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Immunogenicity Study of an Anti-pneumococcal Vaccination Strategy in Patients With Sickle Cells Disease (DREVAC)

This study is currently recruiting participants.
See Contacts and Locations
Verified October 2015 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT02274415
First received: September 22, 2014
Last updated: October 18, 2015
Last verified: October 2015
  Purpose

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 Intervention 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
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 180
Study Start Date: September 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 ®)

  Eligibility

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

Inclusion Criteria:

  • Age ≥ 18 years
  • Adult patient with sickle cell anemia (SS homozygous, SC heterozygous compound Sbetathal heterozygous)

Exclusion Criteria:

  • Heterozygous sickle cell anemia
  • Active infection
  • Hypersensitivity known or suspected to Prevenar 13® or to Pneumo 23® or to any of the excipients included in the formulation or in the administration system
  • Coagulation abnormality indicating against an intramuscular injection (Platelets <50 000 or TP<50%)
  • Current chemotherapy or radiotherapy, except for using Siklos®/Hydrea® in the context of sickle cell anemia
  • Vaccination whatever in the last 2 months before inclusion, except influenza vaccination (within 30 days)
  • Vaccination whatever, provided in the first 2 months of participation in research, except influenza vaccination (in the first month of participation in the research)
  • History of pneumococcal vaccination with Pneumo 23® in the previous 3 years
  • History of pneumococcal vaccination with Pneumo 23®
  • End-stage renal failure(dialyzed patient, clearance<10ml/mn)
  • HIV infection at baseline
  • Pregnancy or breastfeeding (A dosage of betaHCG will be conducted for women in childbearing age)
  • Contraception during the first 8 weeks of the test for women in childbearing age
  • Participation in a clinical research protocol using a drug or a vaccine in the previous month
  • No medical assurance
  • Adults under tutelage
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02274415

Contacts
Contact: Giovanna MELICA, MD (0) 149812455 ext +33 giovanna.melica2@hmn.aphp.fr
Contact: Yves LEVY, PHD, MD (0) 149812455 ext +33 yves.levy@hmn.aphp.fr

Locations
France
Henri Mondor Hospital Recruiting
Creteil, France, 94010
Contact: Samia Baloul    (0)1 49813385 ext +33    samia.baloul@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Yves LEVY, PHD, MD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02274415     History of Changes
Other Study ID Numbers: AOM10028
P100105 ( Other Identifier: Assistance Publique Hôpitaux de Paris )
Study First Received: September 22, 2014
Last Updated: October 18, 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Streptococcus pneumoniae
Sickle cell disease
Immunogenicity
Antibody response

Additional relevant MeSH terms:
Anemia, Sickle Cell
Pneumococcal Infections
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017