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

NCT02116998 | Completed Phase 2 DMC

• 2 other identifiers: GEN-004-0022014-000944-13
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumococcal Infections; Pneumonia, Pneumococcal

Keywords

GEN-004; Aluminum hydroxide; Vaccine; Streptococcus pneumoniae; Pneumococcal Infections; Strep pneumoniae; Pneumonia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

GEN-004 with Aluminum Hydroxide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Biological: Placebo; Biological: Streptococcus pneumoniae inoculation

Interventions

GEN-004 with Aluminum Hydroxide Adjuvant BIOLOGICAL

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.

Also known as: GEN-004

GEN-004 with Aluminum Hydroxide

Placebo BIOLOGICAL

Placebo: normal saline, 0.5 mL per dose, IM.

Also known as: Saline, Normal saline

Placebo

Streptococcus pneumoniae inoculation BIOLOGICAL

Intranasal inoculation of S. Pneumoniae (80,000 CFU/100μl per nostril) serotype 6B.

Also known as: S. Pneumoniae

GEN-004 with Aluminum Hydroxide; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Genocea Biosciences, Inc.: lead

Study Sites (1)

Royal Liverpool University Hospital, Liverpool School of Tropical Medicine

Liverpool, L35QA, United Kingdom

Location

MeSH Terms

Conditions

Pneumococcal Infections; Pneumonia, Pneumococcal; Pneumonia

Interventions

Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Richard Fitzgerald, MD

  Royal Liverpool University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2014
• First Posted: April 17, 2014
• Study Start: September 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 6, 2018

Record last verified: 2018-04

Locations

GB (1)