Spikevax JN.1 Adverse Reactions

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 than after Dose 1.
Adolescents 12 through 17 years of age: Safety data for Spikevax (original) in adolescents were collected in an ongoing 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.
Tabulated list of adverse reactions: The safety profile presented as follows is based on data generated in several placebo-controlled clinical studies: 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 (see Table 5).

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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.
Adults (booster dose): 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 bivalent Original/Omicron BA.1 (booster dose): The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax bivalent Original/Omicron BA.1 are evaluated in an ongoing Phase 2/3 open-label study in participants 18 years of age and older (mRNA-1273-P205). In this study, 437 participants received the Spikevax bivalent Original/Omicron BA.1 50 microgram booster dose, and 377 participants received the Spikevax (original) 50 microgram booster dose.
Spikevax bivalent Original/Omicron BA.1 had a reactogenicity profile similar to that of the Spikevax (original) booster given as a second booster dose. The frequency of adverse reactions after immunisation with Spikevax bivalent Original/Omicron BA.1 was also similar or lower relative to that of a first booster dose of Spikevax (original) (50 micrograms) and relative to the second dose of the Spikevax (original) primary series (100 micrograms). The safety profile of Spikevax bivalent Original/Omicron BA.1 (median follow-up period of 113 days) was similar to the safety profile of Spikevax (original) (median follow-up period of 127 days).
Spikevax bivalent Original/Omicron BA.4-5 (booster dose): The safety, reactogenicity, and immunogenicity of a bivalent booster dose of Spikevax bivalent Original/Omicron BA.4-5 are evaluated in an ongoing Phase 2/3 open-label study in participants 18 years of age and older (mRNA-1273-P205). In this study, 511 participants received a booster dose of Spikevax bivalent Original/Omicron BA.4-5 (50 micrograms), and 376 participants received a booster dose of Spikevax (original) (50 micrograms).
Spikevax bivalent Original/Omicron BA.4-5 had a reactogenicity profile similar to that of the Spikevax (original) booster given as a second booster dose.
Spikevax XBB.1.5 (booster dose): The safety, reactogenicity and immunogenicity of a booster dose of Spikevax XBB.1.5 are evaluated in an ongoing Phase 2/3 open-label study in adults (mRNA-1273-P205, Part J). In this study, 50 participants received a booster dose of Spikevax XBB.1.5 (50 micrograms) and 51 participants received a booster dose of an investigational bivalent Omicron XBB.1.5/BA.4-5 vaccine (50 micrograms).
The reactogenicity profile of Spikevax XBB.1.5 was similar to that of Spikevax (original) and Spikevax bivalent Original/Omicron BA.4-5. The median follow-up time for both vaccine groups in this interim analysis was 20 days (range of 20 to 22 days with data cut-off date of 16 May 2023).
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 (original) is highest in younger males (see Precautions).
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. Healthcare professionals are asked to report any suspected adverse reactions and include batch/Lot number if available.