Moderna Covid-19 Vaccine

Description

Moderna COVID-19 Vaccine is provided as a white to off-white suspension for intramuscular injection. Each 0.5 mL dose of Moderna COVID-19 Vaccine contains 100 mcg of nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus.

Each dose of the Moderna COVID-19 Vaccine contains the following ingredients: a total lipid content of 1.93 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.31 mg tromethamine, 1.18 mg tromethamine hydrochloride, 0.043 mg acetic acid, 0.12 mg sodium acetate, and 43.5 mg sucrose.

Moderna COVID-19 Vaccine does not contain a preservative.

The vial stoppers are not made with natural rubber latex.

Moderna COVID-19 Vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older.

Dosage And Administration

For intramuscular injection only.

Preparation For Administration

• The Moderna COVID-19 Vaccine multiple-dose vial contains a frozen suspension that does not contain a preservative and must be thawed prior to administration.
• Remove the required number of vial(s) from storage and thaw each vial before use.
• Thaw in refrigerated conditions between 2° to 8°C (36° to 46°F) for 2 hours and 30 minutes. After thawing, let vial stand at room temperature for 15 minutes before administering.
• Alternatively, thaw at room temperature between 15° to 25°C (59° to 77°F) for 1 hour.
• After thawing, do not refreeze.
• Swirl vial gently after thawing and between each withdrawal. Do not shake. Do not dilute the vaccine.
• The Moderna COVID-19 Vaccine is a white to off-white suspension. It may contain white or translucent product-related particulates. Visually inspect the Moderna COVID-19 Vaccine vials for other particulate matter and/or discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered.
• Each dose is 0.5mL.
• After the first dose has been withdrawn, the vial should be held between 2° to 25°C (36° to 77°F). Record the date and time of first use on the Moderna COVID-19 Vaccine vial label. Discard vial after 6 hours. Do not refreeze.

Administration

Visually inspect each dose of the Moderna COVID-19 Vaccine in the dosing syringe prior to administration. The white to off-white suspension may contain white or translucent product-related particulates. During the visual inspection,

• verify the final dosing volume of 0.5 mL.
• confirm there are no other particulates and that no discoloration is observed.
• do not administer if vaccine is discolored or contains other particulate matter.

Administer the Moderna COVID-19 Vaccine intramuscularly.

Dosing And Schedule

The Moderna COVID-19 Vaccine is administered as a series of two doses (0.5 mL each) 1 month apart.

There are no data available on the interchangeability of the Moderna COVID-19 Vaccine with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of Moderna COVID-19 Vaccine should receive a second dose of Moderna COVID-19 Vaccine to complete the vaccination series.

How Supplied

Dosage Forms And Strengths

Moderna COVID-19 Vaccine is a suspension for intramuscular injection. A single dose is 0.5 mL.

Storage And Handling

Moderna COVID-19 Vaccine Suspension for Intramuscular Injection, Multiple-Dose Vials are supplied as a carton of 10 multiple-dose vials (NDC 80777-273-99).

Store frozen between -25° to -15°C (-13° to 5°F). Store in the original carton to protect from light. Do not store on dry ice or below -40°C (-40°F).

Vials can be stored refrigerated between 2° to 8°C (36° to 46°F) for up to 30 days prior to first use. Do not refreeze.

Unpunctured vials may be stored between 8° to 25°C (46° to 77°F) for up to 12 hours. Do not refreeze.

After the first dose has been withdrawn, the vial should be held between 2° to 25°C (36° to 77°F). Discard vial after 6 hours. Do not refreeze.

For general questions, send an email or call the telephone number provided below.
Email: medinfo@modernatx.com, Telephone number{ 1-866-MODERNA, (1-866-663-3762)
This EUA Prescribing Information may have been updated. For the most resent Full EUA Prescribing Information, please visit www.modernatx.com/covid19vaccine-eua.
Patent(s): www.modernatx.com/patents. Revised: Dec 2020

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of Multi-inflammatory Syndrome (MIS) in adults, and hospitalized or fatal cases of COVID-19 following vaccination with the Moderna COVID-19 Vaccine. To the extent feasible, provide a copy of the VAERS form to ModernaTX, Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details on reporting to VAERS and ModernaTX, Inc.

In clinical studies, the adverse reactions in participants 18 years of age and older were pain at the injection site (92.0%), fatigue (70.0%), headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23.0%), axillary swelling/tenderness (19.8%), fever (15.5%), swelling at the injection site (14.7%), and erythema at the injection site (10.0%).

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

Overall, 15,419 participants aged 18 years and older received at least one dose of Moderna COVID- 19 Vaccine in three clinical trials (NCT04283461, NCT04405076, and NCT04470427).

The safety of Moderna COVID-19 Vaccine was evaluated in an ongoing Phase 3 randomized, placebo-controlled, observer-blind clinical trial conducted in the United States involving 30,351 participants 18 years of age and older who received at least one dose of Moderna COVID-19 Vaccine (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. Overall, 52.7% were male, 47.3% were female, 20.5% were Hispanic or Latino, 79.2% were White,10.2% were African American, 4.6% were Asian, 0.8% were American Indian or Alaska Native, 0.2% were Native Hawaiian or Pacific Islander, 2.1% were Other, and 2.1% were Multiracial. Demographic characteristics were similar among participants who received Moderna COVID-19 Vaccine and those who received placebo.

Solicited Adverse Reactions

Data on solicited local and systemic adverse reactions and use of antipyretic medication were collected using standardized diary cards for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine (n=15,179) and participants receiving placebo (n=15,163) with at least 1 documented dose. Solicited adverse reactions were reported more frequently among vaccine participants than placebo participants.

The reported number and percentage of the solicited local and systemic adverse reactions by age group and dose by subject are presented in Table 1 and Table 2, respectively.

Table 1: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Within 7 Days* After Each Dose in Participants 18-64 Years (Solicited Safety Set, Dose 1 and Dose 2)

	Moderna COVID-19 Vaccine		Placeboa
	Dose 1 (N=11,406) n (%)	Dose 2 (N=10,985) n (%)	Dose 1 (N=11,407) n (%)	Dose 2 (N=10,918) n (%)
Local Adverse Reactions
Pain	9,908 (86.9)	9,873 (89.9)	2,177 (19.1)	2,040 (18.7)
Pain, Grade 3b	366 (3.2)	506 (4.6)	23 (0.2)	22 (0.2)
Axillary swelling/tenderness	1,322 (11.6)	1,775 (16.2)	567 (5.0)	470 (4.3)
Axillary swelling/tenderness, Grade 3b	37 (0.3)	46 (0.4)	13 (0.1)	11 (0.1)
Swelling (hardness) ≥25 mm	767 (6.7)	1,389 (12.6)	34 (0.3)	36 (0.3)
Swelling (hardness), Grade 3c	62 (0.5)	182 (1.7)	3 (<0.1)	4 (<0.1)
Erythema (redness) ≥25 mm	344 (3.0)	982 (8.9)	47 (0.4)	43 (0.4)
Erythema (redness), Grade 3c	34 (0.3)	210 (1.9)	11 (<0.1)	12 (0.1)
Systemic Adverse Reactions
Fatigue	4,384 (38.4)	7,430 (67.6)	3,282 (28.8)	2,687 (24.6)
Fatigue, Grade 3d	120 (1.1)	1,174 (10.7)	83 (0.7)	86 (0.8)
Fatigue, Grade 4e	1 (<0.1)	0 (0)	0 (0)	0 (0)
Headache	4,030 (35.3)	6,898 (62.8)	3,304 (29.0)	2,760 (25.3)
Headache, Grade 3f	219 (1.9)	553 (5.0)	162 (1.4)	129 (1.2)
Myalgia	2,699 (23.7)	6,769 (61.6)	1,628 (14.3)	1,411 (12.9)
Myalgia, Grade 3d	73 (0.6)	1,113 (10.1)	38 (0.3)	42 (0.4)
Arthralgia	1,893 (16.6)	4,993 (45.5)	1,327 (11.6)	1,172 (10.7)
Arthralgia, Grade 3d	47 (0.4)	647 (5.9)	29 (0.3)	37 (0.3)
Arthralgia, Grade 4e	1 (<0.1)	0 (0)	0 (0)	0 (0)
Chills	1,051 (9.2)	5,341 (48.6)	730 (6.4)	658 (6.0)
Chills, Grade 3g	17 (0.1)	164 (1.5)	8 (<0.1)	15 (0.1)
Nausea/vomiting	1,068 (9.4)	2,348 (21.4)	908 (8.0)	801 (7.3)
Nausea/vomiting, Grade 3h	6 (<0.1)	10 (<0.1)	8 (<0.1)	8 (<0.1)
Fever	105 (0.9)	1,908 (17.4)	37 (0.3)	39 (0.4)
Fever, Grade 3i	10 (<0.1)	184 (1.7)	1 (<0.1)	2 (<0.1)
Fever, Grade 4j	4 (<0.1)	12 (0.1)	4 (<0.1)	2 (<0.1)
Use of antipyretic or pain medication	2,656 (23.3)	6,292 (57.3)	1,523 (13.4)	1,248 (11.4)
* 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary). a Placebo was a saline solution. b Grade 3 pain and axillary swelling/tenderness: Defined as any use of prescription pain reliever; prevents daily activity. c Grade 3 swelling and erythema: Defined as >100 mm / >10 cm. d Grade 3 fatigue, myalgia, arthralgia: Defined as significant; prevents daily activity. e Grade 4 fatigue, arthralgia: Defined as requires emergency room visit or hospitalization. f Grade 3 headache: Defined as significant; any use of prescription pain reliever or prevents daily activity. g Grade 3 chills: Defined as prevents daily activity and requires medical intervention. h Grade 3 nausea/vomiting: Defined as prevents daily activity, requires outpatient intravenous hydration. i Grade 3 fever: Defined as ≥39.0 – ≤40.0°C / ≥102.1 – ≤104.0°F. j Grade 4 fever: Defined as >40.0°C / >104.0°F.

 

Table 2: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Within 7 Days* After Each Dose in Participants 65 Years and Older (Solicited Safety Set, Dose 1 and Dose 2)

	Moderna COVID-19 Vaccine		Placeboa
	Dose 1 (N=3,762) n (%)	Dose 2 (N=3,692) n (%)	Dose 1 (N=3,748) n (%)	Dose 2 (N=3,648) n (%)
Local Adverse Reactions
Pain	2,782 (74.0)	3,070 (83.2)	481 (12.8)	437 (12.0)
Pain, Grade 3b	50 (1.3)	98 (2.7)	32 (0.9)	18 (0.5)
Axillary swelling/tenderness	231 (6.1)	315 (8.5)	155 (4.1)	97 (2.7)
Axillary swelling/tenderness, Grade 3b	12 (0.3)	21 (0.6)	14 (0.4)	8 (0.2)
Swelling (hardness) ≥25 mm	165 (4.4)	400 (10.8)	18 (0.5)	13 (0.4)
Swelling (hardness), Grade 3c	20 (0.5)	72 (2.0)	3 (<0.1)	7 (0.2)
Erythema (redness) ≥25 mm	86 (2.3)	275 (7.5)	20 (0.5)	13 (0.4)
Erythema (redness), Grade 3c	8 (0.2)	77 (2.1)	2 (<0.1)	3 (<0.1)
Systemic Adverse Reactions
Fatigue	1,251 (33.3)	2,152 (58.3)	851 (22.7)	716 (19.6)
Fatigue, Grade 3d	30 (0.8)	254 (6.9)	22 (0.6)	20 (0.5)
Headache	921 (24.5)	1,704 (46.2)	723 (19.3)	650 (17.8)
Headache, Grade 3e	52 (1.4)	106 (2.9)	34 (0.9)	33 (0.9)
Myalgia	742 (19.7)	1,739 (47.1)	443 (11.8)	398 (10.9)
Myalgia, Grade 3d	17 (0.5)	205 (5.6)	9 (0.2)	10 (0.3)
Arthralgia	618 (16.4)	1,291 (35.0)	456 (12.2)	397 (10.9)
Arthralgia, Grade 3d	13 (0.3)	123 (3.3)	8 (0.2)	7 (0.2)
Chills	202 (5.4)	1,141 (30.9)	148 (4.0)	151 (4.1)
Chills, Grade 3f	7 (0.2)	27 (0.7)	6 (0.2)	2 (<0.1)
Nausea/vomiting	194 (5.2)	437 (11.8)	166 (4.4)	133 (3.6)
Nausea/vomiting, Grade 3g	4 (0.1)	10 (0.3)	4 (0.1)	3 (<0.1)
Nausea/vomiting, Grade 4h	0 (0)	1 (<0.1)	0 (0)	0 (0)
Fever	10 (0.3)	370 (10.0)	7 (0.2)	4 (0.1)
Fever, Grade 3i	1 (<0.1)	18 (0.5)	1 (<0.1)	0 (0)
Fever, Grade 4j	0 (0)	1 (<0.1)	2 (<0.1)	1 (<0.1)
Use of antipyretic or pain medication	673 (17.9)	1,546 (41.9)	477 (12.7)	329 (9.0)
* 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary). a Placebo was a saline solution. b Grade 3 pain and axillary swelling/tenderness: Defined as any use of prescription pain reliever; prevents daily activity. c Grade 3 swelling and erythema: Defined as >100 mm / >10 cm. d Grade 3 fatigue, myalgia, arthralgia: Defined as significant; prevents daily activity. e Grade 3 headache: Defined as significant; any use of prescription pain reliever or prevents daily activity. f Grade 3 chills: Defined as prevents daily activity and requires medical intervention. g Grade 3 Nausea/vomiting: Defined as prevents daily activity, requires outpatient intravenous hydration. h Grade 4 Nausea/vomiting: Defined as requires emergency room visit or hospitalization for hypotensive shock. i Grade 3 fever: Defined as ≥39.0 – ≤40.0°C / ≥102.1 – ≤104.0°F. j Grade 4 fever: Defined as >40.0°C / >104.0°F.

 

Solicited local and systemic adverse reactions reported following administration of Moderna COVID-19 Vaccine had a median duration of 2 to 3 days.

Grade 3 solicited local adverse reactions were more frequently reported after Dose 2 than Dose 1. Solicited systemic adverse reactions were more frequently reported by vaccine recipients after Dose 2 than after Dose 1.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following each dose and follow-up is ongoing. Serious adverse events and medically attended adverse events will be recorded for the entire study duration of 2 years. As of November 25, 2020, among participants who had received at least 1 dose of vaccine or placebo (vaccine=15,185, placebo=15,166), unsolicited adverse events that occurred within 28 days following each vaccination were reported by 23.9% of participants (n=3,632) who received Moderna COVID-19 Vaccine and 21.6% of participants (n=3,277) who received placebo. In these analyses, 87.9% of study participants had at least 28 days of follow-up after Dose 2.

Lymphadenopathy-related events that were not necessarily captured in the 7-day e-Diary were reported by 1.1% of vaccine recipients and 0.6% of placebo recipients. These events included lymphadenopathy, lymphadenitis, lymph node pain, vaccination-site lymphadenopathy, injection-site lymphadenopathy, and axillary mass, which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness in the injected arm.

Hypersensitivity adverse events were reported in 1.5% of vaccine recipients and 1.1% of placebo recipients. Hypersensitivity events in the vaccine group included injection site rash and injection site urticaria, which are likely related to vaccination.

Throughout the same period, there were three reports of Bell’s palsy in the Moderna COVID-19 Vaccine group (one of which was a serious adverse event), which occurred 22, 28, and 32 days after vaccination, and one in the placebo group which occurred 17 days after vaccination. Currently available information on Bell’s palsy is insufficient to determine a causal relationship with the vaccine.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Serious Adverse Events

As of November 25, 2020, serious adverse events were reported by 1.0% (n=147) of participants who received Moderna COVID-19 Vaccine and 1.0% (n=153) of participants who received placebo, one of which was the case of Bell’s palsy which occurred 32 days following receipt of vaccine.

In these analyses, 87.9% of study participants had at least 28 days of follow-up after Dose 2, and the median follow-up time for all participants was 9 weeks after Dose 2.

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 1 and 2 days, respectively, after vaccination and was likely related to vaccination.

There was one serious adverse event of intractable nausea and vomiting in a participant with prior history of severe headache and nausea requiring hospitalization. This event occurred 1 day after vaccination and was likely related to vaccination.

There were no other notable patterns or imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Requirements And Instructions For Reporting Adverse Events And Vaccine Administration Errors

See Overall Safety Summary (Section 6) for additional information.

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for the MANDATORY reporting of the listed events following Moderna COVID-19 Vaccine to the Vaccine Adverse Event Reporting System (VAERS)

• Vaccine administration errors whether or not associated with an adverse event
• Serious adverse events* (irrespective of attribution to vaccination)
• Cases of multisystem inflammatory syndrome (MIS) in adults
• Cases of COVID-19 that results in hospitalization or death

*Serious Adverse Events are defined as:

• Death;
• A life-threatening adverse event;
• Inpatient hospitalization or prolongation of existing hospitalization;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
• A congenital anomaly/birth defect;
• An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above.

Instructions For Reporting To VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using one of the following methods:

• Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
• If you are unable to submit this form electronically, you may fax it to VAERS at 1-877- 721-0366. If you need additional help submitting a report, you may call the VAERS toll- free information line at 1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT

When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

• Patient demographics (e.g., patient name, date of birth)
• Pertinent medical history
• Pertinent details regarding admission and course of illness
• Concomitant medications
• Timing of adverse event(s) in relationship to administration of Moderna COVID-19 Vaccine
• Pertinent laboratory and virology information
• Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

1. In Box 17, provide information on Moderna COVID-19 Vaccine and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within one month prior.
2. In Box 18, description of the event:
   1. Write “Moderna COVID-19 Vaccine EUA” as the first line
   2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
3. Contact information:
   1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
   2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
   3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider’s office address).

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to ModernaTX, Inc. using the contact information below or by providing a copy of the VAERS form to ModernaTX, Inc.

 

Email	Fax number	Telephone number
ModernaPV@modernatx.com	1-866-599-1342	1-866-MODERNA (1-866-663-3762)

Drug Interactions

There are no data to assess the concomitant administration of the Moderna COVID-19 Vaccine with other vaccines.

Included as part of the “PRECAUTIONS” Section

Precautions

Management Of Acute Allergic Reactions

Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the Moderna COVID-19 Vaccine.

Monitor Moderna COVID-19 vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention guidelines (https://www.cdc.gov/vaccines/covid-19/).

Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the Moderna COVID-19 Vaccine.

Limitations Of Vaccine Effectiveness

The Moderna COVID-19 Vaccine may not protect all vaccine recipients.

Use In Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Moderna COVID-19 Vaccine during pregnancy. Women who are vaccinated with Moderna COVID-19 Vaccine during pregnancy are encouraged to enroll in the registry by calling 1-866- MODERNA (1-866-663-3762).

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Moderna COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

In a developmental toxicity study, 0.2 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (100 mcg) and other ingredients included in a single human dose of Moderna COVID-19 Vaccine was administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior to mating, and on gestation days 1 and 13. No vaccine-related adverse effects on female fertility, fetal development or postnatal development were reported in the study.

Lactation

Risk Summary

Data are not available to assess the effects of Moderna COVID-19 Vaccine on the breastfed infant or on milk production/excretion.

Pediatric Use

Safety and effectiveness have not been assessed in persons less than 18 years of age. Emergency Use Authorization of Moderna COVID-19 Vaccine does not include use in individuals younger than 18 years of age.

Geriatric Use

Clinical studies of Moderna COVID-19 Vaccine included participants 65 years of age and older receiving vaccine or placebo, and their data contribute to the overall assessment of safety and efficacy. In an ongoing Phase 3 clinical study, 24.8% (n=7,520) of participants were 65 years of age and older and 4.6% (n=1,399) of participants were 75 years of age and older. Vaccine efficacy in participants 65 years of age and older was 86.4% (95% CI 61.4, 95.2) compared to 95.6% (95% CI 90.6, 97.9) in participants 18 to <65 years of age [see Clinical Trial Results And Supporting Data For EUA]. Overall, there were no notable differences in the safety profiles observed in participants 65 years of age and older and younger participants [see Clinical Trials Experience].

No Information Provided

Contraindications

Do not administer the Moderna COVID-19 Vaccine to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the Moderna COVID-19 Vaccine [see DESCRIPTION].

Mechanism Of Action

The nucleoside-modified mRNA in the Moderna COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

Clinical Trial Results And Supporting Data For EUA

A Phase 3 randomized, placebo-controlled, observer-blind clinical trial to evaluate the efficacy, safety, and immunogenicity of the Moderna COVID-19 Vaccine in participants 18 years of age and older is ongoing in the United States (NCT04470427). Randomization was stratified by age and health risk: 18 to <65 years of age without comorbidities (not at risk for progression to severe COVID-19), 18 to <65 years of age with comorbidities (at risk for progression to severe COVID-19), and 65 years of age and older with or without comorbidities. Participants who were immunocompromised and those with a known history of SARS-CoV-2 infection were excluded from the study. Participants with no known history of SARS-CoV-2 infection but with positive laboratory results indicative of infection at study entry were included. The study allowed for the inclusion of participants with stable pre-existing medical conditions, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 30,420 participants were randomized equally to receive 2 doses of the Moderna COVID-19 Vaccine or saline placebo 1 month apart. Participants will be followed for efficacy and safety until 24 months after the second dose.

The primary efficacy analysis population (referred to as the Per-Protocol Set), included 28,207 participants who received two doses (at 0 and 1 month) of either Moderna COVID-19 Vaccine (n=14,134) or placebo (n=14,073), and had a negative baseline SARS-CoV-2 status. In the Per-Protocol Set, 47.4% were female, 19.7% were Hispanic or Latino; 79.5% were white, 9.7% were African American, 4.6% were Asian, and 2.1% other races. The median age of participants was 53 years (range 18-95) and 25.3% of participants were 65 years of age and older. Of the study participants in the Per Protocol Set, 18.5% were at increased risk of severe COVID-19 due to at least one pre-existing medical condition (chronic lung disease, significant cardiac disease, severe obesity, diabetes, liver disease, or HIV infection) regardless of age. Between participants who received Moderna COVID-19 Vaccine and those who received placebo, there were no notable differences in demographics or pre-existing medical conditions.

Efficacy Against COVID-19

COVID-19 was defined based on the following criteria: The participant must have experienced at least two of the following systemic symptoms: fever (≥38°C), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or the participant must have experienced at least one of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia; and the participant must have at least one NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS- CoV-2 by RT-PCR. COVID-19 cases were adjudicated by a Clinical Adjudication Committee.

The median length of follow up for efficacy for participants in the study was 9 weeks post Dose 2. There were 11 COVID-19 cases in the Moderna COVID-19 Vaccine group and 185 cases in the placebo group, with a vaccine efficacy of 94.1% (95% confidence interval of 89.3% to 96.8%).

Table 3: Primary Efficacy Analysis: COVID-19* in Participants 18 Years of Age and Older Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per-Protocol Set

Moderna COVID-19 Vaccine			Placebo			% Vaccine Efficacy (95% CI)†
Participants (N)	COVID-19 Cases (n)	Incidence Rate of COVID-19 per 1,000 Person-Years	Participants (N)	COVID-19 Cases (n)	Incidence Rate of COVID-19 per 1,000 Person-Years
14,134	11	3.328	14,073	185	56.510	94.1 (89.3, 96.8)
* COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom. Cases starting 14 days after Dose 2. † VE and 95% CI from the stratified Cox proportional hazard model

 

The subgroup analyses of vaccine efficacy are presented in Table 4.

Table 4: Subgroup Analyses of Vaccine Efficacy: COVID-19* Cases Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per- Protocol Set

Age Subgroup (Years)	Moderna COVID-19 Vaccine			Placebo			% Vaccine Efficacy (95% CI)*
	Participants (N)	COVID-19 Cases (n)	Incidence Rate of COVID-19 per 1,000 Person-Years	Participants (N)	COVID-19 Cases (n)	Incidence Rate of COVID-19 per 1,000 Person-Years
18 to <65	10,551	7	2.875	10,521	156	64.625	95.6 (90.6, 97.9)
≥65	3,583	4	4.595	3,552	29	33.728	86.4 (61.4, 95.2)
* COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom. Cases starting 14 days after Dose 2. † VE and 95% CI from the stratified Cox proportional hazard model

 

Severe COVID-19 was defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition, plus any of the following: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS, (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death.

Among all participants in the Per-Protocol Set analysis, which included COVID-19 cases confirmed by an adjudication committee, no cases of severe COVID-19 were reported in the Moderna COVID-19 Vaccine group compared with 30 cases reported in the placebo group (incidence rate 9.138 per 1,000 person-years). One PCR-positive case of severe COVID-19 in a vaccine recipient was awaiting adjudication at the time of the analysis.