Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults (SPLENEVAC)
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|ClinicalTrials.gov Identifier: NCT02052154|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2014
Last Update Posted : May 1, 2018
Evaluate the immunogenicity of an innovative pneumococcal vaccination strategy in splenectomized adults comprising 1 dose of Prevenar13® conjugate vaccine (PCV) at M0 followed by 1 dose of Pneumo23® or Pneumovax® polysaccharide vaccine (PPSV) at M2. Duration of follow-up of 36 months.
The main endpoint will be the proportion of subjects responsive to 9 of the 13 serotypes common to the PCV and PPSV vaccines, selected because of their frequency in invasive infections in adults in France and their potentially reduced susceptibility to penicillin (serotypes 1, 3, 6A, 7F, 9V, 14, 19A, 19F, 23F).
|Condition or disease||Intervention/treatment||Phase|
|Splenectomized Patients||Biological: Prime-boost pneumococcal immunization||Phase 2|
The splenectomized patient is more susceptible to infections because of the lack of specific response to the polysaccharide antigens that compose the capsules of certain bacteria. These very severe infections are known as Overwhelming Post Splenectomy Infections, or OPSI; they are characterized by very rapid onset with no prodrome and carry a high mortality rate. The annual incidence of OPSI is estimated at 0.23-0.42% with a lifetime risk of 5%. The role of pneumococcus in particular has been clearly established in these infections.
The most effective strategy to minimize the risk of pneumococcal infection is pneumococcal vaccination. Currently there are two types of vaccines available in France: polysaccharide and conjugate, both of which induce the production of anti-capsular IgG with both neutralizing and opsonic activity.
Since one of the consequences of asplenia is the absence of IgM production elicited by a polysaccharide challenge, due to an absence of splenic B cells, it is difficult to imagine that such patients would mount a satisfactory immune response to PPSV vaccination. And in fact, several studies have described the occurrence of pneumococcal OPSI in patients who were correctly vaccinated.
The study hypothesis is that a vaccination strategy combining PCV vaccine followed by PPSV vaccine will induce a good immune response in splenectomized patients, with good tolerability. All available data suggest that the optimum schedule consists of a primovaccination with one dose of PCV followed two months later by one dose of PPSV, in order to achieve a T-dependent memory response to the 13 serotypes common to the two vaccines.
The proposed endpoint is therefore to evaluate the immunogenicity and safety of a vaccination strategy comprising priming with one dose of Prevenar13® PCV vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, + 1, 3, 5, 6A, 7F, 19A) to induce a T cell memory response, followed by the classical administration of one dose of Pneumo23® or Pneumovax® vaccine (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F). Secondary endpoints will evaluate the safety of this strategy in terms of post-immunization local and systemic side effects, frequency of invasive pneumococcal infections, predictors of immunogenicity, and persistence of immunogenicity 30 months post-immunization.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults|
|Actual Study Start Date :||March 10, 2014|
|Actual Primary Completion Date :||July 19, 2016|
|Estimated Study Completion Date :||April 2019|
|Experimental: Prime-boost pneumococcal immunization||
Biological: Prime-boost pneumococcal immunization
2 months between the 2 vaccines
Other Name: Prevenar13® followed by Pneumo23®
- Proportion of subjects responsive to 9 of the 13 serotypes common (serotypes 1, 3, 6A, 7F, 9V, 14, 19A, 19F, 23F). [ Time Frame: M3 ]According to currently accepted international guidelines, a subject is considered to be responsive to a given serotype if one month after PPSV vaccination (at M3) the specific IgG titer is ≥ 1 μg/mL by ELISA and the opsonophagocytosis assay (OPA) threshold response is ≥ at LLOQ (Lower limit of quantification)
- IgG dosage [ Time Frame: one month ]Immunologic Response after one injection PnCj (Specific IgG ≥1 µg/ml)
- ELISA dosages [ Time Frame: 4 months after PPSV vaccine ]Evaluation of persistent responses 4 months after PPSV vaccine
- ELISA dosages [ Time Frame: 10 months after PPSV vaccine ]Evaluation of persistent responses 10 months after PPSV vaccine
- ELISA dosages [ Time Frame: 34 months after PPSV vaccine ]Evaluation of persistent responses 34 months after PPSV vaccine
- Identification of predictive factors for immunogenicity [ Time Frame: M0 to M36 ]Identification of predictive factors for immunogenicity: age, gender, indication for splenectomy, time since splenectomy, time since previous vaccination with polysaccharide vaccine, number of PPSV vaccinations previously received
- Percentage of patients presenting local or systemic reactions post-immunization [ Time Frame: M0 to M36 ]Estimate the clinical and biological tolerance of the vaccinal strategy
- Evaluation of severe infectious episode [ Time Frame: M0 to M36 ]
the evaluation of severe infectious episode are assessed with microbiological documentation (with serotype if Streptococcus pneumoniae), site of infection, occurrence under antibiotic prophylaxis or not.
this will allow to list and characterize the serotype involved during possible episodes of invasive infections in pneumocoque
- OPA dosages [ Time Frame: 4 months after PPSV vaccine ]Evaluation of persistent responses 4 months after PPSV vaccine
- OPA dosages [ Time Frame: 10 months after PPSV vaccine ]Evaluation of persistent responses 10 months after PPSV vaccine
- OPA dosages [ Time Frame: 34 months after PPSV vaccine ]Evaluation of persistent responses 34 months after PPSV vaccine
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): NCT02052154
|Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants|
|Paris, France, 75015|
|Principal Investigator:||Hélène COIGNARD-BIEHLER, MD||Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, APHP|
|Study Director:||Olivier LORTHOLARY, MD, PhD||Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, APHP|
|Study Director:||Odile LAUNAY, MD, PhD||CIC Vaccinologie Cochin-Pasteur (CIC BT505) - Hôpital Cochin|
|Study Director:||Marc MICHEL, MD, PhD||Service de médecine interne, Hôpital Henri Mondor|
|Study Chair:||Frédéric BATTEUX, MD, PhD||Assistance Publique - Hôpitaux de Paris|
|Study Chair:||Claude-Agnès REYNAUD, PhD||Institut National de la Santé Et de la Recherche Médicale, France|
|Study Chair:||Pierre BUFFET, MD, PhD||INTS|