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

Pneumococcal Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02116998
• Other study ID #: GEN-004-002
• Secondary ID: 2014-000944-13
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2014
• Last updated: April 4, 2018
• Start date: September 2014
• Est. completion date: April 2016

Study information

• Verified date: April 2018
• Source: Genocea Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections
• Pneumonia
• Pneumonia, Pneumococcal

Intervention

Biological:
• GEN-004 with Aluminum Hydroxide Adjuvant
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.
• Placebo
Placebo: normal saline, 0.5 mL per dose, IM.
• Streptococcus pneumoniae inoculation
Intranasal inoculation of S. Pneumoniae (80,000 CFU/100µl per nostril) serotype 6B.

Locations

Country	Name	City	State
United Kingdom	Royal Liverpool University Hospital, Liverpool School of Tropical Medicine	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Genocea Biosciences, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

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