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Nimenrix

Last Updated on eMC 20-Oct-2016 View changes  | Pfizer Limited Contact details

 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

1. Name of the medicinal product

Nimenrix powder and solvent for solution for injection in pre-filled syringe

Nimenrix powder and solvent for solution for injection in ampoule

Meningococcal group A, C, W-135, and Y conjugate vaccine

2. Qualitative and quantitative composition

After reconstitution, 1 dose (0.5 ml) contains:

Neisseria meningitidis group A polysaccharide1

5 micrograms

Neisseria meningitidis group C polysaccharide1

5 micrograms

Neisseria meningitidis group W-135 polysaccharide1

5 micrograms

Neisseria meningitidis group Y polysaccharide1

5 micrograms

1conjugated to tetanus toxoid carrier protein

44 micrograms

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Powder and solvent for solution for injection.

The powder or cake is white.

The solvent is clear and colourless.

4. Clinical particulars
4.1 Therapeutic indications

Nimenrix is indicated for active immunisation of individuals from the age of 12 months and above against invasive meningococcal diseases caused by Neisseria meningitidis group A, C, W-135, and Y.

4.2 Posology and method of administration

Posology

Nimenrix should be used in accordance with available official recommendations.

A single 0.5 ml dose of the reconstituted vaccine is used for immunisation.

Nimenrix may be given as a booster dose to individuals who have previously received primary vaccination with Nimenrix or other conjugated or plain polysaccharide meningococcal vaccines (see sections 4.4 and 5.1).

A second dose of Nimenrix may be considered appropriate for some individuals (see section 4.4).

Paediatric population

The safety and efficacy of Nimenrix in children under 12 months of age has not yet been established. No data are available.

Method of administration

Immunisation should be carried out by intramuscular injection only, preferably into the deltoid muscle.

In children 12 to 23 months of age, the vaccine may also be administered in the anterolateral part of the thigh (see sections 4.4 and 4.5).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Nimenrix should under no circumstances be administered intravascularly, intradermally or subcutaneously.

It is good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable effects) and a clinical examination.

Appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Intercurrent illness

Vaccination with Nimenrix should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

Syncope

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Thrombocytopenia and coagulation disorders

Nimenrix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.

Immunodeficiency

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited.

Safety and immunogenicity have not been assessed in patients with increased susceptibility to meningococcal infection due to conditions such as terminal complement deficiencies and anatomic or functional asplenia. In these individuals, an adequate immune response may not be elicited.

Protection against meningococcal disease

Nimenrix will only confer protection against Neisseria meningitidis group A, C, W-135 and Y. The vaccine will not protect against any other Neisseria meningitidis groups.

A protective immune response may not be elicited in all vaccinees.

Effect of prior vaccination with plain polysaccharide meningococcal vaccine

Subjects previously vaccinated with a plain polysaccharide meningococcal vaccine and vaccinated with Nimenrix 30 to 42 months later had lower Geometric Mean Titres (GMTs) measured with rabbit complement serum bactericidal assay (rSBA) than subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years (see section 5.1). The clinical relevance of this observation is unknown.

Effect of pre-vaccination antibody to tetanus toxoid

The safety and immunogenicity of Nimenrix was evaluated when sequentially administered or co-administered with a DTaP-HBV-IPV/Hib vaccine in the second year of life. The administration of Nimenrix one month after the DTaP-HBV-IPV/Hib vaccine resulted in lower rSBA GMTs against groups A, C and W-135 compared with co-administration (see section 4.5). The clinical relevance of this observation is unknown.

Immune responses in toddlers aged 12-14 months

Toddlers aged 12-14 months had similar rSBA responses to groups A, C, W-135 and Y at one month after one dose of Nimenrix or at one month after two doses of Nimenrix given two months apart.

A single dose was associated with lower human complement serum bactericidal assay (hSBA) titres to groups W-135 and Y compared with two doses given two months apart. Similar responses to groups A and C were observed after one or two doses (see section 5.1). The clinical relevance of the findings is unknown. If a toddler is expected to be at particular risk of invasive meningococcal disease due to exposure to groups W-135 and Y, consideration may be given to administering a second dose of Nimenrix after an interval of 2 months. Regarding waning of antibody against group A or group C after a first dose of Nimenrix in children aged 12-23 months, see under Persistence of serum bactericidal antibody titres.

Persistence of serum bactericidal antibody titres

Following administration of Nimenrix there is a waning of serum bactericidal antibody titres against group A when using human complement in the assay (hSBA) (see section 5.1). The clinical relevance of the waning of hSBA antibody titres against group A is unknown. However, if an individual is expected to be at particular risk of exposure to group A and received a dose of Nimenrix more than approximately one year previously, consideration may be given to administering a booster dose.

A decline in antibody titres over time has been observed for groups A, C, W-135 and Y. The clinical relevance of the waning antibody titres is unknown. A booster dose might be considered in individuals vaccinated at toddler age remaining at high risk of exposure to meningococcal disease caused by groups A, C, W-135 or Y (see section 5.1).

Effect of Nimenrix on anti-tetanus antibody concentrations

Although an increase of the anti-tetanus toxoid (TT) antibody concentrations was observed following vaccination with Nimenrix, Nimenrix does not substitute for tetanus immunisation.

Giving Nimenrix with or one month before a TT-containing vaccine in the second year of life does not impair the response to TT or significantly affect safety. No data are available beyond the age of 2 years.

4.5 Interaction with other medicinal products and other forms of interaction

Nimenrix can be given concomitantly with any of the following vaccines: hepatitis A (HAV) and hepatitis B (HBV) vaccines, measles - mumps - rubella (MMR) vaccine, measles - mumps - rubella - varicella (MMRV) vaccine, 10-valent pneumococcal conjugate vaccine or unadjuvanted seasonal influenza vaccine.

Nimenrix can also be given concomitantly with combined diphtheria - tetanus - acellular pertussis vaccines, including combination DTaP vaccines with hepatitis B, inactivated polio or Haemophilus influenzae type b, such as DTaP-HBV-IPV/Hib vaccine and 13-valent pneumococcal conjugate vaccine in the second year of life.

Whenever possible, Nimenrix and a TT containing vaccine, such as DTaP-HBV-IPV/Hib vaccine, should be co-administered or Nimenrix should be administered at least one month before the TT containing vaccine. The sequential administration of Nimenrix one month after a DTaP-HBV-IPV/Hib vaccine resulted in lower GMTs for antibody against groups A, C and W-135. Clinical relevance of this observation is unknown, since at least 99.4% of subjects (N=178) had rSBA titres ≥ 8 for each group (A, C, W-135, Y) (see section 4.4).

One month after co-administration with a 10-valent pneumococcal conjugate vaccine, lower Geometric Mean antibody Concentrations (GMCs) and opsonophagocytic assay (OPA) antibody GMTs were observed for one pneumococcal serotype (18C conjugated to tetanus toxoid carrier protein). Clinical relevance of this observation is unknown. There was no impact of co-administration on the other nine pneumococcal serotypes.

If Nimenrix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

It may be expected that in patients receiving immunosuppressive treatment, an adequate response may not be elicited.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is limited experience with use of Nimenrix in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3).

Nimenrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.

Breast-feeding

It is unknown whether Nimenrix is excreted in human milk.

Nimenrix should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

4.7 Effects on ability to drive and use machines

No studies on the effects of Nimenrix on the ability to drive and use machines have been performed.

However, some of the effects mentioned under section 4.8 “Undesirable effects” may affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

The safety profile presented below is based on a pooled analysis on 9,621 subjects who have been vaccinated with one dose of Nimenrix in clinical studies. This pooled analysis includes data for 3,079 toddlers (12 months to 23 months), 909 children between 2 and 5 years of age, 990 children between 6 and 10 years of age, 2,317 adolescents (11 to 17 years) and 2,326 adults (18 to 55 years).

In all age groups the most frequently reported local adverse reactions after vaccination were pain (24.1% to 41.3%), redness (15.5% to 35.6%), and swelling (11.3% to 19.9%).

In the 12-23 months and 2-5 years age groups, the most frequently reported general adverse reactions after vaccination were irritability (44.0% and 9.2% respectively), drowsiness (34.1% and 10.8% respectively), loss of appetite (26.6% and 8.2% respectively), and fever (17.1% and 8.1% respectively).

In the 12-14 months age group who received 2 doses of Nimenrix given 2 months apart, the first and second doses were associated with similar local and systemic reactogenicity.

In the 6-10, 11-17, and ≥ 18 years age groups, the most frequently reported general adverse reactions after vaccination were headache (15.7%, 22.0% and 21.5% respectively), fatigue (15.6%, 21.9% and 20.7% respectively), gastrointestinal symptoms (9.3%, 9.4% and 8.3% respectively) and fever (8.0%, 5.3%, and 4.9% respectively).

The local and general adverse reaction profile of a booster dose of Nimenrix after primary vaccination with Nimenrix or other conjugated or plain polysaccharide meningococcal vaccines, was similar to the local and general adverse reaction profile observed after primary vaccination with Nimenrix, except gastrointestinal symptoms (including diarrhoea, vomiting, and nausea) which were very common.

In a separate study a single dose of Nimenrix was administered to 274 individuals aged 56 years and older. All adverse reactions reported in this study were already observed in younger age groups.

Tabulated list of adverse reactions

Adverse reactions reported are listed according to the following frequency categories:

Very common:

(≥ 1/10)

Common:

(≥1/100 to <1/10)

Uncommon:

(≥1/1,000 to <1/100)

Rare:

(≥1/10,000 to <1/1,000)

Very rare:

(<1/10,000)

System Organ Class

Frequency

Adverse reactions

Clinical trials

Metabolism and nutrition disorders

Very common

Appetite lost

Psychiatric disorders

Very common

Irritability

Uncommon

Insomnia, crying

Nervous system disorders

Very common

Drowsiness, headache

Uncommon

Hypoaesthesia, dizziness

Gastrointestinal disorders

Common

Gastrointestinal symptoms (including diarrhoea, vomiting and nausea)

Skin and subcutaneous tissue disorders

Uncommon

Pruritus, rash

Musculoskeletal and connective tissue disorders

Uncommon

Myalgia, pain in extremity

General disorders and administration site conditions

Very common

Fever, swelling, pain and redness at injection site, fatigue

Common

Injection site haematoma

Uncommon

Malaise, injection site reaction (including induration, pruritus, warmth, anaesthesia)

Post-marketing experience

General disorders and administration site conditions

Rare

Extensive limb swelling at the injection site, frequently associated with erythema, sometimes involving the adjacent joint or swelling of the entire injected limb

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via

United Kingdom

Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

No case of overdose has been reported.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, meningococcal vaccines, ATC code: J07AH08

Mechanism of action

Anti-capsular meningococcal antibodies protect against meningococcal diseases via complement mediated bactericidal activity. Nimenrix induces the production of bactericidal antibodies against capsular polysaccharides of group A, C, W-135 and Y when measured by assays using either rabbit complement (rSBA) or human complement (hSBA).

Pharmacodynamic effects

Immunogenicity

The immunogenicity of one dose of Nimenrix has been evaluated in more than 8,000 subjects aged ≥ 12 months.

Vaccine efficacy was inferred from the demonstration of immunologic non inferiority (based mainly on comparing proportions with rSBA titres at least 8) to licensed meningococcal vaccines. Immunogenicity was measured by using rSBA or hSBA which are biomarkers for protective efficacy against meningococcal groups A, C, W-135 and Y.

Persistence of immune response

The persistence of the immune response elicited by Nimenrix was evaluated up to 60 months after vaccination in subjects aged 12 months to 55 years.

The antibodies elicited by Nimenrix were similar or higher than those induced by licensed meningococcal vaccines (i.e., MenC-CRM vaccine in subjects aged 12-23 months and ACWY-PS vaccine in subjects older than 2 years of age).

Booster response

In clinical trials, the use of Nimenrix as a booster following primary vaccination with Nimenrix or other meningococcal vaccines (quadrivalent meningococcal A, C, W, and Y-DT conjugate vaccine or monovalent group C conjugate vaccines) was evaluated.

Toddlers

Immunogenicity in toddlers aged 12-23 months

In clinical studies MenACWY-TT-039 and MenACWY-TT-040 a single dose of Nimenrix elicited rSBA responses against the four meningococcal groups, with a response against group C that was comparable to the one elicited by the licensed MenC-CRM vaccine in terms of percentages with rSBA titres ≥8 (Table 1).

Table 1: Bactericidal antibody responses (rSBA*) in toddlers aged 12-23 months

Group

Response to

Study MenACWY-TT-039(1)

Study MenACWY-TT-040(2)

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

Nimenrix

354

99.7%

(98.4; 100)

2205

(2008; 2422)

183

98.4%

(95.3; 99.7)

3170

(2577; 3899)

C

Nimenrix

354

99.7%

(98.4; 100)

478

(437; 522)

183

97.3%

(93.7; 99.1)

829

(672; 1021)

MenC-CRM vaccine

121

97.5%

(92.9; 99.5)

212

(170; 265)

114

98.2%

(93.8; 99.8)

691

(521; 918)

W-135

Nimenrix

354

100%

(99.0; 100)

2682

(2453; 2932)

186

98.4%

(95.4; 99.7)

4022

(3269; 4949)

Y

Nimenrix

354

100%

(99.0; 100)

2729

(2473; 3013)

185

97.3%

(93.8; 99.1)

3168

(2522; 3979)

The analysis of immunogenicity was conducted on the ATP cohorts for immunogenicity.

(1) blood sampling performed 42 to 56 days post vaccination

(2) blood sampling performed 30 to 42 days post vaccination

* tested at GSK laboratories

In study MenACWY-TT-039, serum bactericidal activity was also measured using human serum as the source of complement (hSBA) as a secondary endpoint (Table 2).

Table 2: Bactericidal antibody responses (hSBA*) in toddlers aged 12-23 months

Group

Response to

N

Study MenACWY-TT-039(1)*

≥8

(95% CI)

GMT

(95%CI)

A

Nimenrix

338

77.2%

(72.4; 81.6)

19.0

(16.4; 22.1)

C

Nimenrix

341

98.5%

(96.6; 99.5)

196

(175; 219)

MenC-CRM vaccine

116

81.9%

(73.7; 88.4)

40.3

(29.5; 55.1)

W-135

Nimenrix

336

87.5%

(83.5 ; 90.8)

48.9

(41.2; 58.0)

Y

Nimenrix

329

79.3%

(74.5; 83.6)

30.9

(25.8; 37.1)

The analysis of immunogenicity was conducted on ATP cohort for immunogenicity.

(1) blood sampling performed 42 to 56 days post vaccination

* tested at GSK laboratories

In Study Men ACWY-TT-104 the immune response following one or two doses of Nimenrix given 2 months apart was evaluated one month after the last vaccination. Nimenrix elicited bactericidal responses against all four groups that were similar in terms of % with rSBA titre ≥8 and GMT after one or two doses (Table 3).

Table 3: Bactericidal antibody responses (rSBA)* in toddlers aged 12-14 months

Group

Response to

Timing

Study MenACWY-TT-104 (1)

N

≥8

(95%CI)

GMT

(95% CI)

A

Nimenrix

1 dose

Post dose 1

180

97.8%

(94.4, 99.4)

1437

(1118.3, 1846.6)

Nimenrix

2 doses

Post dose 1

158

96.8%

(92.8, 99.0)

1275.2

(970.5, 1675.4)

Post dose 2

150

98.0%

(94.3, 99.6)

1176.3

(921.8, 1501)

C

Nimenrix

1 dose

Post dose 1

179

95.0%

(90.7, 97.7)

452.3

(345.6, 591.9)

Nimenrix

2 doses

Post dose 1

157

95.5%

(91.0, 98.2)

369.3

(280.9, 485.5)

Post dose 2

150

98.7%

(95.3, 99.8)

639.1

(521.8, 782.9)

W-135

Nimenrix

1 dose

Post dose 1

180

95.0%

(90.8, 97.7)

2120.2

(1601.0, 2807.8)

Nimenrix

2 doses

Post dose 1

158

94.9%

(90.3, 97.8)

2030.1

(1510.7, 2728.2)

Post dose 2

150

100%

(97.6, 100)

3533

(2914.5, 4282.7)

Y

Nimenrix

1 dose

Post dose 1

180

92.8%

(88.0, 96.1)

951.8

(705.0, 1284.9)

Nimenrix

2 doses

Post dose 1

157

93.6%

(88.6, 96.9)

933.3

(692.3, 1258.3)

Post dose 2

150

99.3%

(96.3, 100)

1133.6

(944.5, 1360.5)

The analysis of immunogenicity was conducted on the according-to-protocol (ATP) cohort for immunogenicity

(1) blood sampling performed 21-48 days post vaccination

*tested at Public Health England laboratories

In study MenACWY-TT-104, serum bactericidal activity was also measured using hSBA as a secondary endpoint. Nimenrix elicited bactericidal responses against groups W-135 and Y that were higher in terms of % with hSBA titre ≥8 when two doses were given compared with one. Similar responses in terms of % with hSBA titre ≥8 were observed with groups A and C (Table 4).

Table 4: Bactericidal antibody responses (hSBA)* in toddlers aged 12-14 months

Group

Response to

Timing

Study MenACWY-TT-104 (1)

N

≥8

(95%CI)

GMT

(95% CI)

A

Nimenrix

1 dose

Post dose 1

74

95.9%

(88.6, 99.2)

118.0

(86.8, 160.5)

Nimenrix

2 doses

Post dose 1

66

97.0%

(89.5, 99.6)

132.9

(98.1, 180.1)

Post dose 2

66

97.0%

(89.5, 99.6)

170.5

(126.2, 230.2)

C

Nimenrix

1 dose

Post dose 1

78

98.7%

(93.1, 100)

151.9

(104.8, 220.4)

Nimenrix

2 doses

Post dose 1

70

95.7%

(88.0, 99.1)

161

(110, 236)

Post dose 2

69

100%

(94.8, 100)

1753.3

(1277.7, 2404.2)

W-135

Nimenrix

1 dose

Post dose 1

72

62.5%

(50.3, 73.6)

27.5

(16.1, 46.8)

Nimenrix

2 doses

Post dose 1

61

68.9%

(55.7, 80.1)

26.2

(16.0, 43.0)

Post dose 2

70

97.1%

(90.1, 99.7)

756.8

(550.1, 1041.3)

Y

Nimenrix

1 dose

Post dose 1

71

67.6%

(55.5, 78.20)

41.2

(23.7, 71.5)

Nimenrix

2 doses

Post dose 1

56

64.3%

(50.4, 76.6)

31.9

(17.6, 57.9)

Post dose 2

64

95.3%

(86.9, 99.0)

513.0

(339.4, 775.4)

The analysis of immunogenicity was conducted on the according-to-protocol (ATP) cohort for immunogenicity

(1) blood sampling performed 21-48 days post vaccination

*tested at GSK laboratories

Persistence of immune response in toddlers aged 12-23 months

In children primed at toddler age, the persistence of the immune response was evaluated by rSBA and hSBA in studies MenACWY-TT-048 and MenACWY-TT-032, up to 4 years after priming in study MenACWY-TT-039 (Table 5) and up to 5 years after priming in study MenACWY-TT-027 (Table 6) respectively.

Table 5: 4 years persistence data in toddlers aged 12-23 months at vaccination (study MenACWY-TT-048)

Group

Response to

Time-point

(year)

rSBA*

hSBA**

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A***

Nimenrix

3

262

59.9%

(53.7; 65.9)

19.3

(15.7; 23.6)

251

35.9%

(29.9; 42.1)

5.8

(4.8; 7.0)

4

224

74.1%

(67.9; 79.7)

107

(77.6; 148)

198

28.8%

(22.6; 35.6)

4.9

(4.0; 6.0)

C

Nimenrix

3

262

35.9%

(30.1; 42.0)

9.8

(8.1; 11.7)

253

78.3%

(72.7; 83.2)

37.8

(29.4; 48.6)

4

225

40.4%

(34.0; 47.2)

12.3

(9.8; 15.3)

209

73.2%

(66.7; 79.1)

32.0

(23.8; 43.0)

MenC-CRM vaccine

3

46

13.0%

(4.9; 26.3)

5.7

(4.2; 7.7)

31

41.9%

(24.5; 60.9)

6.2

(3.7; 10.3)

4

45

35.6%

(21.9; 51.2)

13.5

(7.4; 24.5)

32

46.9%

(29.1; 65.3)

11.3

(4.9; 25.6)

W-135

Nimenrix

3

261

49.8%

(43.6; 56.0)

24.9

(19.2; 32.4)

254

82.3%

(77.0; 86.8)

52.0

(41.4; 65.2)

4

225

49.3%

(42.6; 56.1)

30.5

(22.4; 41.5)

165

80.6%

(73.7; 86.3)

47.1

(35.7; 62.2)

Y

Nimenrix

3

262

53.8%

(47.6; 60.0)

22.3

(17.6; 28.4)

250

72.0%

(66.0; 77.5)

33.2

(25.9; 42.5)

4

225

58.2%

(51.5; 64.7)

36.2

(27.1; 48.4)

130

65.4%

(56.5; 73.5)

29.8

(20.2; 44.1)

The analysis of immunogenicity was conducted on ATP cohort for persistence adapted for each time-point.

*rSBA testing performed at Public Health England (PHE) laboratories in UK

** tested at GSK laboratories

*** Similar to the increase in rSBA group A GMTs, an increase in group A IgG Geometric Mean Concentrations was observed between Y3 and Y4 time-points

Table 6: 5 years persistence data in toddlers aged 12-23 months at vaccination (study MenACWY-TT-032)

Group

Response to

Time-point

(year)

rSBA*

hSBA**

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

Nimenrix

4

45

64.4%

(48.8; 78.1)

35.1

(19.4; 63.4)

44

52.3%

(36.7; 67.5)

8.8

(5.4; 14.2)

5

49

73.5%

(58.9; 85.1)

37.4

(22.1; 63.2)

45

35.6%

(21.9: 51.2)

5.2

(3.4; 7.8)

C

Nimenrix

4

45

97.8%

(88.2; 99.9)

110

(62.7; 192)

45

97.8%

(88.2; 99.9)

370

(214; 640)

5

49

77.6%

(63.4; 88.2)

48.9

(28.5; 84.0)

48

91.7%

(80.0; 97.7)

216

(124; 379)

MenC-CRM

vaccine

4

10

80.0%

(44.4; 97.5)

137

(22.6; 832)

10

70.0%

(34.8; 93.3)

91.9

(9.8; 859)

5

11

63.6%

(30.8; 89.1)

26.5

(6.5; 107)

11

90.9%

(58.7; 99.8)

109

(21.2; 557)

W-135

Nimenrix

4

45

60.0%

(44.3; 74.3)

50.8

(24.0; 108)

45

84.4%

(70.5; 93.5)

76.9

(44.0; 134)

5

49

34.7%

(21.7; 49.6)

18.2

(9.3; 35.3)

46

82.6%

(68.6; 92.2)

59.7

(35.1; 101)

Y

Nimenrix

4

45

62.2%

(46.5; 76.2)

44.9

(22.6; 89.3)

41

87.8%

(73.8; 95.9)

74.6

(44.5; 125)

5

49

42.9%

(28.8; 57.8)

20.6

(10.9; 39.2)

45

80.0%

(65.4; 90.4)

70.6

(38.7; 129)

Persistence of immunogenicity was analysed using the year 5 ATP cohort. A selection bias mainly due to revaccination of subjects with group C rSBA titres <8 and their exclusion from subsequent time-point(s) may have led to an overestimation of the titres.

*rSBA testing performed at PHE laboratories in UK

** tested at GSK laboratories

Immune memory

In study MenACWY-TT-014, the induction of immune memory was assessed one month after the administration of a fifth of the dose of ACWY-PS vaccine (10 µg of each polysaccharide) to children in the third year of life previously primed in the study MenACWY-TT-013 with Nimenrix or a licensed Men C-CRM vaccine at the age of 12 to 14 months.

One month after the challenge dose, the GMTs elicited by the subjects primed with Nimenrix increased by 6.5 to 8 fold for groups A, C, W-135 and Y and indicate that Nimenrix induces immune memory to groups A, W-135, and Y. The post-challenge rSBA-group C GMT was similar in both study groups, indicating that Nimenrix induces an analogous immune memory to group C as the licensed MenC-CRM vaccine (Table 7).

Table 7: Immune response (rSBA*) 1 month after a challenge vaccination in subjects primed with Nimenrix or a MenC-CRM vaccine at the age of 12 to 14 months

Group

Response to

Pre-challenge

Post-challenge

N

GMT

(95%CI)

N

GMT

(95%CI)

A

Nimenrix

32

544

(325; 911)

25

3322

(2294; 4810)

C

Nimenrix

31

174

(105; 289)

32

5966

(4128; 8621)

MenC-CRM vaccine

28

34.4

(15.8; 75.3)

30

5265

(3437; 8065)

W-135

Nimenrix

32

644

(394; 1052)

32

11058

(8587; 14240)

Y

Nimenrix

32

440

(274; 706)

32

5737

(4216; 7806)

The analysis of immunogenicity was conducted on ATP cohort for immunogenicity.

* tested at GSK laboratories

Children

Immunogenicity in children aged 2-10 years

In two comparative studies conducted in subjects aged 2-10 years, one group of subjects received a dose of Nimenrix and a second group a dose of either a licensed MenC-CRM vaccine (study MenACWY-TT-081) or the licensed GlaxoSmithKline Biologicals' plain polysaccharide meningococcal group A, C, W-135, Y (ACWY-PS) vaccine (study MenACWY-TT-038 ) as comparator.

In MenACWY-TT-038, Nimenrix was demonstrated to be non-inferior to the licensed ACWY-PS vaccine in terms of vaccine response to the four groups (A, C, W-135 and Y) (See Table 8).

The vaccine response was defined as the proportion of subjects with:

• rSBA titres ≥ 32 for initially seronegative subjects (i.e, pre-vaccination rSBA titre < 8)

• at least a 4-fold increase in rSBA titres from pre- to post-vaccination for initially seropositive subjects (i.e., pre-vaccination rSBA titre ≥ 8)

In MenACWY-TT-081, Nimenrix was demonstrated to be non-inferior to another licensed MenC-CRM vaccine in terms of vaccine response to group C [94.8% (95% CI: 91.4; 97.1) and 95.7% (95% CI: 89.2; 98.8) respectively], GMTs were lower for the Nimenrix group [2795 (95% CI: 2393; 3263)] versus the MenC-CRM vaccine [5292 (95% CI: 3815; 7340)].

Table 8: Bactericidal antibody responses (rSBA*) to Nimenrix and the ACWY-PS vaccine in children aged 2-10 years 1 month after vaccination (study MenACWY-TT-038)

Group

Nimenrix

ACWY-PS vaccine

N

VR

(95%CI)

GMT

(95%CI)

N

VR

(95%CI)

GMT

(95%CI)

A

594

89.1%

(86.3; 91.5)

6343

(5998; 6708)

192

64.6%

(57.4; 71.3)

2283

(2023; 2577)

C

691

96.1%

(94.4; 97.4)

4813

(4342; 5335)

234

89.7%

(85.1; 93.3)

1317

(1043; 1663)

W-135

691

97.4%

(95.9; 98.4)

11543

(10873; 12255)

236

82.6%

(77.2; 87.2)

2158

(1815; 2565)

Y

723

92.7%

(90.5; 94.5)

10825

(10233; 11452)

240

68.8%

(62.5; 74.6)

2613

(2237; 3052)

The analysis of immunogenicity was conducted on ATP cohort for immunogenicity.

VR: vaccine response

* tested at GSK laboratories

Persistence of immune response in children aged 2-10 years

Persistence of immune response in children aged 2-10 years

In study MenACWY-TT-088, the persistence of the immune response was evaluated by rSBA and hSBA up to 44 months after vaccination in children 2-10 years of age primed in study MenACWY-TT-081 (Table 9).

Table 9: 44 months persistence data in children 2-10 years of age at vaccination

Group

Response to

Time-point

(months)

rSBA*

hSBA**

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

Nimenrix

32

193

86.5%

(80.9; 91.0)

196

(144; 267)

90

25.6%

(16.9; 35.8)

4.6

(3.3; 6.3)

44

189

85.7%

(79.9; 90.4)

307

(224; 423)

89

25.8%

(17.1; 36.2)

4.8

(3.4; 6.7)

C

Nimenrix

32

192

64.6%

(57.4; 71.3)

34.8

(26.0; 46.4)

90

95.6%

(89.0; 98.8)

75.9

(53.4; 108)

44

189

37.0%

(30.1; 44.3)

14.5

(10.9; 19.2)

82

76.8%

(66.2; 85.4)

36.4

(23.1; 57.2)

MenC-CRM vaccine

32

69

76.8%

(65.1; 86.1)

86.5

(47.3; 158)

33

90.9%

(75.7; 98.1)

82.2

(34.6; 196)

44

66

45.5%

(33.1; 58.2)

31.0

(16.6; 58.0)

31

64.5%

(45.4; 80.8)

38.8

(13.3; 113)

W-135

Nimenrix

32

193

77.2%

(70.6; 82.9)

214

(149; 307)

86

84.9%

(75.5; 91.7)

69.9

(48.2; 101)

44

189

68.3%

(61.1; 74.8)

103

(72.5; 148)

87

80.5%

(70.6; 88.2)

64.3

(42.7; 96.8)

Y

Nimenrix

32

193

81.3%

(75.1; 86.6)

227

(165; 314)

91

81.3%

(71.8; 88.7)

79.2

(52.5; 119)

44

189

62.4%

(55.1; 69.4)

78.9

(54.6; 114)

76

82.9%

(72.5; 90.6)

127

(78.0; 206)

The analysis of immunogenicity was conducted on ATP cohort for persistence adapted for each time-point.

*rSBA testing performed at PHE laboratories in UK

** tested at GSK laboratories

Persistence of immune response in children aged 6-10 years

In study MenACWY-TT-028, the persistence of the immune response was evaluated by hSBA 1 year after vaccination in children 6-10 years of age primed in study MenACWY-TT-027 (Table 10) (see section 4.4).

Table 10: 1 month post-vaccination and 1 year persistence data (hSBA*) in children 6-10 years of age

Group

Response to

1 month post-vaccination

1 year persistence

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

Nimenrix

105

80.0 %

(71.1; 87.2)

53.4

(37.3; 76.2)

104

16.3%

(9.8; 24.9)

3.5

(2.7; 4.4)

ACWY-PS

35

25.7%

(12.5;43.3)

4.1

(2.6;6.5)

35

5.7%

(0.7;19.2)

2.5

(1.9;3.3)

C

Nimenrix

101

89.1%

(81.3;94.4)

156

(99.3;244)

105

95.2%

(89.2;98.4)

129

(95.4;176)

ACWY-PS

38

39.5%

(24.0;56.6)

13.1

(5.4;32.0)

31

32.3%

(16.7;51.4)

7.7

(3.5;17.3)

W-135

Nimenrix

103

95.1%

(89.0;98.4)

133

(99.9;178)

103

100%

(96.5;100)

257

(218;302)

ACWY-PS

35

34.3%

(19.1;52.2)

5.8

(3.3;9.9)

31

12.9%

(3.6;29.8)

3.4

(2.0;5.8)

Y

Nimenrix

89

83.1%

(73.7;90.2)

95.1

(62.4;145)

106

99.1%

(94.9;100)

265

(213;330)

ACWY-PS

32

43.8%

(26.4;62.3)

12.5

(5.6;27.7)

36

33.3%

(18.6;51.0)

9.3

(4.3;19.9)

The analysis of immunogenicity was conducted on ATP cohort for persistence.

* tested at GSK laboratories

Adolescents and Adults

Immunogenicity in adolescents aged 11-17 years and adults aged ≥ 18 years

In two clinical studies, conducted in adolescents 11-17 years of age (study MenACWY-TT-036) and in adults 18-55 years of age (study MenACWY-TT-035), either one dose of Nimenrix or one dose of the ACWY-PS vaccine were administered.

In both adolescents and adults, Nimenrix was demonstrated to be immunologically non-inferior to the ACWY-PS vaccine in terms of vaccine response as defined above (Table 11). The response to the four meningococcal groups elicited by Nimenrix was either similar or higher than the one elicited by the ACWY-PS vaccine.

Table 11: Bactericidal antibody responses (rSBA*) to Nimenrix and the ACWY-PS vaccine in adolescents aged 11-17 years and adults aged ≥ 18 years 1 month after vaccination

Study

(Age range)

Group

Nimenrix

ACWY-PS vaccine

N

VR

(95%CI)

GMT

(95%CI)

N

VR

(95%CI)

GMT

(95%CI)

Study MenACWY-TT-036

(11-17 years)

A

553

85.4%

(82.1; 88.2)

5928

(5557; 6324)

191

77.5%

(70.9; 83.2)

2947

(2612; 3326)

C

642

97.4%

(95.8; 98.5)

13110

(11939; 14395)

211

96.7%

(93.3; 98.7)

8222

(6807; 9930)

W-135

639

96.4%

(94.6; 97.7)

8247

(7639; 8903)

216

87.5%

(82.3; 91.6)

2633

(2299; 3014)

Y

657

93.8%

(91.6; 95.5)

14086

(13168; 15069)

219

78.5%

(72.5; 83.8)

5066

(4463; 5751)

Study MenACWY-TT-035

(18-55 years)

A

743

80.1%

(77.0; 82.9)

3625

(3372; 3897)

252

69.8%

(63.8; 75.4)

2127

(1909; 2370)

C

849

91.5%

(89.4; 93.3)

8866

(8011; 9812)

288

92.0%

(88.3; 94.9)

7371

(6297; 8628)

W-135

860

90.2%

(88.1; 92.1)

5136

(4699; 5614)

283

85.5%

(80.9; 89.4)

2461

(2081; 2911)

Y

862

87.0%

(84.6; 89.2)

7711

(7100; 8374)

288

78.8%

(73.6; 83.4)

4314

(3782; 4921)

The analysis of immunogenicity was conducted on ATP cohorts for immunogenicity.

VR: vaccine response

* tested at GSK laboratories

In a separate study (MenACWY-TT-085) a single dose of Nimenrix was administered to 194 Lebanese adults 56 years of age and older (including 133 aged 56-65 years and 61 aged > 65 years). The percentage of subjects with rSBA titres (measured at GSK's laboratories) ≥ 128 before vaccination ranged from 45% (group C) to 62% (group Y). Overall, at one month post-vaccination the percentage of vaccinees with rSBA titres ≥ 128 ranged from 93% (group C) to 97% (group Y). In the subgroup aged > 65 years the percentage of vaccinees with rSBA titres ≥ 128 at one month post-vaccination ranged from 90% (group A) to 97% (group Y).

Persistence of immune response in adolescents aged 11-17 years of age

In study MenACWY-TT-043, the persistence of the immune response was evaluated 5 years after vaccination in adolescents primed in study MenACWY-TT-036 (Table 12). See table 11 for primary results in this study.

Table 12: 5 years persistence data (rSBA*) in adolescents aged 11-17 years at vaccination

Group

Time-point

(Years)

Nimenrix

ACWY-PS vaccine

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

3

449

92.9%

(90.1; 95.1)

448

(381; 527)

150

82.7%

(75.6; 88.4)

206

(147; 288)

5

236

97.5%

(94.5; 99.1)

644

(531; 781)

86

93.0%

(85.4; 97.4)

296

(202; 433)

C

3

449

91.1%

(88.1; 93.6)

371

(309; 446)

150

86.0%

(79.4; 91.1)

390

(262; 580)

5

236

88.6%

(83.8; 92.3)

249

(194; 318)

85

87.1%

(78.0; 93.4)

366

(224; 599)

W-135

3

449

82.0%

(78.1; 85.4)

338

(268; 426)

150

30.0%

(22.8; 38.0)

16.0

(10.9; 23.6)

5

236

86.0%

(80.9; 90.2)

437

(324; 588)

86

34.9%

(24.9; 45.9)

19.7

(11.8; 32.9)

Y

3

449

93.1%

(90.3; 95.3)

740

(620; 884)

150

58.0%

(49.7; 66.0)

69.6

(44.6; 109)

5

236

96.6%

(93.4; 98.5)

1000

(824; 1214)

86

66.3%

(55.3; 76.1)

125

(71.2; 219)

The analysis of immunogenicity was conducted on ATP cohort for persistence adapted for each time-point.

*rSBA testing performed at PHE laboratories in UK.

Persistence of immune response in adolescents and adults aged 11-25 years

In study MenACWY-TT-059, the persistence of the immune response was evaluated by hSBA 1 and 5 years after vaccination in adolescents and adults 11-25 years of age primed in study MenACWY-TT-052 (Table 13) (see section 4.4).

Table 13: 1 month post-vaccination and 5 years persistence data (hSBA*) in adolescents and adults 11-25 years of age

Group

Response to

Time-point

N

≥8 (95%CI)

GMT (95%CI)

A

Nimenrix

Month 1

356

82.0% (77.6; 85.9)

58.7 (48.6; 70.9)

Year 1

350

29.1% (24.4; 34.2)

5.4 (4.5; 6.4)

Year 5

141

48.9% (40.4; 57.5)

8.9 (6.8; 11.8)

C

Nimenrix

Month 1

359

96.1% (93.5; 97.9)

532 (424; 668)

Year 1

336

94.9% (92.0; 97.0)

172 (142; 207)

Year 5

140

92.9% (87.3; 96.5)

94.6 (65.9; 136)

W-135

Nimenrix

Month 1

334

91.0% (87.4; 93.9)

117 (96.8; 141)

Year 1

327

98.5% (96.5; 99.5)

197 (173; 225)

Year 5

138

87.0% (80.2; 92.1)

103 (76.3; 140)

Y

Nimenrix

Month 1

364

95.1% (92.3; 97.0)

246 (208; 291)

Year 1

356

97.8% (95.6; 99.0)

272 (237; 311)

Year 5

142

94.4% (89.2; 97.5)

225 (174; 290)

The analysis of immunogenicity was conducted on ATP cohort for persistence adapted for each time-point.

* tested at GSK laboratories

Booster response for subjects previously vaccinated with a conjugate meningococcal vaccine against Neisseria meningitidis

Nimenrix booster vaccination after priming in toddlers, children, adolescents and adults: For subjects primed with Nimenrix aged 1 year and above and boosted with Nimenrix 4 or 5 years later, more than 99.0% of all subjects achieved post-booster SBA titres ≥ 1:8 for both assays (studies MenACWY-TT-062, 048, 059, 088). One month after the booster vaccination, the GMTs elicited were significantly higher than those elicited by age matched naïve control groups, indicating that Nimenrix induces immune memory to groups A, C, W-135, and Y.

The observed group C booster response with Nimenrix was similar to that observed in subjects primed and boosted with a monovalent MenC-CRM conjugate vaccine. One year after Nimenrix booster, SBA titres ≥ 1:8 persisted in at least 95.5% of subjects (study MenACWY-TT-048, 12 to 23 months of age at primary vaccination).

When Nimenrix was used as a booster following primary vaccination with a MenACWY-DT conjugate vaccine or a monovalent group C conjugate vaccine (study MenACWY-TT-059, 10 to 25 years of age at primary vaccination and study MenACWY-TT-088, 2 to 10 years of age at primary vaccination), the titres increased by 48-340 fold for all groups and 100% of the subjects reached SBA titres ≥ 1:8.

Booster response for subjects previously vaccinated with a plain polysaccharide vaccine against Neisseria meningitidis

In study MenACWY-TT-021 conducted in subjects aged 4.5-34 years, the immunogenicity of Nimenrix administered between 30 and 42 months after vaccination with a ACWY-PS vaccine was compared to the immunogenicity of Nimenrix administered to age-matched subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years. An immune response (rSBA titre ≥8) was observed against all groups (A, C, W-135, Y) in all subjects regardless of the meningococcal vaccine history. The rSBA GMTs were significantly lower in the subjects who had received a dose of ACWY-PS vaccine 30-42 months prior to Nimenrix (Table 14) (see section 4.4).

Table 14: Immune response (rSBA*) 1 month after Nimenrix vaccination in subjects according to their meningococcal vaccine history

Group

Subjects vaccinated 30 to 42 months previously with ACWY-PS

Subjects who had not received a meningococcal vaccine in the preceding 10 years

N

≥8

(95%CI)

GMT

(95%CI)

N

≥8

(95%CI)

GMT

(95%CI)

A

146

100%

(97.5; 100)

6869

(6045; 7805)

69

100%

(94.8; 100)

13015

(10722; 15798)

C

169

100%

(97.8; 100)

1946

(1583; 2391)

75

100%

(95.2; 100)

5495

(4266; 7076)

W-135

169

100%

(97.8; 100)

4636

(3942; 5451)

75

100%

(95.2; 100)

9078

(7088; 11627)

Y

169

100%

(97.8; 100)

7800

(6683; 9104)

75

100%

(95.2; 100)

13895

(11186; 17261)

The analysis of immunogenicity was conducted on ATP cohort for immunogenicity.

* tested at GSK laboratories

The European Medicines Agency has deferred the obligation to submit the results of studies with Nimenrix in one or more subsets of the paediatric population in the prevention of meningococcal disease caused by Neisseria meningitidis group A, C, W-135 and Y (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on local tolerance, acute toxicity, repeated dose toxicity, developmental/reproductive toxicity and fertility studies.

6. Pharmaceutical particulars
6.1 List of excipients

Powder:

Sucrose

Trometamol

Solvent:

Sodium chloride

Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

3 years

After reconstitution:

After reconstitution, the vaccine should be used promptly. Although delay is not recommended, stability has been demonstrated for 8 hours at 30°C after reconstitution. If not used within 8 hours, do not administer the vaccine.

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Powder in a vial (type I glass) with a stopper (butyl rubber) and solvent in a pre-filled syringe with a stopper (butyl rubber).

Pack sizes of 1 and 10 with or without needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Instructions for reconstitution of the vaccine with the solvent presented in pre-filled syringe

Nimenrix must be reconstituted by adding the entire content of the pre-filled syringe of solvent to the vial containing the powder.

To attach the needle to the syringe, refer to the below picture. However, the syringe provided with Nimenrix might be slightly different (without screw thread) than the syringe described in the picture. In that case, the needle should be attached without screwing.

1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock (See picture).

3. Remove the needle protector, which on occasion can be a little stiff.

4. Add the solvent to the powder. After the addition of the solvent to the powder, the mixture should be well shaken until the powder is completely dissolved in the solvent.

The reconstituted vaccine is a clear colourless solution.

The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the vaccine.

After reconstitution, the vaccine should be used promptly.

A new needle should be used to administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Instructions for reconstitution of the vaccine with the solvent presented in ampoules

Nimenrix must be reconstituted by adding the entire content of the ampoule of solvent to the vial containing the powder.

1. Break the top of the ampoule, draw up the solvent with a syringe and add the solvent to the powder.

2. The mixture should be well shaken until the powder is completely dissolved in the solvent.

The reconstituted vaccine is a clear colourless solution.

The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the vaccine.

After reconstitution, the vaccine should be used promptly.

A new needle should be used to administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

8. Marketing authorisation number(s)

pre-filled syringe

EU/1/12/767/001

EU/1/12/767/002

EU/1/12/767/003

EU/1/12/767/004

ampoule

EU/1/12/767/005

EU/1/12/767/006

EU/1/12/767/007

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 20 April 2012.

10. Date of revision of the text

09/2016

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu

Company contact details

Pfizer Limited

Company image
Address

Ramsgate Road, Sandwich, Kent, CT13 9NJ

Fax

+44 (0)1304 656 221

Telephone

+44 (0)1304 616 161

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Active ingredients

meningococcal Group A, C, W135 and Y conjugate vaccine

Legal categories

POM - Prescription Only Medicine

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