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Trial record 3 of 43 for:    ANTI-PNEUMOCOCCAL VACCINE

Open Randomized Trial Evaluating Four Anti-pneumococcal Vaccine Strategies With Fractionated Doses of Non Conjugate Polysaccharide Vaccine to Prevent Hyporesponse in Healthy Volunteers (HYPOPNEUMO)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT02279589
First received: October 16, 2014
Last updated: March 24, 2017
Last verified: March 2017
  Purpose

Immune response analysis after the combination of PCV13 and PPV23 will lead to evaluate if a prime with PCV13 help to obtain a good response to repeated dose of PPV23.The hyporesponsiveness following the unconjugated vaccine is associated with high polysaccharide antigen concentration. Several issues limit the development and recommendation of anti-pneumococcal vaccine in adult's patients at risk. Reduced doses of unconjugated polysaccharide antigens would bypass the hyporesponsiveness and maintain the expanded coverage serotype.

A better knowledge of immune response following the combination of two vaccines in adults is essential. In addition, adults are required to be exposed to repeated doses of polysaccharide antigens by vaccine or by natural exposure, it is important to determine the extend and duration of any hyporesponsiveness.

The main objective is to evaluate if non conjugate polysaccharidique fractionated doses administered after a conjugate vaccine help to avoid hyporesponse in a schedule with repeated injections of pneumococcal polysaccharidique vaccine


Condition Intervention Phase
Pneumococcal Infection Biological: Pneumo 23® 0,5 Biological: Pneumo 23® 0,1 Biological: Prevenar13® 0,5 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Open Randomized Trial Evaluating Four Anti-pneumococcal Vaccine Strategies With Fractionated Doses of Non Conjugate Polysaccharide Vaccine to Prevent Hyporesponse in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Geometric mean antibody titers measured by OpsonoPhagocytose Assay (OPA) at 13 months [ Time Frame: 13 months ]
    The primary end point is the geometric mean antibody titers measured by OPA (OpsonoPhagocytose Assay) for 9 common serotypes to both PPV23 and PCV13 (3, 6B, 7F, 9V, 14,18C, 19A, 19F, 23F), at 1 month after the third dose of vaccine (at M13)


Secondary Outcome Measures:
  • Immune response at 13 months [ Time Frame: 13 months ]

    The immune response involved when combining conjugate vaccine (PCV13) and non-conjugate polysaccharide vaccine (PPV23) and an eventual prime-boost effect will be evaluated by:

    • ELISA antibody concentration against nine common serotypes (3, 6B, 9V, 14,18C, 19A, 19F, 23F, 7F) at month 0, month 1, month 3 and month 13 and proportion of positive serotypes
    • OPA titers against 9 common serotypes (3, 6B, 9V, 14,18C, 19A, 19F, 23F, 7F) at M0, M1, M3 and proportion of positive serotype
    • Measurement of IgG subtypes, measurement of lymphocyte cell phenotypes (memory and naives B cells, marginal zone B cells, follicular zone B cells, B1b and B1a cells), at M0, M1, M3 and M13

  • Immune response evaluated by ELISA antibody concentration at 36 months [ Time Frame: 36 months ]
    The immune response will be evaluated by ELISA antibody concentration, against 3 uncommon specific serotypes of PPV23 (12F/10A/15B) at M0, M1, M3, M12, M13, M18, M24, M36 and the proportion of positive serotypes (impact of fractionated PPV23)

  • Sustainability and evolution of the immune response at 36 months [ Time Frame: 36 months ]
    The sustainability and evolution of the immune response over time will be measured by ELISA concentration and OPA titres at regular intervals (M0, M12, M18, M24, and M36) for the 9 PCV13 serotypes to measure changes over time in the immune response.

  • Clinical tolerance at 36 months [ Time Frame: 36 months ]
    • For 7 days following each vaccination

      • local and/or systemic solicited reactions : Proportion of participants with an event; number, nature, grade and time of occurrence.

    • During the study :

      • Any event related or possibly related to vaccine immunisation: proportion of participant with an event; number, nature, grade and time of occurrence.
      • Any event related to vaccine immunisation and leading to discontinuation of the immunisation regimen: proportion of participant with an event; number, nature, grade and time of occurrence.
      • Serious adverse event, regardless of the relationship to vaccine immunisation: proportion number, nature, grade and time of occurrence

  • Description of any invasive infections pneumococcal and community acquired pneumonia occurring during 36 months of follow-up [ Time Frame: 36 months ]
    The description of any invasive infections pneumococcal and community acquired pneumonia occurring during the time course of the study will be evaluated by the documentation of invasive bacterial infections with biological and radiological examinations in case of suspected invasive infection (clinical effectiveness)


Enrollment: 60
Study Start Date: December 2014
Estimated Study Completion Date: May 2018
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A

Description :

15 subjects with : Prevenar13® 0,5 then Pneumo 23® 0,5 then Pneumo 23® 0,1

Route : Intramuscular vaccination schedule : M0, M2, M12

Biological: Pneumo 23® 0,5
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at full dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Pneumo 23® 0,1
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at a 1/5 of the dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Prevenar13® 0,5

The conjugate vaccine Prevenar13® (Pfizer) containing 13 valencies Pneumoccocus (4, 6B, 9V, 14, 18C, 19F, 23F), conjugated with diphtheria anatoxin (CRM 197) administered by intramuscular route (deltoid).

One dose contains: 0, 5 ml of 2 - 4μg of polysaccharide of the13 serotypes pneumococcus which 12 are shared with Pneumo 23® vaccine conjugated to diphtheria toxoid (CRM 197).

Active Comparator: Group B

Description 15 subjects with : Prevenar13® 0,5 then Pneumo 23® 0,1 then Pneumo 23® 0,1

Route : Intramuscular vaccination schedule : M0, M2, M12

Biological: Pneumo 23® 0,1
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at a 1/5 of the dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Prevenar13® 0,5

The conjugate vaccine Prevenar13® (Pfizer) containing 13 valencies Pneumoccocus (4, 6B, 9V, 14, 18C, 19F, 23F), conjugated with diphtheria anatoxin (CRM 197) administered by intramuscular route (deltoid).

One dose contains: 0, 5 ml of 2 - 4μg of polysaccharide of the13 serotypes pneumococcus which 12 are shared with Pneumo 23® vaccine conjugated to diphtheria toxoid (CRM 197).

Active Comparator: Group C

Description :

15 subjects with : Prevenar13® 0,5 then Pneumo 23® 0,1 then Pneumo 23® 0,5

Route : Intramuscular vaccination schedule : M0, M2, M12

Biological: Pneumo 23® 0,5
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at full dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Pneumo 23® 0,1
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at a 1/5 of the dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Prevenar13® 0,5

The conjugate vaccine Prevenar13® (Pfizer) containing 13 valencies Pneumoccocus (4, 6B, 9V, 14, 18C, 19F, 23F), conjugated with diphtheria anatoxin (CRM 197) administered by intramuscular route (deltoid).

One dose contains: 0, 5 ml of 2 - 4μg of polysaccharide of the13 serotypes pneumococcus which 12 are shared with Pneumo 23® vaccine conjugated to diphtheria toxoid (CRM 197).

Active Comparator: Group D

Description:

15 subjects with : Prevenar13® 0,5 then Pneumo 23® 0,5 then Pneumo 23® 0,5

Route : Intramuscular vaccination schedule : M0, M2, M12

Biological: Pneumo 23® 0,5
Polysaccharide vaccine Pneumo 23® (Sanofi Pasteur MSD), containing 23 valencies Pneumococcus (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) administered by intramuscular route. (Deltoid) at full dose. One dose contains: 0, 5 mL of 25 μg of polysaccharide of the 23 serotypes pneumococcus.
Biological: Prevenar13® 0,5

The conjugate vaccine Prevenar13® (Pfizer) containing 13 valencies Pneumoccocus (4, 6B, 9V, 14, 18C, 19F, 23F), conjugated with diphtheria anatoxin (CRM 197) administered by intramuscular route (deltoid).

One dose contains: 0, 5 ml of 2 - 4μg of polysaccharide of the13 serotypes pneumococcus which 12 are shared with Pneumo 23® vaccine conjugated to diphtheria toxoid (CRM 197).


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Individuals (males and females) of age ≥ 18 to ≤ 49 years old;
  • Individuals, who, after the nature of the study have been explained to them, have given written consent according to local regulatory requirements.
  • Individuals in good health as determined by the outcome of medical history, physical examination clinical judgement of the investigator.
  • Women of childbearing potential must have a negative pregnancy test and an effective contraception during the first 13 months of the study;
  • Individuals able to participate and to follow up during the 36 months of the study
  • Individuals covered by social security regimen

Exclusion Criteria:

  • Individuals with behavioural or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
  • Individuals with indication to anti-pneumococcal vaccination at the time of enrolment according to the French vaccination schedule (vaccinal calender BEHn°14-15/2013);
  • Individuals with history of pneumococcal vaccination;
  • Individuals with history of suspected or low documented invasive pneumococcal infection within the year before enrolment;
  • Individuals who have received any another vaccines within 4 weeks prior to enrolment or who are planning to receive any vaccine within the first 13 months of the study; (except Annual influenza vaccination which is permitted 4 weeks before and after each vaccination visit of the study and then allowed at any time during the study follow up)
  • Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks before enrolment
  • Individuals who have received systemic antibiotic within 7 days before inclusion (except 14 days concerning azithromycine), regardless the duration or dosage
  • Individuals with body temperature ≥ 38.0 degrees Celsius within 3 days of study vaccination.
  • Individuals with personal or familial history of any illness that, in the opinion of the investigator, might pose additional risk to the subjects due to participation in the study.
  • Individual with personal or familial (first degree relatives) history of an auto-immune disorder, or any other known or suspected impairment /alteration of the immune system or under immunosuppressive therapy, including use of systemic corticosteroids (i.e. prednisone, or equivalent) ≥ 10mg/day more than 6 days within the previous 28 days or within 3 days regardless dosage and duration, or in chemotherapy treatment or other immunosuppressive or immunomodulating therapy within the past 168 days (6 months). Topical or inhaled uses of steroid including intranasal are allowed.
  • Individuals with thrombocytopenia or coagulation disorder contra-indicating intramuscularly injections; coagulation disorder contra-indicating intramuscularly injections;
  • Individuals with evolutionary cancer, cirrhosis, known infection to HIV/ HBV/ HCV or any serious chronic or progressive disease according to the judgment of the investigator
  • Individuals with acute respiratory tract infection within the month before enrolment;
  • Individuals with history of known allergies/hypersensitivity to any component of both study vaccines;
  • Women, who are pregnant or breast-feeding
  • Individuals under a measure of legal protection or unable to consent.
  • Individuals participating in any clinical trial 28 days prior to first study visit until the M24 visit of the study (+ the day of M36 visit).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02279589

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Hélène BODILIS Assistance Publique - Hôpitaux de Paris
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02279589     History of Changes
Other Study ID Numbers: P130903
Study First Received: October 16, 2014
Last Updated: March 24, 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:
hyporesponsiveness
vaccination
recommendations
improvement
schedule
fractional dose
conjugate polysaccharide vaccine

Additional relevant MeSH terms:
Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2017