"Prime Boost" Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency

NCT ID: NCT01489618

Last Updated: 2016-02-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2013-03-31

Brief Summary

The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.

Detailed Description

Main objective :

The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.

Secondary objectives :

• Evaluation and comparison the specific antibody response to seven pneumococcal serotypes, shared by the PnCj and PPS vaccines (4, 6B, 9V, 14, 18C, 19F, 23F), and two serotypes of the PPS vaccine (1, 5) 4 weeks after the single (W8 for patients from Group 1) or the first vaccination (W4 for patients from group 2).
• Evaluation of the duration of the specific antibody response at week 24
• Evaluation of the T CD4 lymphocyte response (proliferation and cytokine production) to the CRM protein
• Study of the Immunoglobulin V gene repertoire (immunoscope) before and after vaccination.
• Safety of the vaccines
• Effect of the vaccine strategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)

EXPERIMENTAL METHODS

Study design

Randomised, multicentric, controlled phase II study of the immunological efficacy of a "prime boost" strategy combining the sequential administration of the PnjC and PPS anti-pneumococcal vaccines, compared to the administration of the PPS vaccine alone, in patients with common variable immunodeficiency.

After randomisation (at W-4) 72 patients will be assigned to the two following groups:

• Group 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group.
• Group 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group.

R : 1 :2 (Group1 :2)

The final evaluation of this study is at week 12; i.e 4 weeks after the administration of the PPS vaccine in the two groups of patients. A follow up of patients until week 48 will be proposed to patients in order to evaluate the duration of the antibody response at wek 48.

DURATION OF THE STUDY

• Inclusion period : 18 months
• vaccination period: 2 months
• Patients follow-up : 7 months

Number of patients : 72

PRIMARY AND SECONDARY EFFICACY ENDPOINTS

The pneumococcal conjugate vaccine (PnCj) vaccin contains the following 7 pneumococcal serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F.

The pneumococcal capsular polysaccharide vaccine (PPS) contains 23 pneumococcal serotypes and shares the seven serotypes included in PnCJ.

Primary endpoint :

The primary end point of this study is the proportion of responders to each serotype contained in the PnjC vaccine in the two groups of this study according to 4 categories: 5-7; 3-4; 2-1 and 0. A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes.

Secondary endpoints :

• The following parameters will be evaluated and compared in the two groups of the study : La réponse immunitaire anticorps vis-à-vis des différents sérotypes vaccinaux communs

• geometric mean of the specific antibody titers
• proportion of patients who experienced an increase of specific antibody levels >1 µg/ml
• Evaluation of the priming effect of the PnCj vaccine in the group 2
• Duration of the specific antibody reponses at week 24
• CD4 T lymphocyte responses to the CRM protein (proliferative and cytokine production) in the two groups of the study at weeks 0, 8 and 12.
• Safety of the vaccines
• Effect of the vaccine stategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)

STATISTICAL CONSIDERATIONS

The initial hypothesis for this study is the superiority of the priming strategy. Expected responses are : 0% in group 1 (PPS alone) and 30% in group 2 (PnCj vace and PPS). The number of patients is based on power of 84%.

The primary end point is the proportion of responders to each serotype contained in the PnCj vaccine in the 2 groups. The percentage of patients in each group will be compared by a Fisher's exact test. Mann-Whitney test and Wilcoxon paired test will be used for the comparison of antibody levels and percentage of responding patients respectively.

Conditions

Common Variable Immunodeficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PPS

Group 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group.

Group Type: ACTIVE_COMPARATOR

PPS

Intervention Type: BIOLOGICAL

POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE

PnCJ PPS

Group 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group.

Group Type: EXPERIMENTAL

PnCJ PPS

Intervention Type: BIOLOGICAL

PRIMEBOOST CONJUGATED ANTI- PNEUMOCOCCAL VACCINE (Week 0) POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE (Week 4)

Interventions

PPS

POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE

Intervention Type: BIOLOGICAL

PnCJ PPS

PRIMEBOOST CONJUGATED ANTI- PNEUMOCOCCAL VACCINE (Week 0) POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE (Week 4)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age > 18 years and < 65 years
• Common variable immunodeficiency according to the WHO criteria,
• Patients treated with intravenous or subcutaneous immunoglobulin.
• Written informed consent
• Absence of acute infections, or other evolutive diseases related to the (cancer, auto-immune disease…)

Exclusion Criteria

• IgG subclass deficiency
• IgA selective deficiency,
• Other primary humoral deficiency (X-linked agammaglobulinemia, Hyper IgM syndrome),
• Long course treatment with corticosteroids > 5mg per day
• Chemotherapy in the last 3 years,
• Prior pneumococcal vaccination in the last 2 years.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Service d'Immunologie Clinique Hôpital Henri Mondor

Créteil, , France

Countries

France

Other Identifiers

2007-003235-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RBM04-34

Identifier Type: -

Identifier Source: org_study_id