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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pneumococcal Infections, Pneumonia, Pneumococcal

Intervention / Treatment
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* Biological: GEN-004 with Aluminum Hydroxide Adjuvant
* Biological: Placebo
* Biological: Streptococcus pneumoniae inoculation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEN-004 with Aluminum Hydroxide<br> | Biological: GEN-004 with Aluminum Hydroxide Adjuvant<br>* 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.<br>* Other names: GEN-004;Biological: Streptococcus pneumoniae inoculation<br>* Intranasal inoculation of S. Pneumoniae (80,000 CFU/100μl per nostril) serotype 6B.<br>* Other names: S. Pneumoniae;|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo: normal saline, 0.5 mL per dose, IM.<br>* Other names: Normal saline;Biological: Streptococcus pneumoniae inoculation<br>* Intranasal inoculation of S. Pneumoniae (80,000 CFU/100μl per nostril) serotype 6B.<br>* Other names: S. Pneumoniae;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GEN-004, Aluminum hydroxide, Vaccine, Streptococcus pneumoniae, Pneumococcal Infections, Strep pneumoniae, Pneumonia