NCT02446743

Combined Study - Phase 3b MenB Long Term Persistence in Adolescents

Completed Phase 3 Results posted Last updated 8 November 2018

What this trial tests

Phase 3 trial testing rMenB+OMV NZ (Meningococcal (Group B) multi component recombinant adsorbed vaccine) in Infections, Meningococcal in 531 participants. Completed in 23 September 2016.

Timeline

17 November 2015

Primary endpoint
23 September 2016

23 September 2016

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	531
Start date	17 November 2015
Primary completion	23 September 2016
Estimated completion	23 September 2016
Sites	12 locations across Chile, Canada, Australia

Drugs / interventions tested

• rMenB+OMV NZ (Meningococcal (Group B) multi component recombinant adsorbed vaccine) — full drug profile →

Conditions studied

• Infections, Meningococcal — all drugs for Infections, Meningococcal →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 15 to 24, any sex, with Infections, Meningococcal. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Subjects With Human Serum Bactericidal Activity (hSBA)≥1:4 Primary · Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254.

5/99

Group	Value	95% CI
Group 3B (V72_41)	84	77 – 90
Group 3B (V72P10)	84	76.4 – 90.2
Group 3B	84	79.2 – 88.5
Group B_0_1 (V72_41)	7	2.9 – 13.9
Group B_0_1 (V72P10)	24	16.9 – 31.7
Group B_0_1	17	12.2 – 22.1

NZ98/254

Group	Value	95% CI
Group 3B (V72_41)	9	4.9 – 14.9
Group 3B (V72P10)	29	21.1 – 37.3
Group 3B	18	13.9 – 23.4
Group B_0_1 (V72_41)	0	0 – 3.5
Group B_0_1 (V72P10)	14	9 – 20.9
Group B_0_1	8	5.2 – 12.4

Percentage of Subjects With hSBA≥1:5 Primary · Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713.

H44/76

Group	Value	95% CI
Group 3B (V72_41)	26	19.4 – 34.4
Group 3B (V72P10)	41	32.7 – 50.2
Group 3B	33	27.9 – 39.4
Group B_0_1 (V72_41)	5	1.6 – 10.8
Group B_0_1 (V72P10)	11	6.7 – 17.5
Group B_0_1	9	5.5 – 12.8

M10713

Group	Value	95% CI
Group 3B (V72_41)	71	63.2 – 78.6
Group 3B (V72P10)	78	69.8 – 84.6
Group 3B	74	68.9 – 79.5
Group B_0_1 (V72_41)	59	49.0 – 68.5
Group B_0_1 (V72P10)	78	70.5 – 84.3
Group B_0_1	70	64.2 – 75.7

Percentage of Subjects With hSBA Titers≥1:5 in Parent Studies-V72P10 and V72_41 Primary · At one month after last vaccination in parent studies- V72P10 (Month 7) and V72_41 (Month 2)

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713

H44/76- Baseline in Parent study

Group	Value	95% CI
Group 3B (V72_41)	1	0.17 – 4.9
Group 3B (V72P10)	23	16 – 31.1

H44/76- 1 month after last vacc in Parent study

Group	Value	95% CI
Group 3B (V72_41)	99	95.1 – 99.83
Group 3B (V72P10)	100	97.2 – 100

M10713- Baseline in Parent study

Group	Value	95% CI
Group 3B (V72_41)	34	25.9 – 41.9
Group 3B (V72P10)	73	64 – 80

M10713- 1 month after last vacc in Parent study

Group	Value	95% CI
Group 3B (V72_41)	68	59.4 – 75.5
Group 3B (V72P10)	98	94.6 – 99.81

Percentage of Subjects With hSBA≥1:8 Primary · Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713

H44/76

Group	Value	95% CI
Group 3B (V72_41)	22	15.7 – 29.9
Group 3B (V72P10)	35	27.0 – 43.9
Group 3B	28	23.1 – 34.1
Group B_0_1 (V72_41)	1	0.02 – 5.2
Group B_0_1 (V72P10)	9	5.2 – 15.2
Group B_0_1	6	3.3 – 9.5

5/99

Group	Value	95% CI
Group 3B (V72_41)	78	70.4 – 85.0
Group 3B (V72P10)	83	75.4 – 89.5
Group 3B	81	75.3 – 85.4
Group B_0_1 (V72_41)	4	1.1 – 9.9
Group B_0_1 (V72P10)	19	13.2 – 27.0
Group B_0_1	13	9.0 – 17.9

NZ98/254

Group	Value	95% CI
Group 3B (V72_41)	7	3.4 – 12.4
Group 3B (V72P10)	22	15.6 – 30.7
Group 3B	14	10.4 – 19.0
Group B_0_1 (V72_41)	0	0.0 – 3.5
Group B_0_1 (V72P10)	9	5.3 – 15.4
Group B_0_1	6	3.1 – 9.1

M10713

Group	Value	95% CI
Group 3B (V72_41)	62	53.0 – 69.5
Group 3B (V72P10)	75	66.5 – 82.0
Group 3B	68	62.0 – 73.4
Group B_0_1 (V72_41)	52	42.4 – 62.2
Group B_0_1 (V72P10)	71	62.7 – 77.8
Group B_0_1	63	56.9 – 69.1

Percentage of Subjects With hSBA≥1:16 Primary · Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

Bactericidal activity was measured against each of the N. meningitidis group B Indicator strains H44/76,5/99,NZ98/254 and M10713

H44/76

Group	Value	95% CI
Group 3B (V72_41)	12	7.0 – 18.2
Group 3B (V72P10)	28	20.7 – 36.8
Group 3B	20	15.1 – 24.8
Group B_0_1 (V72_41)	0	0.0 – 3.5
Group B_0_1 (V72P10)	7	3.7 – 12.7
Group B_0_1	4	2.2 – 7.6

5/99

Group	Value	95% CI
Group 3B (V72_41)	72	63.2 – 79.1
Group 3B (V72P10)	78	69.9 – 85.3
Group 3B	75	69.0 – 80.0
Group B_0_1 (V72_41)	2	0.24 – 7.0
Group B_0_1 (V72P10)	13	7.9 – 19.7
Group B_0_1	8	5.2 – 12.6

NZ98/254

Group	Value	95% CI
Group 3B (V72_41)	5	2.0 – 9.8
Group 3B (V72P10)	19	12.3 – 26.4
Group 3B	11	7.8 – 15.7
Group B_0_1 (V72_41)	0	0.0 – 3.5
Group B_0_1 (V72P10)	4	1.5 – 8.6
Group B_0_1	2	0.9 – 5.1

M10713

Group	Value	95% CI
Group 3B (V72_41)	50	41.9 – 58.8
Group 3B (V72P10)	65	56.1 – 73.0
Group 3B	57	51.2 – 63.2
Group B_0_1 (V72_41)	48	37.8 – 57.6
Group B_0_1 (V72P10)	61	53.0 – 69.2
Group B_0_1	56	49.4 – 61.9

hSBA Geometric Mean Titers (GMTs) After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study. Primary · Group 3B: 1 month after the last rMenB+OMV NZ vaccination in parent study and Day 1(prior to booster dose); Group B_0_1: Day 1(prior to first dose)

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99, NZ98/254 a nd M10713.

H44/76(1 month post last vacc in parent study)

Group	Value	95% CI
Group 3B (V72_41)	99	82 – 119
Group 3B (V72P10)	197	165 – 235
Group 3B	124	108 – 143

H44/76( Day 1)

Group	Value	95% CI
Group 3B (V72_41)	2.43	2.04 – 2.89
Group 3B (V72P10)	4.51	3.57 – 5.69
Group 3B	3.05	2.61 – 3.56
Group B_0_1 (V72_41)	1.14	0.93 – 1.40
Group B_0_1 (V72P10)	1.52	1.23 – 1.90
Group B_0_1	1.20	1.02 – 1.42

5/99(1 month post last vacc in parent study)

Group	Value	95% CI
Group 3B (V72_41)	180	153 – 211
Group 3B (V72P10)	606	492 – 746
Group 3B	270	234 – 311

5/99 (Day 1)

Group	Value	95% CI
Group 3B (V72_41)	24	19 – 30
Group 3B (V72P10)	31	23 – 42
Group 3B	26	21 – 31
Group B_0_1 (V72_41)	1.20	0.91 – 1.58
Group B_0_1 (V72P10)	2.30	1.75 – 3.04
Group B_0_1	1.57	1.26 – 1.95

NZ98/254(1 month post last vacc in parent study)

Group	Value	95% CI
Group 3B (V72_41)	11	8.67 – 14
Group 3B (V72P10)	93	75 – 117
Group 3B	22	19 – 27

NZ98/254( Day 1)

Group	Value	95% CI
Group 3B (V72_41)	1.31	1.17 – 1.45
Group 3B (V72P10)	2.56	2.07 – 3.17
Group 3B	1.66	1.46 – 1.89
Group B_0_1 (V72_41)	1.01	0.89 – 1.14
Group B_0_1 (V72P10)	1.50	1.23 – 1.84
Group B_0_1	1.11	0.97 – 1.27

M10713(1 month post last vacc in parent study)

Group	Value	95% CI
Group 3B (V72_41)	10	7.65 – 14
Group 3B (V72P10)	66	53 – 81
Group 3B	19	16 – 24

M10713(Day 1)

Group	Value	95% CI
Group 3B (V72_41)	13	9.86 – 18
Group 3B (V72P10)	22	16 – 29
Group 3B	16	13 – 20
Group B_0_1 (V72_41)	10	7.13 – 15
Group B_0_1 (V72P10)	18	14 – 24
Group B_0_1	12	9.86 – 16

Geometric Mean Ratios (GMRs) of GMTs After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study Versus Day 1. Primary · Group 3B: 1 month after the last vaccination in parent study and Day 1 (prior to booster dose)

The GMRs of GMTs at Day 1 versus one month after the last dose of rMenB+OMV NZ vaccination in the parent study were calculated. Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713.

H44/76

Group	Value	95% CI
Group 3B (V72_41)	0.026	0.020 – 0.033
Group 3B (V72P10)	0.023	0.018 – 0.029
Group 3B	0.025	0.020 – 0.030

5/99

Group	Value	95% CI
Group 3B (V72_41)	0.13	0.10 – 0.18
Group 3B (V72P10)	0.052	0.039 – 0.068
Group 3B	0.098	0.079 – 0.12

NZ98/254

Group	Value	95% CI
Group 3B (V72_41)	0.12	0.092 – 0.15
Group 3B (V72P10)	0.027	0.021 – 0.036
Group 3B	0.073	0.059 – 0.089

M10713

Group	Value	95% CI
Group 3B (V72_41)	1.26	0.92 – 1.73
Group 3B (V72P10)	0.33	0.25 – 0.43
Group 3B	0.81	0.65 – 1.01

Number of Subjects With Solicited Local and Systemic AEs. Primary · 7 days (including the day of vaccination) after each vaccination

Solicited adverse events are signs and symptoms derived from organized data collection systems, such as Subject Diaries or interview. The percentage and frequencies of subjects reporting solicited local and systemic AEs were tabulated. Threshold for any Erythema, Swelling and Induration: \>= 25 mm Note:Vaccination 2 was performed only on group B\_0\_1 subjects. Threshold for any Erythema, Swelling and Induration: \>= 25 mm

Any

Group	Value	95% CI
Group 3B	263
Group B_0_1	251

Any Local (vaccination 1)

Group	Value	95% CI
Group 3B	258
Group B_0_1	247

Injection site pain (vaccination 1)

Group	Value	95% CI
Group 3B	258
Group B_0_1	247

Erythema (vaccination 1)

Group	Value	95% CI
Group 3B	54
Group B_0_1	18

Swelling (vaccination 1)

Group	Value	95% CI
Group 3B	60
Group B_0_1	34

Induration (vaccination 1)

Group	Value	95% CI
Group 3B	54
Group B_0_1	26

Any systemic (vaccination 1)

Group	Value	95% CI
Group 3B	203
Group B_0_1	163

Fever (≥ 38.0°C) (vaccination 1)

Group	Value	95% CI
Group 3B	16
Group B_0_1	4

Number of Subjects With Any Unsolicited Adverse Events (AEs). Primary · 30 days (including the day of vaccination) after each vaccination.

An unsolicited adverse event is an adverse event that was not solicited using a subject Diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. Note : Vaccination 2 was performed only on group B\_0\_1 subjects.

Any

Group	Value	95% CI
Group 3B	87
Group B_0_1	131

Any unsolicited AEs ( vaccination 1)

Group	Value	95% CI
Group 3B	87
Group B_0_1	96

Any unsolicited AEs (vaccination 2)

Group	Value	95% CI
Group B_0_1	73

Number of Subjects With Any SAEs, AEs Leading to Withdrawal and Medically Attended AEs. Primary · Group 3B: from Day 1 to Day 31 (study termination visit) and Group B_0_1: from Day 1 to Day 61 (study termination visit)

A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to Persistent or significant disability/incapacity.

Any SAEs

Group	Value	95% CI
Group 3B	0
Group B_0_1	1

Any Medically Attended AEs

Group	Value	95% CI
Group 3B	17
Group B_0_1	34

Any AEs leading to premature withdrawal

Group	Value	95% CI
Group 3B	0
Group B_0_1	1

Percentage of Subjects With hSBA ≥1:4 After Booster Dose/First Vaccination of rMenB+OMV NZ. Secondary · Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254.

5/99

Group	Value	95% CI
Group 3B (V72_41)	100	97.1 – 100.0
Group 3B (V72P10)	100	96.4 – 100.0
Group 3B	100	98.4 – 100.0
Group B_0_1 (V72_41)	87	78.2 – 92.7
Group B_0_1 (V72P10)	84	76.7 – 89.7
Group B_0_1	85	79.8 – 89.4

NZ98/254

Group	Value	95% CI
Group 3B (V72_41)	94	89.2 – 97.5
Group 3B (V72P10)	93	87.3 – 97.1
Group 3B	94	90.3 – 96.5
Group B_0_1 (V72_41)	41	31.2 – 50.9
Group B_0_1 (V72P10)	62	53.8 – 70.0
Group B_0_1	53	47.0 – 59.7

Percentage of Subjects With hSBA ≥1:5 After Booster Dose/First Vaccination of rMenB+OMV NZ. Secondary · Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713.

H44/76

Group	Value	95% CI
Group 3B (V72_41)	98	93.9 – 99.56
Group 3B (V72P10)	100	97.1 – 100.0
Group 3B	99	96.8 – 99.77
Group B_0_1 (V72_41)	80	70.8 – 87.0
Group B_0_1 (V72P10)	79	71.1 – 84.8
Group B_0_1	79	73.5 – 83.9

M10713

Group	Value	95% CI
Group 3B (V72_41)	99	96.1 – 99.98
Group 3B (V72P10)	98	94.4 – 99.81
Group 3B	99	96.8 – 99.77
Group B_0_1 (V72_41)	80	70.5 – 86.9
Group B_0_1 (V72P10)	92	86.4 – 95.8
Group B_0_1	87	82.1 – 90.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Solicited AEs were collected until 7 days after vaccinations. Unsolicited AEs were collected 30 days after each vaccination at day 31 (all subjects) and at day 61 (group B_0_1 subjects only).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 3B

Serious: 0/275 (0%)

Deaths: 0/275

Group B_0_1

Serious: 1/255 (0%)

Deaths: 0/255

Serious adverse events (1 terms)

Reaction	System	Group 3B	Group B_0_1
Appendicitis	Infections and infestations	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Group 3B	Group B_0_1
Injectioon site pain	General disorders	—	—
Injection site erythema	General disorders	—	—
Fatigue	General disorders	—	—
Headache	Nervous system disorders	—	—
Injection site induration	General disorders	—	—
Injection site swelling	General disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Pyrexia	General disorders	—	—

Most-reported serious reactions: Appendicitis.

Data from ClinicalTrials.gov NCT02446743 adverse events section.

Sponsor's own description

The purpose/aim of this study is to assess 1) the long-term persistence (4 to 7.5 years after the last dose) of bactericidal activity following primary vaccination with rMenB+OMV NZ in adolescents \[who previously participated in parent studies V72\_41 (NCT0142384) and V72P10 (NCT00661713)\] and 2) the kinetics of immune response following booster vaccination with rMenB+OMV NZ

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine.
   Nolan T, Santolaya ME, de Looze F, Marshall H, et al · · 2019 · cited 34× · PMID 30691980 · DOI 10.1016/j.vaccine.2018.12.059
2. Persistence of the immune response after 4CMenB vaccination, and the response to an additional booster dose in infants, children, adolescents, and young adults.
   Martinón-Torres F, Nolan T, Toneatto D, Banzhoff A. · · 2019 · cited 18× · PMID 31246520 · DOI 10.1080/21645515.2019.1627159
3. Meningococcal B Immunisation in Adults and Potential Broader Immunisation Strategies: A Narrative Review.
   Kassianos G, Barasheed O, Abbing-Karahagopian V, Khalaf M, et al · · 2023 · cited 6× · PMID 37428339 · DOI 10.1007/s40121-023-00836-8
4. Persistence of Bactericidal Activity at 4 Years After 2 Primary Doses of a Recombinant, 4-Component, Meningococcal Serogroup B Vaccine (4CMenB) and Response to a Booster Dose in Adolescents and Young Adults
   Nolan T, Garfield H, Gupta A, Ferguson M, et al · · 2017 · cited 1×
5. 154. Diagnosis and Genotyping of Coxiella burnetii Causing Endocarditis in a Patient With Prosthetic Pulmonary Valve Replacement (PVR) Using Next-Generation Sequencing (NGS) of Plasma
   Kondo M, Dalai S, Westblade L, Venkatasubrahmanyam S, et al · · 2018
6. 153. The Effect of Timing of Tetanus–Diphtheria and Pertussis Vaccine Administration in Pregnancy on The Avidity of Pertussis Antibodies
   Raya B, Giles M, Kollmann T, Sadarangani M. · · 2018
7. 152. Protective Antibody Levels 7.5 Years After Primary Vaccination in Adolescence With a Recombinant, 4-Component, Meningococcal Serogroup B Vaccine (4CMenB) and Response to a Booster Dose in Adolescents and Young Adults: Phase IIIb Clinical Findings
   Nolan T, O’Ryan M, Santolaya M, De Looze F, et al · · 2018
8. 151. Evaluation of Pneumococcal Vaccine Effectiveness Against Invasive Pneumococcal Disease Among US Medicare Beneficiaries ≥65 Years Old
   Pilishvili T, Almendares O, Nanduri S, Warnock R, et al · · 2018