NACI statement: Recommendations on the use of Moderna Spikevax COVID-19 vaccine in children 6 to 11 years of age

Publication: March 17, 2022

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Organization: Public Health Agency of Canada

Published: 2022-03-17

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Preamble

The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.

In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.

The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI Statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.

This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge. This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Introduction

On January 25, 2022, NACI published updated recommendations on the use of the Pfizer-BioNTech Comirnaty (10 mcg) COVID-19 vaccine in children 5 to 11 years of age, including strengthening their recommendation to strongly recommend a 2-dose primary series. In children 5 to 11 years of age who are moderately to severely immunocompromised, a 3-dose primary series is recommended.

Since this guidance:

NACI has reviewed the evolving evidence and has updated evidence-informed recommendations on the use of COVID-19 vaccines in pediatric populations.

Methods

On February 1, 2022, and February 15, 2022, NACI reviewed the available evidence on the use of the Moderna Spikevax COVID-19 vaccine (50 mcg dose) in children 6 to 11 years of age (including manufacturer's clinical data in the regulatory submission to Health Canada, and post-market safety data on the use of the Moderna Spikevax 50 mcg and 100 mcg dose in older age groups, see Appendix A). Ethical considerations related to COVID-19 vaccination in pediatric populations were discussed with the Public Health Ethics Consultative Group (PHECG) on May 3, 2021, July 6, 2021 and September 21, 2021.

Following a comprehensive review and discussion, NACI approved this updated guidance on COVID-19 vaccines for individuals 6 to 11 years of age on March 11, 2022.

NACI continues to review the evidence on the use of COVID-19 vaccines and will update its recommendations as needed. Details of NACI's evidence-informed recommendation development process can be found elsewhereFootnote 1Footnote 2.

Vaccine

Moderna Spikevax COVID-19 vaccine preparations authorized for use among pediatric and adult/adolescent populations in Canada

Table 1. Use of the Moderna Spikevax COVID-19 vaccine for children (6 to 11 years of age) and adults/adolescents (≥12 years of age)
Product specification Use in children (6 to 11 years of age)   Use in adults/adolescents (≥12 years of age; primary series)
Age 6 to 11 years 12 years of age and over
Dose 50 mcg (0.25 mL) 100 mcg (0.50 mL)
Doses per vial 20 10
Diluent No dilution required
Potential allergens Polyethylene glycol (PEG) Tromethamine (Tris, Trometamol)Table 1 Footnote a
StorageTable 1 Footnote bTable 1 Footnote cTable 1 Footnote dTable 1 Footnote e
TransportTable 1 Footnote c

For complete prescribing information for the pediatric and adult formulations of the Moderna Spikevax and Pfizer-BioNTech COVID-19 vaccines, consult the product leaflets or information contained within Health Canada's authorized product monographs available through the Drug Product Database.

Schedule

Refer to Table 2 for a summary of immunization schedules for authorized COVID-19 vaccines among children 5 to 11 or 6 to 11 years of age.

Table 2. Immunization schedule for primary series, by COVID-19 vaccine
Vaccine product Age Dose Immunization schedule Minimum interval Authorized interval NACI - recommended intervalTable 2 Footnote a
Pfizer-BioNTech (Comirnaty; 10 mcg) 5 to 11 years 10 mcg (0.2mL) 2-dose schedule 19 days 21 days At least 8 weeks
Moderna (Spikevax; 50 mcg) 6 to 11 years 50 mcg (0.25 mL) 2-dose schedule 21 days 28 days At least 8 weeks

Recommendations

  1. NACI recommends that a complete series with an mRNA COVID-19 vaccine should be offered to children in the authorized age groups without contraindications to the vaccine, with a dosing interval of at least 8 weeks between the first and second dose. (Strong NACI Recommendation)

For children 6 to 11 years of age (which is the age group in which the Moderna Spikevax 50 mcg primary series vaccine is authorized):

  • Moderna Spikevax (50 mcg dose) may be offered as an alternative to Pfizer-BioNTech Comirnaty (10 mcg dose), however the use of Pfizer-BioNTech Comirnaty (10 mcg dose) is preferred to Moderna Spikevax (50 mcg dose) to start or continue the primary vaccine series.

Indirect data from adult populations (≥18 years of age) suggest Moderna Spikevax (100 mcg) may result in higher vaccine effectiveness after a 2-dose primary series compared to Pfizer-BioNTech Comirnaty (30 mcg) and is associated with a higher seroconversion rate among adult immunocompromised patientsFootnote 5. Given this potential benefit, administration of the Moderna Spikevax (50 mcg) vaccine as a 3-dose primary series may be considered for some immunocompromised individuals 6 to 11 years of age, as outlined in the product monograph. Each dose would be provided 4 to 8 weeks apart, as per the NACI recommended schedule for immunocompromised populations.

Rationale and summary of evidence

Additional considerations

NACI will closely review emerging evidence on the safety and effectiveness of COVID-19 vaccines in this age group, and will update their recommendations, as well as its strength, as the evidence base evolves.

For further information on NACI's recommendations on the use of pediatric COVID-19 vaccines, please refer to the COVID-19 vaccine chapter in the Canadian Immunization Guide (CIG).

For detailed NACI recommendations on the use of COVID-19 vaccines in children 5 to 11 years of age considered moderately to severely immunocompromised, please refer to the January 25, 2022 NACI Rapid Response: Updated recommendations on the use of COVID-19 vaccines in children 5-11 years of age.

Abbreviations

Abbreviation Term

AE
Adverse event
AEFI
Adverse event following immunization
COVID-19
Coronavirus disease 2019
GMR
Geometric mean ratio
MIS-C
Multisystem inflammatory syndrome in children
mcg
microgram
NACI
National Advisory Committee on Immunization
PHAC
Public Health Agency of Canada
SAE
Serious adverse event
US
United States

Acknowledgments

This statement was prepared by: N Forbes, M Salvadori, J Montroy, J Zafack, R Stirling, R Krishnan, SJ Ismail, B Warshawsky, K Young, MC Tunis, B Sander, and R Harrison, on behalf of NACI.

NACI gratefully acknowledges the contribution of: C Jensen, L Coward, E Wong, E Tarrataca, SH Lim, K Ramotar, and N St-Pierre.

NACI members: S Deeks (Chair), R Harrison (Vice-Chair), M Andrew, J Bettinger, N Brousseau, H Decaluwe, P De Wals, E Dubé, V Dubey, K Hildebrand, K Klein, J Papenburg, A Pham-Huy, B Sander, S Smith, and S Wilson.

Liaison representatives: L Bill / M Nowgesic (Canadian Indigenous Nurses Association), LM Bucci (Canadian Public Health Association), E Castillo (Society of Obstetricians and Gynaecologists of Canada), A Cohn (Centers for Disease Control and Prevention, United States), L Dupuis (Canadian Nurses Association), D Fell (Canadian Association for Immunization Research and Evaluation), S Funnell (Indigenous Physicians Association of Canada), J Hu (College of Family Physicians of Canada), M Lavoie (Council of Chief Medical Officers of Health), D Moore (Canadian Paediatric Society), M Naus (Canadian Immunization Committee), A Ung (Canadian Pharmacists Association).

Ex-officio representatives: V Beswick-Escanlar (National Defence and the Canadian Armed Forces), E Henry (Centre for Immunization and Respiratory Infectious Diseases (CIRID), PHAC), M Lacroix (Public Health Ethics Consultative Group, PHAC), C Lourenco (Biologic and Radiopharmaceutical Drugs Directorate, Health Canada), D MacDonald (COVID-19 Epidemiology and Surveillance, PHAC), S Ogunnaike-Cooke (CIRID, PHAC), K Robinson (Marketed Health Products Directorate, HC), G Poliquin (National Microbiology Laboratory, PHAC), and T Wong (First Nations and Inuit Health Branch, Indigenous Services Canada).

NACI High Consequence Infectious Disease Working Group

Members: R Harrison (Chair), N Brousseau, Y-G Bui, S Deeks, K Dooling, K Hildebrand, M Miller, M Murti, J Papenburg, D Smith, and S Vaughan.

PHAC participants: NK Abraham, N Alluqmani, L Coward, N Forbes, C Jensen, CY Jeong, A Jirovec, A Killikelly, R Krishnan, SH Lim, N Mohamed, J Montroy, A Nam, S Pierre, R Pless, M Salvadori, A Sinilaite, A Stevens, R Stirling, E Tice, A Tuite, MC Tunis, B Warshawsky, E Wong, R Ximenes, MW Yeung, J Zafack.

Appendix A: Clinical trail data on the Moderna Spikevax mRNA COVID-19 vaccine in children 6 to 11 years of age

Trial design

The Moderna Spikevax COVID-19 vaccine was evaluated in an ongoing, randomized, observer-blind, placebo-controlled Phase 1/2/3 clinical trial in healthy children from 6 months to 11 years of age (P204)Footnote 14 Based on the reactogenicity and immunogenicity observed in the initial cohort of children 6 to 11 years of age in the open-label Phase 1 trial, a dose of 50 mcg was selected for the Phase 2/3 trial for this age group. A total of 4,011 participants 6 to 11 years of age were randomized 3:1 to receive either two doses of the vaccine (50 mcg mRNA) or placebo, 28 days apart. At time of reporting, median follow-up of participants was 51 days since dose 2. Follow-up is planned for up to approximately 12 months following the second dose. The trial was conducted at a time of predominant Delta variant of concern circulation (data cut off: November 10, 2021).

Study population

All pediatric study participants for the Phase 2/3 trial were recruited from the US and Canada. Individuals with known history of SARS-CoV-2 infection within 2 weeks prior to administration of vaccine or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to administration of vaccine were excluded from the trial. Individuals with known immunodeficiency or immunocompromised conditions were excluded from the trial.

Immunogenicity comparator group

The immunogenicity comparator group for the children (6 to 11 years) was a randomly selected subset (n=295) of participants aged 18 to ≤25 years from the earlier Phase 2/3 study P301 who received two doses of the Moderna Spikevax COVID-19 vaccine (100 mcg), 28 days apart.

Demographics

Demographic characteristics were similar among vaccine and placebo groups in the P204 trial. Overall, 49.2% of participants were female, with a median age at vaccination of 8.0 years (range: 5-11 years) in the vaccine group and 9.0 (range: 6-11 years) in the placebo group. About two-thirds of participants were white (65.5%), with participants from other race/ethnic groups each comprising significantly less of the study population: Multiracial (10.8%), Black or African American (10.0% overall), Asian (9.9%), and all other groups comprising <2% of participants. All race and ethnicity groups had similar proportions in the vaccine and placebo groups. A total of 20% of participants were defined as obese. A total of 4 participants 6 to 11 years of age with known HIV were enrolled in the trial (all in the vaccine group), and 10 participants had cardiac disorders. The prevalence of SARS-CoV-2 infection or prior infection at baseline (determined by a positive RT-PCR or serological assay) in the vaccine and placebo groups in the safety population was comparable at 8.5% and 8.7%, respectively.

Safety

Safety evidence for participants is based on the phase 2/3 randomized, observer-blind, placebo-controlled expansion study of children (focused on the cohort 6 years to 11 years of age) who received 2 intramuscular injections of Moderna Spikevax 50 mcg (n=3,007) or placebo (n=995) approximately 28 days apart. Data on solicited local and systemic reactions were collected daily for 7 days following each injection. Participants (6 to 11 years of age) were monitored for unsolicited adverse events for up to 28 days following each dose and follow-up is ongoing. Median duration of safety follow-up after second vaccination for study participants in the blinded phase was 51 days.

Local reactions

Local reactions were increased in frequency in vaccine recipients (93.7% for dose 1, 95.3% for dose 2) compared to placebo recipients (48.3% for dose 1, 50.6% for dose 2). Most solicited local reactions were grade 1 or grade 2. Grade 3 reactions were more common in the vaccine recipients than in the placebo recipients (5.6% vs 0.8% respectively). The most frequent grade 3 reaction was injection site pain. There were no grade 4 solicited local adverse reactions in either group. The majority of solicited local reactions occurred within the first 1 to 2 days after any dose and persisted for a median of 3 days. Local reactions were very common and mostly mild to moderate in severity. In the vaccine recipient group, solicited local adverse reactions that persisted beyond 7 days after injection were injection site pain (0.8% dose 1, 0.5% dose 2), erythema (0.5% dose 1, 0.3% dose 2) injection site swelling (0.4% dose 1, 0.2% dose 2) and axillary/groin swelling or tenderness (1.7% dose 1, 0.7% dose 2). See Table 1 for the frequency of solicited local AEs for the Moderna Spikevax COVID-19 vaccine among children 6 to 11 years of age.

Systemic reactions

Systemic events were increased in frequency in vaccine recipients compared to placebo recipients, with frequencies increasing with the number of doses in vaccine recipients (57.9% after dose 1 compared to 78.1% after dose 2 in vaccine recipients, and 52.2% after dose 1 and 50.1% after dose 2 in placebo recipients). Headache (31.2% and 54.3% after dose 1 and 2 respectively in vaccine recipients, and 30.8% and 28.4% after dose 1 and 2 respectively in placebo recipients), fatigue (43.2% and 64.5% after dose 1 and 2 respectively in vaccine recipients, and 33.6% and 34.6% after dose 1 and 2 respectively in placebo recipients), myalgias (14.6% and 28.2% after dose 1 and 2 respectively in vaccine recipients, and 9.7% and 10.8% after dose 1 and 2 respectively in placebo recipients), nausea/vomiting (10.8% and 24.0% after dose 1 and 2 respectively in vaccine recipients, and 10.8% and 10.0% after dose 1 and 2 respectively in placebo recipients) and chills (10.3% and 30.3% after dose 1 and 2 respectively in vaccine recipients, and 6.7% and 7.6% after dose 1 and 2 respectively in placebo recipients) were very common after dose 1 and dose 2 in vaccine recipients. Arthralgias were common after the first dose (8.7% in vaccine recipients and 7.6% in placebo recipients) and very common after the second dose in vaccine recipients (16.1% in vaccine recipients and 8.7% in placebo recipients). Fever was common after the first dose (3.3% in vaccine recipients and 1.5% in placebo recipients) and very common after the second dose in vaccine recipients (23.9% in vaccine recipients and 2.0% in placebo recipients). Grade 3 events were more common in the vaccine recipients (1.8% after dose 1, 12.2% after dose 2) than the placebo recipients (1.3% and 1.4% respectively). There were no grade 4 events in the vaccine recipients. See Table 2 for the frequency of solicited systemic AEs for the Moderna Spikevax COVID-19 vaccine among children 6 to 11 years of age.

Serious adverse events and other adverse events of interest

There were no serious AEs assessed as related to the study interventions, either the vaccine or placebo, no deaths, no cases of MIS-C, and no cases of myocarditis or pericarditis reported during the study period. Monitoring for serious adverse events and medically attended adverse events will continue throughout the study period (up to 12 months following the second dose).

Immunogenicity

An immunobridging analysis evaluating SARS-CoV-2 50% neutralising titres (ID50) and seroresponse rates 28 days after dose 2 was conducted in subset of children 6 to 11 years of age (Study P204; N=320) and in participants aged 18 through ≤25 from the Phase 3 efficacy study (Study P301; N=295). Subjects had no immunologic or virologic evidence of prior SARS-CoV-2 infection at baseline. The geometric mean ratio (GMR) of the neutralising antibody titres in children 6 to 11 years of age compared to the 18- to 25-year-olds was 1.2 (95% CI: 1.1, 1.4). The difference in seroresponse rate was 0.1% (95% CI: -1.9, 2.1%). Both pre-specified non-inferiority criteria (lower bound of the 95% CI for GMR greater than 0.67 and lower bound of the 95% CI of the seroresponse rate difference greater than -10%) were met. Immunogenicity data was also assessed following dose 1 in the same subset of participants; at day 29 from baseline, and GMR was similar across the two groups (108.1 in children 6 to 11 years of age, compared to 96.7 in adults 18 to 25 years of age).

Samples from a randomly selected subset of 20 participants 6 to 11 years of age were assessed for neutralization titres against the Delta variant and Omicron variant. Among children 6-11 years of age, the level of neutralizing antibodies against Omicron 28 days after dose 2 were 22.1 fold lower than those against D614G. However, the neutralizing antibody response against both Omicron and D614G among children 6 to 11 years of age was higher than among adults 18 years of age and olderFootnote 15.

As no correlate of protection has been established for any COVID-19 outcome at this time, it is unknown how reported immune responses are related to prevention of SARS-CoV-2 infection or disease or the ability to transmit infection to others.

Efficacy

The evaluable efficacy population consisted of 2,687 participants randomized to receive vaccine and 880 participants randomized to receive placebo, all of whom had a negative baseline SARS-CoV-2 serostatus. As of November 10, 2021 (data cut-off for analysis), a total of 25 confirmed, symptomatic cases of COVID-19 were identified starting 14 days after dose 1 (7 in vaccine group, 18 in placebo group) in participants 6 to 11 years of age. The estimated efficacy of the vaccine against confirmed COVID-19 from 14 days after dose 1 was 88.0% (95% CI: 70.0 to 95.8%). The estimated efficacy against SARS-CoV-2 infection from 14 days after dose 1 (regardless of symptoms) and against asymptomatic SARS-CoV-2 infection was 74.0% (95% CI: 57.9 to 84.1%) and 62.5% (95% CI: 30.9 to 79.4%), respectively. However, these estimates of vaccine efficacy should be interpreted with caution. The definition of asymptomatic infection was based on either a positive RT-PCR result (generally performed as a result of symptoms) or a positive serology result based on samples collected at pre-specified times (Days 1, 29, 43, 57, 209 and 394). Therefore, the identification of asymptomatic cases based on positive serology do not correspond to identification of infection at a discrete point in time, but rather could reflect infection acquired at any time after collection of negative serology sample at baseline. Most confirmed cases in study participants were identified at a time when the Delta variant was the predominant circulating strain in the US and Canada. However, no sequence analysis was reported on case isolates to determine whether they were caused by the Delta variant or another variant.

There were too few cases identified beginning 14 days after dose 2 to generate estimates of vaccine efficacy for dose 2, however it is important to note the majority of participants (99.4%) randomized to receive vaccine received 2 doses, and therefore estimates of efficacy beginning 14 days after dose 1 cannot only be attributed to protection conferred from the first dose alone.

There were no subgroup analyses (e.g., age, sex, race/ethnicity, presence of underlying medical conditions) presented for vaccine efficacy against any outcome.

None of the identified cases met the pre-defined criteria for a severe case of COVID-19, therefore the data did not include estimates of vaccine efficacy against severe outcomes such as hospitalization, MIS-C or death.

Appendix B: Frequency of solicited adverse events following immunization for COVID-19 in clinical trial

Table 1. Frequency of solicited local AEFIs in 6 to 11 year olds for the Moderna COVID-19 vaccine (SpikevaxTM)Table 3 Footnote aTable 3 Footnote b
AEFI Vaccine Placebo control

Dose 1

N=3004

Dose 2

N=2988

Dose 1

N=993

Dose 2

N=969

Pain at injection site Very common Very common Very common Very common
Redness/erythema Very common Very common Common Common
Swelling Very common Very common Common Common
Axillary (or groin) swelling or tenderness Very common Very common Common Common
Table 2. Frequency of solicited systemic AEFIs in 6 to 11 year olds for the Moderna COVID-19 vaccine (SpikevaxTM)Table 4 Footnote aTable 4 Footnote b
AEFI Vaccine Placebo control

Dose 1

N=3004

Dose 2

N=2988

Dose 1

N=993

Dose 2

N=969

Fatigue Very common Very common Very common Very common
Headache Very common Very common Very common Very common
Muscle Pain Very common Very common Common Very common
Chills Very common Very common Common Common
Joint pain Common Very common Common Common
FeverTable 4 Footnote c> Common Very common Common Common
Nausea or vomiting Very common Very common Very common Very common
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