorbent assay (ELISA) and also by ImmunoCAP, on serum obtained prior to each study vaccination and at time points after each vaccination; antibody affinity by Surface Plasmon Resonance; functional activity of vaccine-induced antibodies via in vitro enzyme neutralization assays; and, 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 6 groups of 10.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Hookworm Infection
• Hookworm Disease

Intervention

• Biological: Na-GST-1/Alhydrogel plus GLA-AF
• Biological: Na-APR-1 (M74)/Alhydrogel
• Biological: Na-APR-1 (M74)/Alhydrogel plus GLA-AF
• Biological: Sterile Saline Placebo

Study Arms

• Experimental: Group 1
  • 5 subjects will receive 10µg Na-APR-1 (M74)/Alhydrogel with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 10µg Na-APR-1 (M74)/Alhydrogel with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel
  • Biological: Sterile Saline Placebo
• Experimental: Group 2
  • 5 subjects will receive 10µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 10µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel plus GLA-AF
  • Biological: Sterile Saline Placebo
• Experimental: Group 3
  • 5 subjects will receive 30µg Na-APR-1 (M74)/Alhydrogel, with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 30µg Na-APR-1 (M74)/Alhydrogel, with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel
  • Biological: Sterile Saline Placebo
• Experimental: Group 4
  • 5 subjects will receive 30µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 30µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel plus GLA-AF
  • Biological: Sterile Saline Placebo
• Experimental: Group 5
  • 5 subjects will receive 100µg Na-APR-1 (M74)/Alhydrogel, with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 100µg Na-APR-1 (M74)/Alhydrogel, with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel
  • Biological: Sterile Saline Placebo
• Experimental: Group 6
  • 5 subjects will receive 100µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with Sterile Saline Placebo administered to the alternate arm.
  • 5 subjects will receive 100µg Na-APR-1 (M74)/Alhydrogel plus GLA-AF, with 100µg Na-GST-1/Alhydrogel plus GLA-AF administered to the alternate arm.
  Interventions:

  • Biological: Na-GST-1/Alhydrogel plus GLA-AF
  • Biological: Na-APR-1 (M74)/Alhydrogel plus GLA-AF
  • Biological: Sterile Saline Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 18, 2015): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2017
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males or non-pregnant females between 18 and 45 years, inclusive.
2. Good general health as determined by means of the screening procedure.
3. Available for the duration of individual subject study participation (16 months).
4. Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

1. Pregnancy as determined by a positive urine hCG (if female).
2. Subject unwilling to use reliable contraception (as described in Section 2.3.1) from 30 days prior to the first immunization and up until one month following the third immunization (if female and not surgically sterile, abstinent or 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 (a history of essential hypertension that is well controlled by medication will not be considered exclusionary.)
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 trace protein or blood on urine dipstick testing with the exception of greater than trace blood detected in females during menses).
10. Laboratory evidence of hematologic disease (absolute leukocyte count <3200/mm3; absolute leukocyte count >10.8 x 103/mm3; hemoglobin <11.4 g/dl [females] or <12.1 g/dl [males]; or, platelet count <130,000/mm3).
11. Serum glucose (random) greater than 1.2-times the upper reference limit.
12. 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.
13. Participation in another investigational vaccine or drug trial within 30 days of starting this study.
14. Previous receipt of the Na-GST-1/Alhydrogel® hookworm vaccine.
15. Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
16. History of a severe allergic reaction or anaphylaxis.
17. Severe asthma as defined by the need for daily use of inhalers or emergency clinic visit or hospitalization within the last 6 months.
18. Positive test for hepatitis B surface antigen (HBsAg).
19. Positive confirmatory test for HIV infection.
20. Positive confirmatory test for hepatitis C virus (HCV) infection.
21. Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of the volunteer's expected first vaccination in this study or planned use up to one month following the last vaccination.
22. Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to the volunteer's expected first vaccination in the study.
23. History of a surgical splenectomy.
24. Receipt of blood products within the past 6 months.
25. Anti-Na-GST-1 IgE antibody level above 0.35 kUA/L by the ImmunoCAP method.
26. Anti-Na-APR-1 IgE antibody level above ELISA reactivity threshold.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT02476773
• Other Study ID Numbers: SVI-DBL-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Maria Elena Bottazzi PhD, Baylor College of Medicine
• Original Responsible Party: Albert B. Sabin Vaccine Institute
• Current Study Sponsor: Baylor College of Medicine
• Original Study Sponsor: Albert B. Sabin Vaccine Institute

Collaborators

• Centro de Pesquisas René Rachou
• Johns Hopkins University
• University of California, San Francisco
• George Washington University

Investigators

• Principal Investigator: David Diemert, MD; George Washington University
• Study Director: Rodrigo Correa-Oliveira, PhD; Centro de Pesquisas René Rachou

• PRS Account: Baylor College of Medicine
• Verification Date: November 2019