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

NCT02274415 | Completed Phase 2 DMC

• 2 other identifiers: AOM10028P100105
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Invasive Pneumococcal Infections; Sickle Cells Disease

Keywords

Streptococcus pneumoniae; Sickle cell disease; Immunogenicity; Antibody response

Outcome Measures

Primary Outcomes (1)

• the proportion of responders at least to 10 of thirteen serotypes

  A responder is defined by a rise least two fold from baseline) of antibody titers specific to pneumococcal serotypes;

  at Week 8

Secondary Outcomes (7)

• Proportion of responders according to 4 categories of responders: 5-7; 3-4; 2-1 and 0.

  at Week 8

• Evaluation of the pneumococcal opsonophagocytic activity (OPA) for each serotype,

  at baseline and Week 8

• The antibody response of the conjugate vaccine

  at week 4

• The antibody response to the 13 serotypes of the conjugate vaccine in terms of proportion of patients

  at week 4

• In the group 1 antibodies titers (µg/ml)

  at week 24 and W96

Study Arms (2)

PCV vaccine following by the PSV vaccine

EXPERIMENTAL

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 ®)

vaccine Pneumo 23

ACTIVE COMPARATOR

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 ®)

Interventions

Vaccination with the combined vaccine (Prevenar13 ®) BIOLOGICAL

PCV vaccine following by the PSV vaccine

Vaccination with the polysaccharide vaccine (Pneumo 23 ®) BIOLOGICAL

PCV vaccine following by the PSV vaccine; vaccine Pneumo 23

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 the protocol vaccination, except influenza vaccination (within 30 days)
• Vaccination whatever, provided in the first 2 months following the protocol vaccinations, except influenza vaccination (within the first month following the protocol vaccinations))
• History of pneumococcal vaccination with Pneumo 23® in the previous year
• 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 recommendation the first 8 weeks of the test for women in childbearing age
• No medical assurance
• Adults under tutelage

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

Location

Related Publications (1)

• Melica G, Bartolucci P, Audureau E, Le Corvoisier P, Habibi A, Gellen J, Selmane D, Michel M, Lacabaratz C, Levy Y. Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial. Clin Infect Dis. 2023 Jun 8;76(11):1949-1958. doi: 10.1093/cid/ciad037.

  PMID: 36705266 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Vaccination; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immunotherapy, Active; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health

Study Officials

• Yves LEVY, PHD, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2014
• First Posted: October 24, 2014
• Study Start: September 16, 2013
• Primary Completion: September 18, 2017
• Study Completion: April 10, 2019
• Last Updated: September 9, 2022

Record last verified: 2017-10

Locations

FR (1)