A Phase 1, Dose Escalation Study, to Evaluate a New Shigella Sonnei Vaccine in Healthy Adults.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GSK Vaccines Institute For Global Health S.r.l.
ClinicalTrials.gov Identifier:
NCT02017899
First received: December 17, 2013
Last updated: June 20, 2016
Last verified: June 2016
  Purpose

This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of 5 sequentially escalating dosages of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) administered by intramuscular route in healthy adults (18 to 45 years of age at enrollment). The safety profile of the 1790GAHB vaccine is evaluated in comparison to that of placebo (GAHB-Placebo), constituted by an aluminum hydroxide suspension having the same concentration as study vaccine formulations. A total of 50 eligible subjects will be assigned to one of five sequential cohorts of 10 subjects each.

Within each cohort, in an observer-blind fashion, subjects will be randomized to receive three vaccinations, four weeks apart, of either 1790GAHB vaccine (at five antigen concentrations) or GAHB placebo. A Data Safety Monitoring Board will be in place to receive a summary of all safety data obtained during one week follow-up post-first vaccination with the lower dose. Based on evaluation of the safety data, the Data Safety Monitoring Board will make a recommendation, as to whether the next cohort should be vaccinated with higher antigen concentration or not.

Expected duration of the study for an individual subject is 9 months. Each subject will be followed-up for 6 months after the 3rd vaccination.


Condition Intervention Phase
Shigellosis
Biological: S. sonnei 1790GAHB
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1, Randomized, Observer Blinded, Placebo Controlled, Single Center, Dose Escalation Study to Evaluate the Safety and Immunogenicity of 3 Vaccinations With Shigella Sonnei Vaccine (1790GAHB) Administered Intramuscularly in Healthy Adults.

Resource links provided by NLM:


Further study details as provided by GSK Vaccines Institute For Global Health S.r.l.:

Primary Outcome Measures:
  • Number of subjects with solicited local reaction after any vaccination [ Time Frame: During a 7-day (Days 1-7) post vaccination period following any injection ] [ Designated as safety issue: Yes ]
    Any erythema/induration refers to: ≥25 mm in diameter. Grade 3 (severe) refers to erythema/induration >100 mm in diameter. Grade 3 (severe) for injection site pain refers to: prevents daily activity

  • Number of subjects with solicited systemic reaction after any vaccination [ Time Frame: During a 7-day (Days 1 to 7) post vaccination period following any injection ] [ Designated as safety issue: Yes ]
    Any= Incidence of any symptom regardless of intensity grade. Grade 3 = symptom that prevented daily activities

  • Number of subjects with Neutrophils results below and above the normal ranges [ Time Frame: At Day 8 ] [ Designated as safety issue: Yes ]
    Day 8: VISIT 2 (D7 post 1st vac)

  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 36 ] [ Designated as safety issue: Yes ]
    Day 36: VISIT 3.1 (D7 post 2nd vac.)

  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 57 ] [ Designated as safety issue: Yes ]
    Day 57: VISIT 4 (3rd vac.)

  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 64 ] [ Designated as safety issue: Yes ]
    Day 64: VISIT 4.1 (D7 post 3rd vac.)

  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 85 ] [ Designated as safety issue: Yes ]
    Day 85: VISIT 5 (1 month post 3rd vac.)

  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 225 ] [ Designated as safety issue: Yes ]
    Day 225: VISIT 6 (6 months post 3rd vac.)


Secondary Outcome Measures:
  • Anti-LPS S. sonnei serum IgG Geometric mean concentration (GMCs) [ Time Frame: At baseline, at 28 days after each vaccination and at 168 days after last vaccination ] [ Designated as safety issue: No ]
  • Number of subjects with seroresponse for anti-LPS S. sonnei [ Time Frame: At 28 days after each vaccination and 168 days after last vaccination ] [ Designated as safety issue: No ]
    Seroresponse is defined as: If half of the baseline value is greater than 25 ELISA Unit (EU) then an increase of at least 50% in the post-vaccination sample as compared to baseline [i.e. ((Post-vac minus baseline)/baseline)100% ≥ 50%]. If half of the baseline value is less or equal to 25 EU then an increase of at least 25 EU in the post-vaccination sample as compared to baseline (i.e. [post-vac minus baseline] ≥25 EU)

  • Number of subjects with high seroresponse for anti-LPS S. sonnei (IgG ELISA ≥121 EU) [ Time Frame: At baseline, at 28 days after each vaccination and at 168 days after last vaccination ] [ Designated as safety issue: No ]
    High seroresponse is defined as a post vaccination titer ≥X anti-LPS serum IgG units in the GSK (former Novartis) ELISA that correspond to a titer of 1:800 in the ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). To determine the value for 'X' the GSK (former Novartis) anti-LPS ELISA was calibrated against the Cohen ELISA and it was found that a concentration of 121 EU EU/mL corresponds to a titer of 1:800 in the Cohen assay


Enrollment: 50
Study Start Date: February 2014
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: S. sonnei 1790GAHB - 1 mcg
Subjects enrolled in COHORT A receiving 3 injections of S. sonnei 1790GAHB - 1 mcg
Biological: S. sonnei 1790GAHB
Other Name: Shigella sonnei vaccine
Experimental: S. sonnei 1790GAHB - 5 mcg
Subjects enrolled in COHORT B receiving 3 injections of S. sonnei 1790GAHB - 5 mcg
Biological: S. sonnei 1790GAHB
Other Name: Shigella sonnei vaccine
Experimental: S. sonnei 1790GAHB - 25 mcg
Subjects enrolled in COHORT C receiving 3 injections of S. sonnei 1790GAHB - 25 mcg
Biological: S. sonnei 1790GAHB
Other Name: Shigella sonnei vaccine
Experimental: S. sonnei 1790GAHB - 50 mcg
Subjects enrolled in COHORT D receiving 3 injections of S. sonnei 1790GAHB - 50 mcg
Biological: S. sonnei 1790GAHB
Other Name: Shigella sonnei vaccine
Experimental: S. sonnei 1790GAHB - 100 mcg
Subjects enrolled in COHORT E receiving 3 injections of S. sonnei 1790GAHB - 100 mcg
Biological: S. sonnei 1790GAHB
Other Name: Shigella sonnei vaccine
Placebo Comparator: Placebo
2 subjects enrolled in each COHORT A, B, C, D, E receiving 3 injections of Placebo. These were pooled in one Placebo group in the analyses
Biological: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males and females of age ≥18 years to ≤45 years.
  2. Individuals who, after the nature of the study has been explained to them, and prior to any protocol specific procedures being performed, have given written consent according to local regulatory requirements.
  3. Individuals in good health as determined by the outcome of medical history, physical examination, hematological / hematochemical blood tests (including presence of high antibody titers against S. sonnei by agglutination test), urinalysis and clinical judgment of the investigator.
  4. If women of child-bearing potential, have a negative pregnancy test prior study vaccination and willingness to use acceptable birth control measures for the entire study duration.
  5. Individuals affiliated to a social security regimen.

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 Guillain-Barré syndrome.
  3. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study.
  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 human leukocyte antigen (HLA) -B27 positive and/or with history of reactive arthritis.
  6. Individuals with known or suspected HIV infection or HIV related disease, with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy including use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids (i.e. prednisone, or equivalent ≥10 mg/day) within the previous 28 days, or in chemotherapy treatment within the past 168 days.
  7. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  8. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
  9. Individuals who have any malignancy or lymphoproliferative disorder.
  10. Individuals with history of allergy to vaccine components.
  11. Individuals participating in any clinical trial with another investigational product 28 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
  12. Individuals who received any other vaccines within 4 weeks prior to enrollment in this study or who are planning to receive any vaccine within the entire study duration except influenza vaccination, which is not allowed within the period included between 28 days before 1st vaccination and 28 days after 3rd vaccination.
  13. Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks.
  14. Individuals who are part of study personnel or close family members to the personnel conducting this study or employees of the clinical trial site institution.
  15. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study vaccination.
  16. Individuals with Body Mass Index (BMI)> 30 kg/m2
  17. Individuals with history of substance or alcohol abuse within the past 2 years.
  18. Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study.
  19. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.
  20. Individuals who have a previously laboratory confirmed or suspected disease caused by S. sonnei.
  21. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. sonnei.
  22. Any condition, which, in the opinion of the investigator may pose an increased and unreasonable safety risk to the subject if participating to the present study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02017899

Locations
France
Centre d'Investigation Clinique en Vaccinologie Cochin-Pasteur (CIC1417)
Paris, Paris cedex 14, France, 75679
Sponsors and Collaborators
GSK Vaccines Institute For Global Health S.r.l.
Investigators
Principal Investigator: Odile Launay, Prof Centre d'Investigation Clinique en Vaccinologie Cochin-Pasteur (CIC1417)
  More Information

Responsible Party: GSK Vaccines Institute For Global Health S.r.l.
ClinicalTrials.gov Identifier: NCT02017899     History of Changes
Other Study ID Numbers: H03_01TP 
Study First Received: December 17, 2013
Last Updated: June 20, 2016
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by GSK Vaccines Institute For Global Health S.r.l.:
prevention
Shigella sonnei

Additional relevant MeSH terms:
Dysentery, Bacillary
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Dysentery
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2016