Safety, Tolerability, and Efficacy Study of Prophylactic S. Pneumoniae Vaccine Following Challenge With S. Pneumoniae

Phase 2

Completed

Conditions: Pneumonia, Pneumococcal
Pneumococcal Infections

Interventions: Biological: GEN-004 with Aluminum Hydroxide Adjuvant
Biological: Placebo
Biological: Streptococcus pneumoniae inoculation

Registration Number: NCT02116998

Lead Sponsor: Genocea Biosciences, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GEN-004 with Aluminum Hydroxide	GEN-004 with Aluminum Hydroxide Adjuvant	-
Placebo	Placebo	-
GEN-004 with Aluminum Hydroxide	Streptococcus pneumoniae inoculation	-
Placebo	Streptococcus pneumoniae inoculation	-

Primary Outcome Measures

Name	Time	Method
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	56 weeks

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of GEN-004 with aluminum hydroxide	56 weeks
Duration of S. pneumoniae colonization through 14 days after inoculation	12 weeks
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	56 weeks
Impact of GEN-004 on the density of colonization as measured by S. pneumoniae colony forming units (CFUs) post-inoculation	56 weeks