Active ingredients: Meningococcal conjugate vaccine of groups A, C, W135 and Y
Powder and solution for solution for injection (powder and solution for injection).
Why is Menveo used? What is it for?
Menveo is a vaccine used for the active immunization of children (from the age of 2 years), adolescents (from the age of 11 years) and adults at risk of exposure to serogroups A, C, W135 and Y of a bacterium called Neisseria meningitidis to prevent the onset of invasive diseases. The vaccine works by triggering protection (antibodies) against these bacteria in the body.
Neisseria meningitidis bacteria of groups A, C, W135 and Y can cause serious and sometimes life-threatening infections such as meningitis and sepsis (blood poisoning).
Menveo cannot cause bacterial meningitis. The vaccine contains a protein (called CRM197) from the bacterium that causes diphtheria. Menveo does not protect against diphtheria. This means that you (or your child) will need to have other vaccinations to be protected from diphtheria, when these are needed or advised by your doctor.
Contraindications When Menveo should not be used
Do not use Menveo if the person to be vaccinated
- have had an allergic reaction to the active substances or any component of this vaccine (listed in section 6)
- have had an allergic reaction to diphtheria toxoid (a substance used in several other vaccines)
- has a disease with a high fever. However, a mild febrile event and / or an "upper respiratory infection (eg a cold)" alone are not a sufficient reason to postpone vaccination.
Precautions for use What you need to know before you take Menveo
Tell your doctor or nurse before receiving Menveo if the person to be vaccinated has
- a weakened immune system. There are few data on the effectiveness of Menveo given to people whose immune systems are weakened due to the use of immunosuppressive drugs, HIV infection and other possible causes. Menveo's effectiveness may be reduced in these people.
- haemophilia or any other problem that can stop proper blood clotting, such as in patients receiving anticoagulants.
Fainting, feeling faint or other stress-related reactions may occur in response to any needle injection. Talk to your doctor or nurse if you have had this type of reaction before.
This vaccine can only protect against meningococcal group A, C, W135 and Y bacteria. It cannot protect against other types of meningococcal bacteria other than groups A, C, W135 and Y or other factors that cause meningitis and sepsis (blood poisoning ).
As with other vaccines, Menveo may not protect 100% of those who receive the vaccine.
It is possible to consider the hypothesis of administering a booster dose to maintain protection if the vaccinated person has received a dose of Menveo for over a year and is still at particular risk of exposure to the meningococcal bacterium of group A. The doctor will advise you if and when to receive a booster dose.
Interactions Which drugs or foods can modify the effect of Menveo
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.
Menveo can be administered concomitantly with other vaccinations but any other vaccines should preferably be injected into an arm other than the Menveo injection site.
These include: diphto-tetanus-acellular pertussis (Tdap) vaccine, human papilloma virus (HPV) vaccine, yellow fever vaccine, typhoid fever vaccine (Vi polysaccharide), Japanese encephalitis vaccine, rabies vaccine and hepatitis A and B vaccine.
The action of Menveo may be reduced if given to people taking medicines to inhibit the immune system.
If multiple vaccines are injected at the same time, separate injection sites should be used.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Tell your doctor before taking this medicine if you are pregnant, breastfeeding, suspect pregnancy or planning to become pregnant. However, your doctor or nurse may recommend Menveo if the risk of infection with meningococcal bacteria of groups A, C, W-135 and Y is high.
Driving and using machines
No studies on the ability to drive and use machines have been performed. Very rare cases of dizziness have been reported following vaccination. The ability to drive and use machines may be temporarily impaired.
Menveo contains
This medicine contains less than 1 mmol sodium (23 mg) per dose and is therefore essentially 'sodium-free'.
This medicine contains less than 1 mmol of potassium (39 mg) per dose and is therefore essentially 'potassium-free'.
Dosage and method of use How to use Menveo: Dosage
Menveo will be given to you or your child by a doctor or nurse.
The vaccine is normally injected into the upper arm (deltoid) muscle in children (from 2 years of age), adolescents and adults. Your doctor or nurse will be careful not to inject the vaccine into a blood vessel and will verify that it is injected into the muscle and not the skin.
For children (from 2 years of age), adolescents and adults: a single injection (0.5 ml) will be given.
The safety and efficacy of Menveo in children less than 2 years of age have not yet been established. Data in subjects aged 56 to 65 are limited and there are no data for subjects over 65 years of age.
Tell your doctor if you have previously received an "injection of Menveo or another meningococcal vaccine. Your doctor will tell you if you need another" injection of Menveo.
For information on reconstitution of the vaccine see the section for your doctor or healthcare professional at the end of this leaflet.
If you have any further questions on the use of this medicine, ask your doctor or nurse.
Side Effects What are the side effects of Menveo
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most common side effects reported during clinical trials generally only lasted from one day to two days and were generally not serious.
In children (2-10 years of age), side effects reported during clinical trials are listed below.
Very common (may affect more than 1 in 10 people): drowsiness, headache, irritability, generally feeling unwell, injection site pain, injection site redness (≤50 mm), injection site induration injection (≤50 mm)
Common (may affect up to 1 in 10 people): change in eating habits, nausea, vomiting, diarrhea, rash, muscle pain, joint pain, chills, fever ≥38 ° C, redness at the injection site (> 50 mm ) and hardening of the injection site (> 50 mm)
Uncommon (may affect up to 1 in 100 people): itching at the injection site
In adolescents (aged 11 years and above) and adults, the most common side effects reported during clinical trials are listed below.
Very common: headache, nausea, injection site pain, injection site redness (≤50 mm), injection site induration (≤50 mm), muscle pain, generally feeling unwell
Common: rash, injection site redness (> 50 mm), injection site induration (> 50 mm), joint pain, fever ≥38 ° C, chills
Uncommon: dizziness, itching at the injection site
Side effects that have been reported since Menveo has been marketed: Allergic reactions which may include severe swelling of the lips, mouth, throat (which may cause difficulty in swallowing), difficulty breathing with wheezing or coughing, rash and swelling of the hands , feet and ankles, loss of consciousness, very low blood pressure; fits (fits), including fits associated with fever; balance disturbances; fainting; injection site skin infection; injection site swelling, including extensive swelling of the injected limb.
If you experience a severe allergic reaction, contact your doctor immediately or go / take your child to the emergency room, as they may need "urgent medical attention."
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and vial after the indication EXP. The expiry date refers to the last day of the month.
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze. Keep the vials in the outer carton to protect the medicine from light.
The product should be used immediately after reconstitution. However, physico-chemical stability has been demonstrated for 8 hours after reconstitution at a temperature below 25 ° C.
Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will arrange for the disposal of the medication. This will help protect the environment.
Deadline "> Other information
What Menveo contains
One dose (0.5 ml of reconstituted vaccine) contains:
The active ingredients are:
- originally contained in the powder
- meningococcal group A oligosaccharide 10 micrograms conjugated to the protein Corynebacterium diphtheriae CRM197 16.7 to 33.3 micrograms
- originally contained in the solution
- Meningococcal group C oligosaccharide 5 micrograms conjugated to Corynebacterium diphtheriae CRM197 protein 7.1 to 12.5 micrograms
- meningococcal group W135 oligosaccharide 5 micrograms conjugated to the protein Corynebacterium diphtheriae CRM197 from 3.3 to 8.3 micrograms
- Meningococcal group Y oligosaccharide 5 micrograms conjugated to Corynebacterium diphtheriae CRM197 protein 5.6 to 10.0 micrograms
The other ingredients (excipients) are:
In the powder: monobasic potassium phosphate and sucrose.
In the solution: sodium chloride, sodium dihydrogen phosphate monohydrate, sodium hydrogen phosphate dihydrate and water for injections (see also end of section 2).
Description of what Menveo looks like and contents of the pack
Menveo is a powder and solution for injection.
Each dose of Menveo is provided as:
- 1 vial containing the lyophilized MenA conjugate component as a white to off-white powder;
- 1 vial containing the liquid MenCWY conjugate component as a clear solution;
- Pack size of one dose (2 vials) or five doses (10 vials).
Not all pack sizes may be marketed.
The contents of the two components (vial and vial) must be mixed before vaccination to obtain 1 dose of 0.5 ml.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
LESS POWDER AND SOLUTION FOR SOLUTION FOR INJECTION
CONJUGATED MENINGOCOCCAL VACCINE OF GROUP A, C, W135 AND Y
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
One dose (0.5 ml of reconstituted vaccine) contains:
(originally contained in the powder)
• 10 mcg meningococcal group A oligosaccharide conjugated to the protein Corynebacterium diphtheriae CRM197 from 16.7 to 33.3 mcg (originally contained in the solution)
• oligosaccharide of meningococcal group C 5 mcg conjugated to the protein Corynebacterium diphtheriae CRM197 from 7.1 to 12.5 mcg
• oligosaccharide of the meningococcal group W135 5 mcg conjugated to the protein Corynebacterium diphtheriae CRM197 from 3.3 to 8.3 mcg
• oligosaccharide of meningococcal group Y 5 mcg conjugated to the protein Corynebacterium diphtheriae CRM197 from 5.6 to 10.0 mcg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Powder and solution for solution for injection (powder and solution for injection).
The powder is a white to off-white agglomerate.
The solution is clear and colorless.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Menveo is indicated for the active immunization of children (2 years of age and older), adolescents and adults at risk of exposure to groups A, C, W135 and Y of Neisseria meningitidis to prevent the onset of invasive diseases.
Use of this vaccine must comply with official recommendations.
04.2 Posology and method of administration -
Dosage
Children (2 years of age and older), teenagers and adults
Menveo should be administered as a single dose (0.5 ml).
To ensure optimal antibody levels against all vaccine serogroups, the schedule of primary vaccination with Menveo should be completed one month before the risk of exposure to Neisseria meningitidis groups A, C, W135 and Y; bactericidal antibodies (hSBA≥1: 8) were observed in at least 64% of subjects 1 week after vaccination (see section 5.1 for immunogenicity data for individual serogroups).
Senior citizens
Data for subjects aged 56-65 are limited and data for subjects aged> 65 are not available.
Booster vaccination
Long-term persistence data of antibodies after vaccination with Menveo for up to 5 years are available (see sections 4.4 and 5.1).
Menveo can be given as a booster dose in individuals who have previously received primary vaccination with Menveo, another meningococcal conjugate vaccine or a meningococcal polysaccharide unconjugated vaccine. The need and timing of a booster dose in subjects previously vaccinated with Menveo should be defined according to national recommendations.
Pediatric population (less than 2 years of age)
The safety and efficacy of Menveo in children aged less than 2 years have not yet been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made.
Method of administration
Menveo is given by injection into a muscle, preferably into the deltoid muscle.
It must not be administered intravascularly, subcutaneously or intradermally.
Separate injection sites should be used to administer more than one vaccine at the same time.
For instructions on preparation and reconstitution of the medicinal product before administration, see section 6.6.
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or to diphtheria toxoid (CRM197), or life-threatening reaction following previous administration of a vaccine containing similar components (see section 4.4).
As with other vaccines, administration of Menveo should be postponed in subjects suffering from an acute severe febrile event. The presence of a minor infection is not a contraindication.
04.4 Special warnings and appropriate precautions for use -
Before injecting any vaccine, the person responsible for administering must take all known precautions to prevent allergic or any other reactions, including gathering information about the patient's medical history and current health. As with all vaccines. Injectables, appropriate medical treatment and supervision should always be readily available in the rare event of anaphylactic reactions following administration of the vaccine.
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions, as a psychogenic response to needle administration may occur in association with vaccination (see section 4.8 Undesirable effects). It is therefore important that procedures are in place to avoid fainting injuries.
Menveo should under no circumstances be administered intravascularly.
Menveo does not protect against infections caused by any other serogroup of N. meningitidis not present in the vaccine.
As with all vaccines, a protective immune response may not be produced in all vaccines (see section 5.1).
Studies with Menveo have shown a decrease in serum bactericidal antibody titers relative to serogroup A when using human complement in the test (hSBA) (see section 5.1).
The clinical relevance of the decrease in serogroup A hSBA antibody titers is unknown.
The need for a booster dose should be considered if an individual is believed to be at particular risk of exposure to MenA and has received a previous dose of Menveo for more than a year.
There are no data on the applicability of the vaccine for post-exposure prophylaxis.
In immunocompromised individuals, vaccination may not produce the adequate protective antibody response. Human immunodeficiency virus (HIV) infection is not a contraindication, however Menveo has not been specifically evaluated in immunocompromised people. Individuals with complement deficiency and individuals with anatomic or functional asplenia may not develop an immune response to group A, C, W135, and Y meningococcal conjugate vaccines.
Menveo has not been evaluated in people with thrombocytopenia, haemostasis disorders or being treated with anticoagulant therapy due to the risk of hematoma. Healthcare professionals should evaluate the benefit-risk balance for people who are at risk of hematoma formation in following the intramuscular injection.
04.5 Interactions with other medicinal products and other forms of interaction -
Menveo can be co-administered with any of the following vaccines: monovalent and combined hepatitis A and B vaccine, yellow fever vaccine, typhoid fever vaccine (Vi polysaccharide), Japanese encephalitis vaccine, and rabies vaccine.
In adolescents (11-18 years of age), Menveo was evaluated in two co-administration studies with adsorbed diphto-tetanus-acellular pertussis (Tdap) vaccine alone or
Tdap and quadrivalent recombinant vaccine against papilloma virus (types 6, 11, 16 and 18) (HPV); both studies support co-administration of vaccines.
There was no evidence from the studies for the increase in the rate of reactogenicity or for the change in the safety profile of the vaccines. Antibody responses to Menveo and the diphto-tetanus-acellular pertussis or HPV vaccine components were not impaired by co-administration.
Administration of Menveo one month after Tdap resulted in statistically significantly reduced serogroup W135 seroresponses. Since no direct impact on the seroprotection rate was recorded, the clinical consequences are currently unknown. There was evidence of some suppression of the antibody response to two of the three pertussis antigens. The clinical relevance of this observation is unknown.
After vaccination, more than 97% of subjects had detectable pertussis titers to all three pertussis antigens.
In children aged 2 to 10 years, no data are available to evaluate the safety and immunogenicity of other childhood vaccines given concomitantly with Menveo.
Co-administration of Menveo and other vaccines other than those listed above has not been studied. Concomitant vaccines should always be administered at separate injection sites, preferably in the contralateral limbs. It should be investigated whether adverse reactions can be intensified by co-administration.
If the vaccinee is receiving immunosuppressive therapy, the immunological response may be reduced.
04.6 Pregnancy and breastfeeding -
There are insufficient clinical data on exposures in pregnancy.
Non-clinical studies show that Menveo has no direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. Given the severity of invasive meningococcal disease caused by serogroups A, C, W135 and Y of Neisseria meningitidis, pregnancy is not an impediment to vaccination when the risk of exposure is clearly defined.
Although the clinical data on the use of Menveo during breastfeeding are not complete, the antibodies secreted in milk are unlikely to pose a hazard when assimilated by a nursing infant. Therefore, Menveo can be used while breastfeeding.
04.7 Effects on ability to drive and use machines -
No studies on the ability to drive and use machines have been performed. Very rare cases of dizziness have been reported following vaccination. The ability to drive and use machines may be temporarily impaired.
04.8 Undesirable effects -
Within each frequency class, adverse reactions are reported in order of decreasing severity.
Frequency is defined as follows:
Very common: (≥ 1/10)
Common: (≥1 / 100 to
Uncommon: (≥1 / 1,000 to
Rare: (≥1 / 10,000 to
Very rare: (
Not known (frequency cannot be estimated from the available data)
Adverse reactions observed in clinical studies
Children between the ages of 2 and 10
A total of 3464 subjects aged 2 to 10 years were exposed to vaccination with Menveo in completed clinical trials. The characterization of the safety profile of Menveo in children aged 2 to 10 years is based on data from four clinical studies in which 3,181 subjects received Menveo.
The most common adverse reactions during clinical trials generally lasted one or two days and were not serious. Adverse reactions were:
Metabolism and nutrition disorders:
Common: eating disorders
Nervous system disorders:
Very common: somnolence, headache
Gastrointestinal disorders:
Common: nausea, vomiting, diarrhea
Skin and subcutaneous tissue disorders:
Common: rash
Musculoskeletal and connective tissue disorders:
Common: myalgia, arthralgia
General disorders and administration site conditions:
Very common: irritability, malaise, injection site pain, injection site erythema (≤ 50 mm), injection site induration (≤ 50 mm)
Common: Injection site erythema (> 50 mm), injection site induration (> 50 mm), chills, fever ≥38 ° C
Uncommon: itching at the injection site
Subjects aged between 11 and 65 years
The characterization of the safety profile of Menveo in adolescents and adults is based on data from five randomized controlled trials with the inclusion of 6401 participants (aged 11 to 65 years) who received Menveo. they received
Menveo belonged respectively, in the percentages of 58.9%, 16.4%, 21.3% and 3.4%, to the following age groups 11-18 years, 19-34 years, 35-55 years and 56-65 years. The two main safety studies were randomized and actively controlled trials, which enrolled participants aged 11 to 55 (N = 2663) and 19 and 55 years (N = 1606), respectively.
The incidence and severity of any local, systemic and other reactions were generally overlapping in the groups of all studies treated with Menveo and within the age groups of adolescents and adults. The reactogenicity profile and percentages of adverse events in subjects 56 to 65 years of age who received Menveo (N = 216) were similar to those seen in subjects who received Menveo ages 11 to 55 years.
The most common systemic and local adverse reactions observed in clinical trials were: injection site pain and headache.
The list provided below presents the adverse reactions reported in the three main clinical studies and the two supportive studies, broken down by system organ class. The most common undesirable effects reported during the clinical studies generally lasted from only one day to two days and were generally not serious.
Nervous system disorders:
Very common: headache
Uncommon: dizziness
Gastrointestinal disorders:
Very common: nausea
Skin and subcutaneous tissue disorders:
Common: rash
Musculoskeletal and connective tissue disorders:
Very common: myalgia
Common: arthralgia
General disorders and administration site conditions:
Very common: injection site pain, injection site erythema (≤50 mm), injection site induration (≤50 mm), malaise
Common: Injection site erythema (> 50 mm), injection site induration (> 50 mm), fever ≥38 ° C, chills
Uncommon: itching at the injection site
In the adolescent group, the safety and tolerability of the vaccine were favorable with respect to Tdap and did not substantially change with co-administration or subsequent other vaccines.
Post-marketing experience (all age groups)
Disorders of the immune system
Not known: hypersensitivity, including anaphylaxis
Nervous system disorders
Not known: tonic convulsion, febrile convulsion, syncope
Ear and labyrinth disorders
Not known: vertigo
General disorders and administration site conditions
Not known: injection site cellulitis, injection site swelling, including extensive swelling of the injected limb
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. in "Annex V
04.9 Overdose -
No cases of overdose have been reported.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: meningococcal vaccines.
ATC code: J07AH08.
Immunogenicity
The efficacy of Menveo was inferred by measuring the production of serogroup-specific anti-capsular antibodies with bactericidal activity. Serum bactericidal activity (SBA) was measured using human serum as a source of exogenous complement (hSBA). HSBA was the original correlate of protection against meningococcal disease.
Immunogenicity was evaluated in randomized, multicentre, actively controlled clinical trials that enrolled children (2-10 years), adolescents (11-18 years), adults (19-55 years) and older adults (56-65 years). ).
Immunogenicity in children aged 2 to 10 years
In the pivotal study V59P20 the immunogenicity of Menveo was compared to that of ACWY-D; 1170 children were vaccinated with Menveo and 1161 received the comparator vaccine in the per protocol populations. In two supportive studies V59P8 and V59P10 the immunogenicity of Menveo was compared with that of ACWY-PS.
In the pivotal, randomized, observer-blinded study V59P20, in which participants were stratified by age (2 to 5 years and 6 to 10 years), the immunogenicity of a single dose of Menveo, one month later vaccination was compared with that of a single dose of ACWY-D. Immunogenicity results one month after vaccination with Menveo in subjects aged 2 to 5 and 6 to 10 are summarized in Table 1
Table 1: Serum bactericidal antibody responses after Menveo administration one month after vaccination in subjects aged 2 to 5 to 6 to 10 years
In another randomized, observer-blinded study (V59P8), US children were immunized with a single dose of Menveo (N = 284) or ACWY-PS (N = 285). In children aged 2 and 10 years, as well as in each age stratification (2-5 and 6-10 years), the immune responses measured as a percentage of subjects with seroresponse, hSBA≥1: 8, and GMT not only were not inferior to the comparator vaccine ACWY -PS, but they were also all statistically greater than the comparator for all serogroups and all immune measurements one month after vaccination. One year after vaccination, Menveo remained statistically superior to ACWY-PS for serogroups A, W-135 and Y, measured as a percentage of subjects with hSBA≥1: 8 and GMT.
Menveo was non-inferior for these endpoints for serogroup C (Table 2). The clinical relevance of the higher post-vaccination immune responses is unknown.
Table 2: Immunogenicity of a dose of Menveo or ACWY-PS in subjects aged 2 to 10 years, measured one month and twelve months after vaccination
In a randomized, observer-blinded study (V59P10) conducted in Argentina, children were immunized with a single dose of Menveo (N = 949) or ACWY-PS (N = 551).
Immunogenicity was evaluated in a subgroup of 150 subjects in each vaccine group.
The immune response observed in children aged 2 to 10 years was very similar to that observed in study V59P8 shown above: the immune response to Menveo one month after vaccination, measured as a percentage of subjects with seroresponse, hSBA ≥1: 8 and GMT, it was not less than ACWY-PS.
A randomized, observer-blinded study was conducted in children aged 12 to 59 months in Finland and Poland (V59P7). A total of 199 subjects aged 2 to 5 years were in the per protocol population. for the immunogenicity of Menveo and 81 subjects aged between 3 and 5 years made up the ACWY-PS group.
One month after the first vaccination, the proportion of subjects with hSBA ≥ 1: 8 was significantly higher in the Menveo group for all four serogroups (63% vs 39%, 46% vs 39%, 78% vs 59%, and 65% % vs 57% for Menveo when compared with ACWY-PS for serogroups A, C, W135, and Y, respectively).
In a randomized observer-blinded study (V59_57) conducted in the United States, the immunogenicity of a 2-dose and single-dose regimen of Menveo in children aged 2 to 5 to 6 to 10 years was compared. years (N = 715).
At baseline, the percentage of subjects with hSBA ≥ 1: 8 in the two age stratifications was 1% -5% for serogroup A, 13% -28% for serogroup C, 42% -64% for serogroup W135 and 6% -19% for serogroup Y. One month after the last vaccination, the percentages of subjects with hSBA ≥ 1: 8 in the 2-dose group and in the single-dose group in the two age groups were: 90 % -95% vs 76% -80% for serogroup A, 98% -99% vs 76% -87% for serogroup C, 99% vs 93% -96% for serogroup W135 and 96% vs 65% - 69% for serogroup Y. One month after vaccination, GMTs were higher in the 2-dose group than in the single-dose group in both age stratifications; however, this difference was less pronounced in the older age stratification.
One year after the last vaccination, the percentages of subjects with hSBA ≥ 1: 8 after treatment with the two-dose and single-dose regimen were both lower than those recorded 1 month after vaccination (30% after the regimen at 2 doses, 11% -20% after the single dose regimen for serogroup A; 61% -81% and 41% -55% for serogroup C; 92% -94% and 90% -91% for serogroup W135; 67% -75% and 57% -65% for serogroup Y). One year after vaccination, the differences between hSBA GMTs in the 2-dose and single-dose groups were less than those found. 1 month after vaccination.
The clinical benefit of a 2-dose regimen in children aged 2 to 10 years is unknown.
Persistence of the immune response and booster dose response in aged children between 2 and 10 years
Persistence of antibodies 5 years after primary vaccination was evaluated in study V59P20E1, an extension of study V59P20. Persistence of antibodies against serogroups C, W135 and Y was observed. Percentages of subjects with hSBA ≥1: 8 were equal to 32% and 56% against serogroup C respectively in subjects aged between 2 and 5 years and between 6 and 10 years, 74% and 80% against serogroup W135 and 48% and 53% against serogroup Y, with GMTs of 6.5 and 12 respectively for serogroup C, 19 and 26 for serogroup W135 and 8.13 and 10 for serogroup Y. For serogroup A, 14% and 22% of subjects aged 2 to 5 and 6 to 10 years, respectively, reported hSBA ≥1: 8 (GMT 2.95 and 3.73).
Five years after the primary single dose vaccination, the children were also given a booster dose of Menveo. All subjects in both age groups reported hSBA ≥1: 8 for all serogroups, with antibody titers several times higher than those observed after primary vaccination (Table 3).
Table 3: Persistence of the immune response 5 years after primary vaccination with Menveo and immune response 1 month after a booster dose in subjects 2 to 5 years of age and 6 to 10 years at the time of the first vaccination
Immunogenicity in subjects aged 11 years or older
In the pivotal study (V59P13) adolescents or adults received one dose of Menveo (N = 2649) or ACWY-D comparator vaccine (N = 875). Sera were collected before vaccination and one month after vaccination.
In another study (V59P6) conducted in 524 adolescents, the immunogenicity of Menveo was compared with that of ACWY-PS.
Immunogenicity in adolescents
In the 11-18 year old population of the pivotal study V59P13, the immunogenicity of a single dose of Menveo one month after vaccination was compared with that of ACWY-D.
The immunogenicity results one month after Menveo administration are summarized in Table 4 below.
Table 4: Serum bactericidal antibody responses after Menveo administration one month after vaccination in subjects aged 11 to 18 years
In the subset of subjects aged 11 to 18 who were seronegative at baseline (hSBA
In the non-inferiority study V59P6, immunogenicity was evaluated in adolescents aged 11-17 who were randomized to receive Menveo or ACWY-PS. Menveo was shown to be non-inferior to ACWY-PS vaccine for all. and four serogroups (A, C, W135 and Y) based on seroresponse, with percentages reaching hSBA ≥1: 8 and GMT.
Table 5: Immunogenicity of a dose of Menveo or ACWY-PS in adolescents, measured one month after vaccination
One year after vaccination in the same subjects, compared to ACWY-PS, a higher percentage of subjects vaccinated with Menveo had hSBA ≥1: 8 for serogroups C, W135 and Y, with comparable levels for serogroup A. Similar results were observed. in the comparison of hSBA GMT.
Persistence of the immune response and booster dose response in adolescents
In study V59P13E1, the persistence of immune responses against serogroups A, C, W135 and Y at 21 months, 3 years and 5 years after primary vaccination was evaluated in subjects aged 11 to 18 years at the time of vaccination. The percentages of subjects with hSBA ≥1: 8 remained constant for antibodies against serogroups C, W135 and Y from 21 months to 5 years after vaccination in the Menveo group, while that for antibodies against serogroup A decreased slightly over time. (Table 6). 5 years after primary vaccination, significantly higher percentages of subjects with hSBA ≥1: 8 were observed in the Menveo group compared to vaccine-naïve control subjects for all four serogroups.
Table 6: Persistence of immune responses at approximately 21 months, 3 and 5 years after vaccination with Menveo (subjects aged 11 to 18 years at the time of vaccination)
A booster dose of Menveo was given 3 years after primary vaccination with Menveo or ACWY-D. Both groups showed a robust response to the booster dose of Menveo one month after vaccination (100% of subjects had hSBA ≥1: 8 for all serogroups) and this response persisted largely in the 2 years following the booster dose for serogroups C, W135 and Y (87% -100% of subjects had hSBA ≥1: 8 for serogroups).
There was a slight decrease in the percentages of subjects with hSBA ≥1: 8 for serogroup A, although the percentages were still high (77% -79%). GMTs decreased over time, as expected, but remained 2 to 8 times higher than the pre-booster values (Table 8).
In study V59P6E1 one year after vaccination the percentage of subjects who received Menveo with hSBA ≥1: 8 remained significantly higher than those who received ACWY-PS for serogroups C, W135 and Y and similarly between the two study groups for serogroup A. The hSBA GMTs for serogroups W135 and Y were higher among subjects who received Menveo. 5 years after vaccination the percentage of subjects who received Menveo with hSBA ≥1: 8 remained significantly higher than those who received ACWY-PS for serogroups C and Y. Higher hSBA GMTs were observed for serogroups W135 and Y (Table 7).
Table 7: Persistence of immune responses approximately 12 months and 5 years after vaccination with Menveo and ACWY-PS (subjects aged 11 to 18 years at the time of vaccination)
A booster dose of Menveo was given 5 years after primary vaccination with Menveo or ACWY-PS. 7 days after the booster dose 98% -100% of subjects who previously received Menveo and 73% -84% of subjects who previously received ACWY-PS developed hSBA ≥1: 8 versus serogroups A, C , W135 and Y. One month after vaccination the percentages of subjects with hSBA≥1: 8 were 98% -100% and 84% -96%, respectively. 7 and 28 days after the booster dose there was a significant increase in hSBA GMTs against all four serogroups (Table 8).
Table 8: Responses to the booster dose: Bactericidal antibody responses to the booster dose of Menveo given 3 and 5 years after primary vaccination with Menveo and ACWY-PS in subjects 11 to 17 years of age
Immunogenicity in adults
In the pivotal immunogenicity study V59P13, immune responses to Menveo were evaluated in adults aged 19 to 55. Results are presented in Table 9. In the subset of subjects aged 19 to 55 who were seronegative at baseline, the percentage of subjects achieving an hSBA ≥ 1: 8 after a dose of Menveo was as follows: serogroup A 67% (582/875); serogroup C 71% (401/563); serogroup W135 82% (131 / 160); serogroup Y 66% (173/263).
Table 9: Serum bactericidal antibody responses after Menveo administration one month after vaccination in subjects aged 19 to 55 years
Study V59P6E1 evaluated the appearance of the immune response after primary vaccination with Menveo in healthy subjects aged 18-22 years. 7 days after vaccination 64% of subjects developed hSBA ≥1: 8 against serogroup A and between 88% and 90% of subjects had bactericidal antibodies against serogroups C, W135 and Y. One month after vaccination, 92% -98% of subjects had hSBA ≥1: 8 against serogroups A, C, W135, and Y. A robust immune response measured as hSBA GMT against all serogroups at 7 days (GMT 34 to 70) was also observed and at 28 days (GMT 79 to 127) after a single vaccination dose.
Immunogenicity in older adults
The comparative immunogenicity of Menveo vs. ACWY-PS was assessed in subjects aged 56 to 65 years in study V59P17. The percentage of subjects with hSBA ≥ 1: 8 was not less than ACWY-PS for all four serogroups and statistically superior for serogroups A and Y (Table 10).
Table 10: Immunogenicity of a dose of Menveo or ACWY-PS in adults aged 56 to 65 years, measured one month after vaccination
Data available in children aged 2 to 23 months
The immunogenicity of Menveo in children aged 2-23 months has been evaluated in several studies. Although an hSBA titre greater than 1: 8 was achieved in a high percentage of subjects immunized with Menveo with a 4-dose regimen. doses, with lower rates achieved in studies with 2-dose, single-dose regimens, Menveo was compared with another meningococcal vaccine only in one pivotal study in which it did not demonstrate a response at least equivalent to that of a monovalent serogroup conjugate vaccine C (after single dose at 12 months of age). Currently available data are insufficient to establish the efficacy of Menveo in children less than 2 years of age. For information on pediatric use, see section 4.2.
05.2 "Pharmacokinetic properties -
Not relevant.
05.3 Preclinical safety data -
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and reproductive and developmental toxicity.
In laboratory animals, no adverse reactions were found in vaccinated pregnant rabbits or their offspring until postnatal day 29.
No effects on fertility were observed in female rabbits who received Menveo prior to mating and during pregnancy.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Dust
Sucrose
Monobasic potassium phosphate
Solution
Monobasic sodium phosphate monohydrate
Disodium phosphate dihydrate
Sodium chloride
Water for injections
06.2 Incompatibility "-
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
06.3 Period of validity "-
3 years.
The medicinal product should be used immediately after reconstitution. However, physico-chemical stability has been demonstrated for 8 hours after reconstitution at a temperature below 25 ° C.
06.4 Special precautions for storage -
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze.
Keep the vials in the cardboard box to protect the medicine from light.
For storage conditions of the medicinal product after reconstitution, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package -
Powder in vial (type I glass) with a stopper (halobutyl rubber) and solution in a vial (type I glass) with a stopper (butyl rubber).
Pack size of one dose (2 vials) or five doses (10 vials).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Menveo must be prepared for administration by reconstituting the powder (in the vial) with the solution (in the vial).
The contents of the two different vials (MenA powder and MenCWY solution) must be mixed before vaccination to obtain 1 dose of 0.5 ml.
Vaccine components should be visually inspected before and after reconstitution.
With a syringe and a suitable needle (21G, length 40 mm or 21G, length 1 ½ ") withdraw the entire contents of the solution vial and inject it into the powder vial to reconstitute the MenA conjugate component.
Invert and shake the vial vigorously, then withdraw 0.5 ml of the reconstituted product. Note that it is normal for a small amount of liquid to remain in the vial after the dose has been withdrawn.
After reconstitution, the vaccine is a clear, colorless to pale yellow solution, free from visible foreign particles. If the presence of foreign particulate matter and / or change in physical appearance is observed, the vaccine should be discarded.
Before injection, replace the needle with one suitable for administering the vaccine. Check that there are no air bubbles in the syringe before injecting the vaccine.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
GSK Vaccines S.r.l.
Via Fiorentina 1
53100 Siena, Italy
08.0 MARKETING AUTHORIZATION NUMBER -
EU / 1/10/614/002
039766023
EU / 1/10/614/003
039766035
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 15 March 2010
Date of most recent renewal: 4 December 2014
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