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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT02017899
First received: December 17, 2013
Last updated: September 23, 2014
Last verified: September 2014
  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: 1790GAHB vaccine
Biological: GAHB-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 Novartis:

Primary Outcome Measures:
  • To evaluate the safety profile of 5 different dosages of 1790GAHB vaccine in healthy adults. [ Time Frame: 7 and 28 days after each vaccination and entire study duration ] [ Designated as safety issue: Yes ]
    • Numbers of subjects with deviations from normal values of hematological, haematochemical blood tests and urinalysis after vaccination.
    • Numbers of subjects with solicited local and systemic reactions during 7 days following each vaccination.
    • Numbers of subjects with reported unsolicited adverse events during 28 days following each vaccination.
    • Number of subjects with reported Serious Adverse Events throughout the study duration.
    • Number of subjects with reported reactive arthritis (AE of special interest).


Secondary Outcome Measures:
  • To evaluate the immunogenicity profile of 5 different dosages of 1790GAHB vaccine in healthy adults. [ Time Frame: At 28 days after 1st vaccination, 28 days after 2nd vaccination and 28 and 168 days after 3rd vaccination ] [ Designated as safety issue: No ]
    • IgG Geometric mean concentrations (GMCs) before (day 1), 28 days after 1st vaccination, 28 days after 2nd vaccination, 28 and 168 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios between post vaccination and baseline samples.
    • Percentage of subjects achieving at least a four-fold rise in IgG ELISA antibody concentration 28 days after 1st vaccination, 28 days after 2nd vaccination, and 28 and 168 days after 3rd vaccination relative to the baseline concentration.
    • Stool IgA Geometric mean concentrations (GMCs as determined by ELISA, and applicable geometric mean ratios relative to the baseline concentration), may be calculated in the stool specimens of at least one cohort , provided before (day 1), 28 days after 1st vaccination, 28 days after 2nd vaccination, and 28 days after 3rd vaccination


Estimated Enrollment: 50
Study Start Date: February 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: COHORT A / 1790GAHB vaccine - 1 µg
Subjects receiving treatment in cohort A
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Experimental: COHORT B / 1790GAHB vaccine - 5 µg
Subjects receiving treatment in cohort B
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Experimental: COHORT C / 1790GAHB vaccine - 25 µg
Subjects receiving treatment in cohort C
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Experimental: COHORT D / 1790GAHB vaccine - 50 µg
Subjects receiving treatment in cohort D
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Experimental: COHORT E / 1790GAHB vaccine - 100 µg
Subjects receiving treatment in cohort E
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT A / GAHB-Placebo
Subjects receiving placebo in cohort A
Biological: GAHB-Placebo
Other Name: Placebo
Placebo Comparator: COHORT B / GAHB-Placebo
Subjects receiving placebo in cohort B
Biological: GAHB-Placebo
Other Name: Placebo
Placebo Comparator: COHORT C / GAHB-Placebo
Subjects receiving placebo in cohort C
Biological: GAHB-Placebo
Other Name: Placebo
Placebo Comparator: COHORT D / GAHB-Placebo
Subjects receiving placebo in cohort D
Biological: GAHB-Placebo
Other Name: Placebo
Placebo Comparator: COHORT E / GAHB-Placebo
Subjects receiving placebo in cohort E
Biological: GAHB-Placebo
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
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
Novartis
Investigators
Principal Investigator: Odile Launay, Prof Centre d'Investigation Clinique en Vaccinologie Cochin-Pasteur (CIC1417)
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT02017899     History of Changes
Other Study ID Numbers: H03_01TP
Study First Received: December 17, 2013
Last Updated: September 23, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Novartis:
prevention
Shigella sonnei

ClinicalTrials.gov processed this record on October 30, 2014