JCOVDEN *

Pharmacy Only: Prescription

4.2    Posology and method of administration

Posology

Individuals 18 years of age and older

Primary vaccination

JCOVDEN is administered as a single-dose of 0.5 mL by intramuscular injection only.

Booster dose

A booster dose (second dose) of 0.5 mL of JCOVDEN may be administered intramuscularly at least 2 months after the primary vaccination in individuals 18 years of age and older (see also sections 4.4, 4.8 and 5.1).

A booster dose of JCOVDEN (0.5 mL) may be administered in individuals 18 years of age and older as a heterologous booster dose following completion of primary vaccination with an approved mRNA COVID-19 vaccine or an adenoviral vector-based COVID-19 vaccine. The dosing interval for the heterologous booster dose is the same as that authorised for a booster dose of the vaccine used for primary vaccination (see also sections 4.4, 4.8 and 5.1).

4.8 Undesirable effects

Booster dose (second dose) following primary vaccination with JCOVDEN

 The safety of a booster dose (second dose) with JCOVDEN administered approximately 2 months after the primary vaccination was evaluated in an ongoing randomised, double-blind, placebo-controlled Phase 3 Study (COV3009). In the FAS (full analysis set), from the 15708 adults aged 18 years and older who received 1 dose of JCOVDEN, a total of 8646 individuals received a second dose during the double-blind phase. In the reactogenicity subset, from the 3016 individuals who received 1 dose of JCOVDEN, 1559 individuals received a second dose during the double-blind phase. The median age of individuals was 53.0 years (range: 18-99 years). At the data-cut off (25 June 2021), the median follow-up duration after the booster dose with JCOVDEN was 38 days. The solicited adverse reaction profile for the booster dose was similar to that after the first dose. There were no new safety signals identified.

The safety of a booster dose (second dose) with JCOVDEN administered at least 6 months after the primary vaccination was evaluated in a randomised, double-blind Phase 2 Study (COV2008 Cohort 1 N=330).

Overall, the solicited adverse reaction profile for the homologous booster dose was similar to that after the first dose. There were no new safety signals identified.

Booster dose following primary vaccination with an approved mRNA COVID-19 vaccine

Overall, in 3 clinical studies (including 2 independent studies) approximately 500 adults have received primary vaccination with 2 doses of an mRNA COVID‑19 vaccine and received a single booster dose of JCOVDEN, at least 3 months after primary vaccination (COV2008, COV-BOOST and DMID 21-0012 studies). There were no new safety concerns identified. However, a trend towards an increase in frequency and severity of solicited local and systemic adverse events after the heterologous booster dose was observed when compared with the homologous booster dose of JCOVDEN.

Booster dose following primary vaccination with an adenoviral vector-based COVID-19 vaccine

The safety of a heterologous booster dose of JCOVDEN was evaluated in the COV-BOOST study following primary vaccination with an adenoviral vector-based COVID-19 vaccine. Participants received 2 doses of Vaxzevria (N=108) followed by a booster dose of JCOVDEN 77 days post second dose (median; IQR: 72-83 days). There were no new safety concerns identified.

The safety of a booster dose with JCOVDEN administered at least 12 weeks after the primary vaccination with an approved mRNA COVID-19 vaccine regimen was assessed after 2 doses of Spikevax (49 individuals) or Comirnaty (51 individuals), or 1 dose of JCOVDEN (50 individuals). The median age of individuals was 55.0 years (range: 20-77 years). At the data-cut off (24 September 2021), 98.7% of the subjects had completed the Day 29 visit after booster vaccination (none has reached Day 91). Following a JCOVDEN heterologous booster, the solicited adverse reaction profile was similar to that following a JCOVDEN primary vaccination or homologous booster dose.

5.      PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Neutralising antibody (wtVNA) and S-binding antibody (enzyme-linked immunosorbent assay)  increases against the reference SARS-CoV-2 strain were also observed in studies COV1001, COV1002 and COV2001 in a limited number of study participants after a boost given at 2, 3 and 6 months, when compared to pre-boost values. Overall, the increases of geometric mean titres (GMTs) pre-boost to 1 month post-boost ranged from 1.5 to 4.4 fold for neutralising antibodies, and from 2.5 to 5.8 fold for binding antibodies. A 2-fold decrease in antibody levels was observed 4 months following 2-month booster dose, compared to 1 month following 2-month booster dose. Antibody levels were still higher than antibody levels following a single-dose at a similar timepoint. These data support the administration of a booster dose when administered at an interval of 2 months or longer after primary vaccination.

Immunogenicity of a booster dose following primary vaccination with an approved mRNA COVID-19 vaccine

COV-BOOST study is a multicentre, randomised Phase 2 investigator‑initiated study (NCT73765130) conducted in the United Kingdom, to evaluate a booster vaccination against COVID‑19. Participants were adults aged 30 years or older. A cohort of participants received two doses of Comirnaty (N=89), followed by a booster dose of JCOVDEN. The median interval (IQR) was 106 (91-144) days between the second and booster dose. JCOVDEN boosted binding (N=88), pseudovirus neutralising (N=77) and wild type neutralising antibody responses (N=21) against the reference strain, as observed at Day 28. At Day 84 post-boost, GMTs were still higher than pre-boost values. Furthermore, JCOVDEN boosted pseudovirus neutralising antibody responses against the Delta variant assessed at Day 28 (N=89).

 An DMID 21-0012, an independent Phase 1/2 open-label clinical trial study (NCT04889209) conducted in the United States that evaluated a heterologous booster dose of JCOVDEN. Immunogenicity was assessed by using a psVNA based on a lentivirus expressing the SARS-CoV-2 Spike protein with D614G mutation. Due to the limited sample size, differences observed are only descriptive. A booster dose of JCOVDEN was administered In this study, to adults who had completed primary vaccination with a Spikevax 2-dose series (N=151), a JCOVDEN single-dose (N=156), or a Comirnaty 2-dose series (N=151) at least 12 weeks prior to enrollment (mean interval [range] of 20 [13-26] and 21 [12-41] weeks for Spikevax and Comirnaty, respectively) and who reported no history of SARS-CoV-2 infection. were randomised 1:1:1 to receive a booster dose of one of three vaccines: Spikevax, JCOVDEN, or Comirnaty. Neutralising antibody titres were assessed on Day 1 prior to administration of the booster dose and on Day 15 and Day 29 after the booster dose. A booster response to JCOVDEN was demonstrated regardless of primary vaccination. JCOVDEN boosted binding and pseudovirus neutralising antibody responses against the reference strain and the Delta variant in individuals primed with Spikevax 2-dose series (N=49) or Comirnaty 2-dose series (N=50), as observed at Day 15 post-boost. JCOVDEN boosted pseudovirus neutralising antibody responses against the Omicron BA.1 variant in individuals primed with Comirnaty 2-dose series (N=50), as observed at Day 29. The antibody level on Day 15 after a heterologous boost by JCOVDEN is lower than after a homologous boost by a licensed mRNA vaccine while on Day 29, neutralising antibody titers are roughly similar between both regimens. Data indicate the homologous regimen with JCOVDEN induces lower antibody responses compared to heterologous boosting with a licensed mRNA vaccine. The clinical relevance of this is unknown. Only short-term immunogenicity data are available, long-term protection and immunological memory are currently unknown.

Immunogenicity of a booster dose following primary vaccination with an adenoviral vector-based COVID-19 vaccine

COV-BOOST study (see study design above) also evaluated a booster dose of JCOVDEN in participants who had received 2 doses of Vaxzevria (N=101). The median interval (IQR) was 77 (72-83) days between the second and booster dose. JCOVDEN boosted binding (N=94), pseudovirus neutralising (N=94) and wild type neutralising antibody responses (N=21) against the reference strain. At Day 84 post-boost, GMTs were still higher than pre-boost values. Furthermore, JCOVDEN boosted pseudovirus neutralising antibody responses against the Delta variant assessed at Day 28 (N=90).

Descriptive data from the COV-BOOST study and DMID 21-0012 study indicate that boosting with JCOVDEN after primary vaccination with an adenoviral vector-based vaccine induces lower antibody responses compared to heterologous boosting with a licensed mRNA vaccine after primary vaccination with an adenoviral vector-based vaccine. The studies also indicate that neutralising antibody titres reached at 1 month post-boost with JCOVDEN after primary vaccination with an mRNA vaccine are comparable to after a homologous boost with an mRNA vaccine.

3.      How JCOVDEN is given

Your doctor, pharmacist or nurse will inject the vaccine into the muscle - usually in the upper arm.

How much vaccine will you receive

A single-dose primary vaccination (0.5 mL) of JCOVDEN is injected.

A booster dose (second dose) of JCOVDEN may be given at least 2 months after the primary vaccination in individuals 18 years of age and older.

JCOVDEN may be administered as a single booster dose to eligible individuals 18 years of age and older who have completed primary vaccination with an approved mRNA COVID-19 vaccine or an adenoviral vector-based COVID-19 vaccine. The dosing interval for the booster dose is the same as that authorised for a booster dose of the vaccine used for primary vaccination.

6. Contents of the pack and other information

For any additional information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Ireland

Janssen Sciences Ireland UC

Tel: 1 800 709 122+353212356806/0080056540088

United Kingdom (Northern Ireland)

Janssen Sciences Ireland UC

Tel:  +44 1 494 567 4442076602872/0080056540088

4.8    Undesirable effects



4.      Possible side effects

Rare: may affect up to 1 in 1000 people

·               allergic reaction

·               hives

·               excessive sweating

·               swollen lymph nodes (lymphadenopathy)

·               unusual feeling in the skin, such as tingling or a crawling feeling (paraesthesia)

·               decreased feeling or sensitivity, especially in the skin (hypoaesthesia)

·               persistent ringing in the ears (tinnitus)

·               blood clots in veins (venous thromboembolism (VTE))

·               temporary, usually one-sided facial drooping (including Bell’s palsy)

4.      Possible side effects

Like all vaccines, JCOVDEN can cause side effects, although not everybody gets them. Most of the side effects occur in the 1 or 2 days of getting the vaccination.

Get medical attention immediately if within 3 weeks of vaccination you get any of the following symptoms:

· experience severe or persistent headaches, blurred vision, mental status changes or seizures (fits);

· develop shortness of breath, chest pain, leg swelling, leg pain or persistent abdominal pain;

· notice unusual skin bruising or pinpoint round spots beyond the site of vaccination.

Get urgent medical attention if you get symptoms of a severe allergic reaction. Such reactions may include a combination of any of the following symptoms:

· feeling faint or light-headed

· changes in your heartbeat

· shortness of breath

· wheezing

· swelling of your lips, face, or throat

· hives or rash

· nausea or vomiting

· stomach pain

The following side effects can happen with this vaccine.

Very common: may affect more than 1 in 10 people

· headache

· nausea

· muscle aches

· pain where the injection is given

· feeling very tired

Common: may affect up to 1 in 10 people

·  redness where the injection is given

·  swelling where the injection is given

·  chills

·  joint pain

·  cough

·  fever

Uncommon: may affect up to 1 in 100 people

· rash

· joint pain

· muscle weakness

· arm or leg pain

· feeling weak

· feeling generally unwell

· cough

· sneezing

· sore throat

· back pain

· tremor

·  excessive sweating

·  unusual feeling in the skin, such as tingling or a crawling feeling (paraesthesia)

· diarrhoea

· vomiting

· dizziness

Rare: may affect up to 1 in 1000 people

· allergic reaction

· hives

· excessive sweating

· swollen lymph nodes (lymphadenopathy)

· unusual feeling in the skin, such as tingling or a crawling feeling (paraesthesia)

· decreased feeling or sensitivity, especially in the skin (hypoaesthesia)

· persistent ringing in the ears (tinnitus)

· vomiting

· blood clots in veins (venous thromboembolism (VTE))

Very Rare: may affect up to 1 in 10000 people

· blood clots often in unusual locations (e.g., brain, liver, bowel, spleen) in combination with low level of blood platelets

· serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barré syndrome (GBS))

Unknown (cannot be estimated from the available data)

· severe allergic reaction

· capillary leak syndrome (a condition causing fluid leakage from small blood vessels)

· low levels of blood platelets (immune thrombocytopenia) that can be associated with bleeding (see section 2, ‘Blood Disorders’)

· inflammation of the spinal cord

· inflammation of small blood vessels (small vessel vasculitis) with skin rash or small red or purple, flat, round spots under the skin’s surface or bruising

Tell your doctor, pharmacist or nurse if you have any side effects that bother you or do not go away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

Ireland

HPRA Pharmacovigilance

Website: www.hpra.ie. and include batch/Lot number if available.

United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: https://coronavirus-yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. and include batch/Lot number if available.

For any additional information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

10.    DATE OF REVISION OF THE TEXT

15 Sep 2022

4.8    Undesirable effects

Summary of safety profile

Primary vaccination (primary pooled analysis)

 The safety of JCOVDEN was evaluated in an ongoing Phase 3 study (the primary pooled analysis from the double-blind phase of the randomised, placebo-controlled studies COV1001, COV1002, COV2001, COV3001 and COV3009. A total of 21,895 38,538 adults aged 18 years and older received at least a single-dose primary vaccination of JCOVDEN). The median age of individuals was 52 years (range 18-100 years). The safety analysis was performed once For the primary pooled analysis, the median follow-up duration of 2for individuals who received JCOVDEN was approximately 4 months after completion of primary vaccination  was reached.. Longer safety follow-up of ≥ 2≥ 6 months is available for 6,136 11948 adults who received JCOVDEN.

In study COV3001the primary pooled analysis, the most common local adverse reactions reported was injection site pain (54.348.6%). The most common systemic adverse reactions were headache (38.9%),  fatigue (44.0 38.2%), headache (43.0%), myalgia (38.1 33.2%) and nausea (16.9 14.2%). Pyrexia (defined as body temperature ≥ 38.0°C) was observed in 7.2 9% of participants. Most adverse reactions  occurred within 1–2 days following vaccination and were mild to moderate in severity. Across the studies, most adverse reactions occurred within 1–2 days following vaccination and were of short duration (1–2 days).

Reactogenicity was generally milder and reported less frequently in older adults.(763 adults ≥ 65 years old).

The safety profile was generally consistent across participants with or without prior evidence of SARS-CoV-2 infection at baseline.; a total of 2151 adults seropositive at baseline received JCOVDEN (9.8%). A total of 10.6% of individuals that received JCOVDEN were SARS-CoV-2 positive at baseline (based on serology or RT-PCR assessment).

4.8    Undesirable effects

10.    DATE OF REVISION OF THE TEXT

18 May 2022

4.      Possible side effects

Unknown (cannot be estimated from the available data)

·               severe allergic reaction

·               capillary leak syndrome (a condition causing fluid leakage from small blood vessels)

·               low levels of blood platelets (immune thrombocytopenia) that can be associated with bleeding (see section 2, ‘Blood Disorders’)

·               inflammation of the spinal cord

·               inflammation of small blood vessels (small vessel vasculitis) with skin rash or small red or purple, flat, round spots under the skin’s surface or bruising

6.      Contents of the pack and other information

For any additional information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Ireland

Janssen Sciences Ireland UC

Tel: +353212356806/0080056540088

United Kingdom (Northern Ireland)

Janssen Sciences Ireland UC

Tel:  +442076602872/0080056540088 +441494 56744 

JCOVDEN brand name (previously COVID-19 Vaccine Janssen) was approved by EMA on 28-Apr-2022. The SmPC with JCOVDEN brand name was amended on the medicines.ie site on 9-May-2022 and the brand name was replaced where applicable in the following sections.

Change to section 1 - Name of medicinal product; Change to section 2 - Qualitative and quantitative composition; Change to section 3 - Pharmaceutical form; Change to section 4.1 - Therapeutic indications; Change to section 4.2 - Posology and method of administration; Change to section 4.4 - Special warnings and precautions for use; Change to section 4.6 - Pregnancy and lactation; Change to section 4.7 - Effects on ability to drive and use machines; Change to section 4.8 - Undesirable effects; Change to section 4.9 - Overdose; Change to section 5.1 - Pharmacodynamic properties; Change to section 5.3 - Preclinical safety data; Change to section 6.4 - Special precautions for storage; Change to section 10 - Date of revision of the text  

However, the following correction to Section 4.8 Undesirable effects - "Reporting of suspected adverse reactions" has been made to add the Country Specific information to the SmPC.

 Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V and include batch/Lot number if available.

Ireland

HPRA Pharmacovigilance

Website: www.hpra.ie. and include batch/Lot number if available.

 United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: https://coronavirus-yellowcard.mhra.gov.uk/

or search for MHRA Yellow Card in the Google Play or Apple App Store. and include batch/Lot number if available.

JCOVDEN brand name (previously COVID-19 Vaccine Janssen) was approved by EMA on 28-Apr-2022. The PIL with JCOVDEN brand name was amended on the medicines.ie site on 9-May-2022 where applicable in the following sections.

Change to Section 1 - what the product is; Change to section 2 - what you need to know - warnings and precautions; Change to section 3 - how to take/use; Change to section 4 - possible side effects; Change to section 5 - how to store or dispose; Change to section 6 - what the product contains However, the following correction to Section 4. Possible side effects - "Reporting of side effects" has been made to add the Country Specific information to the PIL.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V and include batch/Lot number if available see details below). By reporting side effects you can help provide more information on the safety of this medicine.

Ireland

HPRA Pharmacovigilance

Website: www.hpra.ie. and include batch/Lot number if available.

 United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: https://coronavirus-yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. and include batch/Lot number if available.

COVID-19 Vaccine Janssen JCOVDEN suspension for injection

Throughout the SmPC where applicable, Brand name has been changed from "COVID-19 Vaccine Janssen" to "JCOVDEN".

COVID-19 Vaccine Janssen JCOVDEN suspension for injection

Throughout the PIL, brand name has been changed from "COVID-19 Vaccine Janssen" to "JCOVDEN"

6.3     Shelf life

Unopened vial

2 years when stored at -25°C to ‑15°C.

Once removed from the freezer, the unopened vaccine may be stored refrigerated at 2°C to 8°C, protected from light, for a single period of up to 4.5 11 months, not exceeding the printed expiry date (EXP).

6.4     Special precautions for storage

Store and transport frozen at -25°C to -15°C. The expiry date for storage at -25°C to -15°C is printed on the vial and outer carton after “EXP”.

When stored frozen at -25°C to -15°C, the vaccine can be thawed either at 2°C to 8°C or at room temperature:

• at 2°C to 8°C: a carton of 10 or 20 vials will take approximately 13 hours to thaw, and a single vial will take approximately 2 hours to thaw.
• at room temperature (maximally 25°C): a carton of 10 or 20 vials will take approximately 4 hours to thaw, and a single vial will take approximately 1 hour to thaw.

The vaccine can also be stored in a refrigerator or transported at 2°C to 8°C for a single period of up to 4.5 11 months, not exceeding the original expiry date (EXP). Upon moving the product to 2°C to 8°C storage, the updated expiry date must be written on the outer carton and the vaccine should be used or discarded by the updated expiry date. The original expiry date should be crossed out. The vaccine can also be transported at 2°C to 8°C as long as the appropriate storage conditions (temperature, time) are applied.

Once thawed, the vaccine cannot be re-frozen.

Keep the vials in the original carton in order to protect from light.

Unopened COVID-19 Vaccine Janssen is stable for a total of 12 hours at 9°C to 25°C. It is not a recommended storage or shipping condition but may guide decisions for use in case of temporary temperature excursions during the 4.5 11 month storage at 2°C to 8°C.

6.6     Special precautions for disposal and other handling

Handling instructions and administration

This vaccine should be handled by a healthcare professional using aseptic technique to ensure the sterility of each dose.

• The vaccine comes ready to use once thawed.
• The vaccine may be supplied frozen at -25°C to -15°C or thawed at 2°C to 8°C.
• Do not re-freeze vaccine once thawed.
• Keep the vials in the original carton in order to protect from light and to record the expiry for the different storage conditions, if applicable.

a.       Storage upon receipt of vaccine
IF YOU RECEIVE YOUR VACCINE FROZEN AT -25°C to -15°C you may:
-25°C to -15°C	OR		2°C to 8°C
Store in a freezer The vaccine can be stored and transported frozen at -25°C to -15°C. The expiry date for storage is printed on the vial and outer carton after “EXP” (see section 6.4).		Store in a refrigerator The vaccine can also be stored and transported at 2°C to 8°C for a single period of up to 4.5 11 months, not exceeding the original expiry date (EXP). Upon moving the product to a refrigerator at 2°C to 8°C, the updated expiry date must be written on the outer carton and the vaccine should be used or discarded by the updated expiry date. The original expiry date should be crossed out (see section 6.4).

5.       How to store COVID-19 Vaccine Janssen

The vaccine can also be stored in a refrigerator or transported at 2°C to 8°C for a single period of up to 4.5 11 months, not exceeding the original expiry date (EXP). Upon moving the product to 2°C to 8°C storage, the updated expiry date must be written on the outer carton and the vaccine should be used or discarded by the updated expiry date. The original expiry date should be crossed out. The vaccine can also be transported at 2°C to 8°C as long as the appropriate storage conditions (temperature, time) are applied.

The following information is intended for healthcare professionals only:

The vaccine can also be stored in a refrigerator or transported at 2°C to 8°C for a single period of up to 4.5 11 months, not exceeding the original expiry date (EXP). Upon moving the product to 2°C to 8°C storage, the updated expiry date must be written on the outer carton and the vaccine should be used or discarded by the updated expiry date. The original expiry date should be crossed out. The vaccine can also be transported at 2°C to 8°C as long as the appropriate storage conditions (temperature, time) are applied.

4.4       Special warnings and precautions for use

Coagulation disorders

• Thrombosis with thrombocytopenia syndrome: A combination of thrombosis and thrombocytopenia, in some cases accompanied by bleeding, has been observed very rarely following vaccination with COVID-19 Vaccine Janssen. This includes severe cases of venous thrombosis at unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis as well as arterial thrombosis concomitant with thrombocytopenia. Fatal outcome has been reported. These cases occurred within the first three weeks following vaccination, and mostly in women individuals under 60 years of age.

• Guillain-Barré syndrome and transverse myelitis
• Guillain-Barré syndrome (GBS) and transverse myelitis (TM) have has been reported very rarely following vaccination with COVID-19 Vaccine Janssen. Healthcare professionals should be alert to of GBS and TM signs and symptoms to ensure correct diagnosis, in order to initiate adequate supportive care and treatment and to rule out other causes.

• 4.8       Undesirable effects

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 11 March 2021

Date of latest renewal: 03 January 2022

2.         What you need to know before you are given COVID-19 Vaccine Janssen

Warnings and precautions

Blood disorders

• Venous thromboembolism: Blood clots in veins (venous thromboembolism (VTE)) have been observed rarely following vaccination with COVID-19 Vaccine Janssen.
• Thrombosis with thrombocytopenia syndrome: A combination of blood clots and low levels of ‘platelets’ in the blood has been observed very rarely following vaccination with COVID-19 Vaccine Janssen. This includes severe cases with blood clots, including in unusual locations, such as the brain, liver, bowel and spleen in some cases in combination with bleeding. These cases mostly occurred within the first three weeks following vaccination and in women individuals below 60 years of age. Fatal outcome has been reported.
• Neurological disorders

Guillain-Barré syndrome

• Seek immediate medical attention if you develop weakness and paralysis in the extremities that can progress to the chest and face (Guillain-Barré syndrome, GBS). This has been reported very rarely after vaccination with COVID-19 Vaccine Janssen.
• Inflammation of the spinal cord (transverse myelitis)
• Seek immediate medical attention if you develop weakness in the arms or legs, sensory symptoms (such as tingling, numbness, pain or loss of pain sensation) or problems with bladder or bowel function. This has been reported very rarely after vaccination with COVID-19 Vaccine Janssen.

• 4.            Possible side effects
• Unknown (cannot be estimated from the available data)
• severe allergic reaction
• capillary leak syndrome (a condition causing fluid leakage from small blood vessels)
• low levels of blood platelets (immune thrombocytopenia) that can be associated with bleeding (see section 2, ‘Blood Disorders’)
• inflammation of the spinal cord

4.2     Posology and method of administration

Posology

Individuals 18 years of age and older

Primary vaccination

COVID-19 Vaccine Janssen is administered as a single-dose of 0.5 mL by intramuscular injection only.

Booster dose

A booster dose (second dose) of 0.5 mL of COVID-19 Vaccine Janssen may be administered intramuscularly at least 2 months after the primary vaccination in individuals 18 years of age and older (see also sections 4.4, 4.8 and 5.1).

A booster dose of the COVID-19 Vaccine Janssen (0.5 mL) may be administered as a heterologous booster dose following completion of primary vaccination with an approved mRNA COVID-19 vaccine. The dosing interval for the heterologous booster dose is the same as that authorised for a booster dose of the vaccine used for primary vaccination (see also sections 4.4, 4.8 and 5.1).

4.3     Contraindications

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

A history of confirmed thrombosis with thrombocytopenia syndrome (TTS) following vaccination with any COVID-19 vaccine (see also section 4.4).

4.4     Special warnings and precautions for use

Coagulation disorders

• Thrombosis with thrombocytopenia syndrome: A combination of thrombosis and thrombocytopenia, in some cases accompanied by bleeding, has been observed very rarely following vaccination with COVID-19 Vaccine Janssen. This includes severe cases of venous thrombosis at unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis as well as arterial thrombosis concomitant with thrombocytopenia. Fatal outcome has been reported. These cases occurred within the first three weeks following vaccination, and mostly in women under 60 years of age.

Thrombosis in combination with thrombocytopenia requires specialised clinical management. Healthcare professionals should consult applicable guidance and/or consult specialists (e.g., haematologists, specialists in coagulation) to diagnose and treat this condition.

Individuals who have experienced thrombosis with thrombocytopenia syndrome following vaccination with any COVID-19 vaccine should not receive COVID-19 Vaccine Janssen (See also section 4.3).

• Venous thromboembolism: Venous thromboembolism (VTE) has been observed rarely following vaccination with COVID-19 Vaccine Janssen (see section 4.8). This should be considered for individuals at increased risk for VTE.

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) has been reported very rarely following vaccination with COVID-19 Vaccine Janssen. Healthcare professionals should be alert of GBS signs and symptoms to ensure correct diagnosis, in order to initiate adequate supportive care and treatment and to rule out other causes.

Risk of very rare events after a booster dose

The risk of very rare events (such as coagulation disorders including thrombosis with thrombocytopenia syndrome, CLS and GBS) after a booster dose of COVID-19 Vaccine Janssen has not yet been characterised.

4.8     Undesirable effects

Summary of safety profile

Primary vaccination (primary analysis)

The safety of COVID-19 Vaccine Janssen was evaluated in an ongoing Phase 3 study (COV3001). A total of 21895 adults aged 18 years and older received a single-dose primary vaccination of COVID‑19 Vaccine Janssen. The median age of individuals was 52 years (range 18-100 years). The safety analysis was performed once the median follow-up duration of 2 months after vaccination was reached. Longer safety follow-up of > 2 months is available for 11948 adults who received COVID-19 Vaccine Janssen.

In study COV3001, the most common local adverse reactions reported was injection site pain (48.6%). The most common systemic adverse reactions were headache (38.9%), fatigue (38.2%), myalgia (33.2%) and nausea (14.2%). Pyrexia (defined as body temperature ≥ 38.0°C) was observed in 9% of participants. Most adverse reactions occurred within 1–2 days following vaccination and were mild to moderate in severity and of short duration (1–2 days).

Reactogenicity was generally milder and reported less frequently in older adults (763 adults ≥ 65 years old).

The safety profile was generally consistent across participants with or without prior evidence of SARS-CoV-2 infection at baseline; a total of 2151 adults seropositive at baseline received COVID-19 Vaccine Janssen (9.8%).

Booster dose (second dose) following primary vaccination with COVID-19 Vaccine Janssen

The safety of a booster dose (second dose) with COVID-19 Vaccine Janssen administered approximately 2 months after the primary vaccination was evaluated in an ongoing randomised, double-blind, placebo-controlled Phase 3 Study (COV3009). In the FAS (full analysis set), from the 15708 adults aged 18 years and older who received 1 dose of COVID-19 Vaccine Janssen, a total of 8646 individuals received a second dose during the double-blind phase. In the reactogenicity subset, from the 3016 individuals who received 1 dose of COVID-19 Vaccine Janssen, 1559 individuals received a second dose during the double-blind phase. The median age of individuals was 53.0 years (range: 18-99 years). At the data-cut off (25 June 2021), the median follow-up duration after the booster dose with COVID-19 Vaccine Janssen was 38 days. The solicited adverse reaction profile for the booster dose was similar to that after the first dose. There were no new safety signals identified.

Booster dose following primary vaccination with an approved mRNA COVID-19 vaccine

The safety of a booster dose with COVID-19 Vaccine Janssen administered at least 12 weeks after the primary vaccination with an approved mRNA COVID-19 vaccine regimen was assessed after 2 doses of Spikevax (49 individuals) or Comirnaty (51 individuals), or 1 dose of COVID-19 Vaccine Janssen (50 individuals). The median age of individuals was 55.0 years (range: 20-77 years). At the data-cut off (24 September 2021), 98.7% of the subjects had completed the Day 29 visit after booster vaccination (none has reached Day 91). Following the COVID-19 Vaccine Janssen heterologous booster, the solicited adverse reaction profile was similar to that following a COVID-19 Vaccine Janssen primary vaccination or homologous booster dose.

4.9     Overdose

No case of overdose has been reported. In pPhase 1/2 studies where a higher dose (up to 2-fold) was administered COVID-19 Vaccine Janssen remained well-tolerated, however vaccinated individuals reported an increase in reactogenicity (increased vaccination site pain, fatigue, headache, myalgia, nausea and pyrexia).

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

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

Pharmacotherapeutic group: Vaccines, other viral vaccines, ATC code: J07BX03

Mechanism of action

COVID-19 Vaccine Janssen is a monovalent vaccine composed of a recombinant, replication-incompetent human adenovirus type 26 vector that encodes a SARS-CoV-2 full-length spike (S) glycoprotein in a stabilised conformation. Following administration, the S glycoprotein of SARS‑CoV-2 is transiently expressed, stimulating both neutralising and other functional S-specific antibodies, as well as cellular immune responses directed against the S antigen, which may contribute to protection against COVID-19.

Clinical efficacy

Efficacy from a single-dose primary vaccination

Primary analysis

An A primary analysis (cut-off date 22 January 2021) ongoing of a multicentre, randomised, double-blind, placebo-controlled Phase 3 study (COV3001) is being was conducted in the United States, South Africa and Latin American countries to assess the efficacy, safety, and immunogenicity of a single-dose primary vaccination of COVID-19 Vaccine Janssen for the prevention of COVID-19 in adults aged 18 years and older. The study excluded individuals with abnormal function of the immune system resulting from a clinical condition, individuals who are under immunosuppressive therapies within 6 months, as well as pregnant women. Participants with stable HIV infection under treatment were not excluded. Licensed vaccines, excluding live vaccines, could be administered more than 14 days before or more than 14 days after the vaccination in the study. Licensed live attenuated vaccines could be administered more than 28 days before or more than 28 days after the vaccination in the study.

A total of 44325 individuals were randomised in parallel in a 1:1 ratio to receive an intramuscular injection of COVID-19 Vaccine Janssen or placebo. A total of 21895 adults received COVID-19 Vaccine Janssen and 21888 adults received placebo. Participants were followed for a median follow-up of approximately 2 months 58 days (range: 1-124 days)after vaccination.

The primary efficacy analysis population of 39321 individuals included 38059 SARS-CoV-2 seronegative individuals at baseline and 1262 individuals with an unknown serostatus.

Demographic and baseline characteristics were similar among individuals who received the COVID‑19 Vaccine Janssen and those who received placebo. In the primary efficacy analysis population, among the individuals who received COVID-19 Vaccine Janssen, the median age was 52.0 years (range: 18 to 100 years); 79.7% (N=15646) of individuals were 18 to 64 years old [with 20.3% (N=3984) aged 65 or older and 3.8% (N=755) aged 75 or older]; 44.3% of individuals were female; 46.8% were from Northern America (United States), 40.6% were from Latin America and 12.6% were from Southern Africa (South Africa). A total of 7830 (39.9%) individuals had at least one pre-existing comorbidity associated with increased risk of progression to severe COVID-19 at baseline. Comorbidities included: obesity defined as BMI ≥ 30 kg/m² (27.5%), hypertension (10.3%), type 2 diabetes (7.2%), stable/well-controlled HIV infection (2.5%), serious heart conditions (2.4%) and asthma (1.3%). Other comorbidities were present in ≤ 1% of the individuals.

COVID-19 cases were confirmed by a central laboratory based on a positive SARS-CoV-2 viral RNA result using a polymerase chain reaction (PCR)-based test. Vaccine efficacy overall and by key age groups are presented in Table 2.

The primary efficacy analysis population of 39321 individuals included 38059 SARS-CoV-2 seronegative individuals at baseline and 1262 individuals with an unknown serostatus.

Demographic and baseline characteristics were similar among individuals who received the COVID‑19 Vaccine Janssen and those who received placebo. In the primary efficacy analysis population, among the individuals who received COVID-19 Vaccine Janssen, the median age was 52.0 years (range: 18 to 100 years); 79.7% (N=15646) of individuals were 18 to 64 years old [with 20.3% (N=3984) aged 65 or older and 3.8% (N=755) aged 75 or older]; 44.3% of individuals were female; 46.8% were from Northern America (United States), 40.6% were from Latin America and 12.6% were from Southern Africa (South Africa). A total of 7830 (39.9%) individuals had at least one pre-existing comorbidity associated with increased risk of progression to severe COVID-19 at baseline. Ccomorbidities included: obesity defined as BMI ≥ 30 kg/m² (27.5%), hypertension (10.3%), type 2 diabetes (7.2%), stable/well-controlled HIV  infection (2.5%), serious heart conditions (2.4%) and asthma (1.3%). Other comorbidities were present in ≤ 1% of the individuals.

Prior to unblinding, supplementary analyses, considered post-hoc, of positive cases using PCR-based tests regardless of confirmation by the central laboratory generally support the results of the primary analysis.

Beyond 14 days after vaccination, 2 vs. 8 cases of molecularly confirmed COVID-19 were hospitalised, respectively in the COVID-19 Vaccine Janssen vs. placebo group. One case in the placebo group required Intensive Care Unit (ICU) admission and mechanical ventilation. The finding was supported by post-hoc analysis of all COVID-19 related hospitalisations implementing a broader search based on all available information from any source (2 vs. 29 cases in the extended data set).

Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants, as well as for participants with and without medical comorbidities associated with high risk of severe COVID-19.

Exploratory subgroup analyses of vaccine efficacy against COVID-19 and severe COVID-19 for Brazil, South Africa, and the United States were conducted (see Table 4). For the subgroup analyses, all COVID-19 cases accrued up to the primary efficacy analysis data cut-off date, including cases confirmed by the central laboratory and cases with documented positive SARS-CoV-2 PCR from a local laboratory which are still awaiting confirmation by the central laboratory, were included.

Samples from 71.7% of central laboratory confirmed primary analysis cases had been sequenced [United States (73.5%), South Africa (66.9%) and Brazil (69.3%)]. Of the sequenced samples there is an imbalance in the completeness of the dataset between COVID‑19 Vaccine Janssen and placebo. In the United States, 96.4% of strains were identified as the Wuhan-H1 variant D614G; in South Africa, 94.5% of strains were identified as the 20H/501Y.V2 variant (B.1.351 lineage); in Brazil, 69.4% of strains were identified to be a variant of the P.2 lineage and 30.6% of strains were identified as the Wuhan-H1 variant D614G. 

Updated Final analyses

The final updated efficacy analyses at the end of the  double-blind phase (cut-off date 09 July 2021) were performed with additional confirmed COVID-19 cases accrued during blinded, placebo-controlled follow‑up, with a median follow-up of 4 months after a single-dose of the COVID-19 Vaccine Janssen.    

Beyond 14 days after vaccination, 18 vs. 74 cases of molecularly confirmed COVID-19 were hospitalised, respectively in the COVID-19 Vaccine Janssen vs. placebo group, resulting in 76.1% (adjusted 95% CI: 56.9; 87.7) vaccine efficacy. A total of 5 cases in the COVID-19 Vaccine Janssen group vs. 17 cases in the placebo group required Intensive Care Unit (ICU) admission and 4 vs. 8 cases in the COVID-19 Vaccine Janssen and placebo group respectively required mechanical ventilation.

Vaccine efficacy against asymptomatic infections at least 28 days after vaccination was 28.9% (95% CI: 20.0; 36.8) and against all SARS-CoV-2 infections was 41.7% (95% CI: 36.3; 46.7).

Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants, as well as for participants with and without medical comorbidities associated with high risk of severe COVID-19.

A summary of vaccine efficacy by variant strain is presented in Table 5 below:

Efficacy of two-doses of COVID-19 Vaccine Janssen administered 2 months apart

A final analysis (cut-off date 25 June 2021) of a multicenter, randomised, double-blind, placebo-controlled Phase 3 study (COV3009) was conducted in North and Latin America, Africa, Europe and Asia to assess the efficacy, safety, and immunogenicity of 2 doses of COVID-19 Vaccine Janssen administered with a 56-day interval. The study excluded individuals with abnormal function of the immune system resulting from a clinical condition, individuals who were under immunosuppressive therapies within 6 months, as well as pregnant women. Participants with stable HIV infection under treatment were not excluded. Licensed vaccines, excluding live vaccines, could be administered more than 14 days before or more than 14 days after the vaccination in the study. Licensed live attenuated vaccines could be administered more than 28 days before or more than 28 days after the vaccination in the study.

A total of 31300 individuals were randomised in the double-blind phase of the study. In total, 14492 (46.3%) individuals were included in the per-protocol efficacy population (7484 individuals received COVID-19 Vaccine Janssen and 7008 individuals received placebo). Participants were followed for a median of 36 days (range: 0-172 days) after vaccination.

Demographic and baseline characteristics were similar among individuals who received at least two doses of the COVID‑19 Vaccine Janssen and those who received placebo. In the primary efficacy analysis population, among the individuals who received 2 doses of COVID-19 Vaccine Janssen, the median age was 50.0 years (range: 18 to 99 years); 87.0% (N=6512) of individuals were 18 to 64 years old [with 13.0% (N=972) aged 65 or older and 1.9% (N=144) aged 75 or older]; 45.4% of individuals were female; 37.5% were from North America (United States), 51.0% were from Europe (including UK), 5.4% were from South Africa, 1.9% from Philippines and 4.2% from Latin America. A total of 2747 (36.7%) individuals had at least one pre-existing comorbidity associated with increased risk of progression to severe COVID-19 at baseline. Comorbidities included: obesity defined as BMI ≥ 30 kg/m² (24.6%), hypertension (8.9%), sleep apnea (6.7%), type 2 diabetes (5.2%), serious heart conditions (3.6%), asthma (1.7%) and stable/well-controlled HIV infection (1.3%). Other comorbidities were present in ≤ 1% of the individuals.

Vaccine efficacy against symptomatic COVID-19 and severe COVID-19 is presented in Table 6 below: