4.1. Therapeutic indications

IXCHIQ is indicated for active immunisation for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 to 59 years.

The use of this vaccine should be in accordance with official recommendations.

4.2. Posology and method of administration

Posology

Individuals from 18-59 years of age

IXCHIQ is administered as a single dose of 0.5 mL.

Revaccination (Booster dose)

The need for revaccination has not been established.

Paediatric population

The safety and immunogenicity of IXCHIQ in children and adolescents aged 0 to 17 years have not yet been established. Only limited safety (see section 4.8) and immunogenicity data in adolescents 12 years of age and older are available.

Method of administration

For intramuscular injection only, after reconstitution.

IXCHIQ should be administered intramuscularly in the deltoid muscle within 2 hours of reconstitution.

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

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

Vaccines must be administered by trained healthcare professionals with experience in benefit ris evaluation of live vaccines. ​

A comprehensive benefit risk assessment must be undertaken before offering IXCHIQ to any individuals. ​ ​

Vaccination should be given no later than 30 days prior to travel.

4.3. Contraindications

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

Immunodeficient or immunosuppressed individuals due to disease or medical therapy (e.g., from malignancies, chemotherapy, immunosuppressive therapy, congenital immunodeficiency, or HIV infection with severe immunosuppression history of thymus disorder or thymectomy, IgA deficiency)

and

Hypertension

Cardiovascular disease

Diabetes mellitus

Chronic kidney disease (CKD)

4.4. Special warnings and precautions for use

IXCHIQ must not be used in individuals 60 years and older (see section 4.1)

IXCHIQ should only be given when there is a significant risk of acquiring chikungunya infection, and after careful consideration of the potential risks and benefits (see Section 4.3 and below).

Serious adverse reactions have been reported with the use of IXCHIQ, particularly in individuals aged 65 years and older and in individuals with two or more underlying chronic and/or uncontrolled medical conditions (see section 4.8). Severe reactogenicity or chikungunya-like adverse reactions may lead to deterioration of general condition including malaise and decreased appetite, exacerbation of pre-existing diseases, confusional state, encephalopathy, or encephalitis, leading to falls, hospitalisation and death. Vaccinees should be instructed to promptly seek medical attention if they experience, after vaccination, symptoms suggestive of severe reactogenicity or severe chikungunya-like adverse reactions.

Due to the risk of adverse events, vaccination should be given no later than 30 days before travel to allow appropriate access to UK healthcare.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity and anaphylaxis

Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine. Close observation for at least 15 minutes is recommended following vaccination.

Anxiety-related reactions

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.

Concurrent illness

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

Thrombocytopenia and coagulation disorders

The vaccine should be given with caution to individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular injection in these individuals.

Limitations of vaccine effectiveness

The ability of IXCHIQ to prevent disease due to chikungunya virus was based on a serological surrogate endpoint (see section 5.1). As with any vaccine, a protective immune response may not be elicited after vaccination in all persons. It is recommended to continue personal protection measures against mosquito bites after vaccination.

Pregnancy

A decision to administer IXCHIQ during pregnancy should take into consideration the individual's risk of wild-type CHIKV infection, gestational age, and risks to the foetus or neonate from vertical transmission of wild-type CHIKV (see section 4.6).

Blood donation

Vaccine viraemia was detected in 90% of subjects 3 days after vaccination, proportions of vaccinees with detectable virus declined to 17% by 7 days after administration of IXCHIQ and no vaccine viraemia was detected 15 days after vaccination. See sections 4.6 and 4.8.

Individuals administered IXCHIQ should not donate blood for at least 4 weeks post-vaccination.

Chikungunya-like Adverse Reactions

IXCHIQ may cause severe or prolonged chikungunya-like adverse reactions (see section 4.8).

Encephalitis

Encephalitis (including with fatal outcome) has been reported during post-marketing use of IXCHIQ (see section 4.8).

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

Potassium

This medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially 'potassium-free'.

This medicine contains 25 mg Sorbitol in each 0.5 mL dose which is equivalent to 0.036 mg Sorbitol/kg/0.5 mL . The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

4.5. Interaction with other medicinal products and other forms of interaction

Concomitant administration with other vaccines

IXCHIQ is not recommended to be co-administered with other vaccines because there are no data on the safety and immunogenicity following concomitant administration of IXCHIQ with other vaccines.

Administration of immune globulins, blood or plasma transfusions 3 months before or up to 1 month after IXCHIQ administration may interfere with the expected immune response.

4.6. Fertility, pregnancy and lactation

Pregnancy

Animal studies did not indicate any direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

There is limited amount of data from the use of IXCHIQ in pregnant women. These data are not sufficient to conclude on the absence of potential effects of IXCHIQ on pregnancy, embryo-foetal development, parturition and post-natal development.

Vertical transmission of wild-type CHIKV from pregnant individuals with viraemia at delivery is common and can cause potentially fatal CHIKV disease in neonates. Vaccine viraemia occurs in the first week following administration of IXCHIQ, with resolution of viraemia by 14 days after vaccination. It is not known if the vaccine virus can be vertically transmitted and cause foetal or neonatal adverse reactions.

Decisions to administer IXCHIQ during pregnancy should take into consideration the individual's risk of exposure to wild-type CHIKV, gestational age, and risks to the foetus or neonate from vertical transmission of wild-type CHIKV.

Breast-feeding

It is unknown if IXCHIQ is excreted in human milk. A risk to the breastfed child cannot be excluded. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IXCHIQ and any potential adverse effects on the breastfed child from IXCHIQ.

Animal studies did not indicate any direct or indirect harmful effects with respect to lactation (see section 5.3).

Fertility

No specific studies have been performed on fertility.

Animal studies did not indicate any harmful effects with respect to female fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

IXCHIQ has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

The overall safety of IXCHIQ is based on an analysis of the pooled safety data from three completed phase I and III clinical studies conducted in the US on 3 610 participants ≥18 years old who received one dose of IXCHIQ with a follow-up of 6 months.

The most common vaccination site reactions were tenderness (10.8%) and pain (6.1%). The most common systemic adverse reactions were headache (32%), fatigue (29.4%), myalgia (23.7%), arthralgia (16.6%), fever (13.8%) and nausea (11.4%).

IXCHIQ must not be used in individuals 60 years and older (see section 4.1)

In the post-marketing setting, serious adverse reactions have been reported, particularly in males aged 65 years and older with underlying chronic medical conditions such as cardiovascular disease, diabetes mellitus or chronic kidney disease. These adverse reactions included neurological events such as fatal encephalitis, deterioration of general condition, and exacerbation of chronic medical conditions (see section 4.4).

Laboratory parameters

The most common abnormal laboratory parameters were neutropenia (41.8%), leukopenia (31.2%), lymphopenia (22.3%), Alanine aminotransferase increased (ALT: 15.5%), and Aspartate aminotransferase increased (AST: 11.7%) (based on an immunogenicity subset of 372 IXCHIQ recipients).

Vaccine Viraemia and Shedding

Vaccine virus was demonstrated to be present in blood and urine and might be present in other body fluids. Vaccine viraemia and shedding (measured by genomic amplification methods) following vaccination with IXCHIQ was assessed in one adult clinical trial (VLA1553-101). Viraemia was detected in 90% of subjects 3 days after vaccination, proportions of vaccinees with detectable virus declined to 17% by 7 days after administration of IXCHIQ and no vaccine viraemia was detected 15 days after vaccination. A single participant shed vaccine virus in urine 7 days after vaccination.

Tabulated list of adverse reactions

Adverse reactions are listed according to the following frequency categories:

Very common: (≥ 1/10),

Common: (≥ 1/100 to < 1/10),

Uncommon: (≥ 1/1 000 to < 1/100),

Rare: (≥ 1/10 000 to < 1/1 000),

Very rare: (<1/10 000),

Not known: (cannot be estimated from available data).

Within each frequency grouping the adverse reactions are presented in the order of decreasing seriousness.

Table 1. Adverse reactions in individuals 18 years of age and older

System organ class

Frequency

Adverse reactions

Blood and lymphatic system disorders

Common

Lymphadenopathy

Uncommon

Thrombocytopenia

Endocrine disorders

Rare

Hypovolaemic hyponatraemia

Nervous system disorders

Very common

Headache

Common

Uncommon

Dizziness, paraesthesia, syncope

Rare

Confusional state

Not known

Encephalopathy, encephalitis, aseptic meningitis.

Eye disorders

Uncommon

Eye pain

Ear and labyrinth disorders

Uncommon

Tinnitus

Respiratory, thoracic and mediastinal disorders

Uncommon

Dyspnoea

Gastrointestinal disorders

Very common

Nausea

Common

Vomiting, diarrhoea

Skin and subcutaneous tissue disorders

Common

Rash

Uncommon

Hyperhidrosis

Musculoskeletal and connective tissue disorders

Very common

Myalgia, arthralgia

Common

Back pain

General disorders and administration site conditions

Very common

Fatigue, fever, vaccination site reactions (tenderness, pain, erythema, induration, swelling)

Common

Chills

Uncommon

Asthenia, oedema peripheral, malaise, decreased appetite

Investigations

Very common

White blood cell count decreased*; liver function test increased**

*. includes: leukopenia (leukocyte decreased), neutropenia (neutrophil decreased) and lymphopenia (lymphocyte decreased).

**. includes: Alanine aminotransferase increased (ALT) and Aspartate aminotransferase increased (AST).

Chikungunya-like Adverse Reactions

The occurrence of certain adverse event combinations, referred to as chikungunya-like adverse reactions, was retrospectively evaluated in the pooled safety data from phase I and III clinical studies (N=3 610). Chikungunya-like adverse reactions were broadly defined, i.e. occurrence of fever (≥38°C) and at least one other symptom also reported for acute-stage chikungunya illness, including arthralgia or arthritis, myalgia, headache, back pain, rash, lymphadenopathy, and certain neurological, cardiac or ocular symptoms; within 30 days after vaccination, regardless of time of onset, severity or duration of the individual symptoms.

Adverse event combinations qualifying as chikungunya-like adverse reactions were reported in 12.1% of participants. Among those, combinations of fever with headache, fatigue, myalgia or arthralgia were the most common, all other symptoms were reported in fewer than 10% of chikungunya-like adverse reactions. The reported symptoms were mostly mild, 1.8% of participants reported at least one severe symptom, most commonly fever or arthralgia. Median onset of chikungunya-like adverse reactions was 3 days after vaccination, and median time to resolution was 4 days. Longer-lasting symptoms ≥30 days occurred in 0.4% of participants.

Paediatric population

Safety in adolescent participants ≥12 years was assessed in 502 participants in Brazil who received one dose of IXCHIQ with a follow-up of 28 days. Approximately 20% of the participants had pre-existing antibodies against chikungunya virus. The proportion of participants that experienced solicited systemic AEs and Chikungunya-like adverse reactions was higher in seronegative participants at baseline vaccinated with VLA1553 (67.9% and 27.2%, respectively) than in seropositive participants at baseline vaccinated with VLA1553 (44.7% and 6.4%, respectively). The proportion of participants who experienced solicited local AEs and unsolicited AEs was similar in the VLA1553 arms of each stratum.”

Reporting of suspected adverse reactions

If you are concerned about an adverse event, it should be reported on a Yellow Card. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store and include the vaccine brand and batch/Lot number if available.

Alternatively, adverse events of concern in association with IXCHIQ can be reported to Valneva Austria GmbH on +43 1 20620 1444 or email to [email protected].

Please do not report the same adverse event(s) to both systems as all reports will be shared between Valneva Austria GmbH and the MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates.

4.9. Overdose

No case of overdose has been reported in clinical studies. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.