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

NCT02141516 | Completed Phase 3 Results

• 2 other identifiers: V72_622013-002454-78
• Study Type: interventional
• Target: 239
• Locations: 5 countries
• Sites: 20

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.

Conditions

Meningococcal Disease

Keywords

Meningitis; vaccination; complement deficiency; asplenia; splenic dysfunction

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine)

• Percentages of Subjects With hSBA Titers ≥ 8 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine).

• Geometric Mean Ratios (GMRs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine).

• Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroup B Strains Following a 2-dose Vaccination Schedule.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine).

• 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.

  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.

  Day 91 (one month after the second dose of the study vaccine).

• Geometric Mean Concentrations (GMCs) of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine).

• ELISA GMRs of Antibodies Against Vaccine Antigen 287-953 Following a 2-dose Vaccination Schedule.

  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.

  Day 1 and Day 91 (one month after the second dose of the study vaccine).

• Percentage of Subjects With Four-fold Increases in ELISA Concentrations Against the Vaccine Antigen 287-953.

  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.

  Day 91 (one month after the second dose of the study vaccine).

• Number Of Subjects With Unsolicited Adverse Events (AEs).

  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).

  At Day1 through Day 7 after any vaccination and throughout the study period (Day 1 to Day 91)

Secondary Outcomes (1)

• Number of Subjects Reporting Solicited Local and Systemic AEs.

  From Day 1 until Day 7 after any vaccination.

Study Arms (3)

Group A

EXPERIMENTAL

Complement deficiency

Biological: rMenB+OMV

Group B

EXPERIMENTAL

asplenia/splenic dysfunction

Biological: rMenB+OMV

Group C

ACTIVE COMPARATOR

age-matched healthy controls

Biological: rMenB+OMV

Interventions

rMenB+OMV BIOLOGICAL

2 doses of vaccine 2 months apart

Group A

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects aged 2 to 17 years (inclusive) at enrollment
• weighing at least 13 Kg at the time of enrollment
• \- Subjects at risk of meningococcal disease because of functional or anatomic asplenia

You may not qualify if:

• 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
• \- Previous known or suspected disease caused by N. meningitidis in the last year.
• Previous known or suspected disease caused by N. meningitidis
• Known or suspected impairment/alteration of the immune system

Sponsors & Collaborators

• Novartis: lead
• Novartis Vaccines: collaborator

Study Sites (20)

12, Novartis Investigational Site

Florence, 50139, Italy

Location

11, Novartis Investigational Site

Genova, 16132, Italy

Location

10, Novartis Investigational Site

Milan, 20122, Italy

Location

14, Novartis Investigational Site

Padua, 35128, Italy

Location

13, Novartis Investigational Site

Roma, 00165, Italy

Location

31, Novartis Investigational Site

Krakow, 31-302, Poland

Location

33, Novartis Investigational Site

Warsaw, 04-730, Poland

Location

30, Novartis Investigational Site

Wroclaw, 50-345, Poland

Location

42, Novartis Investigational Site

Moscow, 117198, Russia

Location

41, Novartis Investigational Site

Moscow, 117997, Russia

Location

43, Novartis Investigational Site

Yekaterinburg, 620149, Russia

Location

21, Novartis Investigational Site

Barcelona, 08035, Spain

Location

22, Novartis Investigational Site

Madrid, 28046, Spain

Location

23, Novartis Investigational Site

Madrid, 46026, Spain

Location

20, Novartis Investigational Site

Santiago de Compostela, 15706, Spain

Location

24, Novartis Investigational Site

Valencia, 46026, Spain

Location

53, Novartis Investigational Site

London, WC1N 3JH, United Kingdom

Location

52, Novartis Investigational Site

Manchester, M13 9WL, United Kingdom

Location

50, Novartis Investigational Site

Oxford, OX3 7LE, United Kingdom

Location

51, Novartis Investigational Site

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Martinon-Torres F, Bernatowska E, Shcherbina A, Esposito S, Szenborn L, Marti MC, Hughes S, Faust SN, Gonzalez-Granado LI, Yu LM, D'Agostino D, Calabresi M, Toneatto D, Snape MD. Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function. Pediatrics. 2018 Sep;142(3):e20174250. doi: 10.1542/peds.2017-4250. Epub 2018 Aug 1.

  PMID: 30068713 DERIVED

MeSH Terms

Conditions

Meningococcal Infections; Meningitis; Hereditary Complement Deficiency Diseases

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neuroinflammatory Diseases; Nervous System Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines and Diagnostics

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: February 15, 2017
• Results First Posted: February 15, 2017

Record last verified: 2016-07

Locations

IT (5); RU (3); ES (5); GB (4); PL (3)