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Safety and Immunogenicity of Novartis Meningococcal B Vaccine When Administered to Immunocompromised Children and Adolescents Compared to Healthy Subjects.

Phase 3
Completed
Conditions
Meningococcal Disease
Interventions
Biological: rMenB+OMV
Registration Number
NCT02141516
Lead Sponsor
Novartis
Brief Summary

The study aims at evaluating the safety and immunogenicity of rMenB+OMV NZ when administered to subjects from 2 to 17 years of age with increased risk of meningococcal disease because either of primary or secondary complement deficiencies or of asplenia or splenic dysfunction. A group of healthy age-matched subjects will be enrolled to serve as a descriptive control for immunogenicity and safety.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
239
Inclusion Criteria

Inclusion criterion applicable to All Groups

  • Subjects aged 2 to 17 years (inclusive) at enrollment
  • weighing at least 13 Kg at the time of enrollment

Inclusion criterion applicable to Group A - Subjects at risk of meningococcal disease because of primary or secondary complement deficiencies

Inclusion criterion applicable to Group B

  • Subjects at risk of meningococcal disease because of functional or anatomic asplenia

Inclusion criterion applicable to Group C - healthy subjects

Exclusion Criteria

Exclusion criteria applicable to All Groups (A, B and C)

  • History of any previous immunization with a meningococcal B vaccine
  • History of severe allergic reaction after previous vaccinations, or hypersensitivity to any component of the vaccine
  • Known HIV infection
  • History of any progressive or severe neurologic disorder or seizure disorder
  • Contraindication to intramuscular injection or blood drawn
  • Females who are pregnant, planning a pregnancy or nursing (breastfeeding)
  • Females of childbearing potential who have not used or do not plan to use acceptable birth control measures
  • History or any illness/condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects

Exclusion criterion applicable to Groups A and B

  • Previous known or suspected disease caused by N. meningitidis in the last year.

Exclusion criteria applicable to Group C

  • Previous known or suspected disease caused by N. meningitidis
  • Known or suspected impairment/alteration of the immune system

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group CrMenB+OMVage-matched healthy controls
Group BrMenB+OMVasplenia/splenic dysfunction
Group ArMenB+OMVComplement deficiency
Primary Outcome Measures
NameTimeMethod
Percentages of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) Titers ≥ 5 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.Day 1 and Day 91 (one month after the second dose of the study vaccine)

Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 5 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+Outer Membrane Vesicle (OMV) NZ, administered on Day 1 and Day 61.

Percentages of Subjects With hSBA Titers ≥ 8 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.Day 1 and Day 91 (one month after the second dose of the study vaccine).

Immunogenicity was assessed in terms of percentage of subjects with hSBA titers ≥ 8 against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Geometric Mean Ratios (GMRs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.Day 1 and Day 91 (one month after the second dose of the study vaccine).

Immunogenicity was assessed in terms of GMRs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.Day 1 and Day 91 (one month after the second dose of the study vaccine).

Immunogenicity was assessed in terms of GMTs against N. meningitidis serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Percentage of Subjects With Four-fold Increases in ELISA Concentrations Against the Vaccine Antigen 287-953.Day 91 (one month after the second dose of the study vaccine).

Antibody responses were assessed in terms of percentage of subjects achieving 4-fold increase in ELISA concentrations against vaccine antigen 287-953 on Day 91 over baseline (Day 1), following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Number Of Subjects With Unsolicited Adverse Events (AEs).At Day1 through Day 7 after any vaccination and throughout the study period (Day 1 to Day 91)

Safety was assessed as the number of subjects who reported unsolicited AEs collected from Day1 through Day 7 after any vaccination; serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs were collected throughout the study period (Day1-Day 91).

Percentages of Subjects With Four-fold Increases in hSBA Titers Against the Serogroup B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.Day 91 (one month after the second dose of the study vaccine).

Antibody responses were assessed in terms of percentage of subjects achieving 4-fold increase in ELISA concentrations against vaccine antigen 287-953 on Day 91 over baseline (Day 1), following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Geometric Mean Concentrations (GMCs) of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.Day 1 and Day 91 (one month after the second dose of the study vaccine).

Immune responses were measured as Enzyme-linked Immunosorbent Assay (ELISA) GMCs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

ELISA GMRs of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.Day 1 and Day 91 (one month after the second dose of the study vaccine).

Immune responses were measured as ELISA GMRs of antibodies against vaccine antigen 287-953 following 2 doses of rMenB+OMV NZ, administered on Day 1 and Day 61.

Secondary Outcome Measures
NameTimeMethod
Number of Subjects Reporting Solicited Local and Systemic AEs.From Day 1 until Day 7 after any vaccination.

Reactogenicity was presented in terms of percentages of subjects reporting solicited local and systemic AEs and other indicators.

Trial Locations

Locations (20)

31, Novartis Investigational Site

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Krakow, Poland

33, Novartis Investigational Site

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Warszawa, Poland

30, Novartis Investigational Site

🇵🇱

Wroclaw, Poland

42, Novartis Investigational Site

🇷🇺

Moscow, Russian Federation

41, Novartis Investigational Site

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Moscow, Russian Federation

43, Novartis Investigational Site

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Yekaterinburg, Russian Federation

13, Novartis Investigational Site

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Roma, Italy

23, Novartis Investigational Site

🇪🇸

Madrid, Spain

52, Novartis Investigational Site

🇬🇧

Manchester, United Kingdom

22, Novartis Investigational Site

🇪🇸

Madrid, Spain

53, Novartis Investigational Site

🇬🇧

London, United Kingdom

21, Novartis Investigational Site

🇪🇸

Barcelona, Spain

20, Novartis Investigational Site

🇪🇸

Santiago De Compostela, Spain

24, Novartis Investigational Site

🇪🇸

Valencia, Spain

51, Novartis Investigational Site

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Southampton, United Kingdom

50, Novartis Investigational Site

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Oxford, United Kingdom

12, Novartis Investigational Site

🇮🇹

Firenze, Italy

10, Novartis Investigational Site

🇮🇹

Milano, Italy

11, Novartis Investigational Site

🇮🇹

Genova, Italy

14, Novartis Investigational Site

🇮🇹

Padova, Italy

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