Clinical trial NCT01767402: Study to Evaluate Safety, Reactogenicity and Immunogenicity of the Pneumococcal Protein PhtD Vaccine in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pneumococcal Disease
Keywords: Safety
Pneumococcal Infections
Immunogenicity
PhtD vaccine
Healthy adults
Reactogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-01-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence, intensity and relationship of any solicited local and general signs and symptoms
timeFrame: During a 7-day follow up period (i.e. Days 0-6) after each vaccine dose
measure: Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms
timeFrame: During a 30-day follow up period (i.e. Days 0-29) after each vaccine dose
measure: Occurrence of all serious adverse events (SAEs)
timeFrame: During the 12 months of the study
measure: Anti-PhtD antibody concentration in all vaccine groups (measured by ELISA)
timeFrame: One month after the first injection
measure: Anti-PhtD antibody concentration in all vaccine groups (measured by ELISA)
timeFrame: One month after two injections
Secondary outcomes:
measure: Number and percentage of subjects with normal or abnormal values, for biochemical assessments and for hematological analysis
timeFrame: At month 0, 1, 3 and 12
measure: Anti-PhtD antibody concentration in all groups (measured by ELISA)
timeFrame: At 12 months after the first vaccination
measure: Anti-PhtD antibody avidity (measured by ELISA)
timeFrame: At month 0, 1, 3 and 12
measure: Evaluation of protection afforded by passive transfer of anti PhtD antibodies sera pooled from all individuals (passive transfer mice model assay)
timeFrame: At month 0, 1, 3 and 12
measure: Frequency of PhtD-specific plasma cells generated by in vitro cultivated memory B-cells in a subset of subjects (measured by B-cell ELISPOT)
timeFrame: At month 0, 3 and 12
measure: 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)
timeFrame: At month 0, 3 and 12
measure: 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)
timeFrame: At month 0, 1 and 12
measure: Opsonophagocytic activity titers in the 23 PPV group for 11 serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F (OPA assay)
timeFrame: At month 0, 1 and 12
measure: 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)
timeFrame: At month 0, 1 and 12
measure: Circulating serum cytokines Interferon-gamma (INFγ) and Tumor necrosis factor-alpha (TNFα) content in all groups (measured by ELISA)
timeFrame: At Day 0, 1, 60 and 61
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.