NEW ZEALAND DATA SHEET

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1 NEW ZEALAND DATA SHEET Mencevax ACWY Serogroups A, C, W-135 and Y polysaccharide meningococcal vaccine Presentation(s) Mencevax ACWY is a lyophilized preparation of purified polysaccharides from Neisseria meningitidis (meningococcus) of serogroups A, C, W-135 and Y. Mencevax ACWY is presented as a white pellet in a glass vial. The sterile diluent is clear and colourless and presented in a glass vial, pre-filled syringe or ampoule. Mencevax ACWY meets the World Health Organisation requirements for biological substances and for meningococcal meningitis vaccines. Each 0.5 ml dose of reconstituted vaccine contains 50 µg of each of the polysaccharide of serogroups A, C, W-135 and Y. Indications Mencevax ACWY is indicated for active immunisation of adults and children over two years against meningococcal meningitis caused by serogroup A, serogroup C, serogroup W-135 and serogroup Y meningococci. The vaccine may also be used for: Subjects who are close contacts of patients with disease caused by meningococci of serogroups A, C, W-135 and Y. Travellers to countries where the disease is epidemic or highly endemic. Controlling epidemics of infection caused by serogroups A, C, W-135, Y meningococci in confined communities. Mencevax ACWY is not recommended for use in infants and children under two years of age, as antigenicity of the vaccine is low in this age group and antibodies persist for shorter duration. Dosage and Administration Mencevax ACWY should be reconstituted only with the sterile diluent supplied by adding the entire contents of the diluent vial/ampoule/syringe to the vaccine vial. The reconstituted vaccine should be inspected for any foreign particulate matter and/or colouration (other than a possible slight pink cloudiness) prior to administration. In the event of either being observed, discard the vaccine. The vaccine pellet should be completely dissolved in the diluent. The reconstituted vaccine should be administered subcutaneously with a sterile syringe and needle. For adults and children over 2 years, one dose of vaccine is contained in 0.5 ml. Mencevax ACWY should under no circumstances be administered intravascularly. Contraindications Mencevax ACWY should not be administered to subjects with known hypersensitivity to any component of the vaccine or to subjects having shown signs of hypersensitivity after previous administration of Mencevax ACWY. 1

2 Warnings and Precautions As with other vaccines, the administration of Mencevax ACWY should be postponed in subjects suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination. Mencevax ACWY will only confer protection against Neisseria meningitidis serogroups A, C, W- 135 and Y. As for any vaccine, complete protection cannot be guaranteed in every vaccinated individual. An adequate immune response may not be elicited in patients receiving immunosuppressive treatment or patients with immunodeficiency. As with all injectable vaccines, appropriate medical treatment should always be readily available for treatment in case of anaphylactic reactions following the administration of the vaccine. Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints. Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination. Re-vaccination with serogroup C polysaccharide containing vaccines may induce lower antibody responses to meningococcal serogroup C polysaccharide compared to primary vaccination. In subjects remaining at high risk of exposure to meningococcal disease caused by serogroups A, C, W-135 and Y, re-vaccination should be considered according to official recommendations (see section Further Information ). Mencevax ACWY should under no circumstances be administered intravascularly. Interactions Use with other vaccines Mencevax ACWY can be administered at the same time as other vaccines. The other injectable vaccines should always be administered at a different injection site. Use with systemic immunosuppressive medications See section Warnings and Precautions. Pregnancy and lactation Pregnancy Adequate human data on use during pregnancy and adequate animal reproduction studies are not available. Mencevax ACWY should be used during pregnancy only when clearly needed and when the possible advantages outweigh the possible risks for the foetus. Lactation Adequate data on the administration of Mencevax ACWY to women who are breast-feeding are not available. However, as with other polysaccharide vaccines, one does not expect vaccination with Mencevax ACWY to harm the mother or the infant. Mencevax ACWY should be administered to women who are breast-feeding when needed and the possible advantages outweigh the possible risks. 2

3 Effects on ability to drive and use machines There have been no studies to investigate the effect of Mencevax ACWY on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance. Nevertheless, the clinical status of the patient and the adverse event profile of Mencevax ACWY should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills. Adverse Effects The safety profile presented below is based on data from clinical studies. Adverse reactions occurring during these studies were mostly reported within 48 hours following vaccination. Frequencies are reported as: Very common: 1/10 Common: 1/100 to < 1/10 Uncommon: 1/1000 to < 1/100 Rare: 1/10000 to < 1/1000 Very rare: < 1/10000 Metabolism and nutrition disorders: Common: decreased appetite Psychiatric disorders: Very common: irritability Nervous system disorders: Very common: somnolence, headache Uncommon: dizziness, hypoaesthesia Gastrointestinal disorders: Common: gastrointestinal symptoms e.g. nausea, vomiting and diarrhoea Musculoskeletal and connective tissue disorders: Common: myalgia General disorders and administration site conditions: Very common: pain and redness at the injection site, fatigue Common: swelling at the injection site, fever Uncommon: injection site anaesthesia and injection site haematoma In addition, the following adverse reactions have been reported during post-marketing surveillance: Immune system disorders Allergic reactions, including anaphylactic and anaphylactoid reactions Skin and subcutaneous tissue disorders Urticaria, rash, angioneurotic oedema Musculoskeletal and connective tissue disorders Arthralgia, musculoskeletal stiffness General disorders and administration site conditions Influenza-like symptoms, chills 3

4 Overdose Cases of overdose (up to 10 times the recommended dose) have been reported during postmarketing surveillance. Adverse events reported following overdosage were similar to those reported with normal vaccine administration. Further Information Pharmacodynamic properties Immunogenicity data Mencevax ACWY induces the production of bactericidal antibodies against meningococci of the serogroups A, C, W-135 and Y. Immunogenicity was measured with a serum bactericidal assay using rabbit complement (rsba). The percentage of subjects with bactericidal antibody titres 1:8 is considered as an immunologic correlate for protective efficacy against meningococcal serogroups A, C, W-135 and Y. The immunogenicity of one dose of Mencevax ACWY has been evaluated in studies involving more than 2200 subjects aged 2 years and above. The vaccine response was defined in subjects as: 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) Immunogenicity in children aged 2-10 years In clinical study MenACWY-TT-038, the immune response to vaccination with one dose of Mencevax ACWY was evaluated one month after vaccination. The results obtained in this clinical study for all seroroups are summarised in the table below: Table 1: Bactericidal antibody responses (rsba*) to Mencevax ACWY in children aged 2-10 years 1 month after vaccination Mencevax ACWY Serogroup VR GMT N (95%CI) (95%CI) A % (57.4; 71.3) 2283 (2023; 2577) C 234 W % (85.1; 93.3) 82.6% (77.2; 87.2) 1317 (1043; 1663) 2158 (1815; 2565) 4

5 Y % (62.5; 74.6) 2613 (2237; 3052) The analysis of immunogenicity was conducted on the according-to-protocol (ATP) cohort for immunogenicity. VR: Vaccine Response GMT: Geometric Mean Titre * tested at GSK laboratories Immunogenicity in adolescents aged years and adults aged years In two clinical studies, conducted in adolescents years of age (study MenACWY-TT-036) and in adults years of age (study MenACWY-TT-035), the immune response to vaccination with one dose of Mencevax ACWY was evaluated one month after vaccination. The results obtained in those clinical studies for all serogroups are summarised in the table below: Table 2: Bactericidal antibody responses (rsba*) to Mencevax ACWY in adolescents aged years and adults aged years 1 month after vaccination Mencevax ACWY Study Serogrou VR GMT (Age range) p N (95%CI) (95%CI) A % 2947 (70.9; 83.2) (2612; 3326) 96.7% 8222 C 211 Study MenACWY-TT-036 (93.3; 98.7) (6807; 9930) (11-17 years) 87.5% 2633 W (82.3; 91.6) (2299; 3014) Y % 5066 (72.5; 83.8) (4463; 5751) A % 2127 (63.8; 75.4) (1909; 2370) 92.0% 7371 C 288 Study MenACWY-TT-035 (88.3; 94.9) (6297; 8628) (18-55 years) 85.5% 2461 W (80.9; 89.4) (2081; 2911) Y % 4314 (73.6; 83.4) (3782; 4921) The analysis of immunogenicity was conducted on ATP cohorts for immunogenicity. VR: Vaccine Response GMT: Geometric Mean Titre * tested in GSK laboratories Immunogenicity in adults aged 56 years In clinical study MenACWY-TT-085, the immune response to vaccination with one dose of Mencevax ACWY was evaluated one month after vaccination. The results obtained for all serogroups are summarised in the table below: 5

6 Table 3: Bactericidal antibody responses (rsba*) to Mencevax ACWY in adults aged 56 years 1 month after vaccination Mencevax ACWY Serogrou VR GMT p N (95%CI) (95%CI) A (60.3;83.9) (2062; 3911) C (62.0;84.2) (2827; 8201) W (65.0;87.1) (1135; 2979) Y (64.3;86.2) (2726; 5670) The analysis of immunogenicity was conducted on ATP cohort for immunogenicity. VR: Vaccine Response GMT: Geometric Mean Titre * tested at GSK laboratories Immunogenicity in high risk population According to data reported in the literature, studies conducted among late complement component deficient subjects (LCCD) (N=31) and subjects after Bone Marrow Transplant (BMT) (N=44) demonstrated that vaccination with Mencevax ACWY elicited a satisfactory immune response. In LCCD patients, geometric mean concentrations (GMCs) of 26.8µg/ml for MenA, 19.2 µg/ml for MenC, 16.4 µg/ml for MenW-135 and 30.7 µg/ml for MenY were observed at 13 weeks after vaccination. In BMT patients, 62% to 84% of subjects had anti-polysaccharide A concentrations 2.0 µg/ml and 76% to 84% of subjects had anti-polysaccharide C concentrations 2.0 µg/ml one month after vaccination. Efficacy data In response to a meningococcal disease epidemic in Burkina Faso, a mass vaccination campaign with Mencevax ACWY was performed in more than 1.68 million children and adults aged from 2 to 29 years. Following this mass vaccination campaign 32 cases of meningitis due to Neisseria meningitidis serogroup A and 3 cases of meningitis due to Neisseria meningitidis serogroup W-135 were reported. Persistence of immune response The persistence of the immune response elicited by Mencevax ACWY was evaluated up to 5 years after vaccination in adolescents and adults aged years primed in study MenACWY-TT-015. The results obtained up to 5 years for all serogroups are summarised in the table below: Table 4: 1 month post-vaccination and 5 year persistence data (rsba*) in adolescents and adults as vaccination Time-point** Mencevax ACWY Serogroup N rsba* 1:8 GMT 6

7 (95%CI) (95%CI) Month % ( ) 1463 ( ) Year % ( ) 218 ( ) A Year % ( ) 386 ( ) Year Year % ( ) 74.3% ( ) 105 ( ) 104 ( ) Month % ( ) 8071 ( ) Year % ( ) 1957 ( ) C Year % ( ) 286 ( ) Year Year % ( ) 71.2% ( ) 315 ( ) 142 ( ) Month % ( ) 882 ( ) Year % ( ) 120 ( ) W-135 Year % ( ) 6.5 ( ) Year Year % ( ) 24.8% ( ) 11.3 ( ) 11.7 ( ) Month % ( ) 2663 ( ) Y Year 1 12 Year % ( ) 44.0% ( ) 22.3 ( ) 19.4 ( ) 43.9% 26.0 Year ( ) ( ) Year %

8 ( ) ( ) GMT: Geometric Mean Titre *rsba testing performed at Public Health England (PHE) laboratories in UK **Month 1, Year 1 and Year 2: the analysis of immunogenicity was performed post-hoc following testing of available samples with PHE rsba Year 4: the analysis of immunogenicity was conducted on the ATP cohort for persistence Year 5: the analysis of immunogenicity was conducted on the Total Cohort for persistence In contrast to the observed rsba-mena persistence, limited data showed a waning of serum bactericidal antibody titres against serogroup A one year post-vaccination when using human complement in the assay (hsba). The clinical relevance of the waning of hsba-mena antibody titres is unknown. Pharmacokinetic properties Evaluation of pharmacokinetic data is not required for vaccines. Preclinical safety data Not applicable. Pharmaceutical Precautions Excipients Powder: sucrose, trometamol Diluent: sodium chloride, water for injections Special precautions for storage The lyophilised vaccine should be stored in a refrigerator between 2 o C and 8 o C. The diluent can be stored at ambient temperatures. After reconstitution, the vaccine should be injected promptly or kept in a refrigerator. If not used within 8 hours, it should be discarded because of the risk of contamination. It is recommended to protect the reconstituted vaccine from direct sunlight. When supplies of Mencevax ACWY are distributed from a central cold-store, it is good practice to arrange transport under refrigerated conditions, particularly in hot climates. Additional information on stability Experimental data show that the powder is stable at 37 C for 1 week. However, these data are not recommendations for storage. Shelf life The expiry date of the vaccine is indicated on the label and packaging. When stored under prescribed conditions of temperatures between 2 o C and 8 o C the shelf-life is 3 years. Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Medicine Schedule Prescription Medicine. 8

9 Package Quantities Monodose vials. A container of sterile diluent is supplied for reconstitution of the lyophilized vaccine. Sponsor Details Pfizer New Zealand Limited P O Box 3998 Auckland, New Zealand, Toll Free Number: Date of Preparation 20 January 2016 Version 8.0 9