COVID-19 VACCINE JANSSEN medication leaflet x20 SUSPENSION FOR INJECTION CILAG

J07BX03 COVID-19 vaccine (Ad26.COV2-S [recombinant])

Medicine COVID-19 VACCINE JANSSEN SUSPENSION FOR INJECTION contains substance COVID-19 vaccine (Ad26.COV2-S [recombinant]) , ATC code J07BX03 - Antiinfectives for systemic use | Viral vaccines | Other viral vaccines .

General data about COVID-19 VACCINE JANSSEN SUSPENSION FOR INJECTION CILAG

Substance: COVID-19 vaccine (Ad26.COV2-S [recombinant])

Date of last drug list: 01-06-2021

Commercial code: W67472002

Pharmaceutical form: SUSPENSION FOR INJECTION

Quantity: 20

Product type: original

Prescription restrictions: P-RF - Medicines prescription that is retained in the pharmacy (not renewable).

Marketing authorisation

Manufacturer:JANSSEN BIOLOGICS B.V. - OLANDA

Holder: JANSSEN CILAG INTERNATIONAL NV - BELGIA

Number: 1525/2021/02

Shelf life: 2 years-unopened bottle, at a temperature between -25ºC and -15ºC

Contents of the package leaflet for the medicine COVID-19 VACCINE JANSSEN x20 SUSPENSION FOR INJECTION CILAG

1. NAME OF THE MEDICINAL PRODUCT

JCOVDEN suspension for injection
COVID-19 vaccine (Ad26.COV2-S [recombinant])

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multi-dose vial which contains 5 doses of 0.5 mL.

One dose (0.5 mL) contains:
Adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein* (Ad26.COV2-S), not less than 8.92 log10 infectious units (Inf.U). * Produced in the PER.C6 TetR Cell Line and by recombinant DNA technology.

The product contains genetically modified organisms (GMOs).

Excipients with known effect
Each dose (0.5 mL) contains approximately 2 mg of ethanol.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection (injection).

Colourless to slightly yellow, clear to very opalescent suspension (pH 6-6.4).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

JCOVDEN is indicated for active immunisation to prevent 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.

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 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, pct. 4.8 and 5.1).

Paediatric population
The safety and efficacy of JCOVDEN in children and adolescents (less than 18 years of age) have not yet been established. No data are available.

Elderly
No dose adjustment is required in elderly individuals ≥ 65 years of age. See also sections 4.8 and 5.1.

Method of administration
JCOVDEN is for intramuscular injection only, preferably in the deltoid muscle of the upper arm.

Do not inject the vaccine intravascularly, intravenously, subcutaneously or intradermally.

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions on handling and disposal of the vaccine, see section 6.6.

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).

Individuals who have previously experienced episodes of capillary leak syndrome (CLS) (see also section 4.4).

4.4 Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity and anaphylaxis
Events of anaphylaxis have been reported. 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.

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. However, the presence of a minor infection and/or low-grade fever should not delay vaccination.

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 JCOVDEN. 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 individuals 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 JCOVDEN (See also section 4.3).

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

- Immune thrombocytopenia: Cases of immune thrombocytopenia with very low platelet levels (<20000 per μL) have been reported very rarely after vaccination with JCOVDEN, usually within the first four weeks after receiving JCOVDEN. This included cases with bleeding and cases with fatal outcome. Some of these cases occurred in individuals with a history of immune thrombocytopenia (ITP). If an individual has a history of ITP, the risks of developing low platelet levels should be considered before vaccination, and platelet monitoring is recommended after vaccination.

Healthcare professionals should be alert to the signs and symptoms of thromboembolism and/or thrombocytopenia. Those vaccinated should be instructed to seek immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg pain, leg swelling, or persistent abdominal pain following vaccination. Additionally, anyone with neurological symptoms including severe or persistent headaches, seizures, mental status changes or blurred vision after vaccination, or who experiences spontaneous bleeding, skin bruising (petechia) beyond the site of vaccination after a few days, should seek prompt medical attention.

Individuals diagnosed with thrombocytopenia within 3 weeks after vaccination with JCOVDEN should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within 3 weeks of vaccination should be evaluated for thrombocytopenia.

Risk of bleeding with intramuscular administration
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.

Capillary leak syndrome
Very rare cases of capillary leak syndrome (CLS) have been reported in the first days after vaccination with JCOVDEN, in some cases with a fatal outcome. A history of CLS has been reported. CLS is a rare disorder characterised by acute episodes of oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia. Patients with an acute episode of CLS following vaccination require prompt recognition and treatment. Intensive supportive therapy is usually

warranted. Individuals with a known history of CLS should not be vaccinated with this vaccine. See also section 4.3.

Guillain-Barré syndrome and transverse myelitis

Guillain-Barré syndrome (GBS) and transverse myelitis (TM) have been reported very rarely following vaccination with JCOVDEN. Healthcare professionals should be alert to 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.

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 JCOVDEN has not yet been characterised.

Immunocompromised individuals
The efficacy, safety and immunogenicity of the vaccine have not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of JCOVDEN 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
Protection starts around 14 days after vaccination. As with all vaccines, vaccination with JCOVDEN may not protect all vaccine recipients (see section 5.1).

Excipients
Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per 0.5 mL dose, that is to say essentially ‘sodium-free’.

Ethanol
This medicinal product contains 2 mg of alcohol (ethanol) per 0.5 mL dose. The small amount of alcohol in this medicinal product will not have any noticeable effects.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. Concomitant administration of JCOVDEN with other vaccines has not been studied.

4.6 Fertility, pregnancy and lactation

Pregnancy
There is limited experience with the use of JCOVDEN in pregnant women. Animal studies with
JCOVDEN do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or postnatal development (see section 5.3).

Administration of JCOVDEN in pregnancy should only be considered when the potential benefits outweigh any potential risks to the mother and foetus.

Breast-feeding
It is unknown whether JCOVDEN is excreted in human milk.

Fertility
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

4.7 Effects on ability to drive and use machines

JCOVDEN has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of safety profile
Primary vaccination (primary analysis)
The safety of JCOVDEN 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 JCOVDEN. 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 JCOVDEN.

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 JCOVDEN (9.8%).

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.

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

Tabulated list of adverse reactions
Adverse drug reactions observed during study COV3001 or from post marketing sources are organised by MedDRA System Organ Class (SOC). Frequency categories are defined as follows:
Very common (≥ 1/10);
Common (≥ 1/100 to < 1/10);
Uncommon (≥ 1/1000 to < 1/100);
Rare (≥ 1/10000 to < 1/1000);
Very rare (< 1/10000); Not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Adverse reactions reported following vaccination with JCOVDEN
Not known (cannot be

Very Common Uncommon Rare estimated from
System Organ common (≥ 1/100 to (≥ 1/1000 to (≥ 1/10000 to Very Rare the available
Class (≥ 1/10) < 1/10) < 1/100) < 1/1000) (< 1/10000) data)
Blood and Lymph- Immune lymphatic system adenopathy thrombo- disorders cytopenia
Immune system Hypersensitivitya; Anaphylaxisb

disorders urticaria
Nervous system Headache Tremor; Hypoaesthesia Guillain- Transverse disorders dizziness; Barré myelitis

paraesthesia syndrome
Ear and labyrinth Tinnitus disorders
Vascular Venous Thrombosis Capillary leak disorders thromboembolism in syndrome;

combination cutaneous with small vessel

thrombo- vasculitis cytopenia

Respiratory, Cough Sneezing; thoracic and oropharyngeal mediastinal pain disorders
Gastrointestinal Nausea Diarrhoea Vomiting disorders
Skin and Rash; subcutaneous hyperhidrosis tissue disorders
Musculoskeletal Myalgia Arthralgia Muscular and connective weakness; pain tissue disorders in extremity;

back pain

General disorders Fatigue; Pyrexia; Asthenia; and injection injection malaise administration site pain site site conditions erythema;

injection site

swelling; chills

a Hypersensitivity refers to allergic reactions of the skin and subcutaneous tissue. b Cases received from an ongoing open-label study in South Africa.

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.

4.9 Overdose

No case of overdose has been reported. In Phase 1/2 studies where a higher dose (up to 2-fold) was administered JCOVDEN 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
JCOVDEN 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
A primary analysis (cut-off date 22 January 2021) of a multicentre, randomised, double-blind, placebo-controlled Phase 3 study (COV3001) 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 JCOVDEN 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 JCOVDEN or placebo. A total of 21895 adults received JCOVDEN and 21888 adults received placebo. Participants were followed for a median follow-up of approximately 2 months 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 JCOVDEN and those who received placebo. In the primary efficacy analysis population, among the individuals who received JCOVDEN, 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.

Table 2: Analysis of vaccine efficacy against COVID-19b in SARS-CoV-2 seronegative adults - primary efficacy analysis population after a single-dose

JCOVDEN Placebo
N=19630 N=19691 % Vaccine

COVID-19 Person- COVID-19 Person- Efficacy
Subgroup Cases (n) Years Cases (n) Years (95% CI)c

14 days post-vaccination
All subjectsa 116 3116.6 348 3096.1 66.9

(59.0; 73.4) 18 to 64 years of age 107 2530.3 297 2511.2 64.2

(55.3; 71.6) 65 years and older 9 586.3 51 584.9 82.4

(63.9; 92.4) 75 years and older 0 107.4 8 99.2 100

(45.9; 100.0) 28 days post-vaccination
All subjectsa 66 3102.0 193 3070.7 66.1

(55.0; 74.8) 18 to 64 years of age 60 2518.7 170 2490.1 65.1

(52.9; 74.5) 65 years and older 6 583.3 23 580.5 74.0

(34.4; 91.4) 75 years and older 0 106.4 3 98.1 -

a Co-primary endpoint as defined in the protocol. b Symptomatic COVID-19 requiring positive RT-PCR result and at least 1 respiratory sign or symptom or 2 other

systemic signs or symptoms, as defined in the protocol. c Confidence intervals for ‘All Subjects’ were adjusted to implement type I error control for multiple testing.

Confidence intervals for age groups are presented unadjusted.

Vaccine efficacy against severe COVID-19 is presented in Table 3 below.

Table 3: Analyses of vaccine efficacy against severe COVID-19a in SARS-CoV-2 seronegative adults - primary efficacy analysis population after a single-dose

JCOVDEN Placebo
N=19630 N=19691 % Vaccine

COVID-19 Person- COVID-19 Person- Efficacy
Subgroup Cases (n) Years Cases (n) Years (95% CI)b

14 days post-vaccination
Severe 76.7

14 3125.1 60 3122.0 (54.6; 89.1) 28 days post-vaccination

Severe 85.4 5 3106.2 34 3082.6 (54.2; 96.9)

a Final determination of severe COVID-19 cases was made by an independent adjudication committee, who also assigned disease severity according to the definition per FDA guidance.

b Confidence intervals were adjusted to implement type I error control for multiple testing.

Of the 14 vs. 60 severe cases with onset at least 14 days after vaccination in the JCOVDEN group vs. placebo group, 2 vs. 6 were hospitalised. Three individuals died (all in the placebo group). The majority of the remaining severe cases fulfilled only the oxygen saturation (SpO2) criterion for severe disease (≤ 93% on room air).

Updated analyses
The 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 JCOVDEN.

Table 4: Analysis of vaccine efficacy against symptomatica and severeb COVID-19 - 14 days and 28 days after a single-dose

% Vaccine
JCOVDEN Placebo

Efficacy
c N=19577d N=19608d (95% CI)
Endpoint

COVID-19 COVID-
Person- Person-

Cases 19 Cases
Years Years

(n) (n) 14 days post-vaccination

56.3
Symptomatic COVID-19 484 6685.6 1067 6440.2

(51.3; 60.9) 55.3

18 to 64 years of age 438 5572.0 944 5363.6 (49.9; 60.2)

63.8 65 years and older 46 1113.6 123 1076.6

(48.9; 74.8) 48.3

75 years and older 9 198.2 15 170.9 (-26.1; 80.1)

73.3
Severe COVID-19 56 6774.6 205 6625.2

(63.9; 80.5) 74.3

18 to 64 years of age 46 5653.8 175 5531.4 (64.2; 81.8)

67.5 65 years and older 10 1120.8 30 1093.8

(31.6; 85.8) 71.2

75 years and older 2 199.4 6 172.4 (-61.2; 97.2)

28 days post-vaccination 52.9

Symptomatic COVID-19 433 6658.4 883 6400.4 (47.1; 58.1)

18 to 64 years of age 393 5549.9 790 5330.5 52.2

(46.0; 57.8) 58.5

65 years and older 40 1108.5 93 1069.9 (39.3; 72.1)

22.3 75 years and older 9 196.0 10 169.3

(-112.8; 72.1) 74.6

Severe COVID-19 46 6733.8 176 6542.1 (64.7; 82.1)

75.4 18 to 64 years of age 38 5619.2 150 5460.5

(64.7; 83.2) 70.1

65 years and older 8 1114.6 26 1081.6 (32.1; 88.3)

65.5 75 years and older 2 197.2 5 170.1

(-110.7; 96.7) a Symptomatic COVID-19 requiring positive RT-PCR result and at least 1 respiratory sign or symptom or 2 other

systemic signs or symptoms, as defined in the protocol. b Final determination of severe COVID-19 cases was made by an independent adjudication committee, who also

assigned disease severity according to the definition per FDA guidance. c Co-primary endpoint as defined in the protocol. d Per-protocol efficacy population

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

Table 5: Summary of vaccine efficacy against symptomatica and severeb COVID-19 by variant strain following a single-dose

Severity
Symptomatic
COVID-19 Severe COVID-19

% Vaccine Efficacy % Vaccine Efficacy
Variant Onset (95% CI) (95% CI)

71.5% 89.7%
At least 14 days after vaccination (57.3; 81.4) (57.3; 98.8)

58.2% 93.1%
Reference At least 28 days after vaccination (35.0; 73.7) (54.4; 99.8)

70.1% 51.1%
At least 14 days after vaccination (35.1; 87.6) (-241.2; 95.6)

70.2% 51.4%
Alpha (B.1.1.7) At least 28 days after vaccination (35.3; 87.6) (-239.0; 95.6)

38.1% 70.2%
At least 14 days after vaccination (4.2; 60.4) (28.4; 89.2)

51.9% 78.4%
Beta (B.1.351) At least 28 days after vaccination (19.1; 72.2) (34.5; 94.7)

36.4% 63.3%
At least 14 days after vaccination (13.9; 53.2) (18.3; 85.0)

36.5% 63.6%
Gamma (P.1) At least 28 days after vaccination (14.1; 53.3) (18.8; 85.1)

64.8% 91.1%
At least 14 days after vaccination (47.3; 77.0) (38.8; 99.8)

64.1% 87.9%
Zeta (P.2) At least 28 days after vaccination (42.5; 78.3) (9.4; 99.7)

35.8% 79.4%
At least 14 days after vaccination (1.5; 58.6) (38.1; 94.9)

35.9% 79.5%
Mu (B.1.621) At least 28 days after vaccination (1.7; 58.7) (38.5; 94.9)

10.0% 67.4%
At least 14 days after vaccination (-39.5; 42.0) (-30.6; 94.3)

10.1% 67.6%
Lambda (C.37) At least 28 days after vaccination (-39.2; 42.1) (-29.8; 94.4)

- 6.0% NE*
Delta At least 14 days after vaccination (-178.3; 59.2) NE* (B.1.617.2/AY. -5.7% NE* 1/AY.2) At least 28 days after vaccination (-177.7; 59.2) NE*

73.2% 81.4%
At least 14 days after vaccination (65.4; 79.4) (59.8; 92.5)

69.0% 75.7%
Other At least 28 days after vaccination (59.1; 76.8) (46.2; 90.3) a Symptomatic COVID-19 requiring positive RT-PCR result and at least 1 respiratory sign or symptom or 2 other

systemic signs or symptoms, as defined in the protocol. b Final determination of severe COVID-19 cases was made by an independent adjudication committee, who also

assigned disease severity according to the definition per FDA guidance. * If less than 6 cases are observed for an endpoint then the VE will not be shown. NE = not estimable.

Efficacy of two-doses of JCOVDEN 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 JCOVDEN 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
JCOVDEN 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 JCOVDEN and those who received placebo. In the primary efficacy analysis population, among the individuals who received 2 doses of JCOVDEN, 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:

Table 6: Analysis of vaccine efficacy against symptomatica and severeb COVID-19 - 14 days post-booster dose (second dose)

JCOVDEN Placebo
N=7484c N=7008c % Vaccine

COVID-19 Person- COVID-19 Person- Efficacy
Endpoint Cases (n) Years Cases (n) Years (95% CI)d

Symptomatic 75.2 14 1730.0 52 1595.0

COVID-19 (54.6; 87.3)

Severe COVID-19 0 1730.7 8e 1598.9 (32.6; 100.0)

a Symptomatic COVID-19 requiring positive RT-PCR result and at least 1 respiratory sign or symptom or 2 other systemic signs or symptoms, as defined in the protocol.

b Final determination of severe COVID-19 cases was made by an independent adjudication committee, who also assigned disease severity according to the definition per FDA guidance.

c Per-protocol efficacy population. d Confidence intervals were adjusted to implement type I error control for multiple testing. e Of the 8 participants with severe disease, 1 was admitted to an intensive care unit.

Approximately 68% of centrally confirmed strains have been sequenced as of this analysis (July 2021). Preliminary analysis results of variants with sufficient cases available for meaningful interpretations (Alpha [B.1.1.7] and Mu [B.1.621]) show that, after the first dose of JCOVDEN, efficacy 14 days post-dose 1 (Day 15-Day 56) for these 2 variants was 71.6% [95% CI: 43.2; 86.9] and 43.9% [95% CI: -43.4; 79.6], respectively. After the second dose (≥71 days), efficacy for Alpha and Mu was 94.2% [95% CI: 62.9; 99.9] and 63.1% [95% CI: -27.9; 91.6], respectively. Therefore, statistically significant efficacy for Mu was not demonstrated. There were only few Delta cases (2 and 1 in the JCOVDEN group and placebo group, respectively) and no reference strain cases in either the JCOVDEN or placebo group in the follow-up 14 days after the booster dose (≥71 days).

Vaccine efficacy against asymptomatic infections at least 14 days after second vaccination was 34.2% (95% CI: -6.4; 59.8).

Immunogenicity of a booster dose (second dose) following primary vaccination with JCOVDEN

It should be noted that there is no established immune correlate of protection. In a Phase 2 Study (COV2001), individuals 18 through 55 years of age and 65 years and older received a booster dose of
JCOVDEN approximately 2 months after the primary vaccination. Immunogenicity was assessed by measuring neutralising antibodies to SARS-CoV-2 Victoria/1/2020 strain using a qualified wild-type virus neutralisation assay (wtVNA). Immunogenicity data are available from 39 individuals, of whom 15 were 65 years of age and older, and are summarised in Table 7.

Table 7: SARS-CoV-2 Neutralisation Wild Type VNA-VICTORIA/1/2020 (IC50), Study
COV2001 Group 1, Per-Protocol Immunogenicity Set*

28 Days 14 Days 28 Days
Post- Post- Post-

Primary Pre-Booster Booster Booster
Baseline Vaccination Dose Dose Dose (Day 1) (Day 29) (Day 57) (Day 71) (Day 85)

N 38 39 39 39 38
Geometric mean <LLOQ

260 (196; 212 (142; 518 (354; 424 (301; titre (95% CI) (<LLOQ,

346) 314) 758) 597) <LLOQ)

Geometric mean fold increase (95% 2.3 1.8

n/a n/a n/a
CI) from pre- (1.7; 3.1) (1.4; 2.4) booster

LLOQ = lower limit of quantification * PPI set: The per-protocol immunogenicity population includes all randomised and vaccinated individuals for whom

immunogenicity data are available excluding individuals with major protocol deviations expected to impact the immunogenicity outcomes. In addition, samples obtained after missed vaccinations or individuals with natural SARS- CoV-2 infection occurring after screening (if applicable) were excluded from the analysis.

Neutralising antibody and binding antibody 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
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. Ab 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

An independent Phase 1/2 open-label clinical trial (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. In this study, 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 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. 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.

Elderly population
JCOVDEN was assessed in individuals 18 years of age and older. The efficacy of JCOVDEN was consistent between elderly (≥ 65 years) and younger individuals (18-64 years).

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with
JCOVDEN in one or more subsets of the paediatric population in prevention of COVID-19 (see section 4.2 for information on paediatric use).

Conditional approval
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This means that further evidence on this medicinal product is awaited. The European Medicines Agency will review new information on this medicinal product at least every year and this SmPC will be updated as necessary.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazards for humans based on conventional studies of repeat-dose toxicity and local tolerance, and reproductive and developmental toxicity.

Genotoxicity and carcinogenicity
JCOVDEN has not been evaluated for its genotoxic or carcinogenic potential. The components of the vaccine are not expected to have genotoxic or carcinogenic potential.

Reproductive toxicity and fertility
Female reproductive toxicity and fertility were assessed in a combined embryo-foetal and pre- and post-natal development study in the rabbit. In this study a first vaccination of JCOVDEN was administered intramuscularly to female rabbits 7 days prior to mating, at a dose equivalent to 2-fold above the recommended human dose, followed by two vaccinations at the same dose during the gestation period (i.e., at gestational days 6 and 20). There were no vaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. The parental females as well as their foetuses and offspring exhibited SARS-CoV-2 S protein-specific antibody titres, indicating that maternal antibodies were transferred to the foetuses during gestation. No JCOVDEN data are available on vaccine excretion in milk.

In addition, a conventional (repeat-dose) toxicity study in rabbits with JCOVDEN did not reveal any effects on male sex organs that would impair male fertility.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

10 vial pack
2-hydroxypropyl-β-cyclodextrin (HBCD)
Citric acid monohydrate

Ethanol
Hydrochloric acid
Polysorbate-80
Sodium chloride
Sodium hydroxide
Trisodium citrate dihydrate
Water for injections

20 vial pack
2-hydroxypropyl-β-cyclodextrin (HBCD)
Citric acid monohydrate

Ethanol
Hydrochloric acid
Polysorbate-80
Sodium chloride
Sodium hydroxide
Water for injections

6.2 Incompatibilities

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

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 11 months, not exceeding the printed expiry date (EXP).

Once thawed, the vaccine should not be re-frozen.

For special precautions for storage, see section 6.4.

Opened vial (after first puncture of the vial)
Chemical and physical in-use stability, including during transportation, of the vaccine has been demonstrated for 6 hours at 2°C to 25°C. From a microbiological point of view, the product should preferably be used immediately after first puncture of the vial; however, the product can be stored between 2°C to 8°C for a maximum of 6 hours or remain at room temperature (maximally 25°C) up to 3 hours after first puncture of the vial. Beyond these times, in-use storage is the responsibility of the user.

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 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 JCOVDEN 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 11 month storage at 2°C to 8°C.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

A 2.5 mL suspension in a multi-dose vial (type I glass) with a rubber stopper (chlorobutyl with fluoropolymer coated surface), aluminium crimp and blue plastic cap. Each vial contains 5 doses of 0.5 mL.

Pack sizes of 10 or 20 multi-dose vials.

Not all pack sizes may be marketed.

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 2°C to 8°C

OR

Store in a freezer Store in a refrigerator
- The vaccine can be stored and transported - The vaccine can also be stored and

frozen at -25°C to -15°C. transported at 2°C to 8°C for a single period
- The expiry date for storage is printed on the of up to 11 months, not exceeding the

vial and outer carton after “EXP” (see original expiry date (EXP). section 6.4). - 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).

IF YOU RECEIVE YOUR VACCINE THAWED AT 2°C to 8°C you should store in a refrigerator:

2°C to 8°C

Do not re-freeze if the product is received already thawed at 2°C to 8°C.

Note: If the vaccine is received refrigerated at 2°C to 8°C, check that the expiry date has been updated by the local supplier upon receipt. If you cannot find the new EXP date, contact the local supplier to confirm the refrigerated EXP date. Write the new expiry date on the outer carton before the vaccine is stored in the refrigerator. The original expiry date should be crossed out (see section 6.4).

b. If stored frozen, thaw vial(s) either in a refrigerator or at room temperature before administration

2°C to 8°C Maximally 25°C

Thaw for OR Thaw for Thaw for 4 hours 1 hour

13 hours

Thaw in refrigerator Thaw at room temperature
- When stored frozen at -25°C to -15°C, a - When stored frozen at -25°C to -15°C, a

carton of 10 or 20 vials will take carton of 10 or 20 vials or individual vials approximately 13 hours to thaw or individual should be thawed at room temperature vials will take approximately 2 hours to thaw maximally 25°C. at 2°C to 8°C. - A carton of 10 or 20 vials will take

- If the vaccine is not used immediately, refer approximately 4 hours to thaw. to the instructions in section ‘Store in a - Individual vials will take approximately refrigerator’. 1 hour to thaw.

- The vial must be kept in the original carton in - The vaccine is stable for a total of 12 hours order to protect from light and to record the at 9°C to 25°C. It is not a recommended expiry for the different storage conditions, if storage or shipping condition but may guide applicable. decisions for use in case of temporary

Do not re-freeze once thawed. temperature excursions.
- If the vaccine is not used immediately, refer

to the instructions in section Store in a refrigerator.

Do not re-freeze once thawed.

c. Inspect vial and vaccine

- JCOVDEN is a colorless to slightly yellow, clear to very opalescent suspension (pH 6-6.4).
- The vaccine should be inspected visually for particulate matter and discoloration prior to

administration.
- The vial should be inspected visually for cracks or any abnormalities, such as evidence of

tampering prior to administration. If any of these should exist, do not administer the vaccine.

d. Prepare and administer vaccine

SEC

Swirl the vial gently Withdraw 0.5 mL Inject 0.5 mL
- Before administering a dose - Use a sterile needle and - Administer by

of vaccine, swirl the vial sterile syringe to extract a intramuscular injection gently in an upright single-dose of 0.5 mL from only into the deltoid muscle position for 10 seconds. the multi-dose vial (see of the upper arm (see

- Do not shake. section 4.2). section 4.2).

A maximum of 5 doses can be withdrawn from the multi-dose vial. Discard any remaining vaccine in the vial after 5 doses have been extracted.

e. Storage after first puncture

2°C to 8°C Maximally 25°C

Store up to 6 hours
Store up to 3 hours

OR

Record date and time the - After the first puncture of - After the first puncture of vial should be discarded the vial, the vaccine can the vial, the vaccine can
- After first puncture of the be held at 2°C to 8°C for be held at room

vial record the date and up to 6 hours. temperature (maximally time the vial should be - Discard if vaccine is not 25°C) for a single period discarded on each vial used within this time. of up to 3 hours. (see label. section 6.3).

Preferably, use - Discard if vaccine is not

immediately after first used within this time.

puncture.

f. Disposal

Any unused vaccine or waste material should be disposed of in compliance with local guidance for pharmaceutical waste. Potential spills should be disinfected with agents with viricidal activity against adenovirus.

7. MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1525/001
EU/1/20/1525/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 11 March 2021
Date of latest renewal: 03 January 2022

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.