Safety, Tolerability, and Efficacy Study of Prophylactic S. Pneumoniae Vaccine Following Challenge With S. Pneumoniae
Primary Purpose
Pneumococcal Infections, Pneumonia, Pneumococcal
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
GEN-004 with Aluminum Hydroxide Adjuvant
Placebo
Streptococcus pneumoniae inoculation
Sponsored by
About this trial
This is an interventional prevention trial for Pneumococcal Infections focused on measuring GEN-004, Aluminum hydroxide, Vaccine, Streptococcus pneumoniae, Pneumococcal Infections, Strep pneumoniae, Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Males and non-pregnant females, ages 18 to 55 years inclusive.
- Willing and able to provide written informed consent.
- Fluent English speakers only (for safety reasons)
- Willing to perform and comply with all study procedures including attending clinic visits as scheduled.
Exclusion Criteria:
- Prior vaccination with pneumococcal vaccine.
- History of invasive pneumococcal disease (i.e., sepsis, meningitis or pneumonia with bacteremia).
- Close contact with at risk individuals (young children [under 5years], immunosuppressed adults, elderly, chronic ill health).
- Current smoker or significant smoking history (>10 pack years).
- Pregnant or breast-feeding woman.
- Women of child-bearing potential (WOCBP) who are deemed not to have sufficient, effective birth control in place for 1 month prior to vaccination and 1 month after the final vaccination.
- Allergy to penicillin or amoxicillin.
- Any screening laboratory value > Grade 1
- Positive serologic test for HIV-1 or hepatitis C infection; positive hepatitis B surface antigen (HBsAg).
- Asthma (on regular medication) or other respiratory disease.
- Immunocompromised individuals, including those receiving corticosteroids or other immunosuppressive agents.
- Presence or history of auto-immune disease (refer to Appendix 4) regardless of current treatment.
- No antibiotic treatment within 1 week of inoculation
- Previous involvement in EHPC study inoculated with pneumococcal bacteria
- In any other clinical trial unless in observational stage or follow-up
- Diabetes, type 1 or type 2.
- Other active, uncontrolled co-morbidities that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements.
NOTE: Subjects who are taking a medication to control an underlying co-morbidity may be enrolled if there have been no changes to their medication within 60 days prior to first dose of Study Drug.
Sites / Locations
- Royal Liverpool University Hospital, Liverpool School of Tropical Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GEN-004 with Aluminum Hydroxide
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Efficacy of GEN-004 with aluminum hydroxide in healthy adult subjects to reduce nasopharyngeal colonization following intranasal inoculation with S. pneumoniae serotype 6 as measured by proportion of colonized subjects
Secondary Outcome Measures
Safety and tolerability of GEN-004 with aluminum hydroxide
Duration of S. pneumoniae colonization through 14 days after inoculation
Immunogenicity of GEN-004 with aluminum hydroxide, as measured by TH17 (IL-17) and IgG responses to the vaccine antigens in sera and nasal fluid
Impact of GEN-004 on the density of colonization as measured by S. pneumoniae colony forming units (CFUs) post-inoculation
Full Information
NCT ID
NCT02116998
First Posted
April 11, 2014
Last Updated
April 4, 2018
Sponsor
Genocea Biosciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02116998
Brief Title
Safety, Tolerability, and Efficacy Study of Prophylactic S. Pneumoniae Vaccine Following Challenge With S. Pneumoniae
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GEN-004, a Pneumococcal Protein Subunit Vaccine, on Colonization Following Intranasal Challenge With S. Pneumoniae
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genocea Biosciences, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled study. Eligible subjects will be randomized in a 1:1 ratio to receive GEN-004 with adjuvant or placebo. Each subject will receive up to 3 doses at 4 week intervals.
Following the third dose, subjects will be inoculated intranasally with S. pneumoniae serotype 6B. Nasal washes to identify S. pneumoniae colonization will be obtained pre-inoculation, and then 2, 7 and 14 days after inoculation.
Subjects will also be monitored for safety and tolerability throughout the dosing period, and then for 12 months after their last dose.
The purpose of this study is to evaluate the effectiveness of GEN-004 in reducing colonization rates and magnitude of colonization following the S. pneumoniae challenge.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumococcal Infections, Pneumonia, Pneumococcal
Keywords
GEN-004, Aluminum hydroxide, Vaccine, Streptococcus pneumoniae, Pneumococcal Infections, Strep pneumoniae, Pneumonia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GEN-004 with Aluminum Hydroxide
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
GEN-004 with Aluminum Hydroxide Adjuvant
Other Intervention Name(s)
GEN-004
Intervention Description
GEN-004: 100 µg of each antigen, with adjuvant, 350 µg aluminum hydroxide, administered as a 0.5 mL intramuscular (IM) injection.
GEN-004 is a recombinant S. pneumoniae protein subunit vaccine consisting of 3 recombinant T cell antigens:
GB104: ABC transporter, substrate-binding protein
GB144: Maltose/maltodextrin binding protein, ABC transporter
GB152: Hypothetical protein
GEN-004 is filled in 2 mL vials containing 0.5 mL (350 µg/mL of each antigen).
Aluminum hydroxide adjuvant is filled in 2 mL vials containing 1 mL at a concentration of 5 mg/mL.
Intervention Type
Biological
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline, Normal saline
Intervention Description
Placebo: normal saline, 0.5 mL per dose, IM.
Intervention Type
Biological
Intervention Name(s)
Streptococcus pneumoniae inoculation
Other Intervention Name(s)
S. Pneumoniae
Intervention Description
Intranasal inoculation of S. Pneumoniae (80,000 CFU/100μl per nostril) serotype 6B.
Primary Outcome Measure Information:
Title
Efficacy of GEN-004 with aluminum hydroxide in healthy adult subjects to reduce nasopharyngeal colonization following intranasal inoculation with S. pneumoniae serotype 6 as measured by proportion of colonized subjects
Time Frame
56 weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability of GEN-004 with aluminum hydroxide
Time Frame
56 weeks
Title
Duration of S. pneumoniae colonization through 14 days after inoculation
Time Frame
12 weeks
Title
Immunogenicity of GEN-004 with aluminum hydroxide, as measured by TH17 (IL-17) and IgG responses to the vaccine antigens in sera and nasal fluid
Time Frame
56 weeks
Title
Impact of GEN-004 on the density of colonization as measured by S. pneumoniae colony forming units (CFUs) post-inoculation
Time Frame
56 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males and non-pregnant females, ages 18 to 55 years inclusive.
Willing and able to provide written informed consent.
Fluent English speakers only (for safety reasons)
Willing to perform and comply with all study procedures including attending clinic visits as scheduled.
Exclusion Criteria:
Prior vaccination with pneumococcal vaccine.
History of invasive pneumococcal disease (i.e., sepsis, meningitis or pneumonia with bacteremia).
Close contact with at risk individuals (young children [under 5years], immunosuppressed adults, elderly, chronic ill health).
Current smoker or significant smoking history (>10 pack years).
Pregnant or breast-feeding woman.
Women of child-bearing potential (WOCBP) who are deemed not to have sufficient, effective birth control in place for 1 month prior to vaccination and 1 month after the final vaccination.
Allergy to penicillin or amoxicillin.
Any screening laboratory value > Grade 1
Positive serologic test for HIV-1 or hepatitis C infection; positive hepatitis B surface antigen (HBsAg).
Asthma (on regular medication) or other respiratory disease.
Immunocompromised individuals, including those receiving corticosteroids or other immunosuppressive agents.
Presence or history of auto-immune disease (refer to Appendix 4) regardless of current treatment.
No antibiotic treatment within 1 week of inoculation
Previous involvement in EHPC study inoculated with pneumococcal bacteria
In any other clinical trial unless in observational stage or follow-up
Diabetes, type 1 or type 2.
Other active, uncontrolled co-morbidities that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements.
NOTE: Subjects who are taking a medication to control an underlying co-morbidity may be enrolled if there have been no changes to their medication within 60 days prior to first dose of Study Drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Fitzgerald, MD
Organizational Affiliation
Royal Liverpool University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Liverpool University Hospital, Liverpool School of Tropical Medicine
City
Liverpool
ZIP/Postal Code
L35QA
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, and Efficacy Study of Prophylactic S. Pneumoniae Vaccine Following Challenge With S. Pneumoniae
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