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

NCT02279589 | Completed Phase 2

• 1 other identifier: P130903
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Pneumococcal Infection

Keywords

hyporesponsiveness; vaccination; recommendations; improvement; schedule; fractional dose; conjugate polysaccharide vaccine

Outcome Measures

Primary Outcomes (1)

• Geometric mean antibody titers measured by OpsonoPhagocytose Assay (OPA) at 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)

  13 months

Secondary Outcomes (5)

• Immune response at 13 months

  13 months

• Immune response evaluated by ELISA antibody concentration at 36 months

  36 months

• Sustainability and evolution of the immune response at 36 months

  36 months

• Clinical tolerance at 36 months

  36 months

• Description of any invasive infections pneumococcal and community acquired pneumonia occurring during 36 months of follow-up

  36 months

Study Arms (4)

Group A

ACTIVE COMPARATOR

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; Biological: Pneumo 23® 0,1; Biological: Prevenar13® 0,5

Group B

ACTIVE COMPARATOR

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; Biological: Prevenar13® 0,5

Group C

ACTIVE COMPARATOR

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; Biological: Pneumo 23® 0,1; Biological: Prevenar13® 0,5

Group D

ACTIVE COMPARATOR

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; Biological: Prevenar13® 0,5

Interventions

Pneumo 23® 0,5 BIOLOGICAL

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.

Group A; Group C; Group D

Pneumo 23® 0,1 BIOLOGICAL

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.

Group A; Group B; Group C

Prevenar13® 0,5 BIOLOGICAL

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).

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Related Publications (5)

• de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis. 2008 Apr 1;46(7):1015-23. doi: 10.1086/529142.

  PMID: 18444818 BACKGROUND

• O'Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect Dis. 2007 Sep;7(9):597-606. doi: 10.1016/S1473-3099(07)70210-4.

  PMID: 17714673 BACKGROUND

• Poolman J, Borrow R. Hyporesponsiveness and its clinical implications after vaccination with polysaccharide or glycoconjugate vaccines. Expert Rev Vaccines. 2011 Mar;10(3):307-22. doi: 10.1586/erv.11.8.

  PMID: 21434799 BACKGROUND

• Russell FM, Carapetis JR, Balloch A, Licciardi PV, Jenney AW, Tikoduadua L, Waqatakirewa L, Pryor J, Nelson J, Byrnes GB, Cheung YB, Tang ML, Mulholland EK. Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial. Vaccine. 2010 Apr 26;28(19):3341-9. doi: 10.1016/j.vaccine.2010.02.087. Epub 2010 Mar 4.

  PMID: 20206670 BACKGROUND

• Ahman H, Kayhty H, Vuorela A, Leroy O, Eskola J. Dose dependency of antibody response in infants and children to pneumococcal polysaccharides conjugated to tetanus toxoid. Vaccine. 1999 Jun 4;17(20-21):2726-32. doi: 10.1016/s0264-410x(99)00048-1.

  PMID: 10418924 BACKGROUND

MeSH Terms

Conditions

Pneumococcal Infections

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Hélène BODILIS

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 31, 2014
• Study Start: December 4, 2014
• Primary Completion: June 1, 2016
• Study Completion: September 6, 2018
• Last Updated: August 3, 2021

Record last verified: 2021-07