Immunogenicity Study of an Anti-pneumococcal Vaccination Strategy in Patients With Sickle Cells Disease (DREVAC)
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|ClinicalTrials.gov Identifier: NCT02274415|
Recruitment Status : Active, not recruiting
First Posted : October 24, 2014
Last Update Posted : October 19, 2017
Streptococcus pneumoniae is the major cause of bacterial infection in patients with sickle cells disease.
The 23-valent pneumococcal polysaccharide vaccine (PSV) is supposed to be poorly immunogenic in these patients. We want to evaluate whether a prime with a 13-valent pneumococcal conjugate vaccine (PCV), able to induce immunologic memory, would improve the immune response against SP polysaccharides (SPP).
Primary objective: To evaluate and compare the specific antibody response to a prime-boost vaccine strategy combining PCV prime at W0 followed by the administration of PSV boost at W4, to the administration of PSV alone at W4 in patients with sickle cells disease.
Secondary objectives: Evaluation and comparison of the specific antibody response to the thirteen pneumococcal serotypes shared by the PCV and PSV vaccines, 4 weeks after the single PSV vaccination for patients from Group 1 or 4 weeks after the boost PSV vaccination for patients from group 2. Evaluation of the duration of the specific antibody response at W24 and 96. Evaluation of the T CD4 lymphocyte response to the CRM 197 protein. Safety of the vaccines.
Study Design: Randomised, monocentric, controlled phase II study of the immunological efficacy of a prime boost strategy combining the sequential administration of the PCV and PSV, compared to the administration of the PSV alone. 180 adults patients with sickle cells disease will be included. The primary endpoint : proportion of responders at W8 to at least 10 of thirteen serotypes. Secondary endpoints : Proportion of responders at W8 according to 4 categories of responders: 5-7; 3-4; 2-1 and 0. Evaluation of the pneumococcal opsonophagocytic activity (OPA) at baseline and W8 for each serotype, defined as the proportion of patients with OPA > 1:8 geometric mean of the specific antibody titers proportion of patients who experienced an increase of specific antibody levels 1 g/ml. Evaluation of the priming effect of the PCV vaccine in the group 1. Duration of the specific antibody responses at week 24 and W96. CD4 T lymphocyte responses to the CRM 197 protein (proliferative and cytokine production) at weeks 0, 8 and 12. Safety of the vaccines frequency of Streptococcus pneumoniae infections.
Statistical Considerations: With a sample size of 180 patients, and a randomization ration of 1:1, the study will have a power of at least 90% to show a difference of 25% category between the group receiving PCV and PSV vs the group receiving PSV alone (two-sided type I error = 5%). The primary comparison between both groups will be performed using a Chi2 test for independent groups or a Fisher exact test where appropriate.
|Condition or disease||Intervention/treatment||Phase|
|Invasive Pneumococcal Infections Sickle Cells Disease||Biological: Vaccination with the combined vaccine (Prevenar13 ®) Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||165 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Study of the Immunogenicity of a Prime Boost Vaccination Strategy Combining Conjugated Anti-pneumococcal and Polysaccharide Anti-pneumococcal Vaccine Compared to Polysaccharide Anti -Pneumococcal Vaccine Alone in Patients With Sickle Cells Disease|
|Actual Study Start Date :||September 16, 2013|
|Primary Completion Date :||May 10, 2017|
|Estimated Study Completion Date :||May 2019|
U.S. FDA Resources
Experimental: PCV vaccine following by the PSV vaccine
Group 1: patients will receive a first boost with 13-valent pneumococcal conjugate vaccine (PCV) (one dose at W0) and then one administration of the PSV vaccines (one dose at W4).
|Biological: Vaccination with the combined vaccine (Prevenar13 ®) Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®)|
Active Comparator: vaccine Pneumo 23
Group 2: patients will receive a single administration of 23-valent pneumococcal polysaccharide vaccine (PSV) (one dose at W4)
|Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®)|
- the proportion of responders at least to 10 of thirteen serotypes [ Time Frame: at Week 8 ]A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes and an absolute titer 1 µg/ml.
- Proportion of responders according to 4 categories of responders: 5-7; 3-4; 2-1 and 0. Response is defined as fold rise of antibody titers (W8 to baseline) and an absolute titer of 1 µg/ml. [ Time Frame: at Week 8 ]
- Evaluation of the pneumococcal opsonophagocytic activity (OPA) for each serotype, defined as the proportion of patients with OPA > 1:8. The unit of measure for OPA is a dilution titer. [ Time Frame: at baseline and Week 8 ]
- The antibody response to the 13 serotypes of the conjugate vaccine in terms of geometric mean of the specific antibody titers (µg/ml) [ Time Frame: at week 4 ]
- The antibody response to the 13 serotypes of the conjugate vaccine in terms of proportion of patients who experienced an increase of specific antibody levels > 1 µg/ml [ Time Frame: at week 4 ]
- In the group 1 antibodies titers (µg/ml) [ Time Frame: at week 24 and W96 ]
- Number of T CD4 cells responsive to the CRM 197 protein (proliferative and cytokine production) in the two groups of the study [ Time Frame: at weeks 0, 8 and 12. ]
- Number of Streptococcus pneumoniae infections (bacteremia, meningitis, pneumonia, sinusitis, upper respiratory tract infections) [ Time Frame: between baseline and W96 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02274415
|Henri Mondor Hospital|
|Creteil, France, 94010|
|Principal Investigator:||Yves LEVY, PHD, MD||Assistance Publique - Hôpitaux de Paris|