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Trial record 1 of 1 for:    splenevac
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Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults (SPLENEVAC)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02052154
First Posted: January 31, 2014
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose

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 Intervention Phase
Splenectomized Patients Biological: Prime-boost pneumococcal immunization Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ≥ 1:8


Secondary Outcome Measures:
  • 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


Enrollment: 70
Actual Study Start Date: March 10, 2014
Estimated Study Completion Date: April 2019
Primary Completion Date: July 19, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prime-boost pneumococcal immunization Biological: Prime-boost pneumococcal immunization
2 months between the 2 vaccines
Other Name: Prevenar13® followed by Pneumo23®

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years and ≤ 75 years
  • Splenectomized since at least 2 weeks, with Howell-Jolly bodies on a blood smear and ultrasonographic confirmation
  • No immunosppressived conditions : mainly trauma , idiopathic thrombocytopathic purpura or autoimmune hemolytic anemia, with no active treatment
  • Available for 37 months of follow-up starting from the screening visit
  • Contraception that the investigator judges effective for the first 2 months of the trial, with a negative pregnancy test
  • Women not planning to become pregnant in the 6 months following inclusion (M0)
  • Signed informed consent

Exclusion Criteria:

  • Pregnancy or planned pregnancy in the 2 months following inclusion (M0)
  • Pathology or conditions which modify immune response (excluding splenectomy) : HIV infection, immunosuppressive therapy ongoing or in 6 months before inclusion (M0), including corticosteroids > 10 mg daily, topic inhaled or dermic corticoid treatments are allowed, hematopoietic stem cell allo / autograft, primary immune deficiency, nephrotic syndrome, sickle cell disease, evolutive neoplasia
  • History of anaphylactic reaction following vaccination
  • Known allergy to any of the ingredients of the vaccines: aluminium phosphate, phenol, Corynebacterium diphtheriae CRM-197 protein
  • Previous vaccination with 7-valent or 13-valent pneumococcal conjugate vaccine (in the 5 last years)
  • Previous vaccination with the pneumococcal polysaccharidic vaccine in the 3 years before inclusion (M0)
  • Other vaccination in the month before inclusion (M0)
  • Polyvalent immunoglobulin infusion in the 3 months before inclusion (M0) or during the planned duration of the study
  • Anticoagulant treatment current or stopped less than 7 days before inclusion (M0); or clotting disorder contra-indicating intramuscular injection
  • Participation to an other vaccine study in the 28 days before inclusion till the end of study
  • Not covered by national health insurance (beneficiary or assignee)
  Contacts and Locations
Information from the National Library of Medicine

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


Locations
France
Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02052154     History of Changes
Other Study ID Numbers: P120131
2013-002631-19 ( EudraCT Number )
First Submitted: January 20, 2014
First Posted: January 31, 2014
Last Update Posted: August 1, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Pneumococcal infection
Splenectomized
vaccination

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs