4.1. Therapeutic indications

Spikevax JN.1 is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older (see sections 4.2 and 5.1).

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

4.2. Posology and method of administration

Posology

Table 1. Spikevax JN.1 posology

Age(s)

Dose

Additional recommendations

Children 6 months through 4 years of age, without prior vaccination and no known history of SARS CoV-2 infection

Two doses of 0.25 mL each, given intramuscularly

The second dose should be administered 28 days after the first dose (see sections 4.4 and 5.1).

If a child has received one prior dose of any Spikevax vaccine, one dose of Spikevax JN.1 should be administered to complete the two-dose series.

Children 6 months through 4 years of age, with prior vaccination or known history of SARS CoV-2 infection

One dose of 0.25 mL, given intramuscularly

Spikevax JN.1 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Children 5 years through 11 years of age, with or without prior vaccination

One dose of 0.25 mL, given intramuscularly

Individuals 12 years of age and older, with or without prior vaccination

One dose of 0.5 mL, given intramuscularly

Individuals 65 years of age and older

One dose of 0.5 mL, given intramuscularly

One additional dose may be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Table 2. Spikevax JN.1 posology for immunocompromised individuals

Age(s)

Dose

Additional recommendations

Immunocompromised children 6 months through 4 years of age, without prior vaccination

Two doses of 0.25 mL, given intramuscularly

A third dose in severely immunocompromised may be given at least 28 days after the second dose.

Immunocompromised children 6 months through 4 years of age, with prior vaccination

One dose of 0.25 mL, given intramuscularly

Additional age-appropriate dose(s) may be administered in severely immunocompromised at least 2 months following the most recent dose of a COVID-19 vaccine at the discretion of the healthcare provider, taking into consideration the individual's clinical circumstances.

Immunocompromised children 5 years through 11 years of age, with or without prior vaccination

One dose of 0.25 mL, given intramuscularly

Immunocompromised individuals 12 years of age and older, with or without prior vaccination

One dose of 0.5 mL, given intramuscularly

Paediatric population

The safety and efficacy of Spikevax in children less than 6 months of age have not yet been established (see section 5.1).

Elderly population

No dosage adjustment is required in elderly individuals ≥65 years of age.

Method of administration

The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm.

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

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions regarding thawing, handling and disposal of the vaccine, see section 6.6.

4.3. Contraindications

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

4.4. Special warnings and precautions for use

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

Anaphylaxis has been reported in individuals who have received Spikevax (original). Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following administration of the vaccine.

Subsequent doses of the vaccine should not be given to those who have experienced severe allergic reactions (e.g. anaphylaxis, generalised urticaria) to an earlier dose of Spikevax.

Myocarditis and pericarditis

There is an increased risk for myocarditis and pericarditis following vaccination with Spikevax.

These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. They have been observed more often in younger males, and more often after the second dose compared to the first dose (see section 4.8).

Available data indicate that most cases recover. Some cases required intensive care support and fatal cases have been observed.

Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Vaccinated individuals should be instructed to seek immediate medical attention if they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chest pain, shortness of breath, or palpitations following vaccination.

Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition.

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

As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals.

Capillary leak syndrome flare-ups

A few cases of capillary leak syndrome (CLS) flare-ups have been reported in the first days after vaccination with Spikevax (original). Healthcare professionals should be aware of signs and symptoms of CLS to promptly recognise and treat the condition. In individuals with a medical history of CLS, planning of vaccination should be made in collaboration with appropriate medical experts.

Duration of protection

The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.

Limitations of vaccine effectiveness

As with all vaccines, vaccination with Spikevax JN.1 may not protect all vaccine recipients.

Excipients with known effect

Sodium

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

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

Spikevax JN.1 may be administered concomitantly with seasonal influenza vaccines (high dose or standard dose, inactivated, unadjuvanted). In clinical trials with Spikevax (original), the antibody responses to Spikevax and the co-administered vaccines were unaffected. The frequency of local and systemic reactions to Spikevax was also unaffected. There are no data on co-administration with adjuvanted seasonal influenza vaccines.

Spikevax JN.1 may be administered concomitantly with herpes zoster vaccine (recombinant, adjuvanted). In a clinical trial with Spikevax (original), the antibody responses to Spikevax and the co-administered vaccine were unaffected. Local reactions to Spikevax were unaffected but most systemic reactions were reported more frequently when it was co-administered with the herpes zoster vaccine, in particular myalgia (46% vs 64%), fatigue (36% vs 52%), chills (19% vs 31%), and fever (5% vs 10%), respectively.

If Spikevax JN.1 is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

Concomitant administration of Spikevax with other vaccines has not been studied.

4.6. Fertility, pregnancy and lactation

Pregnancy

No data are available yet regarding the use of Spikevax JN.1 during pregnancy.

However, a large amount of observational data from pregnant women vaccinated with Spikevax (original) during the second and third trimester has not shown an increase in adverse pregnancy outcomes. While data on pregnancy outcomes following vaccination during the first trimester are presently limited, no increased risk for miscarriage has been seen. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3). Since differences between products are confined to the spike protein sequence, and there are no clinically meaningful differences in reactogenicity, Spikevax JN.1 can be used during pregnancy.

Breast-feeding

No data are available yet regarding the use of Spikevax JN.1 during breastfeeding.

However, no effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breastfeeding woman to the vaccine is negligible. Observational data from women who were breastfeeding after vaccination with Spikevax (original) have not shown a risk for adverse effects in breastfed newborns/infants. Spikevax JN.1 can be used during breastfeeding.

Fertility

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

4.7. Effects on ability to drive and use machines

Spikevax JN.1 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

Adults

The safety of Spikevax (original) was evaluated in an ongoing Phase 3 randomised, placebo-controlled, observer-blind clinical study conducted in the United States involving 30,351 participants 18 years of age and older who received at least one dose of Spikevax (original) (n=15,185) or placebo (n=15,166) (NCT04470427). At the time of vaccination, the mean age of the population was 52 years (range 18-95); 22,831 (75.2%) of participants were 18 to 64 years of age and 7,520 (24.8%) of participants were 65 years of age and older.

The most frequently reported adverse reactions were pain at the injection site (92%), fatigue (70%), headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23%), axillary swelling/tenderness (19.8%), fever (15.5%), injection site swelling (14.7%) and redness (10%). Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.

Overall, there was a higher incidence of some adverse reactions in younger age groups: the incidence of axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting and fever was higher in adults aged 18 to < 65 years than in those aged 65 years and above.

Local and systemic adverse reactions were more frequently reported after Dose 2 (100 mcg) than after Dose 1 (100 mcg).

If required, symptomatic treatment with analgesic and/or anti-pyretic medicinal products (e.g. paracetamol-containing products) may be used.

Adolescents 12 through 17 years of age

Safety data for Spikevax (original) in adolescents were collected in a Phase 2/3 randomised, placebo‑controlled, observer-blind clinical study with multiple parts conducted in the United States. The first portion of the study involved 3,726 participants 12 through 17 years of age who received at least one dose of Spikevax (original) (n=2,486) or placebo (n=1,240) (NCT04649151). Demographic characteristics were similar among participants who received Spikevax (original) and those who received placebo.

The most frequent adverse reactions in adolescents 12 to 17 years of age were injection site pain (97%), headache (78%), fatigue (75%), myalgia (54%), chills (49%), axillary swelling/tenderness (35%), arthralgia (35%), nausea/vomiting (29%), injection site swelling (28%), injection site erythema (26%), and fever (14%).

This study transitioned to an open-label Phase 2/3 study in which 1,346 participants 12 years through 17 years of age received a booster dose of Spikevax at least 5 months after the second dose of the primary series. No additional adverse reactions were identified in the open-label portion of the study.

Children 6 years through 11 years of age

Safety data for Spikevax (original) in children were collected in a Phase 2/3 two-part randomised, observer-blind clinical trial conducted in the United States and Canada (NCT04796896). Part 1 is an open-label phase of the trial for safety, dose selection, and immunogenicity and included 380 participants 6 years through 11 years of age who received at least 1 dose (0.25 mL) of Spikevax (original). Part 2 is the placebo-controlled phase for safety and included 4,016 participants 6 years through 11 years of age who received at least one dose (0.25 mL) of Spikevax (original) (n=3,012) or placebo (n=1,004). No participants in Part 1 participated in Part 2. Demographic characteristics were similar among participants who received Spikevax (original) and those who received placebo.

The most frequent adverse reactions in participants 6 years through 11 years of age following administration of the primary series (in Part 2) were injection site pain (98.4%), fatigue (73.1%), headache (62.1%), myalgia (35.3%), chills (34.6%), nausea/vomiting (29.3%), axillary swelling/tenderness (27.0%), fever (25.7%), injection site erythema (24.0%), injection site swelling (22.3%), and arthralgia (21.3%).

The study protocol was amended to include an open‑label booster dose phase that included 1,294 participants 6 years through 11 years of age who received a booster dose of Spikevax at least 6 months after the second dose of the primary series. No additional adverse reactions were identified in the open-label portion of the study.

Children 6 months through 5 years of age

A Phase 2/3 randomised, placebo-controlled, observer-blind study to evaluate the safety, tolerability, reactogenicity, and efficacy of Spikevax was conducted in the United States and Canada. This study involved 10,390 participants 6 months through 11 years of age who received at least one dose of Spikevax (n=7,798) or placebo (n=2,592).

The study enrolled children in 3 age groups: 6 years through 11 years; 2 years through 5 years; and 6 months through 23 months. This paediatric study involved 6,388 participants 6 months through 5 years of age who received at least one dose of Spikevax (n=4,791) or placebo (n=1,597). Demographic characteristics were similar among participants who received Spikevax and those who received placebo.

In this clinical study, the adverse reactions in participants 6 months through 23 months of age following administration of the primary series were irritability/crying (81.5%), pain at the injection site (56.2%), sleepiness (51.1%), loss of appetite (45.7%), fever (21.8%), swelling at the injection site (18.4%), erythema at the injection site (17.9%), and axillary swelling/tenderness (12.2%).

The adverse reactions in participants 24 months through 36 months of age following administration of the primary series were pain at the injection site (76.8%), irritability/crying (71.0%), sleepiness (49.7%), loss of appetite (42.4%), fever (26.1%), erythema at the injection site (17.9%), swelling at the injection site (15.7%), and axillary swelling/tenderness (11.5%).

The adverse reactions in participants 37 months through 5 years of age following administration of the primary series were pain at the injection site (83.8%), fatigue (61.9%), headache (22.9%), myalgia (22.1%), fever (20.9%), chills (16.8%), nausea/vomiting (15.2%), axillary swelling/tenderness (14.3%), arthralgia (12.8%), erythema at the injection site (9.5%), and swelling at the injection site (8.2%).

Tabulated list of adverse reactions

The safety profile presented below is based on data generated in several placebo-controlled clinical studies of Spikevax (original):

• 30,351 adults ≥ 18 years of age

• 3,726 adolescents 12 through 17 years of age

• 4,002 children 6 years through 11 years of age

• 6,388 children aged 6 months through 5 years of age

• and post-marketing experience.

Adverse reactions reported are listed according to the following frequency 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)

Not known (cannot be estimated from the available data)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness (Table 3).

Table 3. Adverse reactions from Spikevax (original) clinical trials and post-authorisation experience in children and individuals 6 months of age and older

MedDRA System Organ Class

Frequency

Adverse reactions

Blood and lymphatic system disorders

Very common

Lymphadenopathy*

Immune system disorders

Not known

Anaphylaxis

Not known

Hypersensitivity

Metabolism and nutrition disorders

Very common

Decreased appetite†

Psychiatric disorders

Very common

Irritability/crying†

Nervous system disorders

Very common

Headache

Sleepiness†

Uncommon

Dizziness

Rare

Acute peripheral facial paralysis‡

Hypoaesthesia

Paraesthesia

Cardiac disorders

Very rare

Myocarditis

Pericarditis

Gastrointestinal disorders

Very common

Nausea/vomiting

Common

Diarrhoea

Uncommon

Abdominal pain§

Skin and subcutaneous tissue disorders

Common

Rash

Uncommon

Urticaria¶

Not known

Erythema multiforme

Mechanical urticaria

Chronic urticaria

Musculoskeletal and connective tissue disorders

Very common

Myalgia

Arthralgia

Reproductive system and breast disorders

Not known

Heavy menstrual bleeding#

General disorders and administration site conditions

Very common

Injection site pain

Fatigue

Chills

Pyrexia

Injection site swelling

Injection site erythema

Common

Injection site urticaria

Injection site rash

Delayed injection site reaction♠

Uncommon

Injection site pruritus

Rare

Facial swelling♥

Not known

Extensive swelling of vaccinated limb

*Lymphadenopathy was captured as axillary lymphadenopathy on the same side as the injection site. Other lymph nodes (e.g., cervical, supraclavicular) were affected in some cases.

† Observed in the paediatric population (6 months to 5 years of age).

‡ Throughout the safety follow-up period, acute peripheral facial paralysis (or palsy) was reported by three participants in the Spikevax (original) group and one participant in the placebo group. Onset in the vaccine group participants was 22 days, 28 days, and 32 days after Dose 2.

§ Abdominal pain was observed in the paediatric population (6 to 11 years of age): 0.2% in the Spikevax (original) group and 0% in the placebo group.

¶ Urticaria has been observed with either acute onset (within a few days after vaccination) or delayed onset (up to approximately two weeks after vaccination).

# Most cases appeared to be non-serious and temporary in nature.

♠ Median time to onset was 9 days after the first injection, and 11 days after the second injection. Median duration was 4 days after the first injection, and 4 days after the second injection.

♥ There were two serious adverse events of facial swelling in vaccine recipients with a history of injection of dermatological fillers. The onset of swelling was reported on Day 1 and Day 3, respectively, relative to day of vaccination.

The reactogenicity and safety profile in 343 subjects receiving Spikevax (original) that were seropositive for SARS-CoV-2 at baseline, was comparable to that in subjects seronegative for SARS-CoV-2 at baseline.

Spikevax (original) booster dose - Adults

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax (original) are evaluated in an ongoing Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study in participants 18 years of age and older (NCT04405076). In this study, 198 participants received two doses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax (original) vaccine primary series. In an open-label phase of this study, 167 of those participants received a single booster dose (0.25 mL, 50 micrograms) at least 6 months after receiving the second dose of the primary series. The solicited adverse reaction profile for the booster dose (0.25 mL, 50 micrograms) was similar to that after the second dose in the primary series.

Spikevax (original) in solid organ transplant recipients

The safety, reactogenicity, and immunogenicity of Spikevax (original) were evaluated in a two-part Phase 3b open label study in adult solid organ transplant (SOT) recipients, including kidney and liver transplants (mRNA-1273-P304). A 100 microgram (0.5 mL) dose was administered, which was the dose authorised at the time of study conduct.

In Part A, 128 SOT recipients received a third dose of Spikevax (original). In Part B, 159 SOT recipients received a booster dose at least 4 months after the last dose (fourth dose for mRNA vaccines and third dose for non-mRNA vaccines).

Reactogenicity was consistent with the known profile of Spikevax (original). There were no unexpected safety findings.

Description of selected adverse reactions

Myocarditis

The increased risk of myocarditis after vaccination with Spikevax is highest in younger males (see section 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in younger males following the second dose of Spikevax (original). One study showed that in a period of 7 days after the second dose, there were about 1.316 (95% CI 1.299 – 1.333) extra cases of myocarditis in 12 to 29 year-old males per 10,000 compared to unexposed persons. In another study, in a period of 28 days after the second dose, there were 1.88 (95% CI 0.956 – 2.804) extra cases of myocarditis in 16 to 24 year-old males per 10,000 compared to unexposed persons.

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. If you are concerned about an adverse event, it should be reported on a Yellow Card. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk/ 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 Spikevax (original) or Spikevax JN.1 can be reported to Moderna on the toll-free number: 08000857562 or via www.modernacovid19global.com. Please do not report the same adverse event(s) to both systems as all reports will be shared between Moderna and MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates.

4.9. Overdose

In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.