Clinical trial NCT00169234: Pneumococcal Adult-dose Ranging Immunization Study
Official title: Immunogenicity and Safety of Varying Doses of a 7-valent Conjugate Pneumococcal Vaccine in Adults 70-79 Years of Age Who Were Previously Vaccinated With the 23-valent Pneumococcal Polysaccharide Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pneumonia
Keywords: Pneumococcal disease
Vaccination
Immunization
PPV23
PCV7
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2005-09-15
Enrollment: 220
Sex: ALL
Minimum age (years): 70
Maximum age (years): 79
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to give seniors different doses of a new pneumococcal vaccine called PCV7 to evaluate the safety of the vaccine and compare the immune response to find out which amount gives the best immune response. The PCV7 vaccine is currently licensed by the FDA for use in infants and toddlers only.

Detailed description: The purpose of this prospective randomized study is to assess the safety, post-vaccination antibody response, and memory response to a subsequent polysaccharide challenge of varying doses of PCV7 compared with the standard dose of PPV23 in immunocompetent adults 70-79 years of age who were previously vaccinated with PPV23 at age 65 years or above and at least 5 years previously. The study will be conducted among a total of 220 persons recruited from GHC and the Seattle VAMC. Participants will be randomized into one of 5 study groups with 44 participants per group. The antigen content of PCV7 will be varied by administration of different volumes of the licensed pediatric formulation of that vaccine. Four groups will receive one of four volumes (0.1 mL, 0.5 mL, 1.0 mL, 2.0 mL) of the licensed pediatric formulation of PCV7 followed 12 months later by administration of a challenge 0.1 mL dose of PPV23 to assess the induction of immunologic memory. The comparison group will receive the standard 0.5 mL dose of PPV23 following 12 months later by administration of a 0.1 mL dose of PPV23.

Eligibility criteria: Inclusion Criteria:

* Age 70 through 79 years (up to the day prior to the 80th birthday)
* Previously received exactly one dose of PPV23, and that dose was received on or after their 65th birthday and at least 5 years before the date of study enrollment
* Expected to reside in the area for at least 13 months
* Able to understand and give informed consent
* Able to perform study procedures
* Able to be contacted by telephone for follow-up on adverse events

Exclusion Criteria:

* Received \>=2 doses of PPV23 prior to study enrollment.
* Living non-independently in an institutional setting, such as a nursing home. Persons living independently in adult residence communities will be eligible.
* Use of any investigational vaccine within the past 30 days or planned use during the study period.
* Current or planned participation in a research study of an investigational drug. Participation in research studies that involve use of licensed drugs, for either approved or investigational indications, will be permitted with the approval of the site PI, as will participation in research studies that do not involve medications.
* Current use or previous chronic administration, defined as \>=14 days during the previous six months, of immunosuppressants or other immune-modifying drugs. (For oral or injected corticosteroids, the immune-modifying dose is defined as prednisone or its equivalent \>=10 mg/day). Topical steroids are allowed.
* Current use of high doses of inhaled steroids, defined as per Table 3.
* Use of cytotoxic therapy in the previous 5 years.
* Plans to receive cytotoxic therapy during the study period.
* Receipt of parenteral immunoglobulin or blood products within three months of study.
* Plans to receive parenteral immunoglobulin or blood products within the study period.
* Current ongoing use of warfarin or heparin or has a bleeding disorder, such as ITP.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
* Anatomic or known functional asplenia.
* History of a hematologic malignancy or a pre-malignant condition (i.e., leukemia, lymphoma, multiple myeloma, myelodysplasia).
* Active neoplastic disease, excluding local skin cancer or other malignancies (e.g. prostate cancer) that are stable in the absence of immunosuppressive/cytotoxic or radiation therapy.
* End-stage liver disease or hepatic failure (as diagnosed by a physician or evidenced by a history within the last 10 years of bleeding esophageal varices, ascites, or hepatic encephalopathy).
* Renal failure, as evidenced by current or expected dialysis or known creatinine of \>=2.5 ug/ml.
* Known hypersensitivity to PPV23 or to any component of PPV23 or PCV7, including aluminum phosphate or diphtheria protein.
* Presence of any other condition or impairment that in the opinion of the investigator is likely to compromise the participant's ability to complete the study procedures.

Primary outcomes:
measure: To evaluate the immunologic response to varying doses of 7-valent pneumococcal conjugate vaccine (PCV7) among older adults.
timeFrame: Pre/post enrollment vaccination, and pre/post 1 year challenge vaccination
Secondary outcomes:
measure: To evaluate the safety to varying doses of 7-valent pneumococcal conjugate vaccine (PCV7) among older adults.
timeFrame: During the 13 month study period.
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Group Health Research Institute
state: Washington
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: Kaiser Permanente
name: Lisa A Jackson, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jackson LA, Neuzil KM, Nahm MH, Whitney CG, Yu O, Nelson JC, Starkovich PT, Dunstan M, Carste B, Shay DK, Baggs J, Carlone GM. Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide-protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine. 2007 May 16;25(20):4029-37. doi: 10.1016/j.vaccine.2007.02.062. Epub 2007 Mar 12.
citation: Jackson LA, Neuzil KM, Whitney CG, Starkovich P, Dunstan M, Yu O, Nelson JC, Feikin DR, Shay DK, Baggs J, Carste B, Nahm MH, Carlone G. Safety of varying dosages of 7-valent pneumococcal protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine. 2005 May 25;23(28):3697-703. doi: 10.1016/j.vaccine.2005.02.017.