Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults

NCT ID: NCT02052154

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-10
• Study Completion Date: 2019-04-02

Brief Summary

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).

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.

Conditions

Splenectomized Patients

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prime-boost pneumococcal immunization

Group Type: EXPERIMENTAL

Prime-boost pneumococcal immunization

Intervention Type: BIOLOGICAL

2 months between the 2 vaccines

Interventions

Prime-boost pneumococcal immunization

2 months between the 2 vaccines

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevenar13® followed by Pneumo23®

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hélène COIGNARD-BIEHLER, MD

Role: PRINCIPAL_INVESTIGATOR

Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, APHP

Olivier LORTHOLARY, MD, PhD

Role: STUDY_DIRECTOR

Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, APHP

Odile LAUNAY, MD, PhD

Role: STUDY_DIRECTOR

CIC Vaccinologie Cochin-Pasteur (CIC BT505) - Hôpital Cochin

Marc MICHEL, MD, PhD

Role: STUDY_DIRECTOR

Service de médecine interne, Hôpital Henri Mondor

Frédéric BATTEUX, MD, PhD

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Claude-Agnès REYNAUD, PhD

Role: STUDY_CHAIR

Institut National de la Santé Et de la Recherche Médicale, France

Pierre BUFFET, MD, PhD

Role: STUDY_CHAIR

INTS

Locations

Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants

Paris, , France

Countries

France

Other Identifiers

2013-002631-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P120131

Identifier Type: -

Identifier Source: org_study_id