Summary of medicine characteristics - Celvapan
1. NAME OF THE MEDICINAL PRODUCT
Celvapan suspension for injection
Influenza vaccine (H1N1)v (whole virion, Vero cell derived, inactivated)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Whole virion influenza vaccine, inactivated containing antigen of strain
A/California/07/2009 (H1N1)v 7.5 micrograms
per 0.5 ml dose propagated in Vero cells (continuous cell line of mammalian origin) expressed in micrograms haemagglutinin.
This is a multidose container. See section 6.5 for the number of doses per vial.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Suspension for injection.
The vaccine is a clear to opalescent, translucent suspension.
4.
4.1
Prophylaxis of influenza cause
2009 virus (See section 4.4).
Celvapan should be used in accordance with Official Guidance
4.2 Posology and met
administration
Posology
The dose recommendations take into account available data from clinical studies in healthy subjects
who received two doses of Celvapan (H1N1)v. ♦
From clinical studies limited immunogenicity and safety data are available for Celvapan (H1N1)v in
healthy adult and older subjects and in children (see section 4.4, 4.8, and 5.1).
Adults and older people
e dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least three weeks.
Children and adolescents aged 3 to 17 years One dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least three weeks.
Children aged 6 to 35 months
One dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least three weeks.
Children aged less than 6 months
Vaccination is not currently recommended in this age group.
For further information, see sections 4.8 and 5.1.
It is recommended that subjects who receive a first dose of Celvapan, complete the vaccination course with Celvapan (see section 4.4).
Method of administration
♦ J
Immunisation should be carried out by intramuscular injection preferably into the deltoid muscle or anterolateral thigh, depending on the muscle mass.
4.3 Contraindications
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues (e.g. formaldehyde, benzonase, sucrose) of this vaccine.
See section 4.4 for Special warnings and special precautions for use.
4.4 Special warnings and precautions for use
The vaccine can only be expected to protect against influenza caused by
A/California/07/2009 (H1N1)v-like strains.
Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance(s), to any of the excipients and to trace residues e.g. formaldehyde, benzonase, or sucrose.
Hypersensitivity reactions, including anaphylaxis, have been reported following CELVAPAN vaccination (see section 4.8). Such reactions have occurred both in patients with a history of multiple allergies and in patients with no known allergy.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
Immunisation shall be postponed in patients with severe febrile illness or acute infection.
Celvapan should under no circumstances be administered intravascularly.
There are no data with Celvapan using the subcutaneous route. Therefore, healthcare providers need to assess the benefits and potential risks of administering the vaccine in individuals with thrombocytopenia or any bleeding disorder that would contraindicate intramuscular injection unless
thrombocytopenia or any bleeding disorder that would contraindicate intramuscular injection unless the potential benefit outweighs the risk of bleedings.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be elicited in all vaccinees (see section 5.1).
There are no safety, immunogenicity or efficacy data to support interchangeability of Celvapan with other (H1N1)v vaccines.
4.5 Interaction with other medicinal products and other forms of interaction
There are no data on co-administration of Celvapan with other vaccines. However, if co-administration with another vaccine is considered, immunisation should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified.
The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.
Following influenza vaccination, false positive serology test results may be obtained by the ELISA method for antibody to human immunodeficiency virus-1 (HIV-1), hepatitis C virus, and especially, HTLV-1. In such cases, the Western Blot method is negative. These transitory false-positive results may be due to IgM production in response to the vaccine.
4.6 Fertility, pregnancy and lactation
The safety of Celvapan in pregnancy and lactation has been assessed in a limited number of pregnant women.
Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do not suggest malformations or fetal or neonatal toxicity.
opment, parturition or post-natal
Animal reproductive and developmental toxicity studies with H5N1 strain vaccines (A/Vietnam/1203/2004 and A/Indonesia/05/2005) do not indicate direct or indirect harmful effects with respect to female fertility, pregnancy, embryonal/foeta development (see section 5.3).
The use of Celvapan may be considered during pregnancy if this is thought to be necessary, taking into account official recommendations.
Celvapan may be used in lactating women
4.7 Effects on ability to drive and use machines
Some undesirable effects mentioned under section 4.8 “Undesirable effects” may affect the ability to drive or use machines.
4.8 Undesirable effects
- • Clinical tt.als with Celvapan (H1N1)v
Adults and Older People
In a clinical study the 7.5 gg dose of Celvapan (H1N1)v was administered to adults aged 18 to 59 years (N = 101) and older people over 60 years of age (N = 101). Safety data after the first and second vaccination suggest a similar safety profile to that reported for the influenza vaccines using a H5N1 strain.
Adverse reactions from clinical trials with Celvapan (H1N1)v in a healthy adult and older people are listed in the table below.
| Clinical Adverse Reactions (H1N1)v Studies | ||
| System Organ Class (SOC) | Preferred MedDRA Term | Frequency1 |
| INFECTIONS AND INFESTATIONS | Nasopharyngitis | Common |
| PSYCHIATRIC DISORDERS | Insomnia | Common |
| NERVOUS SYSTEM DISORDERS | Headache Dizziness | Very Common Common |
| EYE DISORDERS | Eye irritation | Common |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | Pharyngolaryngeal pain | Common |
| GASTROINTESTINAL DISORDERS | Abdominal pain | Comm on |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | Hyperhidrosis Rash Urticaria | Common common common |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | Arthralgia Myalgia | Common Common |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | Fatigue Pyrexia Chills Malaise Injection site reactions
| Very Common Common Common Common Common Common Common Common Common |
ADR frequency is based upon the following scc'e: Very Common (> 1/10); Common (> 1/100 -< 1/10), Uncommon (> 1/1,000 – < 1/100), Rare (> 1/10,000 – < 1/1,000), Very Rare (< 1/10,000)
Children and adolescents 3 to 17 years of age
In a clinical trial 51 children and adolescents aged 9 to 17 years and 51 children aged 3 to 8 years were administered the 7.5 gg dose of Celv apan (H1N1)v. The incidence and nature of symptoms after the first and second vaccination were similar to that observed in the adult and older population using Celvapan.
Children aged 6 to 35 m onths
In a clinical trial the 7.5 gg dose of Celvapan (H1N1)v was administered to 69 infants and young children aged 6 to 35 months.
1 represents the highest frequency observed either in the healthy adult or healthy older study population.
Adverse reactions from pediatric clinical trials with CELVAPAN (H1N1)v are listed in the table below.
Clinical Trial Adverse Reactions H1N1v studies
| System Organ Class (SOC) | Preferred MedDRA Term | Frequency | ||
| 9 – 17 years | 3 – 8 years | 6 – 35 months | ||
| METABOLISM AND NUTRITION DISORDERS | Decreased appetite | – | – | Common |
| PSYCHIATRIC | Sleep disorder | – | – | Very common |
| DISORDERS | Restlessness | – | Common | |
| NERVOUS SYSTEM | Headache | Common | Common | Common |
| DISORDERS | Crying | – | – | Common |
| Somnolence | – | – | Common | |
| EAR AND LABYRINTH DISORDERS | Vertigo | Common | – | |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | Cough | – | – | Common ► |
| GASTROINTESTINAL | Abdominal pain | Common | – | Common |
| DISORDERS | Nausea | Common | Common | |
| Vomiting | Common | Common | Common | |
| Diarrhea | – 4 | Common | Common | |
| SKIN AND | Hyperhidrosis | – | Common | |
| SUBCUTANEOUS TISSUE DISORDERS | Rash | – | Common | |
| MUSCULOSKELETAL | Myalgia | Common | – | – |
| AND CONNECTIVE TISSUE DISORDERS | Pain in extremity | Common | – | – |
| GENERAL DISORDERS | Fatigue | – | Common | – |
| AND | Pyrexia Chills | – | Common | Very common |
| ADMINISTRATION | Common | Common | Common | |
| SITE CONDITIONS | Irritability | – | – | Common |
| Ma'aist t injection site reactions | – | – | Common | |
| * Injection site pain | Very common | Common | Common | |
| kV |
| Common | Common | Common |
| Common | Common | Common | |
| ♦ |
| Common | Common | Common |
ADR frequency is based upon the following scale: Very Common (> 1/10); Common (> 1/100 -< 1,10), Uncommon (> 1/1,000 – < 1/100), Rare (> 1/10,000 – < 1/1,000), Very Rare (< 1/10,000)
* Clinical trials with a version of Celvapan containing a H5N1 vaccine strain
Clinical trials were conducted with a version of Celvapan containing a H5N1 vaccine strain (see section 5.1) in approximately 3700 subjects (ranging in age from 18 to 60 years and above), and in special risk groups of approximately 300 subjects each, consisting of immune-compromised subjects and patients with chronic disease conditions.
Most of the reactions were mild in nature, of short duration and qualitatively similar to those induced by influenza vaccines. There were fewer reactions after the second dose of the vaccine compared with the first dose. The safety profile in healthy subjects > 60 years of age, in immune-compromised subjects and patients with chronic disease conditions is similar to the safety profile in healthy subjects.
- • Post-marketing surveillance
Pandemic Observational Study with Celvapan (H1N1)v
appetite, crying
orted in the post-marketing experience in
In an observational safety study including 3216 subjects aged 6 months to 60 years and older, the nature of adverse events was consistent with those observed in other clinical studies in adults and children. The following adverse reactions were reported at a higher frequency category than in the other clinical studies:
Adults aged 18 years and older:
Very common: Injection site pain, injection site redness, muscle pain Uncommon: influenza like illness
Children and adolescents aged 5 to 17 years:
Very common: fatigue, headache
Uncommon: cough
Children aged 6 months to 5 years:
Very common: Injection site redness, drowsiness, irritabili
Celvapan (H1N1)v
The following additional adverse reactions have adults and children receiving Celvapan (H1N1)v
The frequency of these adverse reactions is not known.
Immune system disorder:
Nervous system disor
Anaphylactic reaction, Hy
Febrile convulsi Hypoaesthesia
Skin and s ubcutaneous tissue disorders:
Trivalent seasonal influenza vaccines
From post-marketing surveillance with egg-derived trivalent seasonal influenza vaccines, the following serious adverse reactions have been reported:
Uncommon:
Generalised skin reactions
Rare:
Neuralgia, paraesthesia, transient thrombocytopenia.
Very rare:
Vasculitis with transient renal involvement.
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrom
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 the national reporting system listed in Appendix V.
4.9 Overdose
No case of overdose has been reported.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB01
Clinical studies with Celvapan (H1N1)v currently provide:
- • Safety and immunogenicit y data obtained three weeks after administration of two doses of Celvapan (H1N1)v to healthy adults aged 18 years and older.
- • Safety and immunogenicity data obtained three weeks after administration of two doses of Celvapan (H1N1)v to healthy children aged 6 months to 17 years.
Clinical studies in which a version of Celvapan containing HA derived from A/Vietnam/1203/2004 (H5N1) was administered at day 0 and at day 21 provide:
- • Safety and immunogenicity data in healthy adults, including older people.
- • I Sa ety and immunogenicity data in special risk groups (immunocompromised and
chronically ill) mmune response against A/California/07/2009(H1N1)v
The immunogenicity of the vaccine containing 7.5 pg non-adjuvanted HA derived from strain A/California/07/2009 (H1N1)v has been evaluated in clinical studies in adults aged 18 years and older (N = 200), in children and adolescents aged 3 to 17 years (N = 102), and in infants and young children aged 6 to 35 months (N = 68) following a 0, 21 day schedule.
Adults aged 18 years and older
After vaccination the seroprotection rate, seroconversion rate and seroconversion factor for anti-HA antibody as measured by single radial haemolysis (SRH) in adults aged 18 to 59 years and in older subjects aged 60 years and above were as follows:
SRH Assay
All subjects
Seronegative subjects at baseline (< 4mm2)
| 21 Days After | 21 Days After | |||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| 18 to 59 years | N = | : 99 | N = | 33 ♦ C |
| Seroprotection rate* | 75.8% | 80.8% | 69.7% | 78.8% |
| (66.1; 83.8) | (71.7; 88.0) | (51.3; 84.4) | (61.1; 91.0) | |
| Seroconversion rate | 64.6% | 70.7% | 69.7% | 78.8% |
| (54.4; 74.0) | (60.7; 79.4) | (51.3; 84.4) | (61.1; 91.0) | |
| Seroconversion factor | 3.4 | 4.1 | 7.1 9.5 | |
| (2.8; 4.3) | (3.3; 5.1) | (4.5; 11.0) | (6.5; 13.8) | |
| > 60 years | N = | 101 | ZN = | 22 |
| Seroprotection rate* | 76.2% | 82.2% | 50.0% | 63.6% |
| (66.7; 84.1) | (73.3; 89.1) | (28.2; 71.8) | (40.7; 82.8) | |
| Seroconversion rate | 28.7% | 35.6% | 50.0% | 63.6% |
| (20.1; 38.6) | (26.4; 45.8) | (28.2; 71.8) | (40.7; 82.8) | |
| Seroconversion factor | 1.8 | 2.0 | 3.9 | 5.6 |
| (1.5; 2.1) | (1.7; 2.4) | CX-3; 6.7) | (3.4; 9.2) | |
SRH area > 25 mm2
either SRH area > 25 mm2 if baseline sample negativ sample > 4 mm2 geometric mean increase
increase in SRH area if baseline
After vaccination the rate
antibody titres > 40, seroconversion rate and
seroconversion factor as measured by microneutralisation assay (MN) in adults aged 18 to 59 years and in older subjects aged 60 years and above were as follows:
MN Assay
All subjects
1st Dose
Seronegative subjects at baseline (< 1:10) 21 Days After
21 Days After
1st Dose
2nd Dose
2nd Dose
| 18 to 59 years | N = 100 | N = 99 | N = 39 | N = 38 |
| Seroneutralization rate | 87.0% | 98.0% | 74.4% | 97.4% |
| (78.8; 92.9) | (92.9; 99.8) | (57.9; 87.0) | (86.2; 99.9) | |
| Seroconversion rate | 80.0% | 86.9% | 84.6% | 97.4% |
| (70.8; 87.3) | (78.6; 92.8) | (69.5; 94.1) | (86.2; 99.9) | |
| Seroconversion factor | 21.3 | 29.0 | 28.8 | 55.3 |
| (14.6; 31.2) | (20.5; 41.0) | (15.2; 54.5) | (32.0; 95.6) | |
| > 60 years | N = | 101 | N = 34 | N = 38 |
| Seroneutralization rate* | 70.3% | 82.2% | 55.9% | 76.3% |
| v> | (60.4; 79.0) | (73.3; 89.1) | (37.9; 72.8) | (59.8; 88.6) |
| Seroconversion rate | 55.4% | 71.3% | 73.5% | 94.7% |
| ✓ | (45.2; 65.3) | (61.4%; 79.9) | (55.6; 87.1) | (82.3; 99.4) |
| Seroconversion factor | 5.0 | 7.6 | 7.1 | 15.0 |
| (3.8; 6.6) | (5.9; 9.9) | (4.4; 11.3) | (10.1; 22.2) |
MN titre > 1:40
> 4-fold increase in MN titre geometric mean increase
Persistence of anti-HA antibodies 180 days after the first vaccination as measured by single radial haemolysis (SRH) and microneutralisation assay (MN) in adults aged 18 to 59 years and in older subjects aged 60 years and above was as follows:
Antibody persistence
All subjects
Day 181
Seronegative subjects at baseline (< 1:10) Day 181
SRH
MN
SRH
| 18 to 59 years | N = 98 | N = 98 | N = 33 | N = 32 |
| Seroprotection / | 80.6% | 94.9% | 78.8% | 90.6% |
| Seroneutralization rate | (71.4;87.9) | (88.5;98.3) | (61.1;91,0) | (75.0;98.0) |
| Seroconversion rate | 68.4% | 83.7% | 78.8% | 96.9% |
| (58.2;77.4) | (74.8;90.4) | (61.1;91.0) | (83.8;99.9) | |
| Seroconversion factor | 3.6 | 15.0 | 8.0 | 30.0 |
| (2.9;4.4) | (11.0;20.4) | (5.7;11.4) | (■7.7;50.8) | |
| > 60 years | N = 101 | N = 101 | N = 22 | N = 24 |
| Seroprotection / | 80.2% | 79.2% | 59.1% | 66.7% |
| Seroneutralization rate* | (71.1;87.5) | (68.9;85.8) | (36.4;79.3) 59.1% | (44.7;84.4) |
| Seroconversion rate | 30.7% | 54.5% | 83.3% | |
| (21.9;40,7) | (44.2;64.4) | (36.4;79.3) 4.6 | (62.6;95.3) | |
| Seroconversion factor | 1.8 | 4.6 | 8.9 | |
| (1.5;2,1) | (3.7;5.7) | (2.9;7.3) | (5.6;14.0) |
SRH area > 25 mm2; MN titre > 1:40;
either SRH area > 25 mm2 if baseline sample negative o sample > 4 mm2; > 4-fold increase in MN titre;
geometric mean increase
MN
Children and adolescents (3 – 17 years of age^
ase in SRH area if baseline
The seroprotection rate, seroconversion rate an onversion factor for anti-HA antibody as measured by single radial haemolysis (SRH) in children and adolescents aged 3 to 17 years were as follows:
SRH Assay
All subjects
21 Days After
Seronegative subjects at baseline (< 4mm2) 21 Days After
| J 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| 3 to 8 years | N = | 51 | N = | 31 |
| Seroprotection rate | 51.0% | 88.2% | 58.1% | 93.5% |
| \X | (36.6; 65.2) | (76.1; 95.6) | (39.1; 75.5) | (78.6; 99.2) |
| Seroconversion rate | 47.1% | 88.2% | 58.1% | 93.5% |
| (32.9; 61.5) | (76.1; 95.6) | (39.1; 75.5) | (78.6; 99.2) | |
| Seroconversion factor | 3.5 | 8.6 | 5.8 | 15.0 |
| (2.5; 4.9) | (6.6; 11.3) | (3.9; 8.8) | (12.4; 18.1) | |
| 9 to 17 years | N = | 50 | N = | 29 |
| Seroprotection rate* | 80.0% | 88.0% | 82.8% | 93.1% |
| v> | (66.3; 90.0) | (75.7; 95.5) | (64.2; 94.2) | (77.2; 99.2) |
| Seroconversion rate | 74.0% | 84.0% | 82.8% | 93.1% |
| ✓ | (59.7; 85.4) | (70.9; 92.8) | (64.2; 94.2) | (77.2; 99.2) |
| Seroconversion factor | 6.8 | 8.9 | 9.8 | 13.8 |
| (5.0; 9.2) | (6.6; 11.9) | (6.9; 14.0) | (10.3; 18.4) |
SRH area > 25 mm2
either SRH area > 25 mm2 if baseline sample negative or 50% increase in SRH area if baseline sample > 4 mm2
geometric mean increase
After vaccination the rate of subjects with neutralizing antibody titres > 40, seroconversion rate and seroconversion factor as measured by microneutralisation assay (MN) in children and adolescents aged 3 to 17 years were as follows:
| MN Assay | All subjects 21 Days After | Seronegative subjects at baseline (< 1:10) 21 Days After | ||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| 3 to 8 years | N = | 51 | N = | 47 |
| Seroneutralization rate | 84.3% | 100.0% | 83.0% | 100.0% ~ |
| (71.4; 93.0) | (93.0; 100.0) | (69.2; 92.4) | (92.5; 100.0) | |
| Seroconversion rate | 94.1% | 100.0% | 93.6% | 100.0% |
| (83.8; 98.8) | (93.0; 100.0) | (82.5; 98.7) | (92.5; 100.0) | |
| Seroconversion factor | 12.9 | 156.9 | 13.5 | 168.2 |
| (9.5; 17.5) | (119.4; 206.2) | (9.7; 18.8) | (131.1; 215.7) | |
| 9 to 17 years | N = | 51 | N = | 34 |
| Seroneutralization rate* | 94.1 % | 100.0% | 91.2% | 100.0% |
| (83.8; 98.8) | (93.0; 100.0) | (76.3; 98.1) | (89.7; 100.0) | |
| Seroconversion rate | 100.0% | 100.0% | 100.0% | 100.0% |
| (93.0; 100.0) | (93.0; 100.0) | (89.7; 100.0) 29.2 | (89.7; 100.0) | |
| Seroconversion factor | 33.3 | 115.6 | 137.5 | |
| (22.2; 50.0) | (87.4; 152.8) | <^(1 7.9; 47.7) | (99.5; 189.9) | |
MN titre > 1:40
> 4-fold increase in MN titre geometric mean increase
Persistence of anti-HA antibodies 180 days and 360 days after the first vaccination as measured by
single radial hemolysis (SRH) and microneutralization (MN) assay in children and adolescents aged 3 to 17 years was as follows:
Antibody persistence Day 181 Day 361
| SRH | MN | SRH | MN | |
| 9 to 17 years | N=50 | N=47 | N=29 | N=27 |
| Seroprotection / | ^J?8.0% | 100% | 96.6% | 88.9% |
| Seroneutralization rate | (89.4; 99.9) | (92.5; 100.0) | (82.2; 99.9) | (70.8; 97.6) |
| Seroconversion rate | 92.0% | 100% | 93.1% | 96.3% |
| (80.8; 97.8) | (92.5; 100.0) | (77.2; 99.2) | (81.0; 99.9) | |
| Seroconversion factor | 7.8 | 66.4 | 6.5 | 26.7 |
| K V | (6.2; 9.9) | (47.4; 93.1) | (4.7; 9.0) | (16.6; 43.1) |
| 3 to 8 years | N=51 | N=47 | N=33 | N=31 |
| Seroprotection / | 79.6% | 100% | 54.5% | 100% |
| Seroneutralization rate* | (65.7; 89.8) | (92.5; 100.0) | (36.4; 71.9) | (88.8; 100.0) |
| Seroconversion rate | 77.6% | 100% | 57.6% | 96.8% |
| (63.4; 88.2) | (92.5; 100.0) | (39.2; 74.5) | (83.3; 99.9) | |
| Seroconversion factor | 5.6 | 59.5 | 4.5 | 26.5 |
| (4.5; 7.1) | (45.1; 78.3) | (3.4; 6.1) | (18.5; 37.9) |
SRH area > 25 mm2; MN titer >1:40;
either SRH area > 25 mm2 if baseline sample negative or 50% increase in SRH area if baseline sample > 4 mm2; > 4-fold increase in MN titer;
geometric mean increase
Infants and children aged 6–35 months
The seroprotection rate, seroconversion rate and seroconversion factor for anti-HA antibody as measured by single radial haemolysis (SRH) in children aged 6 to 35 months were as follows:
SRH Assay
All subjects Seronegative subjects at baseline
| 21 Days After | 21 Days After | |||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| 6 to 11 months | N = | 19 | N = | 15 |
| Seroprotection rate* | 31.6% | 78.9% | 33.3% | 80.0% |
| (12.6; 56.6) | (54.4; 93.9) | (11.8; 61.6) | (51.9; 95.7) | |
| Seroconversion rate | 31.6% | 84.2% | 33.3% | 80.0% |
| (12.6; 56.6) | (60.4; 96.6) | (11.8; 61.6) | (51.9; 95.7) | |
| Seroconversion factor | 1.9 | 7.6 | 2.1 | 9.0 |
| (1.2; 3.0) | (4.9; 11.7) | (1.1; 3.7) | $(5.6; 14.5) | |
| 12 to 35 months | N = | 49 | N = | 40 |
| Seroprotection rate | 24.5% | 95.9% | 20.0%>^X | 95.0% |
| (13.3; 38.9) | (86.0; 99.5) | (9.1;35.6) | (83.1;99.4) | |
| Seroconversion rate | 22.4% | 91.8% | 20.0% | 95.0% |
| (11.8; 36.6) | (80.4; 97.7) | (9.1; 35.6) | (83.1; 99.4) | |
| Seroconversion factor | 1.8 | 11.2 | 1.8 | 12.5 |
| (1.4; 2.5) | (9.3; 13.4) | 7.3; 2.5) | (10.7; 14.5) | |
% increase in SRH area if baseline
(< 4mm2)
|
| SRH area > 25 mm2 |
| either SRH area > 25 mm2 if baseline sample negativ< sample > 4 mm2 | |
| geometric mean increase |
After vaccination the rate of subjects with neutr seroconversion factor as measured by microneu were as follows:
MN Assay
ll subjects
tibody titres > 40, seroconversion rate and ion assay (MN) in children aged 6 to 35 months
21 Days After
Seronegative subjects at baseline (< 1:10) 21 Days After
| /v | 1st Dose | 2nd Dose | 1st Dose | 2nd Dose |
| 6 to 11 months | N = 17 | N = 19 | N = 17 | N = 19 |
| Seroneutralization rate | 35.3% | 100% | 35.3% | 100% |
| (14.2; 61.7) | (82.4; 100.0) | (14.2; 61.7) | (82.4; 100.0) | |
| Seroconversion rate | 76.5% | 100% | 76.5% | 100% |
| (50.1; 93.2) | (82.4;100.0) | (50.1; 93.2) | (82.4;100.0) | |
| Seroconversion factor | 4.5 | 60.6 | 4.5 | 60.6 |
| (2.7; 7.5) | (27.9; 131.7) | (2.7; 7.5) | (27.9; 131.7) | |
| 12 to 35 m onths | N = | 49 | N = | 48 |
| Seroneutralization rate* | 55.1% | 100% | 54.2% | 100.0% |
| (40.2; 69.3) | (92.7; 100.0) | (39.2; 68.6) | (92.6; 100.0) | |
| Seroconversion rate | 75.5% | 100% | 75.0% | 100.0% |
| (61.1; 86.7) | (92.7;100.0) | (60.4; 86.4) | (92.6; 100.0) | |
| Seroconversion factor | 6.6 | 108.0 | 6.7 | 112.4 |
| (4.6; 9.4) | (75.5; 154.5) | (4.7; 9.6) | (78.7; 160.5) |
|
| MN titre > 1:40 |
|
| > 4-fold increase in MN titre |
|
| geometric mean increase |
Persistence of anti-HA antibodies 180 days and 360 days after the first vaccination as measured by single radial hemolysis (SRH) and microneutralization assay (MN) in infants and young children aged 6 to 35 months was as follows:
| Antibody persistence | Day 181 | Day 361 | ||
| SRH | MN | SRH | MN | |
| 12 to 35 months | N=47 | N=47 | N=31 | N=31 |
| Seroprotection / | 68.1% | 100% | 48.8% | 90.3% |
| Seroneutralization rate | (52.9; 80.9) | (92.5; 100.0) | (30.2; 66.9) | (74.2; 98.0) |
| Seroconversion rate | 63.8% | 100% | 45.2% | 93.5% |
| (48.5; 77.3) | (92.5; 100.0) | (27.3; 64.0) | (78.6; 99.2) | |
| Seroconversion factor | 5.7 | 40.2 | 4.1 | 18.3 |
| (4.7; 7.0) | (29.2; 55.4) | (3.0; 5.5) | (11.2; 29 8) | |
| 6 to 11 months | N=16 | N=13 | N=13 | N=11 |
| Seroprotection / | 37.5% | 100% | 30.8% | ^¿81.8% |
| Seroneutralization rate* | (15.2; 64.6) | (75.3; 100.0) | (9.1; 61.4) | (48.2; 97.7) |
| Seroconversion rate | 37.5% | 100% | 30.8% | 100% |
| (15.2; 64.6) | (75.3; 100.0) | (9.1; 61.4) | (71.5; 100.0) | |
| Seroconversion factor | 2.9 | 19.3 | 2.6 | 17.6 |
| (2.0; 4.4) | (13.8; 27.0) | (1.5 4.5) | (7.1; 43.4) | |
SRH area > 25 mm2; MN titer > 1:40;
either SRH area > 25 mm2 if baseline sample negative or 50% i sample >4 mm2; > 4-fold increase in MN titer;
geometric mean increase
Following a 12-month booster vaccination with a
in SRH area if baseline
nt virosomal influenza vaccine for
the 2010/2011 Northern hemisphere influenza season, seroprotection rates, seroconversion rates and serconversion factors (compared to pre-booster antibody levels) for the H1N1 component as measured
by SRH and MN assays were as follows:
SRH
SRH
MN
MN
21–28 Days Post Booster
| 9 to : N=29 | 7 years N=27 | 3 to 8 years | ||
| N=33 | N=31 | |||
| Seroprotection / | \100% | 100% | 100% | 100% |
| Seroneutralization rate | (88.1; 100.0) | (87.2; 100.0) | (89.4; 100.0) | (88.8; 100.0) |
| Seroconversion rate | 40.0% | 93.1% | 85.3% | 100% |
| (22.7; 59.4) | (77.2; 99.2) | (68.9; 95.0) | (89.7; 100.0) | |
| Seroconversion factor | 1.5 | 13.7 | 2.7 | 29.8 |
| (1.3; 1.7) | (9.4; 20.0) | (2.2; 3.4) | (20.1; 44.1) | |
12 to 35 months
6 to 11 months
| N=31 | N=29 | N=11 | N=9 | |
| _ Seroprotection. | 100% | 100% | 100% | 100% |
| Seroneutralization rate* | (88.8; 100.0) | (88.1; 100.0) | (71.5; 100.0) | (66.4; 100.0) |
| Seroconversion rate | 87.1% | 96.6% | 90.9% | 100% |
| (70.2; 96.4) | (82.2; 99.9) | (58.7; 99.8) | (71.5; 100.0) | |
| Seroconversion factor | 3.6 | 38.7 | 4.9 | 29.1 |
| (2.8; 4.6) | (23.9; 62.7) | (2.7; 8.9) | (11.6; 73.1) |
SRH area > 25 mm2; MN titer >1:40;
either SRH area > 25 mm2 if baseline sample negative or 50% increase in SRH area if baseline sample >4 mm2; > 4-fold increase in MN titer;
*** geometric mean increase
Immune response against a version of Celvapan containing A/H5N1 vaccine strains
The immunogenicity of the vaccine containing 7.5 gg non-adjuvanted HA derived from strain A/Vietnam/1203/2004 has been evaluated in two clinical studies in adults aged 18 – 59 years (N = 312) and in older subjects aged 60 years and older (N = 272) following a 0, 21 day schedule.
The seroprotection rates, seroconversion rates and seroconversion factors reported in adults and older subjects were comparable with Celvapan (H1N1)v.
Results from Vaccine Effectiveness Study in Jersey
Pandemic vaccine effectiveness against the medically-attended influenza like illness (ILI) with laboratory-confirmation as A(H1N1)v, was assessed for the vaccination campaign in
Jersey 2009/2010 in a case control study (test-negative design). Younger children 6 months to 9 years received Celvapan, while older children from 9 to 18 years of age received an adjuvanted split pandemic vaccine. There were no reported vaccine failures in either of these paediatric age grou Crude vaccine effectiveness of one dose of pandemic vaccine among children was 100% (95% CI: 70–100%).
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-Clinical data obtained with Celvapan containing a H5N1 vaccine strain demonstrated alterations
in liver enzymes and calcium levels in repeat dose toxicity studies
h alterations in liver
function have not been seen to date in human clinical studies. Alterations in calcium metabolism have not been examined in human clinical studies.
Animal reproductive toxicology studies do not indicate embryo-foetal and pre- and post-natal toxicity.
6.1 List of excipients
In the absence products.
6. PHARMACEUTICAL PARTICULARS
6.2 Incompatibili
Trometamol Sodium chloride Water for injections
Polysorbate 80
ility studies, this medicinal product must not be mixed with other medicinal
6.3 Shelf-life
6.4 Special precautions for storage
onths
first opening, the product should be used immediately. However, chemical and physical in-use ity has been demonstrated for 3 hours at room temperature.
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 first opening of the medicinal product, see section 6.3.
-
6.5 Nature and contents of the container
One pack of 20 multidose vials (type I glass) of 5 ml suspension (10 × 0.5 ml doses) with a stopper (bromobutyl rubber).