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Safety Study of Two Vaccine Strategies in Patients With Systemic Lupus Erythematosus

Phase 2
Completed
Conditions
Lupus Erythematosus, Systemic
Interventions
Biological: Placebo, Pneumo23®
Biological: Prevenar® and Pneumo23®
Registration Number
NCT00611663
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

The aim of this study is to compare the immunological efficacy of two pneumococcal vaccination strategies in patients with systemic lupus erythematosus (SLE) treated with corticosteroids associated or not with other immunosuppressive drugs : 1) a prime-boost strategy using vaccination with conjugate vaccine (Prevenar®) at week 0 and Poly Saccharidic vaccine (Pneumo23®) after 6 months (W24)2) compared to the standard vaccination with Poly Saccharidic vaccine (Pneumo23®) at W24 after placebo at W0

Detailed Description

Infections are more frequent and potentially more serious in patients with SLE compared to healthy subjects. This risk increases when patients are treated with corticosteroids and/or immunosuppressive drugs.Among serious infections which can happen in this context, respiratory infections are among the most frequent and Streptococcus pneumoniae is one of the most often responsible germs.Although there are no specific study in SLE, these findings indicate that patients with SLE could benefit from a preventive vaccination against pneumococcal infections.Two pneumococcal vaccines are available: Pneumo23®, a Poly Saccharidic vaccine indicated for adults and children \> 2 years at risk of pneumococcal infections; and Prevenar®, a conjugate vaccine, indicated for children \< 2 years.Pneumo23® has been found to be safe in SLE but less immunogenic than in general population.Prevenar® has already been studied in immunocompromised patients (HIV-infected patients, patients after renal transplantation). It has been shown that immunological efficacy is better when Prevenar® is administrated prior to Pneumo23®, compared to Pneumo23® administrated alone.To our knowledge, this prime-boost strategy has not been assessed in patients with SLEThe primary objective of the study is to compare immunological efficacy of two pneumococcal vaccination strategies in patients with systemic lupus erythematosus (SLE) treated with corticosteroids associated or not with other immunosuppressive drugs : 1) Vaccination with conjugate vaccine (Prevenar®) at week 0 and Poly Saccharidic vaccine (Pneumo23®) after 6 months (W24)2) Vaccination with placebo at W0 and Poly Saccharidic vaccine (Pneumo23®) at W24Secondary objectives are:

* To compare the clinical and biological tolerance of the two vaccinal strategies·

* To evaluate the durability of sero protection at 6 and 24 months after vaccination by Pneumo23®

* To search predictive factors determinant of the pneumococcal vaccine response

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
47
Inclusion Criteria
  • age 18 to 65 years
  • SLE as defined by the ACR classification
  • Stable SLE (treatment not modified during the 2 months preceding the inclusion date W0)
  • SLE treated by immunosuppressant only or systemic corticosteroids at a dose ≥ 5 mg/j or systemic corticosteroids at any dose associated with one or more immunosuppressive drugs
  • SLE treated by hydroxychloroquine only
  • 31 months following
  • females must have an effective method of contraception during the first 7 months of the study and with a negative serum or urinary pregnancy test
  • females not wishing to have a child during the 7 months following W0
  • physical examination
  • signed written and informed consent
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Exclusion Criteria
  • pregnant females or females wishing to have a child during the 7 months following W0
  • subjects infected with HIV and/or HBV( Ag HBs+) and or HVC
  • medical history of allergy to any vaccine component
  • receipt of any pneumococcal vaccine less than 5 years
  • receipt of other vaccine within one month prior to enrolment (inclusion visit W0)
  • receipt of immunoglobulin within three months prior to enrolment (inclusion visit W0)
  • splenectomy
  • hematopoietic disorders which give contra-indications to intramuscular and hypodermic route injections,
  • active malignancy , cirrhosis
  • intercurrent illness within one month prior to enrolment (inclusion visit W0)
  • patients under biotherapy (anti-CD20)must not been included if the interval between vaccination and the end of the biotherapy is less than one year.
  • participation to another clinical study during the first 7 months of the study
  • subject not covered by Health Insurance
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2Placebo, Pneumo23®Vaccination with placebo at W0 and Poly Saccharidic vaccine Pneumo23® at W24
1Prevenar® and Pneumo23®Vaccination with conjugate vaccine Prevenar® (WYETH-LEDERLE) at week 0 and Poly Saccharidic vaccine Pneumo23® (Sanofi Pasteur MSD) after 6 months (W24)
Primary Outcome Measures
NameTimeMethod
Proportion of responders for more than 5 serotypes among the 7 serotypes common between conjugate and Poly Saccharidic vaccines (ie. serotypes 4, 6B, 9V, 14, 18C, 19F and 23F).31 months
Secondary Outcome Measures
NameTimeMethod
Proportion of patients presenting a disease exacerbation(defined as an increase of ³3 points on the SLEDAI score and/or need to increase treatment with corticosteroids or immunosuppressive drugs) during the 12 months following the first vaccination13 months
Proportion of patients with local or systemic reactions following vaccination31 months
Comparison of serum antibodies titers obtained at W28 for each of the tested serotypes28 weeks
Comparison of ELISA persistent responses six months and 2 years after vaccination with Pneumo23® (M12 and M30)12 months + 30 months
Research of predictive factors of immunological response disease activity at M0 (defined by SLEDAI), SLE treatment and others variables witch can affect the response.31 months

Trial Locations

Locations (1)

CIC Vaccinologie - Hopital Cochin

🇫🇷

Paris, France

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