Clinical trial NCT02676895: A Study of the Safety and Immune Response of 2 Doses of a New Shigella Vaccine in Kenyan Adults
Official title: A Phase 2a, Observer Blind, Randomized, Controlled, Single Center Study To Evaluate The Safety, Reactogenicity And Immunogenicity Of 2 Doses Of The GVGH 1790GAHB Vaccine Against Shigella Sonnei, Administered Intramuscularly In Adult Subjects From A Country Endemic For Shigellosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Shigella Sonnei Infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-02-08
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and the immunogenicity of two different doses of the GVGH S. sonnei vaccine in healthy adults and represents the first step towards testing of the GMMA vaccine in the vaccine target population of children from developing countries where shigellosis is endemic.


Eligibility criteria: Inclusion Criteria:

1. Individuals ≥18 years to ≤45 years of age on the day of informed consent who are resident in the study area and are not planning to leave during the study period.
2. Individuals who, after the nature of the study has been explained, have voluntarily given written consent according to local regulatory requirements, prior to study entry.
3. Individuals who can comply with study procedures including follow-up.
4. Individuals in good health as determined by the outcome of medical history, physical examination, hematology, renal function, and liver function tests, urine dipstick/urinalysis and the clinical judgment of the investigator.
5. Males Or Females of childbearing potential who are using an effective birth control method which they intend to use for the duration of the study Or Females without childbearing potential (i.e. irrespective of birth control method) Prior to receipt of second study vaccination, subjects must be evaluated to confirm that they are eligible for subsequent vaccination. If subjects do not meet any of the original inclusion criteria listed above, they should not receive additional vaccinations.

Exclusion Criteria:

1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
2. Individuals with any progressive or severe neurological disorder, seizure disorder or previous Guillain-Barré syndrome.
3. Individuals who, in the judgment of the investigator, may not be able to comply with all the required study procedures.
4. Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
5. Individuals with history of reactive arthritis.
6. Individuals with known HIV or hepatitis B virus infection or HIV related disease, history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system. Individuals under systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to screening.
7. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
8. Individuals with a neutrophil count lower than 1.8 x 10\^9/L (applicable to the initial 18 subjects) or lower than 1.0 x 10\^9/L (applicable to the additional subjects if approved by DSMB) at screening
9. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, Type 2 diabetes mellitus, hypertension, cardiac, renal or hepatic disease and tuberculosis).
10. Individuals who have any malignancy or lymphoproliferative disorder.
11. Individuals with history of allergy to vaccines components or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial.
12. Individuals participating in any clinical trial with another investigational product within 28 days prior to the screening study visit or intent to participate in another clinical study at any time during the conduct of this study.
13. Individuals who received vaccines containing meningococcal A, C, W, Y or tetanus, diphtheria or pertussis antigens within 12 months before screening, or any other vaccines within 4 weeks prior to screening in this study or who are planning to receive any vaccine within the entire study duration.
14. Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the 12 weeks prior to the first dose of the study vaccine.
15. Individuals who are study personnel or immediate family members (parents, children, spouse and brothers/sisters) to the personnel conducting this study.
16. Individuals with body temperature \> 38.0°C within 3 days of intended study vaccination is a reason for delay of vaccination
17. Individuals with Body Mass Index (BMI)\> 30 kg/m\^2
18. Individuals with history of substance or alcohol abuse within the past 2 years.
19. Women who are pregnant or are breast-feeding, or are of childbearing age who have not used (for the two months preceding the 1st vaccination) and are not willing to use acceptable contraceptive measures, for the duration of the study. If subjects are women of childbearing potential, they must have a negative pregnancy test at screening visit and prior to enrollment (visit 1). For the purposes of this study acceptable methods of contraception are oral, injected or implantable contraceptives.
20. Individuals who have a previously laboratory confirmed case of disease caused by S. sonnei.
21. Any condition which, in the opinion of the investigator, may pose an increased and unreasonable safety risk to the subject if they participated in the study.
22. Individuals with a previous history of Benign Ethnic Neutropenia or drug related neutropenia.
23. Individuals who have or are likely to require concomitant treatment with neutropenic agents.

Primary outcomes:
measure: Number of Subjects With Solicited Local and Systemic Adverse Reactions After Each Vaccination
timeFrame: From 30 minutes up to 7 days following each vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During 28 days following each vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the whole study period (from Day 1 up to Day 57)
measure: Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 8 by Baseline Ranges
timeFrame: At Day 8 (7 days after first vaccination)
measure: Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 29 by Baseline Ranges
timeFrame: At Day 29 (28 days after the first vaccination)
measure: Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 36 by Baseline Ranges
timeFrame: At Day 36 (7 days after the second vaccination)
measure: Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 57 by Baseline Ranges
timeFrame: At Day 57 (28 days after the second vaccination)
measure: Number of Subjects With Reported Reactive Arthritis or Neutropenia (AESIs)
timeFrame: Throughout the whole study period (from Day 1 up to Day 57)
Secondary outcomes:
measure: Anti-LPS S.Sonnei IgG ELISA Geometric Mean Concentrations (GMCs), by Baseline Titer
timeFrame: At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)
measure: Anti-LPS S. Sonnei Geometric Mean Ratios (GMRs) Between Post- and Pre-vaccination Samples
timeFrame: At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)
measure: Number of Subjects With Seroresponse to Anti-LPS S. Sonnei IgG ELISA, by Baseline Titer
timeFrame: At Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)
measure: Number of Subjects With Titers Post Vaccination Concentration for Anti-LPS S. Sonnei ≥ 121 U/mL
timeFrame: At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)
Other outcomes:
Locations:
city: Kilifi
country: Kenya
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: