Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Phase 2

Completed

Conditions: Healthy

Registration Number: NCT00381615

Lead Sponsor: Novartis Vaccines

Brief Summary: This study was aimed to explore safety and immunogenicity of two formulations of a Meningococcal B Vaccine when administered to healthy infants.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 147

Inclusion Criteria

Subjects eligible to be enrolled in the study:

healthy 2-month old infants (55-89 days, inclusive), born after full term pregnancy with an estimated gestational age ≥37 weeks and a birth weight ≥2.5 kg;
for whom a parent/legal guardian had provided written informed consent after the nature of the study had been explained;
those available for all the visits scheduled in the study;
those in good health as determined by:
1. medical history
2. physical examination
3. clinical judgment of the investigator

Exclusion Criteria

Individuals were not to be enrolled into the study:

whose parents/legal guardians were unwilling or unable to give written informed consent to participate in the study; 2. who had previously received any meningococcal B vaccine; 3. who had received prior vaccination with Diphtheria Tetanus Pertussis (DTP) (acellular or whole cell), Inactivated Polio Vaccine (IPV) or Oral Polio Vaccine (OPV), H influenzae type b (Hib) or Heptavalent Pneumococcal Conjugate (PC7) vaccine; 4. who had a previous ascertained or suspected disease caused by N meningitidis, S pneumoniae, C diphtheriae, tetani, Poliovirus, Hib, or B pertussis (history of laboratory confirmed, or clinical condition of spasmodic cough for a period ≥2weeks associated with apnea or whooping); 5. who had household contact with and/or intimate exposure to an individual with laboratory confirmed N meningitidis, B pertussis, Hib, C diphtheriae or Polio infection since birth; 6. who had a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component; 7. who had experienced significant acute or chronic infection within the previous 7 days or had experienced fever (≥38.0°C) within the previous 3 days; 8. who had any present or suspected serious acute or chronic disease (e.g., with signs of cardiac, renal failure, hepatic disease, or severe malnutrition or insulin dependent diabetes), or progressive neurological disease, or a genetic anomaly/known cytogenic disorders (e.g., Down's syndrome); 9. who had leukemia, lymphomas; 10. who had a known or suspected autoimmune disease or impairment/alteration of immune function resulting from (for example):
receipt of any immunosuppressive therapy since birth
receipt of immunostimulants since birth
receipt of any systemic corticosteroid since birth 11. with a suspected or known HIV infection or HIV related disease; 12. who had ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation from birth and for the full length of the study; 13. with a known bleeding diathesis, or any condition that might be associated with a prolonged bleeding time; 14. who had experienced any seizure, either associated with fever or as part of an underlying neurological disorder or syndrome 15. who had taken antibiotics within 7 days prior to enrollment (exception: antibiotics taken once daily within 14 days after the last dose); 16. who had either received, or for whom there was intent to immunize with any other vaccine(s), with respect to the study vaccines, within 30 days prior and throughout the study period; 17. who had ever received another investigational agent from birth prior to enrollment and unwilling to refuse participation in another investigational trial through the end of the study; 18. whose parents/legal guardians, were planning to leave the area of the study site before the end of the study period; 19. with any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Reported Solicited Local Reactions After Each Vaccination of DTaP-Hib-IPV Pentavalent Vaccine	Day 1 through day 7 after each vaccination	Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after each vaccination of the pentavalent vaccine DTaP-Hib-IPV administered at 2 months (vaccination 1), 3 months (vaccination 2) and 4 months (vaccination 3).
Number of Subjects Who Reported Solicited Local Reactions After Each Vaccination of rMenB Vaccine With and Without OMV	Day 1 through day 7 after each vaccination	Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after each vaccination of rMenB vaccine with and without OMV administered at 2 months (vaccination 1), 4 months (vaccination 2), 6 months (vaccination 3) and 12 months (vaccination 4; vaccination 1 for Routine and Routine+OMV groups).
Number of Subjects Who Reported Solicited Systemic Reactions And Other Indicator of Reactogenicity After Each Vaccination Administered During Study	Day 1 through day 7 after each vaccination	Safety was assessed as the number of subjects who reported solicited systemic reactions and other indicator of reactogenicity from day 1 through day 7 after each vaccination administered during study as follow: rMenB vaccine with and without OMV, PC7, DTaP-Hib-IPV at 2 months (vaccination 1), MenC-CRM, DTaP-Hib-IPV at 3 months (vaccination 2), rMenB vaccine with and without OMV, PC7, DTaP-Hib-IPV at 4 months (vaccination 3), MenC-CRM at 5 months (vaccination 4), rMenB vaccine with and without OMV at 6 months (vaccination 5; rMenB and rMenB+OMV groups only), rMenB vaccine with and without OMV at 12 months (vaccination 5; routine and routine+OMV groups only), and rMenB vaccine with and without OMV (vaccination 6; rMenB and rMenB+OMV groups only).
Percentage of Subjects With Fourfold Rises in Bactericidal Titers Against Meningococcal Strains One Month After Third-Dose of Infants Series Vaccination or rMenB Vaccine With and Without OMV-NZ.	30 days after the third vaccination	Percentage of subjects fourfold increase in bactericidal titers against meningococcal strains 44/76-SL, 5/99 and NZ98/254 were measured at one month after third-dose and calculated respect to baseline titers.
Geometric Mean Ratios to Baseline Against a Panel of Genetically Distinct Meningococcal Strains 30 Days After the Third Immunization.	At baseline (pre-vaccination) and 30 days after the third vaccination	Geometric Mean Ratios (GMRs) as measure of the bactericidal activity against the for the three major meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) in subjects treated with Novartis rMenB Vaccine +/- OMV NZ (Groups I and II) at 30 days after the third immunization. The analysis was done on the Per Protocol population at one month after third injection.
Number of Subjects Who Reported Solicited Local Reactions After Each Vaccination of PC7	Day 1 through day 7 after each vaccination	Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after each vaccination of PC7 administered at 2 months (vaccination 1) and 4 months (vaccination 3).
Geometric Mean Bactericidal Titers Against Meningococcal Strains One Month After Third-Dose of Infants Series Vaccination of rMenB Vaccine With and Without OMV-NZ	Baseline and one month after third-dose of infants series	The immune response was measured as the geometric mean bactericidal titers directed against meningococcal strains 44/76-SL, 5/99 and NZ98/254, before vaccination (baseline) and at one month after third-dose of infants series vaccination of rMenB vaccine with and without OMV administered at 6 months of age.
Number of Subjects Who Reported Solicited Local Reactions After Each Vaccination of MenC-CRM or MenC-Hib	Day 1 through day 7 after each vaccination	Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after each vaccination of MenC-CRM administered at 2 months (vaccination 1) and 5 months (vaccination 2). MenC-Hib was administered at 12 months of age (vaccination 3).
Percentage of Subjects With Bactericidal Titers, BCA ≥1:4, 30 Days After the Third Immunization	Baseline and one month after third-dose of infants series	Immunogenicity was measured as percentage of subjects who achieved bactericidal titers ≥1:4 against meningococcal strains 44/76-SL, 5/99 and NZ98/254, evaluated using serum bactericidal assay, before vaccination (baseline) and at one month after third-dose of Infants series vaccination of rMenB vaccine with and without OMV administered at 6 months of age.

Secondary Outcome Measures

Name	Time	Method
Percentages of Subjects With Bactericidal Titers, BCA, ≥1:4 After the Second Immunization and at 12 Months Age	At baseline (pre-vaccination) and 30 days after the second vaccination and at 12 months age.	Percentages of subjects treated with Novartis rMenB Vaccine +/- OMV NZ (Groups I and II) with a BCA titer ≥1:4 for the three meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) at 30 days after the second vaccination and at 12 months age, and 1 month after fourth (booster) vaccination. The analysis was done on the Per Protocol population.
Percentages of Subjects With Fourfold Rises in Bactericidal Titers After the Second Immunization and at 12 Months Age	At pre-vaccination and 30 days post the 2nd vaccination and at 12 months age, and 1 month post 4th (booster) vaccination.	Percentages of subjects treated with Novartis rMenB Vaccine +/- OMV NZ (Groups I and II) with fourfold rises in bactericidal titers for the three meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) at 30 days after the second vaccination and at 12 months age, i.e. 6 months after third (pre-booster) vaccination, and 1 month after fourth (booster) vaccination. The analysis was done on the Per Protocol population 30 days after the second vaccination and at 12 months age.
Geometric Mean Ratios to Baseline Against a Panel of Genetically Distinct Meningococcal Strains 30 Days After a Single Dose Administered at 12 Months of Age	1 month after first vaccination	Geometric Mean Ratios to baseline against a panel of genetically distinct meningococcal strains 30 days after a single dose administered at 12 months of age.
Percentages of Subjects With Fourfold Rises in Bactericidal Titers 1 Month After First Vaccination	1 month after first vaccination	Percentages of subjects treated with Routine + Novartis rMenB Vaccine +/- OMV NZ (Groups III and IV) with fourfold rises in bactericidal titers for the three major meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) 1 month after first vaccination. The analysis was done on the Per Protocol population 1 month after first vaccination.
Geometric Mean Ratios (GMRs) to Baseline Against a Panel of Genetically Distinct Meningococcal Strains 30 Days After the Second Immunization and 1 Month After Fourth (Booster) Vaccination	30 days after the second vaccination and 1 month after fourth (booster) vaccination	Geometric Mean Ratios (GMRs) as measure of the bactericidal activity against meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) in subjects treated with Novartis rMenB Vaccine +/- OMV NZ (Groups I and II) at 30 days after the second immunization and 1 month after fourth (booster) vaccination. The analysis was done on the Per Protocol population at 30 days after the second immunization and 1 month after fourth (booster) vaccination.of age.
Percentages of Subjects With Bactericidal Titers ≥1:4 at 12 Months Age	pre-first vaccination and 1 month after first vaccination	Percentages of subjects treated with Routine + Novartis rMenB Vaccine +/- OMV NZ (Groups III and IV) with a bactericidal activity (BCA) measured as BCA titer ≥1:4 for the for three major meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) at 12 months age, i.e. pre-first vaccination, and 1 month after first vaccination. The analysis was done on the Per Protocol population at 12 months age, i.e. pre-first vaccination, and 1 month after first vaccination.
Geometric Mean Titers Against a Panel of Genetically Distinct Meningococcal Strains Prior to the First Dose, 30 Days After the Second Immunization and at 12 Months Age	prior 1st dose, 30 days post-2nd vaccination, 12 months age to 1 month post 4th vaccination	Geometric mean bactericidal titers as measure of the Bactericidal activity against meningococcal strains 44/76-SL, 5/99 and NZ98/254, before vaccination (baseline) and at 30 days after second immunization, at 12 months age,and 30 days after the fourth (booster) vaccination.
Geometric Mean Titers Against a Panel of Genetically Distinct Meningococcal Strains Prior to and 30 Days After a Single Dose Administered at 12 Months of ageVaccination of rMenB Vaccine With and Without OMV-NZ	pre-first vaccination and 1 month after first vaccination	Geometric Mean Titers (GMTs) as measure of the bactericidal activity against the for the three major meningococcal B strains (Strain 44/76-SL, Strain 5/99, Strain NZ98/254) in subjects treated with Routine +Novartis rMenB Vaccine +/- OMV NZ (Groups III and IV) at 12 months age, i.e. pre-first vaccination and 1 month after first vaccination. The analysis was done on the Per Protocol population.