Pneumococcal Conjugate Vaccination in HIV in Comparison to Polysaccharide Vaccine Boosting

Study Overview
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Brief Summary
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Purpose: To study the immune response of the newly licensed pneumococcal conjugate vaccine (PCV) in comparison to the pneumococcal polysaccharide vaccine (PPV) to determine if a significantly better immunologic response to boosting can be elicited in patients previously vaccinated with PPV.

Official Title
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An Open-Label, Phase III, Randomized Study of Pneumococcal Conjugate Vaccination in HIV, in Comparison to Polysaccharide Vaccine Boosting in Previously Vaccinated Patients

Conditions
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HIV Infections, Streptococcus Pneumoniae

Intervention / Treatment
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* Biological: pneumococcal conjugate vaccine
* Biological: pneumococcal polysaccharide vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for HIV positive subjects: At least one prior PPV ≥ 3 and < 8 years ago, while HIV positive. There is no upper limit to the number of previously received PPVs. HIV-positive (except 25 HIV-negative persons as control group). Age between 18 and 60 years of age. Availability of patient to remain within the immediate area for the period of the study and be able to comply with protocol requirements. Exclusion Criteria for HIV positive subjects: Prior allergic reaction to the PPV Allergic to components of PCV, including diphtheria toxin. Pregnant or lactating females as defined by history or positive HCG urine test. History of chronic viral hepatitis or biochemical evidence to include pretreatment AST or ALT values greater than 3 fold higher than upper limit of normal, or a creatinine of greater than 1.8 mg/dl History of splenectomy Temperature of >38C Inability to ambulate for more than 1000 meters secondary to fatigue, pain or weakness. Patients in whom IM vaccination is not possible because of disease or medication. (e.g. hemophilia, coumadin therapy). Patients diagnosed with HIV wasting disease Viral load over 50,000 copies/ml. History or evidence of recent illicit drug or alcohol abuse. Use of immunosuppressive agents, to include corticosteroids and cancer chemotherapeutic agents. Inclusion Criteria for HIV negative subjects: HIV-negative by HIV ELISA within the last 12 months Age between 18 and 60 years of age. Availability of patient to remain within the immediate area for the period of the study and be able to comply with protocol requirements. Exclusion Criteria for HIV negative subjects: Prior PCV and/or PPV vaccination. Prior allergic reaction to the PPV Allergic to components of PCV, including diphtheria toxin. Pregnant or lactating females as defined by history or positive HCG urine test. History of chronic viral hepatitis or biochemical evidence to include pretreatment AST or ALT values greater than 3 fold higher than upper limit of normal, or a creatinine of greater than 1.8 mg/dl History of splenectomy Temperature of >38C Inability to ambulate for more than 1000 meters secondary to fatigue, pain or weakness. Patients in whom IM vaccination is not possible because of disease or medication. (e.g. hemophilia, coumadin therapy). History or evidence of recent illicit drug or alcohol abuse. Use of immunosuppressive agents, to include corticosteroids and cancer chemotherapeutic agents. Works in chain of command of primary/associate investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>PCV, 210 patients | Biological: pneumococcal conjugate vaccine<br>* Prevnar is manufactured as a liquid preparation. Each 0.5 mL dose is formulated to contain: 2 μg of each saccharide for serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 μg of serotype 6B per dose (16 μg total saccharide); approximately 20 μg of CRM197 carrier protein; and 0.125 mg of aluminum per 0.5 mL dose as aluminum phosphate adjuvant. After shaking, the vaccine is a homogeneous, white suspension.<br>* Other names: PCV;|
| Active Comparator: Group 2<br>PPV, 110 patients | Biological: pneumococcal polysaccharide vaccine<br>* PNEUMOVAX 23 is manufactured according to methods developed by the Merck Research Laboratories. Each 0.5 mL dose of vaccine contains 25 μg of each polysaccharide type in isotonic saline solution containing 0.25% phenol as a preservative.<br>* Other names: PPV;|
| Active Comparator: Group 3<br>PPV, HIV-negative, 25 patients | Biological: pneumococcal polysaccharide vaccine<br>* PNEUMOVAX 23 is manufactured according to methods developed by the Merck Research Laboratories. Each 0.5 mL dose of vaccine contains 25 μg of each polysaccharide type in isotonic saline solution containing 0.25% phenol as a preservative.<br>* Other names: PPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The measure of PPV and PCV efficacy will be assessed by the level of serotype-specific antibody levels, measured by ELISA. |  | Day 14 after vaccination | 
| The measure of PPV and PCV efficacy will be assessed by the level of serotype-specific antibody levels, measured by ELISA. |  | Day 60 after vaccination | 
| The measure of PPV and PCV efficacy will be assessed by the level of serotype-specific antibody levels, measured by ELISA. |  | Day 180 after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal conjugate vaccine, polysaccharide vaccine, PPV, PCV, Streptococcus pneumoniae, Prevnar, Pneumovax, HIV