Consumer medicine information

Nuvaxovid Covid-19 Vaccine (adjuvanted)

SARS-CoV-2 rS (NVX-CoV2373) COVID-19 vaccine

BRAND INFORMATION

Brand name

Nuvaxovid

Active ingredient

SARS-CoV-2 rS (NVX-CoV2373) COVID-19 vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Nuvaxovid Covid-19 Vaccine (adjuvanted).

SUMMARY CMI

NUVAXOVID COVID-19 VACCINE (adjuvanted)

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

 This vaccine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I being given NUVAXOVID?

NUVAXOVID contains the active ingredient SARS-CoV-2 rS (NVX-CoV2373). NUVAXOVID is a vaccine used to prevent COVID-19 disease caused by the SARS-CoV-2 virus in adults aged 18 years and older.

For more information, see Section 1. Why am I being given NUVAXOVID? in the full CMI.

2. What should I know before I am given NUVAXOVID?

Do not use if you have ever had an allergic reaction to NUVAXOVID or any of the ingredients listed at the end of the CMI.

Talk to your healthcare provider if you have any other medical conditions, take any other medicines, have been given another vaccine or are pregnant or plan to become pregnant or are breastfeeding.

NUVAXOVID should not be given to children under 18 years.

For more information, see Section 2. What should I know before I am given NUVAXOVID? in the full CMI.

3. What if I am taking other medicines or vaccines?

Some medicines or vaccines may interfere with NUVAXOVID and affect how it works.

A list of these medicines and vaccines is in Section 3. What if I am taking other medicines or vaccines? in the full CMI.

4. How will I be given NUVAXOVID?

NUVAXOVID will be given as an injection into the muscle of your upper arm by a healthcare provider. You will be given one dose followed by a second dose 3 weeks later. It is very important that you receive your second dose. A healthcare provider will observe you for at least 15 minutes after being given NUVAXOVID.

You may receive a booster dose approximately 6 months after the primary vaccination

More instructions can be found in Section 4. How will I be given NUVAXOVID? in the full CMI.

5. What should I know while being given NUVAXOVID?

Things you should do
  • If you receive one dose of NUVAXOVID, you should receive a second dose of the same vaccine 3 to 4 weeks later to complete the vaccination schedule.
  • A booster dose of NUVAXOVID may be given approximately 6 months after the primary vaccination for people 18 years of age and older.
  • You may not be protected against COVID-19 disease until at least seven days after your second dose.
  • You may not be protected if you only receive one dose, so a second dose is important.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how NUVAXOVID affects you. Some of the side effects of COVID-19 Vaccine listed in section 6 may temporarily affect your ability to drive or use machines. Wait until these effects have worn off before you drive or use machines. Do not drive or use machines if you are feeling unwell after vaccination.

For more information, see Section 5. What should I know while being given NUVAXOVID? in the full CMI.

6. Are there any side effects?

Very common side effects of NUVAXOVID include tenderness or pain at injection site, feeling tired, feeling unwell, headache, muscle ache, joint pain, nausea

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

 This vaccine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or in Australia directly at www.tga.gov.au/reporting-problems.



FULL CMI

NUVAXOVID COVID-19 VACCINE (adjuvanted)

Active ingredient(s): SARS-CoV-2 rS (NVX-CoV2373)

This vaccine has provisional approval in Australia to prevent COVID-19 disease caused by SARS-CoV-2 virus in people aged 18 years and older. This approval has been granted on the basis of short-term efficacy and safety data. Evidence of longer term efficacy and safety from ongoing clinical trials and vaccination in the community continues to be gathered and assessed.


Consumer Medicine Information (CMI)

This leaflet provides important information about using NUVAXOVID. You should also speak to your healthcare provider if you would like further information or if you have any concerns or questions about receiving NUVAXOVID.

Where to find information in this leaflet:

1. Why am I being given NUVAXOVID?
2. What should I know before I am given NUVAXOVID?
3. What if I am taking other medicines or vaccines?
4. How will I be given NUVAXOVID?
5. What should I know while being given NUVAXOVID?
6. Are there any side effects?
7. Product details

1. Why am I being given NUVAXOVID?

NUVAXOVID contains the active ingredient SARS-CoV-2 rS (NVX-CoV2373).

NUVAXOVID is a protein vaccine that works by triggering your immune system to produce antibodies and specialised white blood cells to work against the virus, to protect you against COVID-19 disease.

NUVAXOVID also contains an adjuvant, a substance included in certain vaccines to accelerate, improve and/or prolong the protective effects of the vaccine.

NUVAXOVID is a vaccine used to prevent COVID-19 disease caused by the SARS-CoV-2 virus in people aged 18 years and older.

2. What should I know before I am given NUVAXOVID?

Warnings

Do not use NUVAXOVID if:

  • you are allergic to SARS-CoV-2 rS (NVX-CoV2373), or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you :

  • had a severe allergic reaction or breathing problems after any other vaccine or after being given NUVAXOVID in the past.
  • fainted following any needle injection.
  • have a severe illness or infection with high fever.
    However, you can have your vaccination if you have a mild fever or upper airway infection like a cold.
  • have a weakened immune system, such as due to HIV infection or are on a medicine that affects your immune system.
  • have a bleeding disorder, bruise easily or are on a blood thinning medicine.
  • are taking any other medicines or have received any other vaccines or injections (see section 3).

If any of the above apply to you (or you are not sure), talk to your healthcare provider before you are given NUVAXOVID.

You may not be protected against COVID-19 disease until at least seven days after your second dose. As with any vaccine, NUVAXOVID may not fully protect all those who receive it and it is not known how long you will be protected.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your healthcare provider for advice before you receive this vaccine. There are limited data on the use of NUVAXOVID in pregnant or breastfeeding women. Your healthcare provider will discuss with you whether you can be given the vaccine.

Children and adolescents

NUVAXOVID should not be given to children under 18 years.

3. What if I am taking other medicines or vaccines?

Tell your healthcare provider if you are taking, have recently taken, or might take, any other vaccines or medicines including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Medicines (including other vaccines) that may impact whether you should be given this vaccine or not, include the following (see also Section 2 above):

  • medicines that weaken the immune system (such as high-dose corticosteroids, immunosuppressants or cancer medicines);
  • blood thinning medicines (anticoagulant)
  • any other vaccine including any other COVID-19 vaccines

Check with your healthcare provider if you are not sure about what vaccines, medicines, vitamins or supplements you are taking or have recently taken and if these may affect NUVAXOVID.

4. How will I be given NUVAXOVID?

How NUVAXOVID is given

NUVAXOVID will be given to you by a healthcare provider. It is injected into a muscle of your upper arm.

You will receive two (0.5 mL per dose) injections. You will be told when you need to return for your second injection of NUVAXOVID.

The second injection will be given 3 to 4 weeks after the first injection. A healthcare provider will observe you for at least 15 minutes after being given NUVAXOVID.

When NUVAXOVID is given for the first injection, NUVAXOVID (and not another vaccine against COVID-19) should be given for the second injection to complete the vaccination course.

A booster dose of NUVAXOVID may be given approximately 6 months after the primary vaccination for people 18 years of age and older.

If you forget to get your second injection

If you forget to go back at the scheduled time, ask your healthcare provider for advice. It is important that you return for your second injection of NUVAXOVID.

If you miss a scheduled second injection you may not achieve maximum protection.

If you are given too much NUVAXOVID

As NUVAXOVID is given under the close supervision of a healthcare provider it is unlikely that you will be given too much.

If you are concerned that you have been given too much NUVAXOVID, tell your healthcare provider immediately.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while being given NUVAXOVID?

As with any vaccine, the 2-dose vaccination course of NUVAXOVID may not completely protect everyone who is vaccinated from COVID-19. It is not yet known how long you will be protected.

A booster dose of NUVAXOVID may be given approximately 6 months after the primary vaccination for people 18 years of age and older.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how this vaccine affects you.

NUVAXOVID has no known effect on the ability to drive and use machines. However, side effects listed in section 6 may impact your ability to drive and use machines. If you feel unwell, do not drive or use machines.

Looking after your vaccine

Your healthcare provider is responsible for storing this vaccine and disposing of any unused product correctly.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your healthcare provider if you have any further questions about side effects.

Very common side effects

Very common side effectsWhat to do
  • Tenderness or pain at injection site
  • Feeling tired
  • Feeling unwell
  • Headache
  • Muscle aches
  • Joint pain
  • Nausea
  • Vomiting
Speak to your healthcare provider if you have any of these side effects and they worry you.

Common side effects

Common side effectsWhat to do
  • Redness at injection site
  • Swelling at injection site
  • Fever (temperature higher than 38°C)
  • Chills
  • Pain or discomfort in the arms, hands, legs and/or feet
Speak to your healthcare provider if you have any of these side effects and they worry you.

Uncommon

Uncommon side effectsWhat to do
  • Tenderness of lymph glands
  • Raised blood pressure
  • Rash
  • Redness
  • Itchiness at injection site
Speak to your healthcare provider if you have any of these rare side effects.

Tell your healthcare provider if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects, or the healthcare provider may report them for you.

In Australia, report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems and include the vaccine name (NUVAXOVID COVID-19 Vaccine [adjuvanted]) and batch/lot number if available.

In New Zealand, report side effects to the New Zealand Pharmacovigilance Centre online at nzphvc.otago.ac.nz/consumer-reporting and include the vaccine name (NUVAXOVID COVID-19 Vaccine [adjuvanted]) and batch/lot number if available.

By reporting side effects, you can help provide more information on the safety of this vaccine.

7. Product details

What NUVAXOVID contains

Active ingredient
(main ingredient)
SARS-CoV-2 rS (NVX-CoV2373)
Other ingredients
(inactive ingredients)
  • Matrix-M adjuvant, which contains:
    - Quillaja Saponaria saponins fraction A
    - Quillaja Saponaria saponins fraction C
    - cholesterol
    - phosphatidyl choline
    - monobasic potassium phosphate
    - potassium chloride
  • Dibasic sodium phosphate heptahydrate
  • Monobasic sodium phosphate monohydrate
  • Sodium chloride
  • Polysorbate 80
  • Sodium hydroxide (for pH adjustment)
  • Hydrochloric acid (for pH adjustment)
  • Water for injections

Do not receive this vaccine if you are allergic to any of these ingredients.

NUVAXOVID contains:

  • approximately 23 micrograms of sodium per 0.5 mL dose, equivalent to approximately 0.2% of the recommended maximum daily intake of 2 g sodium for an adult.
  • Potassium, less than 39 micrograms per 0.5 mL dose, that is to say, it is essentially potassium-free.

What NUVAXOVID looks like

NUVAXOVID is colourless to slightly yellow, clear to mildly opalescent suspension provided in a multidose clear glass vial.

Each vial contains 10 doses of vaccine. (AUST R 355139).

Who distributes NUVAXOVID

In Australia:

Biocelect Pty Ltd
Suite 5 02 Level 5
139 Macquarie Street
Sydney NSW 2000

In New Zealand:

Biocelect New Zealand Limited
Level 5, Wynn Williams House
47 Hereford Street
Christchurch 8013

For Medical/Technical Enquiries:
Australia: +61 2 7202 1444
New Zealand: +64 4 974 9419

Email: [email protected]
Website: www.biocelect.com

This leaflet was prepared in [June 2022].

Published by MIMS July 2022

BRAND INFORMATION

Brand name

Nuvaxovid

Active ingredient

SARS-CoV-2 rS (NVX-CoV2373) COVID-19 vaccine

Schedule

S4

 

1 Name of Medicine

SARS-CoV-2 rS (NVX-CoV2373).

2 Qualitative and Quantitative Composition

Each multidose vial contains 10 doses of 0.5 mL.
One dose (0.5 mL) contains 5 micrograms of SARS-CoV-2 spike protein* and is adjuvanted with Matrix-M.
Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), see Section 6.5 Nature and Contents of Container.
* Produced by recombinant DNA technology using a baculovirus expressions system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection.
Nuvaxovid is colourless to slightly yellow, clear to mildly opalescent.

4 Clinical Particulars

4.1 Therapeutic Indications

Nuvaxovid has provisional approval for the indication:
Active immunisation to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in individuals 18 years of age and older.
The use of this vaccine should be in accordance with official recommendations.
The decision has been made on the basis of short-term efficacy and safety data. Continued approval depends on the evidence of longer term efficacy and safety from ongoing clinical trials and postmarket assessment.

4.2 Dose and Method of Administration

Dosage.

Primary series.

Nuvaxovid is administered intramuscularly as a course of 2 doses of 0.5 mL each. It is recommended that the second dose is to be administered 3 weeks after the first dose, see Section 5.1 Pharmacodynamic Properties.

Booster dose.

A booster dose of Nuvaxovid (0.5 mL) may be administered intramuscularly approximately 6 months after completion of a primary series in individuals 18 years of age and older.
The decision when and for whom to implement a booster dose of Nuvaxovid should be made based on available vaccine safety and effectiveness data (see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties), in accordance with official recommendations.

Interchangeability.

There are no data available on the interchangeability of Nuvaxovid with other COVID-19 vaccines to complete the primary vaccination course. Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course, see Section 4.4 Special Warnings and Precautions for Use.
For precautions for administering the vaccine, see Section 4.4 Special Warnings and Precautions for Use.

Method of administration.

Nuvaxovid is for intramuscular injection only, preferably into the deltoid muscle of the upper arm.
Do not inject the vaccine intravascularly, subcutaneously, or intradermally.
This vaccine should be handled by a healthcare professional using aseptic techniques to ensure the sterility of each dose. The vaccine contains no antimicrobial preservative.
The vaccine comes ready to use. Do not dilute.

Inspect the vial.

Gently swirl the multidose vial before and in between each dose withdrawal. Do not shake.
Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent suspension free from visible particles.
Visually inspect the contents of the vial for visible particulate matter and/or discolouration prior to administration. Do not administer the vaccine if either are present.

Administer the vaccine.

An overfill is included in the vial to ensure that a maximum of ten (10) doses of 0.5 mL each can be extracted.
Each 0.5 mL dose is withdrawn into a sterile needle and sterile syringe to be administered by intramuscular injection, preferably in the deltoid muscle of the upper arm.
Use a separate sterile needle and syringe for each individual dose, prior to use in a vaccination session.
Do not mix the vaccine in the same syringe with any other vaccines or medicinal products.
Do not pool excess vaccine from multiple vials.

Storage after first needle puncture.

Nuvaxovid contains no antimicrobial preservative. Store the opened vial between 2°C to 25°C for up to 6 hours after first puncture, see Section 6.3 Shelf Life.
Record the date and time of discard on the vial label.

Discard.

Discard this vaccine if not used within 6 hours after first puncture of the vial, see Section 6.3 Shelf Life.
For instructions regarding disposal of the vaccine, see Section 6.6 Special Precautions for Disposal.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in List of Excipients.

4.4 Special Warnings and Precautions for Use

Hypersensitivity and anaphylaxis.

Events of anaphylaxis have been reported with COVID-19 vaccines including Nuvaxovid. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.
Close observation for at least 15 minutes is recommended following vaccination. A second dose of the vaccine should not be given to those who have experienced anaphylaxis to the first dose of Nuvaxovid.

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 an 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.

Immunocompromised individuals.

The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. The efficacy of Nuvaxovid may be lower in immunosuppressed individuals.

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.

Individuals may not be fully protected until 7 days after their second dose. As with all vaccines, vaccination with Nuvaxovid may not protect all vaccine recipients.

Traceability.

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

Use in the elderly.

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

Paediatric use.

The safety and efficacy of Nuvaxovid in children and adolescents less than 18 years of age have not yet been established. Limited data are available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Co-administration of Nuvaxovid with inactivated influenza vaccines has been evaluated in a limited number of participants in an exploratory clinical trial sub-study (2019nCoV-302).
The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. The seroconversion rates of these participants, given Nuvaxovid and flu vaccine concomitantly, were similar to the seroconversion rates of the participants in the main study who received Nuvaxovid alone. The clinical significance of this is unknown, see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties. Concomitant administration of Nuvaxovid with other vaccines has not been studied.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
A developmental and reproductive toxicity study was performed in female rats administered four intramuscular doses (2 prior to mating; 2 during gestation) of 5 micrograms SARS-CoV-2 rS protein (approximately 200-fold excess relative to the human dose of 5 micrograms on a body surface adjusted basis) with 10 micrograms Matrix-M adjuvant (approximately 7-fold excess relative to the human dose of 50 micrograms on a body surface-adjusted basis). No vaccine-related adverse effects on female fertility, pregnancy/lactation, or development of the embryo/fetus and offspring through post-natal Day 21 were observed. The study did not evaluate effects on male fertility.
(Category B1)
There is limited experience with use of Nuvaxovid in pregnant women.
A combined fertility and developmental toxicity study in rats did not show vaccine related adverse effects on embryofetal development (see Effects on fertility).
Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.
It is unknown whether Nuvaxovid is excreted in human milk.

4.7 Effects on Ability to Drive and Use Machines

Nuvaxovid has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under Adverse Effects (Undesirable Effects) may temporarily affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of safety profile.

Participants 18 years of age and older - after 2-dose primary series.

The safety of Nuvaxovid was evaluated from an interim analysis of pooled data from 5 ongoing clinical trials conducted in Australia, South Africa, the United Kingdom, and the United States and Mexico. At the time of the analysis, a total of 49,950 participants age 18 years and older received at least 1 dose of Nuvaxovid (n=30,058) or placebo (n=19,892). At the time of vaccination, the median age was 48 years (range 18 to 95 years). The median duration of follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months follow-up post-Dose 2.
Of the pooled reactogenicity data, which includes participants aged 18 and older enrolled in the 2 Phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue (53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%) and nausea or vomiting (15%). Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination.
Overall, there was a higher incidence of adverse reactions in younger age groups: the incidence of injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, and nausea or vomiting was higher in adults aged 18 to less than 65 years than those aged 65 years and above.
Local and systemic adverse reactions were more frequently reported after Dose 2 than Dose 1.
Licensed inactivated seasonal influenza vaccines were co-administered on the same day as the Dose 1 of Nuvaxovid (n=217) or placebo (n=214) in the opposite deltoid muscle of the arm in 431 participants enrolled in an exploratory Phase 3 (2019nCoV-302) sub-study. The frequency of local and systemic adverse reactions in the influenza sub-study population was higher than in the main study population following Dose 1 in both Nuvaxovid and placebo recipients. Frequencies of solicited local and systemic adverse reactions were similar between the sub-study and main study populations following Dose 2 of Nuvaxovid alone.
Overall, a lower frequency of reactogenicity events was associated with greater age across the 5 main studies and seasonal influenza vaccine sub-study.

Tabulated list of adverse reactions.

Adverse reactions observed during clinical studies are listed in Table 1 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 the available data).

Participants 18 years of age and older - after booster dose.

The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomised, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2) conducted in participants aged 18 to 84 years of age. A total of 254 participants received 2 doses of Nuvaxovid (0.5 mL, 3 weeks apart) as the primary vaccination series. A subset of 105 participants (Safety Analysis Set) were randomised to receive a booster dose of Nuvaxovid approximately 6 months after receiving Dose 2 of the primary series; 104 of the 105 participants received Nuvaxovid. The most frequent solicited adverse reactions were injection site tenderness (81%), fatigue (63%), injection site pain (55%), muscle pain (51%), malaise (47%), headache (46%), joint pain (29%), and fever (17%) with a median duration of 1 to 3 days following vaccination.
In a second ongoing Phase 2a/b randomised, placebo-controlled, observer-blinded clinical study conducted in South Africa (Study 2019nCoV-501), the immunogenicity and safety of a booster dose of Nuvaxovid was evaluated in healthy HIV-negative participants 18 to 84 years of age (Cohort 1) and medically stable people living with HIV (PLWH) 18 to 64 years of age (Cohort 2). Overall, 1,898 participants (Safety Analysis Set) received a booster dose of Nuvaxovid approximately 6 months after receiving the second dose of a 2-dose primary series. Solicited adverse reactions were not collected following the booster dose. The unsolicited adverse reaction profile for the booster dose was similar to that of the primary series presented in Table 1.

Booster dose following primary vaccination with other COVID-19 vaccine.

The safety of Nuvaxovid as a heterologous booster in individuals whose primary vaccination series was with other COVID-19 vaccines has been reported in the COV-BOOST study conducted in the UK (ISRCTN 73765130). This was an independent, randomised, controlled, Phase 2 trial that evaluated a single heterologous booster vaccination against COVID-19 in adults aged 30 years and older, with no history of laboratory-confirmed SARS-CoV-2 infection, at least 10 weeks after a primary vaccination series. Within the group assigned to receive a full dose of Nuvaxovid (0.5 mL) were 115 participants who previously received 2 doses of Vaxzevria (median age 65 years) and 114 who had received 2 doses of Comirnaty (mean age 63 years). The booster dose of Nuvaxovid was given a median of 76 days after the Vaxzevria primary series and 105 days after the Comirnaty primary series. Additionally, another 220 participants received a half dose of Nuvaxovid (0.25 mL). Review of the adverse reactions over the 28 days following receipt of the Nuvaxovid booster did not identify any new safety concerns, as compared with adverse reactions reported following 2 doses of Nuvaxovid given as a primary series. The safety data are limited by the small sample size of the study.

Description of selected adverse reactions.

Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared with placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination.

Post-marketing experience.

The following adverse reactions have been spontaneously reported during post-authorisation use of Nuvaxovid. As these reactions were derived from spontaneous reports, the frequencies could not be determined and are thus considered as not known. See Table 2.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

No case of overdose has been reported. In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Other viral vaccines, ATC code: J07BX03.

Mechanism of action.

Nuvaxovid is composed of purified full-length SARS-CoV-2 recombinant spike (S) protein that is stabilised in its prefusion conformation. The addition of the saponin-based Matrix-M adjuvant facilitates activation of the cells of the innate immune system, which enhances the magnitude of the S protein-specific immune response. The 2 vaccine components elicit B- and T-cell immune responses to the S protein, including neutralising antibodies, which protect against COVID-19.

Clinical trials.

Two early phase clinical trials were conducted as clinical Study 2019nCoV-101; a Phase 1 (first-inhuman)/Phase 2, randomized, observer-blinded, placebo-controlled trial evaluating the safety and immunogenicity of 5-microgram and 25-microgram doses of SARS-CoV-2 rS with or without 50 microgram Matrix-M adjuvant. The Phase 1 study in 131 healthy adult participants aged 18 - 59 was conducted in Australia (Part 1), and the Phase 2 study in 1,283 healthy adult participants aged 18 - 84 was conducted in both Australia and the US (Part 2).
Part 1: Two-dose regimens of 5 microgram or 25 microgram SARS-CoV-2 rS with 50 microgram Matrix-M adjuvant, administered 21 to 28 days apart as a bedside mixture, induced robust immune responses (anti-S protein IgG, wildtype neutralizing, and hACE2 receptor binding inhibition), peaking 2 weeks after second vaccination (Day 35). Matrix-M adjuvant was antigen sparing, induced high levels of functional antibodies, and showed a Th1-biased immune response. No dose response was seen between the 5-microgram and 25-microgram doses.
Part 2: Two-dose regimens of 5 microgram or 25 microgram SARS-CoV-2 rS with 50 microgram Matrix-M adjuvant, administered 21 days apart as co-formulated drug product (Nuvaxovid), showed similar results (to Part 1), at Day 35.
Both dose levels were well tolerated and induced robust immune responses after the second vaccination (Day 35). Collectively, the data from Part 1 and Part 2 of Clinical Study 2019nCoV-101 supported selection and further development of the 2-dose 5 microgram adjuvanted vaccine. The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in 2 pivotal, placebo-controlled, Phase 3 studies: Study 1 (2019nCoV-301) conducted in North America and Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3, conducted in South Africa.

Study 1 (2019nCoV-301) - 2-dose primary series.

Study 1 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study in participants 18 years of age and older in United States and Mexico. Upon enrolment, participants were stratified by age (18 to 64 years and ≥ 65 years) and assigned in a 2:1 ratio to receive Nuvaxovid or placebo. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with clinically stable underlying comorbidity were included as were participants with well controlled human immunodeficiency virus (HIV) infection.
Enrolment of adults was completed in February 2021. Participants will be followed for up to 24 months after the first dose for assessments of safety, and efficacy against COVID-19. Following collection of sufficient safety data to support an application for emergency use authorisation, initial recipients of placebo were invited to receive 2 injections of Nuvaxovid 21 days apart and initial recipients of Nuvaxovid to receive 2 injections of placebo 21 days apart ('blinded crossover'). All participants were offered the opportunity to continue to be followed in the study.
The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis set) included 25,452 participants who received either Nuvaxovid (n=17,312) or placebo (n=8,140), received 2 doses (Dose 1 on Day 0; Dose 2 at Day 21, median 21 days [IQR 21-23], range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose.
Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo. In the PP-EFF analysis set for participants who received Nuvaxovid, the median age range was 47 years (range: 18 to 95 years); 88% (n=15,264) were 18 to 64 years old and 12% (n=2,048) were aged 65 and older; 48% were female; 94% were from the United States and 6% were from Mexico; 76% were White, 11% were Black or African American, 6% were American Indian (including Native Americans) or Alaskan Native, and 4% were Asian; 22% were Hispanic or Latino. At least 1 pre-existing comorbidity or lifestyle characteristic associated with an increased risk of severe COVID-19 was present in 16,493 (95%) participants. Comorbidities included: obesity (body mass index (BMI) ≥ 30 kg/m2); chronic lung disease; diabetes mellitus type 2; cardiovascular disease; chronic kidney disease; or HIV. Other high-risk characteristics included age ≥ 65 years (with or without comorbidities) or age < 65 years with comorbidities and/or living or working conditions involving known frequent exposure to SARS-CoV-2 or to densely populated circumstances.
COVID-19 cases were confirmed by polymerase chain reaction (PCR) testing through a central laboratory. Vaccine efficacy is presented in Table 3.
Vaccine efficacy of Nuvaxovid to prevent the onset of COVID-19 from 7 days after Dose 2 was 90.4% (95% CI 82.9 - 94.6). No cases of moderate or severe COVID-19 were reported in the 17,312 Nuvaxovid participants compared with 4 of severe COVID-19 reported in the 8,140 placebo recipients in the PP-EFF analysis set.
Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. There were no meaningful clinical differences in overall vaccine efficacy in participants who were at increased risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe COVID-19 (eg, BMI ≥ 30 kg/m2, chronic lung disease, diabetes mellitus type 2, cardiovascular disease, and chronic kidney disease).
Efficacy results reflect enrolment that occurred during the time period when strains classified as Variants of Concern or Variants of Interest were predominantly circulating in the 2 countries (US and Mexico) where the study was conducted. Sequencing data were available for 61 of the 77 endpoint cases (79%). Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of Interest. The most common Variants of Concern were Alpha with 31/61 cases (51%), Beta (2/61, 4%) and Gamma (2/61, 4%), while the most common Variants of Interest were Iota with 8/61 cases (13%) and Epsilon 3/61 (5%).

Study 2 (2019nCoV-302) - 2-dose primary series.

Study 2 is an ongoing Phase 3, multicenter, randomised, observer-blinded, placebo-controlled study in participants 18 to 84 years of age in the United Kingdom. Upon enrolment, participants were stratified by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; current diagnosis or treatment for cancer; autoimmune disease/condition; received chronic immunosuppressive therapy or received immunoglobulin or blood derived products within 90 days; bleeding disorder or continuous use of anticoagulants; history of allergic reactions and/or anaphylaxis; were pregnant; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with clinically stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 4 weeks before enrolment were included. Participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not excluded from enrolment.
Enrolment was completed in November 2020. Participants are being followed for up to 12 months after the primary vaccination series for assessments of safety, and efficacy against COVID-19.
The primary efficacy PP-EFF analysis set included 14,039 participants who received either Nuvaxovid (n= 7,020) or placebo (n= 7,019), received 2 doses (Dose 1 on day 0; Dose 2 at median 21 days (IQR 21-23), range 16-45, did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose.
Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. In the PP-EFF analysis set for participants who received Nuvaxovid, the median age was 56.0 years (range: 18 to 84 years); 72% (n=5,067) were 18 to 64 years old and 28% (n=1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were Asian; 1% were multiple races, < 1% were Black or African American; and < 1% were Hispanic or Latino; and 45% had at least 1 comorbid condition. See Table 4.
These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. Identification of the Alpha variant was based on S gene target failure by PCR. Data were available for 95 of the 106 endpoint cases (90%). Of these, 66 out of 95 (69%) were identified as the Alpha variant with the other cases classified as non-Alpha.
No cases of severe COVID-19 were reported in the 7,020 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 7,019 placebo recipients in the PP-EFF analysis set.
Vaccine efficacy of Nuvaxovid to prevent the onset of COVID-19 from 7 days after Dose 2 was 89.7% (PP-EFF analysis set) for any strain or variant of SARS-CoV-2 and 86.3% (post-hoc analysis of the PPEFF analysis set) for the B.1.1.7 (Alpha) variant of SARS-CoV-2, which comprised 66 out of 95 (69%) of the endpoint cases that were sequenced.

Licensed seasonal influenza vaccine co-administration sub-study of study 2 (2019nCoV-302).

Overall, 431 participants were co-vaccinated with inactivated seasonal influenza vaccines; 217 substudy participants received Nuvaxovid and 214 received placebo. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. In the per-protocol immunogenicity (PP-IMM) analysis set for participants who received Nuvaxovid (n = 191), median age was 40.0 years (range: 22 to 70 years); 93% (n = 178) were 18 to 64 years old and 7% (n = 13) were aged 65 to 84, 43% were female; 75% were White; 23% were multiracial or from ethnic minorities; and 27% had at least 1 comorbid condition. Co-administration resulted in no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. A 30% reduction in antibody responses to Nuvaxovid was noted as assessed by an anti-spike IgG assay with seroconversion rates similar to participants who did not receive concomitant influenza vaccine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Study 3 (2019nCoV-501) - 2-dose primary series.

Study 3 is an ongoing Phase 2a/b, multicenter, randomised, observer-blinded, placebo-controlled study in HIV-negative participants 18 to 84 years of age and people living with HIV (PLWH) 18 to 64 years of age in South Africa. PLWH were medically stable (free of opportunistic infections), receiving highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL.
The PP-EFF included 2,770 participants who received either Nuvaxovid (n=1,408) or placebo (n=1,362), received 2 doses (Dose 1 on Day 0; Dose 2 on Day 21), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infections through 7 days after the second dose.
Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo in the RR-EFF analysis set for participants who received Nuvaxovid, median age was 28 years (range 18 to 84 years); 40% were female; 91% were Black/African American; 2% were White; 3% were multiple races; 1% were Asian; and 2% were Hispanic or Latino; and 5.5% were HIV-positive.
A total of 147 symptomatic mild, moderate or severe COVID-19 cases among all adult participants, seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF analysis set) of the primary efficacy endpoint, with 51 (4%) cases for Nuvaxovid versus 96 (7%) cases for placebo. The resultant vaccine efficacy of Nuvaxovid was 48.6% (95% CI: 28.4 - 63.1).
These results reflect enrolment that occurred during the time period when the B.1.351 (Beta) variant was circulating in South Africa.

Immunogenicity of Nuvaxovid as a homologous or heterologous booster dose.

Immunogenicity in participants 18 years of age and older - after booster dose.

Study 2019nCoV-101, part 2.

The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomised, observer-blinded, placebo-controlled clinical study administered as a single booster dose (Study 2019nCoV-101, Part 2) in healthy adult participants aged 18 to 84 years of age who were seronegative to SARS-CoV-2 at baseline. A total of 254 participants (Full Analysis Set) received 2 doses of Nuvaxovid (0.5 mL, 5 micrograms 3 weeks apart) as the primary vaccination series. A subset of 104 participants received a booster dose of Nuvaxovid approximately 6 months after receiving Dose 2 of the primary series.
A single booster dose of Nuvaxovid induced an approximate 34-fold increase in the immune response against the ancestral (Wuhan) strain 28 days after receipt of the dose (Day 217) with serum IgG geometric mean titer (GMT) of 204,367 EU compared with a GMT of 6,064 EU pre-booster (Day 189) and an approximate 4.7-fold increase from peak GMT (43,905 EU), 14 days following Dose 2 of the primary series. An approximate 96-fold increase in neutralizing antibodies was shown from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of 1,470.
For the variants of concern, 2 assays were used to assess immune responses. An assay comparing anti-rS IgG activity (n = 29) across the same strains demonstrated a 5.4-fold (Ancestral), 9.7‑fold (Alpha), 6.5‑fold (Beta), 11.1‑fold (Delta), 9.3‑fold (Omicron BA.1) and 11.0-fold (Omicron BA.2) increase from 2 weeks after the primary series (Day 35) to 28 days post-booster (Day 217). A second assay comparing wild-type neutralization titers (MN99) (n = 32) showed a 15.4‑fold (Ancestral), 14.0-fold (Delta), and 3.5-fold (Omicron BA.1) increase from 2 weeks after the primary series (Day 35) to 28 days post-booster (Day 217).

Study 2019nCoV-501.

In Study 3, an ongoing Phase 2a/b randomised, observer-blinded, placebo-controlled study, the safety and immunogenicity of booster dose was evaluated in healthy HIV-negative adult participants 18 to 84 years of age and medically stable PLWH 18 to 64 years of age who were seronegative to SARS-CoV-2 at baseline. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6 months after completion of the primary series of Nuvaxovid (Day 201).
An approximate 31-fold increase was shown in serum IgG GMT assessed at Day 236 (111,066 EU) from the pre-boost GMT at Day 201 (3,632 EU). An approximate 3.6-fold increase was demonstrated from peak GMT (30,756 EU) at Day 35 following completion of the primary series.
An approximate 52-fold increase in neutralizing antibodies was shown from a GMT of 69 pre-booster (Day 201) to a GMT of 3,600 post-booster (Day 236) and an approximate 5.2-fold increase from a peak GMT (14 days post-Dose 2) of 694.
Immunogenicity of a booster dose following primary vaccination with other COVID-19 vaccines. The effectiveness of Nuvaxovid as a heterologous booster in individuals whose primary vaccination series was with other COVID-19 vaccines, has been reported in the COV-BOOST study conducted in the UK (ISRCTN 73765130). This was an independent randomised, controlled, phase 2 trial that evaluated a heterologous booster vaccination against COVID-19 in adults aged 30 years and older, at least 10 weeks after a primary vaccination series, with no history of laboratory confirmed SARS-CoV2 infection. Within the group assigned to receive Nuvaxovid were 115 individuals who previously received Vaxzevria and 114 who had received Comirnaty. Nuvaxovid induced significantly higher anti-spike IgG at 28 days post booster compared with the control (a quadrivalent meningococcal vaccine). It is noted that the incremental increase in antibody concentrations was lower following a third (booster) dose with Nuvaxovid than following mRNA vaccines. The geometric mean (GM) fold rise after a single booster dose of Nuvaxovid exceeded the prespecified GM-fold rise of 1.75 (compared with control) that was considered to be an immunologically important difference.

Elderly population.

Nuvaxovid was assessed in participants 18 years of age and older. The efficacy of Nuvaxovid was consistent between elderly (≥ 65 years) and younger individuals (18 to 64 years).

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

In vitro genotoxicity studies including bacterial reverse mutation, chromosomal aberrations in Chinese Hamster Ovary (CHO) cells and mammalian micronuclei in CHO cells were conducted with the Matrix-M adjuvant. The adjuvant was shown to be non-genotoxic.

Carcinogenicity.

Carcinogenicity studies were not performed. The components of the vaccine are not expected to have carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, sodium chloride, polysorbate 80, sodium hydroxide (for adjustment of pH), hydrochloric acid (for adjustment of pH), water for injections, adjuvant (Matrix M), Quillaja saponaria saponins fraction A, Quillaja saponaria saponins fraction C, cholesterol, phosphatidyl choline, monobasic potassium phosphate, potassium chloride.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products or be diluted.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

Unopened vial.

The unopened vaccine is stored refrigerated at 2°C to 8°C, protected from light.
Unopened Nuvaxovid vaccine has been shown to be stable up to 12 hours at 25°C. Storage at 25°C is not the recommended storage or shipping condition.

Punctured vial.

Chemical and physical in-use stability has been demonstrated from the time of first needle puncture to administration for 6 hours at 2°C to 25°C.
From a microbiological point of view, after first opening (first needle puncture), the vaccine should be used immediately.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C to 8°C). Do not freeze.
Keep the vials in the outer carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see Section 6.3 Shelf Life.

6.5 Nature and Contents of Container

5 mL of suspension in a vial (type I glass) with a stopper (bromobutyl or chlorobutyl rubber) and an aluminium overseal with blue plastic flip-cap.
Each vial contains 10 doses of 0.5 mL.
Pack size: 10 multidose vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicinal product or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Not applicable.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes