Study to Evaluate Safety, Reactogenicity and Immunogenicity of the Pneumococcal Protein PhtD Vaccine in Healthy Adults

A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Pneumococcal Protein PhtD Vaccine Without or With Adjuvant, Administered at 2 Different Concentrations According to a 0-2 Month Schedule, in Healthy Adults

The purpose of this study is to examine the safety, reactogenicity and immunogenicity of the GlaxoSmithKline (GSK) Biologicals candidate pneumococcal vaccine containing PhtD in healthy elderly population aged 18-45 years of age.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Disease
• Intervention / Treatment: Biological: PhtD vaccine with/without adjuvant; Biological: Pneumovax 23TM; Biological: NaCl

Detailed Description

The safety profile of the PhtD vaccine will be assessed in comparison to a comparator vaccine (Pneumovax 23TM). In order to further increase the immune response to vaccination, a novel adjuvant system will also be examined.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes will comply with the requirements of the protocol should be enrolled in the study.
• A male or female between, and including, 18 and 45 years at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Use of any anticoagulants.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 2 weeks of the first dose of vaccines.
• Previous vaccination against Streptococcus pneumoniae.
• Bacterial pneumonia within 3 years prior to 1st vaccination.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Current serious neurologic or mental disorders.
• Inflammatory processes such as known chronic active infections.
• All malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders diagnosed or treated actively during the past 5 years.
• History of administration of an experimental vaccine containing 3-deacylated Monophosphoryl Lipid A (MPL) or Quillaja saponaria 21 (QS21).
• Acute disease at the time of enrolment. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., Oral temperature <37.5°C or Axillary temperature <37.5°C.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, at the discretion of the investigator.
• Pregnant or lactating female.
• History of chronic alcohol consumption and/or intravenous drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PhtD Group 1; Subjects will receive PhtD vaccine formulation 1 without any adjuvant.	Biological: PhtD vaccine with/without adjuvant; Two doses of different formulations of PhtD vaccine administered intramuscularly in the deltoid region of the right arm at month 0 and month 2.
Experimental: PhtD Group 2; Subjects will receive adjuvanted PhtD vaccine formulation 2.	Biological: PhtD vaccine with/without adjuvant; Two doses of different formulations of PhtD vaccine administered intramuscularly in the deltoid region of the right arm at month 0 and month 2.
Experimental: PhtD Group 3; Subjects will receive adjuvanted PhtD vaccine formulation 3.	Biological: PhtD vaccine with/without adjuvant; Two doses of different formulations of PhtD vaccine administered intramuscularly in the deltoid region of the right arm at month 0 and month 2.
Experimental: PhtD Group 4; Subjects will receive adjuvanted PhtD vaccine formulation 4.	Biological: PhtD vaccine with/without adjuvant; Two doses of different formulations of PhtD vaccine administered intramuscularly in the deltoid region of the right arm at month 0 and month 2.
Experimental: PhtD Group 5; Subjects will receive adjuvanted PhtD vaccine formulation 5.	Biological: PhtD vaccine with/without adjuvant; Two doses of different formulations of PhtD vaccine administered intramuscularly in the deltoid region of the right arm at month 0 and month 2.
Active Comparator: 23 PPV Group; Subjects will receive the Pneumovax 23TM vaccine and NaCl.	Biological: Pneumovax 23TM; One dose of Pneumovax 23TM vaccine administered intramuscularly in the deltoid region of the right arm at month 0.; Biological: NaCl; One dose administered intramuscularly in the deltoid region of the right arm at month 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence, intensity and relationship of any solicited local and general signs and symptoms	During a 7-day follow up period (i.e. Days 0-6) after each vaccine dose
Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms	During a 30-day follow up period (i.e. Days 0-29) after each vaccine dose
Occurrence of all serious adverse events (SAEs)	During the 12 months of the study
Anti-PhtD antibody concentration in all vaccine groups (measured by ELISA)	One month after the first injection
Anti-PhtD antibody concentration in all vaccine groups (measured by ELISA)	One month after two injections

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and percentage of subjects with normal or abnormal values, for biochemical assessments and for hematological analysis	At month 0, 1, 3 and 12
Anti-PhtD antibody concentration in all groups (measured by ELISA)	At 12 months after the first vaccination
Anti-PhtD antibody avidity (measured by ELISA)	At month 0, 1, 3 and 12
Evaluation of protection afforded by passive transfer of anti PhtD antibodies sera pooled from all individuals (passive transfer mice model assay)	At month 0, 1, 3 and 12
Frequency of PhtD-specific plasma cells generated by in vitro cultivated memory B-cells in a subset of subjects (measured by B-cell ELISPOT)	At month 0, 3 and 12
Frequency of CD4 and/or CD8 T cells that produce cytokines IL-2, IL-4, IFNg, CD40L and/or GM-CSF, upon PhtD re-stimulation in vitro, to evaluate the T-cell response, in a subset of subjects (measured by intracellular cytokine cytometry)	At month 0, 3 and 12
Anti-polysaccharide total gamma class immunoglobulin (IgG) concentration in the 23 valent Polysaccharide Pneumococcal Vaccine(23 PPV) group for 11 serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F) (ELISA)	At month 0, 1 and 12
Opsonophagocytic activity titers in the 23 PPV group for 11 serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F (OPA assay)	At month 0, 1 and 12
Frequency of polysaccharide(PS)-specific plasma cells generated by in vitro cultivated memory B-cells in the 23 PPV group in a subset of subjects (measured by B-cell ELISPOT)	At month 0, 1 and 12
Circulating serum cytokines Interferon-gamma (INFγ) and Tumor necrosis factor-alpha (TNFα) content in all groups (measured by ELISA)	At Day 0, 1, 60 and 61

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Leroux-Roels I, Devaster JM, Leroux-Roels G, Verlant V, Henckaerts I, Moris P, Hermand P, Van Belle P, Poolman JT, Vandepapeliere P, Horsmans Y. Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: randomised, controlled trials. Vaccine. 2015 Jan 15;33(4):577-84. doi: 10.1016/j.vaccine.2013.10.052. Epub 2013 Oct 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): November 1, 2004
• Study Completion (Actual): November 1, 2004

Study Registration Dates

• First Submitted: January 10, 2013
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimate): January 14, 2013

Study Record Updates

• Last Update Posted (Estimate): January 14, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Reactogenicity; Healthy adults; Pneumococcal Infections; PhtD vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 100417