Effectiveness, Immunogenicity and Safety of Meningococcal ABCWY Vaccine Administered to Healthy Adolescents

Phase 2

Completed

Conditions: Meningococcal Disease

Interventions: Biological: MenABCWY
Other: Placebo
Biological: MenACWY

Registration Number: NCT02140762

Lead Sponsor: Novartis Vaccines

Brief Summary: Evaluate the effectiveness of 2 doses of MenABCWY vaccine in adolescents compared to a single dose of MenACWY vaccine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 305

Inclusion Criteria

Adolescents from 10-18 years of age, generally in good health, and available for all study visits, who/whose legally acceptable representative has given written informed consent at the time of enrollment.
Female subjects of childbearing potential must have a negative urine pregnancy test.

Exclusion Criteria

Serious, acute, or chronic illnesses. Previous or suspected disease caused by N. meningitidis. Previous immunization with any meningococcal vaccine.
Exposure to individuals with clinically proven meningococcal disease or clinical bacterial meningitis without further microbiologic characterization.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MenABCWY	MenABCWY	Subjects received one dose of MenABCWY vaccine at day 1 and a second dose after 2 months
Placebo/MenACWY	Placebo	Subjects received one dose of placebo at day 1 and one dose of MenACWY vaccine after 2 months
Placebo/MenACWY	MenACWY	Subjects received one dose of placebo at day 1 and one dose of MenACWY vaccine after 2 months

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US Neisseria Meningitidis (N. Meningitidis) Serogroup B Strain at One Month After the Second Vaccination.	One month after the second vaccination (month 3)	The combined percentage of subjects without bactericidal activity at 1:4 dilution using the endogenous complement human Serum Bactericidal Assay (enc-hSBA) across all strains in MenABCWY group and MenACWY group is reported at one month after the second injection. The percentage of subjects without bactericidal activity at 1:4 dilution was used to assess the effectiveness of two doses of MenABCWY vaccine when compared to one dose of Men ACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains. Least Square (LS)-mean computed from the generalized linear model.

Secondary Outcome Measures

Name	Time	Method
Percentages of Subjects With HT-hSBA Titers Against Serogroup B Test Strains ≥ Lower Limit of Quantitation (LLQ) at Four Months After the 2-dose Vaccination Series.	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers against serogroup B test strains ≥ LLQ, at four months after the 2-dose vaccination series, is reported. The LLQ cut off values for strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6, 8.9, 8 and 8.2 respectively
Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroups A, C, W and Y ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at One Month After the 2-dose Vaccination Series	One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128, against serogroups A, C, W, Y, at one month after the 2-dose vaccination series.
Percentage of Subjects With 3-fold Rise in hSBA Titer Against N.Meningitidis Serogroup B Strains at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 ( one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a 3-fold rise in HT-hSBA titers against the N.meningitidis serogroup B test strains, at 1 and 4 months after the 2-dose vaccination series.The 3-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥3 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 3 times of the prevaccination hSBA.
Percentage of Subjects With 4-fold Rise in hSBA Titer Against N.Meningitidis Serogroup B Strains at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 ( one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a 4-fold rise in HT-hSBA titers against the N.meningitidis serogroup B test strains, at 1 and 4 months after the 2-dose vaccination series. The 4-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥4 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 4 times of the prevaccination hSBA.
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)	From day 1 (6 hours) until day 7 after any vaccination	Reactogenicity was presented in terms of number of subjects reporting solicited local and systemic AEs and other indicators.
Percentages of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US N. Meningitidis Serogroup B Strain at 4 Months After the Second Vaccination.	Four months after the second vaccination (month 6)	The combined percentage of subjects without bactericidal activity at 1:4 dilution using the endogenous complement human Serum Bactericidal Assay (enc-hSBA) across all strains in MenABCWY group and MenACWY group is reported at four months after the second injection. The percentage of subjects without bactericidal activity at 1:4 dilution was used to assess the effectiveness of two doses of MenABCWY vaccine when compared to one dose of Men ACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains. Least Square (LS)-mean computed from the generalized linear model.
Percentages of Subjects Without Bactericidal Activity at 1:8 Dilution Against Each US N. Meningitidis Serogroup B Strain at Four Months After the Second Vaccination.	Four months after the second vaccination (month 6)	The combined percentage of subjects without bactericidal activity at 1:8 dilution using the endogenous complement human Serum Bactericidal Assay (enc-hSBA) across all strains in MenABCWY group and MenACWY group is reported at four months after the second injection. The percentage of subjects without bactericidal activity at 1:8 dilution was used to assess the effectiveness of two doses of MenABCWY vaccine when compared to one dose of Men ACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains. Least Square (LS)-mean computed from the generalized linear model.
Percentages of N. Meningitidis Serogroup B Invasive Disease Strains Killed at 1:4 and 1:8 Dilutions, for Each Subject	Baseline, four months after second vaccination (month 6)	The mean percentage of N. meningitidis serogroup B invasive disease strains killed by each subject, at 1:4 and 1:8 dilutions at four months after the 2-dose vaccination series is reported.
Percentages of Subjects With Enc-hSBA Titer ≥ 1:4 and Enc-hSBA Titer ≥ 1:8 at Four Months After the 2-dose Vaccination Series	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of percentages of subjects with enc-hSBA ≥ 1:4 and enc-hSBA titer ≥ 1:8 against four N. meningitidis serogroup B test strains at four months after the 2-dose vaccination series is reported.
hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroup B Test Strains	One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of hSBA GMTs against serogroup B test strains, at one month after the 2-dose vaccination series.
HT-hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroup B Test Strains	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs against serogroup B test strains, at four months after the 2-dose vaccination series.
HT-hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroups A, C, W, Y	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs to serogroups A, C, W, and Y, at four months after the 2-dose vaccination series.
Percentages of Subjects Without Bactericidal Activity at 1:8 Dilution Against Each US N. Meningitidis Serogroup B Strain at One Month After the Second Vaccination	One month after the second vaccination (month 3)	The combined percentage of subjects without bactericidal activity at 1:8 dilution using the endogenous complement human Serum Bactericidal Assay (enc-hSBA) across all strains in MenABCWY group and MenACWY group is reported at one month after the second injection. The percentage of subjects without bactericidal activity at 1:8 dilution was used to assess the effectiveness of two doses of MenABCWY vaccine when compared to one dose of Men ACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains. Least Square (LS)-mean computed from the generalized linear model.
Percentages of Subjects With Enc-hSBA Titer >= 1:4 and Enc-hSBA Titer >= 1:8 at One Month After the 2-dose Vaccination Series	One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of percentages of subjects with enc-hSBA \>= 1:4 and enc-hSBA titer \>= 1:8 against four N. meningitidis serogroup B test strains at one month after the 2-dose vaccination series is reported.
hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroups A,C,W,Y	One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of hSBA GMTs to serogroups A, C, W, and Y, at one month after the 2-dose vaccination series.
Percentages of Subjects With HT-hSBA Titers Against Serogroup B Test Strains ≥ Lower Limit of Quantitation (LLQ) at Baseline(Day 1) and One Month After the 2-dose Vaccination Series.	At baseline(day 1) and One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers against serogroup B test strains ≥ LLQ, at baseline(day 1) and one month after the 2-dose vaccination series, is reported. The LLQ cut off values for strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6, 8.9, 8 and 8.2 respectively.
Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroups A, C, W and Y ≥ LLQ at Baseline and One Month After the 2-dose Vaccination Series	At Baseline and One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ against serogroups A, C, W, Y, at baseline(day 1) and one month after the 2-dose vaccination series.The LLQ cut off values for serogroups A,C,W and Y were 22.7,5.2,39.6 and 14.7 respectively.
Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroups A, C, W and Y ≥ Lower Limit of Quantitation (LLQ) at Four Months After the 2-dose Vaccination Series.	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ LLQ against serogroups A, C, W, Y at four months after the 2-dose vaccination series.The LLQ cut off values for serogroups A,C,W and Y were 22.7,5.2,39.6 and 14.7 respectively.
Percentage of Subjects With 2-fold Rise in hSBA Titer Against N.Meningitidis Serogroups A,C,W and Y at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 ( one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N.meningitidis serogroups A,C,W and Y, at 1 and 4 months after the 2-dose vaccination series. The 2-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥2 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 2 times of the prevaccination hSBA.
Percentages of Subjects With HT-hSBA Titers Against Serogroup B Test Strains ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at Four Months After the 2-dose Vaccination Series.	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers against serogroup B test strains ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at four months after the 2-dose vaccination series, is reported.
Percentage of Subjects With 3-fold Rise in hSBA Titer Against N.Meningitidis Serogroups A, C, W and Y at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 (one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a three-fold rise in HT-hSBA titers against the N.meningitidis serogroups A,C,W and Y at 1 and 4 months after the 2-dose vaccination series. The 3-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥3 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 3 times of the prevaccination hSBA.
Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroups A, C, W and Y ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at Four Months After the 2-dose Vaccination Series	Four months after the second vaccination (month 6)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroups A, C, W, Y at four months after the 2-dose vaccination series.
Percentage of Subjects With 2-fold Rise in hSBA Titer Against N.Meningitidis Serogroup B Strains at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 ( one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N.meningitidis serogroup B test strains, at 1 and 4 months after the 2-dose vaccination series.The 2-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥2 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 2 times of the prevaccination hSBA
Percentages of Subjects With HT-hSBA Titers Against Serogroup B Test Strains≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at One Month After the 2-dose Vaccination Series	One month after the second vaccination (month 3)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers against serogroup B test strains ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at one month after the 2-dose vaccination series, is reported.
Percentage of Subjects With 4-fold Rise in hSBA Titer Against N.Meningitidis Serogroups A,C,W and Y at One and Four Months After the 2-dose Vaccination Series.	At Month 3 and Month 6 ( one and four months after 2 doses of vaccination)	The immunogenicity of two doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a 4-fold rise in HT-hSBA titers against the N.meningitidis serogroups A,C,W and Y, at 1 and 4 months after the 2-dose vaccination series. The 4-fold rise in titer is defined as follows: a)for subjects with prevaccination hSBA titers \<LLQ, a postvaccination hSBA ≥4 LLQ; b) for subjects with a prevaccination hSBA titers ≥LLQ, an increase of at least 4 times of the prevaccination hSBA.
Number of Subjects Reporting Unsolicited AEs.	From day 1 to day 30 after any vaccination for any unsolicited AE. From day 1 to study termination (day 181) for all other categories.	Percentages of subjects reporting unsolicited AEs including serious adverse events (SAEs).

Trial Locations

Locations (7): Heartland Research Associates LLC
🇺🇸
Newton, Kansas, United States
Bluegrass Clinical Research, Inc.
🇺🇸
Louisville, Kentucky, United States
Heartland Research Associates, LLC
🇺🇸
Wichita, Kansas, United States
Senders Pediatrics
🇺🇸
Cleveland, Ohio, United States
Accelovance, Inc
🇺🇸
Melbourne, Florida, United States
The Children's Clinic of Jonesboro, P.A.
🇺🇸
Jonesboro, Arkansas, United States
Meridian Clinical Research
🇺🇸
Omaha, Nebraska, United States