“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

Brief Title

"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

Official Title

Randomised, Multicentric, Phase ii Study of the Immunogenicity of a "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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

proportion of responders to each serotype


Condition

Common Variable Immunodeficiency

Intervention

PPS

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

45

Start Date

June 2009

Completion Date

March 2013

Primary Completion Date

March 2013

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.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01489618

Organization ID

RBM04-34

Secondary IDs

2007-003235-23

Responsible Party

Sponsor

Study Sponsor

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


Study Sponsor

, , 


Verification Date

February 2016