Imojev

Imojev

vaccine, japanese encephalitis

Manufacturer:

sanofi pasteur

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Live, attenuated, recombinant Japanese encephalitis virus (propagated in Vero cells).
Description
Imojev is a monovalent, live attenuated viral vaccine. The virus was obtained via recombinant DNA technology. It is based on the 17D-204 yellow fever vaccine virus in which two genes have been replaced by the corresponding genes from Japanese encephalitis (JE) virus. These are the premembrane (prM) and envelope (E) coding sequences of the SA14-14-2 live attenuated JE vaccine virus. The immunizing antigens are the prM and E proteins from SA14-14-2 vaccine virus.
After reconstitution: Active Ingredients: Live, attenuated, recombinant Japanese encephalitis virus*: 4.0 - 5.8 log PFU**.
* Propagated in Vero cells.
** Plaque Forming Unit.
Excipients/Inactive Ingredients: Mannitol, Lactose, Glutamic acid, Potassium hydroxide, Histidine, Human Serum Albumin, Sodium chloride, Water for injections.
No adjuvant or antimicrobial preservative is added.
The diluent is a clear solution. After reconstitution, IMOJEV is a colourless to amber suspension.
Action
Pharmacology: Mechanism of Action: The vaccine is a live attenuated virus. Following administration, the virus replicates locally and elicits neutralising antibodies and cell-mediated immune responses that are specific to the Japanese encephalitis (JE) virus. Available results indicate that protection is mainly mediated by neutralising antibodies.
In nonclinical studies, all animals that received a single dose of the vaccine developed specific neutralising antibodies against JE virus and were protected against infection by a virulent JE virus experimental challenge.
Clinical Trials: Immunogenicity: Passive antibody transfer results in a small animal model indicate that protection is mediated by neutralizing antibodies and that the threshold for protection is a plaque reduction neutralization titre of 1: 10.
Immunogenicity Data in Adult Populations: A single dose administration of IMOJEV is as immunogenic as a three-dose regimen of an inactivated Japanese encephalitis (JE) comparator vaccine administered in adults 18 years of age and over.
A seroprotective level of antibodies is generally reached 14 days after vaccination.
In a randomized comparative Phase III trial, 410 individuals over 18 years of age received a single dose of not less than 4.0 log PFU/ dose of 0.5 mL of IMOJEV and 410 individuals over 18 years of age received a three-dose regimen of 1 mL of an inactivated JE comparator vaccine.
Thirty days after vaccination, the seroprotection rates for the individuals who received IMOJEV were approximately 99% when measured against the homologous virus strain. These results are non-inferior to those observed after the three-dose regimen of the inactivated JE comparator vaccine.
Fourteen days after a single dose of IMOJEV, approximately 93% of the vaccinees showed seroprotective levels of neutralizing antibodies.
Table 1 shows the seroprotection rates measured against the homologous virus strain, 14 and 30 days after vaccination with a single dose of IMOJEV or a three-dose regimen of the inactivated JE comparator vaccine. (See Table 1.)

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Neutralising antibody levels were also assessed against a panel of wild-type strains belonging to the four main genotypes and originating from different countries. In a Phase II trial, approximately 89% of vaccinees showed neutralizing antibody levels above the 1:10 threshold against the tested wild-type strains, 28 days after a single dose administration of IMOJEV.
In a long-term follow-up assessment in a randomized control phase II trial, 97.6% (95% CI, 93.3; 98.8) of individuals showed seroprotective levels six months after a single administration of IMOJEV. The probability of being still seroprotected 60 months after vaccination for those who were seroprotected at six months is 86.8%.
Long-term immunogenicity data up to Month 60 are presented as Kaplan Meier estimates in Table 2. (See Table 2.)

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No long-term immunogenicity data beyond 5 years after the administration of a single dose of IMOJEV are available.
Immunogenicity Data in Paediatric Populations: Primary Vaccination: Immune response 28 days after a single-dose administration of Imojev.
A seroprotective level of antibodies is generally reached 28 days after vaccination.
A single dose administration of IMOJEV in 2 randomized trials in 1,231 toddlers (12 to 24 months) not previously immunized with a Japanese Encephalitis (JE) vaccine showed that approximately 95% of individuals seroconverted and were seroprotected (neutralising antibody level above the threshold of protection) after 28 days.
Table 3 shows the immune response against the homologous virus strain, 28 days after vaccination with a single dose of IMOJEV. (See Table 3.)

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In addition, approximately 96% of a subset of toddlers not previously immunized with a JE vaccine in a Phase II trial seroconverted to three of the four tested JE wild-type strains 28 days after a single dose administration of IMOJEV, and approximately 70% seroconverted to the fourth strain.
A single dose administration of IMOJEV in a randomized comparative Phase III trial in infants and toddlers (9 to 18 months) (N=126) not previously immunized with a JE vaccine showed more than 99% of individuals seroconverted and were seroprotected after 28 days. These results were non-inferior to those observed after the administration of a live attenuated Japanese encephalitis comparator vaccine. (See Table 4.)

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Immune response up to 5 years after a single dose administration of IMOJEV: The persistence of seroprotection was assessed in a Phase II and a Phase III trials in toddlers.
In the Phase II trial, approximately 59% of toddlers who did not receive any JE vaccine before the single dose administration of IMOJEV were shown to still have seroprotective antibody levels 5 years after the vaccination.
Table 5 shows the immune response up to 5 years after vaccination with a single dose of IMOJEV. (See Table 5.)

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In the Phase III trial, approximately 67% of toddlers who did not receive any JE vaccine before the single dose administration of IMOJEV are still seroprotected 5 years after the vaccination. All the toddlers included in this trial with serological data available 28 days after the vaccination were seroprotected at this time point.
Table 6 shows the immune response against the homologous virus strain, up to 5 years after vaccination with a single dose of IMOJEV. (See Table 6.)

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In another Phase III trial in infants and toddlers (9 to 18 months) not previously immunized with a JE vaccine approximately 88% of individuals were still seroprotected 1 year after the single dose administration of IMOJEV. (See Table 7.)

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Booster: Booster dose of IMOJEV after primary vaccination with IMOJEV.
In a Phase III trial, a second dose (booster dose) of IMOJEV was administered in children (36 to 42 months of age) (N=340) 24 months after primary vaccination with IMOJEV. A control group of children (36 to 42 months of age) (N=39) who never received a JE vaccine, received IMOJEV for the first time to characterize the primary response to IMOJEV.
The Geometric Mean Titre (GMT) increased by nearly 6 fold from Day 0 to Day 7 after the administration of IMOJEV in children previously vaccinated. By comparison, the GMT did not increase in the control group, thus demonstrating an anamnestic response in the booster group. The GMT increased by nearly 57 fold from Day 0 to Day 28 in the booster group.
100% of children previously vaccinated with IMOJEV showed seroprotective antibody titres 28 days after the administration of the booster dose 24 months after primary vaccination.
Table 8 shows the immune response against the homologous virus strain, 7 and 28 days after administration of a booster dose of IMOJEV. (See Table 8.)

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In a Phase III trial, a second dose (booster dose) of IMOJEV was administered in children (2 to 4 years of age) (N=97) between 12 and 24 months after primary vaccination with IMOJEV.
The GMT increased by nearly 51 fold from Day 0 to Day 28 in the booster group.
100% of children previously vaccinated with IMOJEV showed seroprotective antibody titres 28 days after the administration of the booster dose between 12 and 24 months after primary vaccination. (See Table 9.)

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In the long-term follow-up assessment of the phase III trial, nearly all children (98.2%) who received the booster dose of IMOJEV 24 months after primary vaccination are still seroprotected 4 years after the vaccination.
Table 10 shows the immune response up to 4 years after vaccination with a booster dose of IMOJEV. (See Table 10.)

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Booster vaccination with IMOJEV after the administration of an inactivated JE vaccine as a primary immunization.
In a Phase II trial, IMOJEV was administered to children (N=97) (2 to 5 years) 6 to 38 months after a two-dose primary vaccination with an inactivated JE vaccine (mouse brain-derived JE).
The GMT increased by nearly 59 fold from Day 0 to Day 28.
Approximately 93% of individuals seroconverted and they were all seroprotected (titre above a threshold considered as protective) 28 days after the administration of IMOJEV.
Table 11 shows the immune response 28 days after the administration of a booster dose of IMOJEV after a primary vaccination with an inactivated JE vaccine. (See Table 11.)

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In addition, approximately 99% of children showed seroprotective antibody levels against JE wild-type strains belonging to the four main genotypes, 28 days after the administration of IMOJEV.
In the long-term follow-up assessment of the phase II trial, nearly all children (96.3%) who received the booster dose of IMOJEV 6 to 38 months after the two-dose primary vaccination with the inactivated JE vaccine are still seroprotected 5 years after the vaccination.
Table 12 shows the immune response up to 5 years after the administration of a booster dose of IMOJEV after a primary vaccination with an inactivated JE vaccine. (See Table 12.)

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Indications/Uses
IMOJEV is indicated for prophylaxis of Japanese encephalitis caused by the Japanese encephalitis virus, in individuals from 9 months of age and over.
Dosage/Direction for Use
Primary Vaccination: Individuals 9 months of age and over: a 0.5 mL single injection of the reconstituted vaccine.
Booster: Adult population (18 years of age and over): There is no need for a booster dose up to 5 years after the administration of a single dose of IMOJEV.
Paediatric population (9 months to 17 years of age inclusive): A booster dose of IMOJEV should be given after primary vaccination in order to confer long term protection. The booster dose should be given preferably 12 months after primary vaccination and can be given up to 24 months after primary vaccination.
IMOJEV can also be given as a booster vaccination in children who were previously given an inactivated Japanese Encephalitis (JE) vaccine for primary vaccination, in accordance with the recommended timing for the booster of the inactivated JE vaccine.
Safety and efficacy of a booster dose in children and adolescents 5 to 17 years of age have not been established. Nevertheless, the booster dose can be considered based on the available data in other age groups.
Once the freeze-dried vaccine has been completely reconstituted using the diluent provided (see Instructions for Use as follows), it is administered via the subcutaneous route.
In individuals 2 years of age and over, the recommended injection site is the deltoid region of the upper arm.
In individuals between 9 and 24 months of age, the recommended injection site is the anterolateral aspect of the thigh or the deltoid region.
Do not administer by intravascular injection.
IMOJEV must not be mixed with any other injectable vaccine(s) or medicinal product(s).
Contact with disinfectants is to be avoided since they may inactivate the vaccine virus.
Product is for single use in one patient only. Discard any residue.
Instructions for Use: Using aseptic technique, IMOJEV vaccine is reconstituted by injecting all the 0.4 % sodium chloride solution into the vial of freeze-dried vaccine, using the syringe and one of the needles provided in the carton. The vial is gently swirled. After complete dissolution, a 0.5 mL dose of the reconstituted suspension is withdrawn into this same syringe. For injection, the syringe is fitted with the second needle provided in the package.
The product should be used once reconstituted and must be discarded if it is not used within one hour of reconstitution.
After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures.
Overdosage
There is no specific information regarding overdose with IMOJEV.
Contraindications
IMOJEV should not be administered to anyone with a history of severe allergic reaction to any component of the vaccine or after previous administration of the vaccine or a vaccine containing the same components or constituents.
Vaccination must be postponed in case of febrile or acute disease.
Congenital or acquired immune deficiency impairing cellular immunity, including immunosuppressive therapies such as chemotherapy, high doses of systemic corticosteroids given generally for 14 days or more.
IMOJEV must not be administrated to individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.
IMOJEV must not be administered to pregnant women (see Use in Pregnancy & Lactation).
IMOJEV must not be administered to breast feeding women (see Use in Pregnancy & Lactation).
Special Precautions
Before the injection of any biological, the person responsible for administration must take all precautions known for the prevention of allergic or any other reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine.
In individuals who have a history of serious or severe reaction within 48 hours of a previous injection with a vaccine containing similar components, the course of the vaccination must be carefully considered.
IMOJEV should under no circumstances be administered intravascularly.
Protection: As with any vaccine, vaccination with IMOJEV may not protect 100% of vaccinated individuals.
Effect on Laboratory Tests: Interference of IMOJEV with laboratory and/or diagnostic tests has not been studied.
Genotoxicity: IMOJEV has not been tested for genotoxic potential.
Carcinogenicity: IMOJEV has not been tested in carcinogenic potential.
Use in Pregnancy (Category B2): Developmental toxicity studies in which female rabbits were subcutaneously administered the human dose of IMOJEV twice prior to mating and three times during gestation, or once between gestation days 6 to 18, or once on postnatal day 15, showed no adverse effects on pregnancy, embryo-fetal development, parturition or postnatal development. Vaccine antigen-specific antibodies were transferred to fetuses.
As with all live attenuated vaccines, pregnancy constitutes a contraindication (see Contraindications).
There is a theoretical risk that a live vaccine virus can cross the placenta and infect the fetus. It is not known whether IMOJEV can cause fetal harm when administered to a pregnant woman.
Women of childbearing age should be advised not to become pregnant for 4 weeks after vaccination.
Use in Lactation: A developmental toxicity study in which female rabbits were subcutaneously administered the human dose of IMOJEV once between gestation days 6 to 18, or once on postnatal day 15, showed no effects on pup survival, growth and development.
It is not known whether this vaccine is excreted in human milk.
IMOJEV vaccination is contraindicated in breastfeeding women (see Contraindications).
Studies with some other live, attenuated virus vaccines have shown that a lactating postpartum woman may secrete the virus in breast milk and transmit virus to a breast-fed infant.
Effects on Fertility: A reproductive and developmental toxicity study in which female rabbits were subcutaneously administered the human dose of IMOJEV twice prior to mating showed no effects on female mating or fertility. No fertility data are available in humans.
Special Patient Groups: For patients following a treatment with high doses of systemic corticosteroids given for 14 days or more, it is advisable to wait for at least one month or more following the interruption of therapy before carrying out the vaccination until immune function has recovered.
Use in Children: IMOJEV is not recommended in children below the age of 9 months.
Use in Elderly: In clinical trials, the seroconversion rates and the safety profiles were similar in elderly and adults after the administration of one dose of IMOJEV.
Use In Pregnancy & Lactation
Effects on Fertility: A reproductive and developmental toxicity study in which female rabbits were subcutaneously administered the human dose of IMOJEV twice prior to mating showed no effects on female mating or fertility. No fertility data are available in humans.
Use in Pregnancy (Category B2): Developmental toxicity studies in which female rabbits were subcutaneously administered the human dose of IMOJEV twice prior to mating and three times during gestation, or once between gestation days 6 to 18, or once on postnatal day 15, showed no adverse effects on pregnancy, embryo-fetal development, parturition or postnatal development. Vaccine antigen-specific antibodies were transferred to fetuses.
As with all live attenuated vaccines, pregnancy constitutes a contraindication (see Contraindications).
There is theoretical risk that a live vaccine virus can cross the placenta and infect the fetus. It is not known whether IMOJEV can cause fetal harm when administered to a pregnant woman.
Women of childbearing age should be advised not to become pregnant for 4 weeks after vaccination.
Use in Lactation: A development toxicity study in which female rabbits were subcutaneously administered the human dose of IMOJEV once between gestation days 6 to 18, or once on postnatal day 15, showed no effects on pup survival, growth and development.
It is not known whether this vaccine is excreted in human milk.
IMOJEV vaccination is contraindicated in breastfeeding women (see Contraindications).
Studies with some other live, attenuated virus vaccines have shown that a lactating postpartum woman may secrete the virus in breast milk and transmit virus to a breast-fed infant.
Adverse Reactions
Clinical Trials Experience: Data in Adult Populations: The safety of IMOJEV has been assessed in 8 randomised clinical trials in individuals over 18 years of age. During the development in the adult population, approximately 2,500 individuals received an injection of IMOJEV.
Safety evaluation was performed for all individuals during the first 4 weeks following vaccination and serious adverse reactions were collected during at least six months of follow-up after a single dose of IMOJEV.
The most frequently reported systemic reactions after the administration of IMOJEV vaccine were headache, fatigue, malaise and myalgia. All these reactions were as frequently reported as after the administration of the inactivated Japanese Encephalitis (JE) comparator vaccine or a placebo.
The most frequently reported reaction at the injection site after the administration of IMOJEV vaccine was injection site pain. All the injection site reactions were less frequently reported than after the administration of the inactivated JE comparator vaccine and as frequently reported as after the administration of a placebo.
Local and systemic reactions are ranked within each system organ class, under headings of frequency, using the following convention [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), including isolated reports].
The following possibly related Adverse Events were reported during clinical trials within 30 days after vaccination: General Disorders and Administration Site Conditions: Very common: Fatigue, malaise, injection site pain. Common: Feeling hot, chills, injection site erythema, injection site pruritus, injection site swelling, injection site bruising. Uncommon: Pyrexia.
Nervous System Disorders: Very Common: Headache. Common: Dizziness.
Muscoloskeletal and Connective Tissue Disorders: Very Common: Myalgia. Common: Arthralgia.
Gastrointestinal Disorders: Common: Diarrhoea, nausea, abdominal pain, vomiting.
Respiratory, Thoracic and Mediastinal Disorders: Common: Pharyngolaryngeal pain, dyspnea, rhinorrhea, cough, wheezing, nasal congestion.
Skin and Subcutaneous Tissue Disorders: Common: Rash.
Infections and Infestations: Rare: Viral infections.
Table 13 as follows summarises the possibly related Adverse Events (frequency ≥ 1.0%) that were reported during clinical trials within 30 days after the administration of a single dose of IMOJEV, of the two first doses and the third dose of the inactivated JE comparator vaccine and of the placebo doses. (See Table 13.)

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Data in Paediatric Populations: The safety of IMOJEV in paediatric populations has been assessed in Phase II and Phase III clinical trials. Overall, approximately 2,200 children received at least one injection of IMOJEV in these studies.
In addition, 10,000 individuals between 9 months and 5 years of age received IMOJEV either primary or booster vaccination in a large scale Phase IV safety trial aimed at identifying serious, rare adverse reactions (see Post-Marketing Surveillance as follows).
Results from 5 Phase II and Phase III clinical trials with similar methodology for recording safety data were included in an integrated analysis of safety. During these clinical trials approximately 2,200 individuals between 9 months and 5 years of age received an injection of IMOJEV (approximately 50 infants from 9 to 12 months old and 2,050 toddlers from 12 months not previously immunised with a JE vaccine, as well as 100 children previously immunised with a two-dose regime of a JE vaccine).
Safety evaluation was performed for all individuals during the first 4 weeks following vaccination and serious adverse reactions were collected during at least six months of follow-up after a single dose of IMOJEV.
The most frequently reported systemic reactions were malaise, fever, headache and myalgia in children (2 to 5 years); and irritability, appetite loss, crying and fever in infants and toddlers (9 to 24 months).
The most frequently reported reactions at the injection site after the administration of IMOJEV vaccine was injection site pain/tenderness and injection site erythema.
These adverse events observed during paediatric clinical trials were generally of mild intensity and of short duration. The onset of systemic reactions was generally seen within 3 days after immunisation.
Table 14 as follows summarises the solicited reactions that were reported during clinical trials after the administration of a single dose of IMOJEV or of a control vaccine (see Table 14).

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Table 15 as follows summarises the non-serious adverse reactions that were reported during clinical trials within 28 days after the administration of a single dose of IMOJEV or of a control vaccine. (See Table 15.)

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Local and systemic reactions are ranked within each system organ class, under headings of frequency, using the following convention [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), including isolated reports].
The following related Adverse Events were reported during clinical trials within 28 days after vaccination: General Disorders and Administration Site Conditions: Very common: Pyrexia, malaise, irritability, injection site pain/tenderness, injection site erythema. Common: Injection site swelling. Uncommon: Injection site reactions (induration, bruising, haematoma, haemorrhage). Rare: Injection site pruritus.
Nervous System Disorders: Very common: Headache, somnolence.
Musculoskeletal and Connective Tissue Disorders: Very common: Myalgia.
Gastrointestinal Disorders: Very common: Vomiting.
Metabolism and Nutrition Disorders: Very common: Appetite loss.
Infections and infestations: Uncommon: Upper respiratory tract infection. Rare: Viral infection.
Skin and Subcutaneous Tissue Disorders: Uncommon: Urticaria. Rare: Rash, maculo-papular rash, post inflammatory pigmentation change.
Psychiatric Disorders: Very common: Inconsolable crying.
No serious adverse events within 28 days of administration of IMOJEV were related to vaccination.
During the paediatric clinical trials, 29 cases of convulsions have been reported, including 28 cases of febrile convulsion and 1 case of convulsion without fever. All cases were assessed as not related to vaccination and were reported to be associated with concurrent infectious diseases (or common cold). In 9 cases, convulsions started within 30 days after IMOJEV vaccination.
In the following studies, the safety of IMOJEV presented no clinically relevant difference with the previously-described safety profile: In a phase III trial in 390 individuals between 36 and 42 months of age (45 out of the 390 received a single dose of IMOJEV, and 345 out of the 390 received a second dose (booster dose) of IMOJEV 2 years after the first dose).
In a Phase III trial in 119 children between 18 and 36 months of age who received a second dose (booster dose) of IMOJEV.
Adverse Reactions from Post-Marketing Surveillance: No additional adverse reactions were identified from the Phase IV safety trial conducted in 10,000 individuals between 9 months and 5 years of age, as well as from spontaneous reporting in post-marketing surveillance.
Drug Interactions
Concomitant Administration with Other Vaccine(s): Separate injection sites and separate syringe should be used when other vaccines are concomitantly administered with IMOJEV (see Dosage & Administration).
From 12 months of age, IMOJEV may be administered at the same time as vaccines against measles, mumps, or rubella, either stand alone or combined.
For children living in or travelling to areas where risk for measles is high, IMOJEV may be administered at the same time as measles vaccine, either stand alone or combined with mumps and/or rubella vaccines, from as early as 9 months of age.
IMOJEV may be administered to adults at the same time as yellow fever vaccine.
Vaccine-drug Interactions: In the case of immunosuppressive therapy or corticosteroid therapy, refer to Contraindications and Precautions.
Administering the vaccine in individuals who have previously received immunoglobulins: In order to avoid any neutralisation of the attenuated viruses contained in the vaccine, vaccination must not be performed within 6 weeks, and preferably not within 3 months of injection of immunoglobulins or blood products containing immunoglobulins, such as blood or plasma.
Storage
Store in a refrigerator (2-8°C). Do not freeze.
Keep the vials in the outer carton in order to protect from light.
ATC Classification
J07BA03 - encephalitis, Japanese, live attenuated ; Belongs to the class of encephalitis viral vaccines.
Presentation/Packing
Vaccine (inj) 0.5 mL (powder is a white to creamy white homogenous cake in a vial) x 1's.
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