Evaluate a New Shigella Sonnei Vaccine Administered Either by Intradermal, Intranasal or Intramuscular Route in Healthy Adults

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT02034500
First received: January 2, 2014
Last updated: September 23, 2014
Last verified: August 2014
  Purpose

This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) when administered at different dosages by different routes (intradermally, intranasally or intramuscularly) 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 52 eligible subjects will be assigned to one of three sequential cohorts as follows:

Cohort A) 0.1 μg ID and 5 μg IN Cohort B) 1 μg ID and 20 μg IN Cohort C) 10 μg ID, 80 μg IN and 5 μg IM 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. Specifically for IN and ID administration routes, 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, Placebo Controlled, Single Center, Dose Escalation Study to Evaluate the Safety and Immunogenicity of 3 Vaccinations With Shigella Sonnei Vaccine (1790GAHB) Administered Either by Intradermal, Intranasal or Intramuscular Route in Healthy Adults.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Day 28 after each vaccination ] [ Designated as safety issue: Yes ]
    • Numbers of subjects with deviations from normal values of hematology, renal, bone and liver panels and urinalysis (after 2nd and 3rd vaccination).
    • Numbers of subjects with reported unsolicited adverse events during 28 days following each vaccination.

  • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Day 7 after each vaccination ] [ Designated as safety issue: Yes ]
    • Numbers of subjects with deviations from normal values of hematology, renal, bone and liver panels and urinalysis (after 1st vaccination)
    • Numbers of subjects with reported solicited adverse events during 7 days following each vaccination.

  • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Throughout the study duration e.g. approximately 9 months ] [ Designated as safety issue: Yes ]
    • Adverse Events leading to study withdrawal
    • All Serious Adverse Events
    • All Adverse Events of special Interest (reactive arthritis according the study protocol).
    • All data resulting from the hematological, haematochemical blood tests and urinalysis.
    • All new onsets of chronic disease (NOCD)


Secondary Outcome Measures:
  • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    • IgG Geometric mean concentrations (GMCs) 28 days after 2nd 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 2nd vaccination relative to the baseline concentration.
    • Stool IgA GMCs 28 days after 2nd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
    • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 2nd vaccination relative to the baseline concentration.

  • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    • IgG Geometric mean concentrations (GMCs) before (day 1) and 28 days after 1st 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 relative to the baseline concentration.
    • Stool IgA GMCs before (day 1), 28 days after 1st vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
    • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 1st vaccination relative to the baseline concentration.

  • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    • IgG Geometric mean concentrations (GMCs) 28 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 3rd vaccination relative to the baseline concentration.
    • Stool IgA GMCs 28 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
    • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 3rd vaccination relative to the baseline concentration.

  • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 252 ] [ Designated as safety issue: No ]
    • IgG Geometric mean concentrations (GMCs) 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 168 days after 3rd vaccination relative to the baseline concentration.
    • Stool IgA GMCs 168 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
    • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 168 days after 3rd vaccination relative to the baseline concentration.


Estimated Enrollment: 52
Study Start Date: March 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 - 0.1 µg ID
Subjects receiving treatment intradermally in cohort A
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT A / GAHB-Placebo ID
Subjects receiving placebo intradermally in cohort A
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT A / 1790GAHB vaccine - 5 µg IN
Subjects receiving treatment intranasally in cohort A
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT A / GAHB-Placebo IN
Subjects receiving placebo intranasally in cohort A
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT B / 1790GAHB vaccine - 1 µg ID
Subjects receiving treatment intradermally in cohort B
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT B / GAHB-Placebo ID
Subjects receiving placebo intradermally in cohort B
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT B / 1790GAHB vaccine - 20 µg IN
Subjects receiving treatment intranasally in cohort B
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT B / GAHB-Placebo IN
Subjects receiving placebo intranasally in cohort B
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT C / 1790GAHB vaccine - 10 µg ID
Subjects receiving treatment intradermally in cohort C
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT C / GAHB-Placebo ID
Subjects receiving placebo intradermally in cohort C
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT C / 1790GAHB vaccine - 80 µg IN
Subjects receiving treatment intranasally in cohort C
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT C / GAHB-Placebo IN
Subjects receiving placebo intranasally in cohort C
Biological: GAHB-Placebo
Other Name: Placebo
Experimental: COHORT C / 1790GAHB vaccine - 5 µg IM
Subjects receiving treatment intramuscularly in cohort C
Biological: 1790GAHB vaccine
Other Name: Shigella sonnei vaccine
Placebo Comparator: COHORT C / GAHB-Placebo IM
Subjects receiving placebo intramuscularly in cohort C
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 have been explained to them, have given written consent according to local regulatory requirements.
  3. Individuals in good health as determined by the outcome of medical history, physical examination, hematology, renal, bone and liver panels (including negative for agglutination testing of S. sonnei), urinalysis and clinical judgment of the investigator.
  4. If women of childbearing potential, have a negative pregnancy test prior to study vaccination and willingness to use acceptable contraceptive measures for the entire study duration.
  5. Individuals available for follow-up for the duration of the study.
  6. Individuals registered with a general practitioner.

Exclusion Criteria:

  1. Individuals with a history of recurrent wheezing, asthma, respiratory allergies, allergic rhinitis, nasal surgery or significant nasal abnormalities (e.g. polyps), and Bell's palsy. Presence of nasal piercings. Symptoms of upper respiratory tract infection within 3 days of intended study vaccination is a temporary exclusion criterion.
  2. Individuals unwilling to abstain from medications or other agents that are applied via the nasal route from 24 hours prior to each nasal dosing through to the safety assessment 1 week later.
  3. 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.
  4. Individuals with any progressive or severe neurological disorder, seizure disorder orGuillain-Barré syndrome.
  5. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study.
  6. 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.
  7. Individuals with human leukocyte antigen (HLA) -B27 positive and/or with history of reactive arthritis
  8. Individuals with known HIV, HBV and HCV 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 within the previous 30 days, or were in chemotherapy treatment within the past 6 months.
  9. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  10. 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).
  11. Individuals who have any malignancy or lymphoproliferative disorder.
  12. Individuals with history of allergy to vaccine components.
  13. Individuals participating in any clinical trial with another investigational product 90 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
  14. 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 4 weeks before 1st vaccination and 4 weeks after 3rd vaccination
  15. Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks.
  16. 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.
  17. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study vaccination.
  18. BMI > 30 kg/m2.
  19. Individuals with history of substance or alcohol abuse within the past 2 years.
  20. Women who are pregnant or breast-feeding or of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study.
  21. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.
  22. Individuals who have a previously ascertained or suspected disease caused by S. sonnei or positive S. sonnei serology at screening
  23. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. sonnei
  24. 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: NCT02034500

Locations
United Kingdom
Surrey Clinical Research Center (Surrey CRC)
Guildford, Surrey, United Kingdom, GU2 7XP
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: David JM Lewis, MD University of Surrey, Guildford, GU2 7XP United Kingdom
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT02034500     History of Changes
Other Study ID Numbers: H03_02TP
Study First Received: January 2, 2014
Last Updated: September 23, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
prevention
Shigella sonnei

ClinicalTrials.gov processed this record on October 22, 2014