CAPVAXIVE injection solution in pre-filled syringe medication leaflet

CAPVAXIVE solution for injection in pre-filled syringe

Pneumococcal polysaccharide conjugate vaccine (21-valent)

1 dose (0.5 mL) contains:

Pneumococcal polysaccharide serotype 31 4 mcg

Pneumococcal polysaccharide serotype 6A1 4 mcg

Pneumococcal polysaccharide serotype 7F1 4 mcg

Pneumococcal polysaccharide serotype 81 4 mcg

Pneumococcal polysaccharide serotype 9N1 4 mcg

Pneumococcal polysaccharide serotype 10A1 4 mcg

Pneumococcal polysaccharide serotype 11A1 4 mcg

Pneumococcal polysaccharide serotype 12F1 4 mcg

Pneumococcal polysaccharide serotype 15A1 4 mcg

Pneumococcal polysaccharide from deOAc15B (de-O-acetylated serotype 15B)1 4 mcg

Pneumococcal polysaccharide serotype 16F1 4 mcg

Pneumococcal polysaccharide serotype 17F1 4 mcg

Pneumococcal polysaccharide serotype 19A1 4 mcg

Pneumococcal polysaccharide serotype 20A1 4 mcg

Pneumococcal polysaccharide serotype 22F1 4 mcg

Pneumococcal polysaccharide serotype 23A1 4 mcg

Pneumococcal polysaccharide serotype 23B1 4 mcg

Pneumococcal polysaccharide serotype 24F1 4 mcg

Pneumococcal polysaccharide serotype 311 4 mcg

Pneumococcal polysaccharide serotype 33F1 4 mcg

Pneumococcal polysaccharide serotype 35B1 4 mcg1Conjugated to CRM197 carrier protein. CRM197 is a nontoxic mutant of diphtheria toxin (originatingfrom Corynebacterium diphtheriae C7) expressed recombinantly in Pseudomonas fluorescens.

1 dose (0.5 mL) contains approximately 65 mcg CRM197 carrier protein.

Excipient(s) with known effect1 dose (0.5 mL) contains 0.5 mg polysorbate 20.

For the full list of excipients, see section 6.1.

Solution for injection (injection).

The vaccine is a colourless, clear to opalescent solution.

CAPVAXIVE is indicated for active immunisation for the prevention of invasive disease andpneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

The use of CAPVAXIVE should be in accordance with official recommendations.

Individuals 18 years of age and older1 dose (0.5 mL).

The need for revaccination with a subsequent dose of CAPVAXIVE has not been established.

The safety and efficacy of CAPVAXIVE in children younger than 18 years of age have not beenestablished. No data are available.

CAPVAXIVE should be administered by intramuscular injection only. This vaccine should beadministered preferably in the deltoid muscle of the upper arm in adults, with care to avoid injectioninto or near nerves and blood vessels.

For instructions on the handling of the vaccine before administration, see section 6.6.

Hypersensitivity to the active substances including diphtheria toxoid, or to any of the excipients listedin section 6.1.

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

Anaphylaxis

As with all injectable vaccines, appropriate medical treatment and supervision should always bereadily available in case of a rare anaphylactic event following the administration of the vaccine.

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acuteinfection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

As with other intramuscular injections, the vaccine should be given with caution in individualsreceiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such ashaemophilia) because bleeding or bruising may occur following an intramuscular administration inthese individuals.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐relatedreactions may occur in association with vaccination as a response to the needle injection.

Stress-related reactions are temporary and resolve on their own. It is important that precautions are inplace to avoid injury from fainting.

Safety and immunogenicity data on CAPVAXIVE are not available for individuals inimmunocompromised groups. Vaccination should be considered on an individual basis.

Based on experience with pneumococcal vaccines, immunocompromised individuals, including thosereceiving immunosuppressive therapy, may have a reduced immune response to CAPVAXIVE.

As with any vaccine, vaccination with CAPVAXIVE may not protect all vaccine recipients. Thisvaccine will only protect against Streptococcus pneumoniae serotypes included in the vaccine and tothe cross-reactive serotype 15B (see sections 2 and 5.1).

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

Polysorbate 20

This medicinal product contains 0.5 mg of polysorbate 20 in each dose. Polysorbates may causeallergic reactions.

Different injectable vaccines should always be administered at different injection sites.

CAPVAXIVE can be administered concomitantly with quadrivalent influenza vaccine (split virion,inactivated). There are no data on the concomitant administration of CAPVAXIVE with vaccinesother than influenza vaccines.

There are no data on the use of CAPVAXIVE in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,embryo/foetal development, parturition or post-natal development (see section 5.3).

Administration of CAPVAXIVE in pregnancy should only be considered when the potential benefitsoutweigh any potential risks for the mother and the foetus.

It is unknown whether CAPVAXIVE is excreted in human milk.

No human data on the effect of CAPVAXIVE on fertility are available. Animal studies in female ratsdo not indicate harmful effects (see section 5.3).

CAPVAXIVE has no or negligible influence on the ability to drive and use machines. However, someof the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability todrive or use machines.

The most frequently reported adverse reactions following vaccination with CAPVAXIVE inindividuals 18 years of age and older were solicited. Overall, the most frequently reported adversereactions were injection-site pain (52.9%), fatigue (25.3%), headache (17.7%), and myalgia (10.4%).

The majority of local and systemic adverse reactions for individuals who received CAPVAXIVE weremild or moderate (based on intensity or size) and of short duration (≤ 3 days); severe reactions(defined as an event that prevents normal daily activity or size ˃ 10 cm) occurred in ≤ 1.0% of adults(see Table 1).

Unless otherwise stated the frequency categories are based on the safety of CAPVAXIVE assessed in6 clinical studies, conducted across the Americas, Europe, Asia Pacific and Africa which included4 914 individuals >18 years of age; with or without stable underlying medical conditions.

Adverse reactions reported for all age groups are listed in this section per system organ class, indecreasing order of frequency and seriousness. The frequency is defined as follows:

- Very common (≥ 1/10)

- Common (≥ 1/100 to < 1/10)

- Uncommon (≥ 1/1 000 to < 1/100)

- Rare (≥ 1/10 000 to < 1/1 000)

- Very rare (< 1/10 000)

- Not known (cannot be estimated from the available data).

Table 1: Tabulated list of adverse reactions

System Organ Class Adverse Reactions Frequency

Blood and lymphatic Lymphadenopathy Uncommonsystem disorders

Immune system Hypersensitivity reaction, including Raredisorders bronchospasm

Nervous system Headache Very Commondisorders Dizziness Uncommon

Gastrointestinal Nausea Uncommondisorders Diarrhoea

Musculoskeletal and Myalgia* Commonconnective tissue Arthralgia Uncommondisorders

General disorders and Injection-site pain Very commonadministration site Fatigueconditions Injection-site erythema* Common

Injection-site swelling*

Injection-site pruritus Uncommon

Chills

Injection-site bruising

* very common in individuals 18 to 49 years of age

Safety in individuals 65 years of age and older

A lower frequency of local injection-site reactions was observed in participants 75 years of age andolder compared to participants 65 to 74 years of age. There were no clinically meaningful differencesfor other adverse events in participants 65 to 74 years of age and 75 years of age and older whoreceived CAPVAXIVE.

Safety in adults living with HIV

The safety profile of CAPVAXIVE in adults living with HIV was generally comparable to the safetyprofile of pneumococcal 15-valent conjugate vaccine (PCV15) followed by pneumococcal 23-valentpolysaccharide vaccine (PPSV23, see section 5.1).

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Overdose with CAPVAXIVE is unlikely due to its presentation as a pre-filled syringe.

Pharmacotherapeutic group: vaccines, pneumococcal vaccines, ATC code: J07AL02

CAPVAXIVE contains 21 pneumococcal capsular polysaccharides from Streptococcus pneumoniae(3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, deOAc15B, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31,33F, and 35B), which are known to contribute to the pathogenicity of pneumococci in adults. Eachserotype of activated polysaccharide is individually conjugated to a carrier protein (CRM197), andelicits antibodies that enhance opsonisation, phagocytosis, and killing of pneumococci to protectagainst pneumococcal disease. CAPVAXIVE elicits a T-cell dependent immune response. Carrierprotein-specific helper T-cells support specificity, functionality, and maturation of serotype-specific

B-cells.

Immune responses following natural exposure to Streptococcus pneumoniae or followingpneumococcal vaccination can be determined through the assessments of opsonophagocytic activity(OPA) responses, to assess functional antibodies capable of opsonizing pneumococcal capsularpolysaccharides for presentation to phagocytic cells for engulfment and subsequent killing. OPAresponses are considered an important immunologic surrogate measure of protection againstpneumococcal disease in adults. Specific threshold values that correlate with protection in adults havenot been defined. There is a positive correlation between OPA responses and anti-capsular

Immunoglobulin G (IgG) responses.

Serotype-specific immune responses (OPA and IgG) for the 21 serotypes contained in CAPVAXIVEand the cross-reactive serotype 15B were measured using a validated multiplexed opsonophagocyticassay (MOPA) and pneumococcal electrochemiluminescence (Pn ECL) assay. Serotype 15Crepresents the immune response to the deOAc15B polysaccharide as the molecular structure fordeOAc15B and 15C are similar.

Clinical trials experience in individuals 18 years of age and older

Six Phase 3, clinical studies (Protocol 003, Protocol 004, Protocol 005, Protocol 006, Protocol 007,and Protocol 010) conducted across the Americas, Europe, Asia Pacific and Africa evaluated theimmunogenicity of CAPVAXIVE in 8 369 individuals 18 years of age and older, of whom 5 450received CAPVAXIVE. Participants enrolled in the Phase 3 studies included adults across differentage groups; approximately 32% were 18 to 49 years of age, 32% were 50 to 64 years of age, 29% were65 to 74 years of age, and 8% were 75 years of age and older. Of those vaccinated, 14% had receivedother prior pneumococcal vaccines, 33% had risk factors for pneumococcal disease (e.g., alcoholism,chronic heart disease, chronic liver disease, chronic lung disease including asthma, diabetes, renaldisorders, smoking) and approximately 4% were adults living with HIV, which is associated with highrisk of pneumococcal disease.

In each study, immunogenicity was assessed by serotype-specific OPA and IgG responses at 1-monthpostvaccination.

Clinical trials conducted in pneumococcal vaccine-naïve adults

CAPVAXIVE effectiveness in adults against invasive pneumococcal disease and pneumonia wasassessed based on comparative immunogenicity to a licensed pneumococcal vaccine (pneumococcal20-valent conjugate vaccine (PCV20) and PPSV23).

Protocol 003

In a double-blind study, 2 362 pneumococcal vaccine-naïve individuals 50 years of age and older wererandomised to receive either CAPVAXIVE or PCV20. The immune response as assessed by thegeometric mean titre (GMT) ratio (CAPVAXIVE/PCV20) is presented in Table 2.

CAPVAXIVE met the pre-defined statistical noninferiority criterion compared to PCV20 for the 10serotypes included in both vaccines as assessed by the geometric mean titre (GMT) ratio(CAPVAXIVE/PCV20) where the noninferiority criterion was met if the lower bound of the 2-sided95% Confidence Interval (CI) were ˃ 0.5. CAPVAXIVE met the predefined superiority criterioncompared to PCV20 for all but one (15C) of the 11 additional serotypes to CAPVAXIVE as assessedby the GMT ratio (CAPVAXIVE/PCV20) where the statistical superiority criterion was met if thelower bound of the 2 sided 95% CI were ˃ 2.0 (see Table 2).

Table 2: Serotype-specific OPA GMTs in pneumococcal vaccine-naïve individuals ≥ 50 years ofage (Protocol 003)

Pneumococcal CAPVAXIVE PCV 20 GMT Ratio*

Serotype (N=1 179) (N=1 177) (CAPVAXIVE/PCV20)n GMT* n GMT* (95% CI)*10 Shared Serotypes†3 1 154 274.0 1 161 176.7 1.55 (1.40, 1.72)6A 1 148 2 302.0 1 153 2 972.5 0.77 (0.68, 0.88)7F 1 152 3 637.4 1 158 3 429.9 1.06 (0.95, 1.18)8 1 155 2 501.3 1 158 1 811.1 1.38 (1.25, 1.53)10A 1 161 3 893.4 1 159 4 678.0 0.83 (0.75, 0.93)11A 1 145 3 232.6 1 150 2 092.8 1.54 (1.39, 1.72)12F 1 160 2 641.2 1 161 2 499.6 1.06 (0.92, 1.21)19A 1 159 2 136.1 1 162 2 871.8 0.76 (0.69, 0.84)22F 1 147 3 874.5 1 154 4 770.1 0.81 (0.72, 0.92)33F 1 154 13 558.9 1 157 11 742.1 1.15 (1.01, 1.32)11 Additional Serotypes in CAPVAXIVE‡9N 1 147 7 470.7 1 150 1 640.4 4.55 (4.12, 5.04)15A 1 107 5 237.2 1 102 1 589.0 3.30 (2.91, 3.74)15C 1 153 4 216.2 1 158 2 072.3 2.03 (1.77, 2.34)16F 1 151 4 868.2 1 153 846.3 5.75 (5.16, 6.41)17F 1 148 7 764.9 1 156 460.4 16.86 (14.90, 19.09)20A 1 161 6 099.2 1 155 631.1 9.66 (8.66, 10.79)23A 1 132 3 737.2 1 104 461.5 8.10 (6.86, 9.55)23B 1 160 1 082.5 1 160 107.3 10.09 (8.48, 12.00)24F 1 153 2 728.6 1 130 70.5 38.71 (33.87, 44.25)31 1 153 3 132.5 1 154 144.4 21.69 (18.68, 25.18)35B 1 153 8 527.8 1 159 1 383.0 6.17 (5.59, 6.80)

Cross-reactive serotype15B 1 140 4 400.6 1 141 4 640.0 0.95 (0.84, 1.07)

* GMTs, GMT ratio, and 95% CI were estimated from a constrained Longitudinal Data Analysis model.† The noninferiority criterion was met if the lower bound of the 2-sided 95% CI for the estimated GMT ratio(CAPVAXIVE/PCV20) was > 0.5.‡ The superiority criterion was met if the lower bound of the 2-sided 95% CI for the estimated GMT ratio(CAPVAXIVE/PCV20) was > 2.0.

N=Number of individuals randomised and vaccinated; n=Number of individuals contributing to the analysis.

CAPVAXIVE met the superiority criterion compared to PCV20 for 10 of additional 11 serotypes(except 15C) in CAPVAXIVE as assessed by the proportion of individuals who achieved a ≥ 4-fold risefrom prevaccination to 1-month postvaccination for OPA responses. The superiority criterion wasdefined as the difference between CAPVAXIVE and PCV20 being ˃ 10 percentage points.

Immunobridging in pneumococcal vaccine-naïve individuals 18 to 49 years of age

In a double-blind study pneumococcal vaccine-naïve individuals 18 to 49 years of age wererandomised in a 2:1 ratio to receive CAPVAXIVE (N=200) or PCV20 (N=100). The 18 to 49 year oldgroup who received CAPVAXIVE (N=200) was compared to the 50 to 64 year old group (N=589)which also had received CAPVAXIVE to evaluate the OPA responses.

CAPVAXIVE successfully immunobridged serotype-specific immune responses to each of the 21vaccine serotypes in individuals 18 to 49 years of age to individuals 50 to 64 years of age, as the lowerbound of the 2-sided 95% CI for the GMT ratio for each serotype was > 0.5 (see Table 3).

Table 3: Comparison of serotype-specific OPA GMTs in pneumococcal vaccine-naïveindividuals 18-49 years of age to 50-64 years of age who received CAPVAXIVE (Protocol 003)

GMT Ratio*†

Pneumococcal 18-49 years 50-64 years(18-49 years/50-64 years)

Serotype (N=200) (N=589)(95% CI)*n GMT n GMT3 194 308.6 572 282.7 1.09 (0.90, 1.33)6A 196 5 289.6 569 2 572.9 2.06 (1.61, 2.62)7F 198 6 447.2 571 4 278.8 1.51 (1.23, 1.84)8 197 4 516.0 571 3 004.7 1.50 (1.26, 1.79)9N 197 17 283.2 570 8 791.4 1.97 (1.59, 2.43)10A 197 6 808.1 575 4 382.6 1.55 (1.26, 1.92)11A 196 5 871.6 564 3 785.8 1.55 (1.26, 1.91)12F 196 6 150.4 574 3 561.2 1.73 (1.37, 2.17)15A 184 11 319.2 550 5 901.2 1.92 (1.55, 2.37)15C 195 10 194.0 570 5 708.0 1.79 (1.36, 2.35)16F 193 8 877.0 571 5 720.0 1.55 (1.26, 1.91)17F 194 16 070.6 568 10 068.0 1.60 (1.26, 2.02)19A 198 2 773.2 574 2 374.6 1.17 (0.97, 1.40)20A 197 13 150.0 575 7 562.7 1.74 (1.39, 2.18)22F 198 9 299.6 568 4 683.6 1.99 (1.58, 2.49)23A 192 8 848.7 561 4 739.5 1.87 (1.43, 2.44)23B 198 2 140.1 575 1 420.0 1.51 (1.11, 2.04)24F 197 4 137.6 570 3 047.2 1.36 (1.10, 1.67)31 195 8 005.6 570 3 820.7 2.10 (1.63, 2.69)33F 197 34 805.5 570 17 607.4 1.98 (1.52, 2.57)35B 198 13 933.4 573 9 053.9 1.54 (1.26, 1.87)

* GMTs, GMT ratio, and 95% CI were estimated from a Longitudinal Data Analysis model.† A conclusion of immunobridging was based on the lower bound of the 95% CI for the estimated GMT ratio(18-49 years/50-64 years) being > 0.5.

N=Number of individuals randomised and vaccinated; n=Number of individuals contributing to the analysis.

Protocol 010

In a double-blind study, 1 484 pneumococcal vaccine-naïve individuals 50 years of age and older wererandomised to receive either CAPVAXIVE or PPSV23; 46% of participants were 50 to 64 years of age,54% were 65 years of age and older, and 10% were 75 years of age and older. The immune response asassessed by the GMT ratio (CAPVAXIVE/PPSV23) is presented in Table 4.

CAPVAXIVE met the pre-defined statistical noninferiority criterion compared to PPSV23 for the12 serotypes included in both vaccines as assessed by the GMT ratio (CAPVAXIVE/PPSV23) wherethe noninferiority criterion was met if the lower bound of the 2-sided 95% Confidence Interval (CI) were˃ 0.5. CAPVAXIVE met the predefined superiority criterion compared to PPSV23 for the 9 additionalserotypes to CAPVAXIVE as assessed by the GMT ratio (CAPVAXIVE/PPSV23) where the statisticalsuperiority criterion was met if the lower bound of the 2 sided 95% CI were ˃ 2.0 (see Table 4).

Table 4: Serotype specific OPA GMTs in pneumococcal vaccine-naïve individuals ≥ 50 years ofage (Protocol 010)

Pneumococcal CAPVAXIVE PPSV23 GMT Ratio*

Serotype (N=739) (N=741) (CAPVAXIVE/PPSV23)n GMT* n GMT* (95% CI)*12 Shared Serotypes†3 725 230.4 729 211.5 1.09 (0.96, 1.23)7F 729 4 876.7 732 3 314.6 1.47 (1.29, 1.68)8 730 3 379.6 733 2 882.1 1.17 (1.04, 1.32)9N 728 7 346.6 729 6 545.9 1.12 (1.00, 1.26)10A 725 4 382.9 726 2 818.7 1.55 (1.37, 1.77)11A 728 3 711.1 729 1 809.7 2.05 (1.82, 2.31)12F 728 3 031.8 732 1 854.9 1.63 (1.40, 1.90)17F 722 8 215.7 730 4 060.5 2.02 (1.77, 2.31)19A 731 2 670.0 732 1 879.9 1.42 (1.26, 1.60)20A 730 6 966.1 733 4 208.4 1.66 (1.46, 1.88)22F 725 4 724.1 728 3 084.9 1.53 (1.34, 1.75)33F 727 15 497.3 731 17 483.0 0.89 (0.76, 1.04)9 Additional Serotypes in CAPVAXIVE‡6A 729 3 193.9 730 964.0 3.31 (2.84, 3.87)15A 715 6 746.5 703 1 462.1 4.61 (3.99, 5.33)15C 729 7 604.8 730 2 605.0 2.92 (2.50, 3.42)16F 726 6 675.4 723 1 482.2 4.50 (3.99, 5.09)23A 711 4 804.2 690 837.2 5.74 (4.81, 6.85)23B 730 2 252.6 726 137.2 16.42 (13.46, 20.03)24F 723 4 568.0 705 1 346.7 3.39 (2.97, 3.87)31 730 5 040.7 731 423.9 11.89 (10.16, 13.91)35B 728 10 707.5 732 1 735.0 6.17 (5.54, 6.87)

Cross-reactive serotype15B 716 5 157.3 727 3 243.2 1.59 (1.37, 1.85)

* GMTs, GMT ratio, and 95% CI were estimated from a constrained Longitudinal Data Analysis model.† The noninferiority criterion was met if the lower bound of the 2-sided 95% CI for the estimated GMT ratio(CAPVAXIVE/PPSV23) was > 0.5.‡ The superiority criterion was met if the lower bound of the 2-sided 95% CI for the estimated GMT ratio(CAPVAXIVE/PPSV23) was > 2.0.

N=Number of individuals randomised and vaccinated; n=Number of individuals contributing to the analysis.

CAPVAXIVE met the superiority criterion compared to PPSV23 for 8 of 9 additional serotypes(except 15C) in CAPVAXIVE as assessed by the proportion of individuals who achieved a ≥ 4-foldrise from prevaccination to 1-month postvaccination for OPA responses. The superiority criterion wasdefined as the difference between CAPVAXIVE and PPSV23 being ˃ 10 percentage points.

Clinical trials conducted in adults with prior pneumococcal vaccination

Protocol 006

A descriptive Phase 3 study, enrolled individuals ≥ 50 years of age who were previously vaccinated withother pneumococcal vaccines at least 1 year prior to study entry. Subjects were randomised to receive

CAPVAXIVE or another pneumococcal vaccine.

Across all 3 cohorts, CAPVAXIVE was immunogenic for all 21 serotypes contained in the vaccine asassessed by serotype-specific OPA GMTs. OPA GMTs were generally comparable between the twovaccination groups for the shared serotypes and higher in the CAPVAXIVE group for the additionalserotypes included only in CAPVAXIVE.

Adults living with HIV

Protocol 007

In a double-blind study, 313 adults living with HIV, with or without a history of prior pneumococcalvaccination, were randomised in a 1:1 ratio to receive either CAPVAXIVE followed by placebo 8 weekslater, or PCV15 followed by PPSV23 (PCV15+PPSV23) 8 weeks later. At screening, of the participantsvaccinated 6.7% had a CD4+ T-cell counts ≥ 50 to < 350 cells/µL, 18.6% had CD4+ T-cell counts ≥ 350to < 500 cells/µL and 74.7% had a CD4+ T-cell counts ≥ 500 cells/µL; 83% had an undetectable HIVviral load (< 20 copies/mL).

CAPVAXIVE was immunogenic for all 21 serotypes contained in the vaccine, as assessed by serotypespecific OPA GMTs at 1-month postvaccination with CAPVAXIVE. CAPVAXIVE elicited immuneresponses that were generally comparable to PCV15+PPSV23 for the 13 common serotypes and higherfor the 8 serotypes additional to CAPVAXIVE as assessed by OPA GMTs at 1-month postvaccinationwith CAPVAXIVE and 1-month postvaccination with PCV15+PPSV23.

The European Medicines Agency has deferred the obligation to submit the results of studies with

CAPVAXIVE in one or more subsets of the paediatric population in prevention of disease caused by

Streptococcus pneumoniae (see section 4.2 for information on paediatric use).

Not applicable.

Non-clinical study data revealed no hazard for humans based on conventional studies of repeated dosetoxicity and toxicity to reproduction and development.

Sodium chloride (NaCl)

Histidine

Polysorbate 20 (E432)

Hydrochloric acid (HCl; for pH adjustment)

Water for injections

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

30 months

Store in a refrigerator (2° C - 8° C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

CAPVAXIVE should be administered as soon as possible after being removed from the refrigerator.

Stability data indicate that CAPVAXIVE is stable at temperatures up to 25° C for 96 hours. At the endof this time period CAPVAXIVE should be used or discarded. These data are intended to guidehealthcare professionals in case of temporary temperature excursions only.

0.5 mL solution in a single-dose pre-filled syringe (Type I glass) with a plunger stopper (bromobutylrubber) and a tip cap (styrene butadiene or isoprene bromobutyl rubber).

Pack sizes of 1 or 10 pre-filled syringes, either without needles, with 1 separate needle, or with2 separate needles per pre-filled syringe.

Not all pack sizes may be marketed.

* The vaccine should be used as supplied.

* Inspect the solution visually for particulate matter and discolouration prior to administration.

Discard the vaccine if particulates are present and/or if it appears discoloured.

* Attach a needle with Luer lock connection by twisting in a clockwise direction until the needlefits securely on the syringe.

* CAPVAXIVE should be administered by intramuscular injection only. This vaccine should beadministered preferably in the deltoid muscle of the upper arm in adults, with care to avoidinjection into or near nerves and blood vessels.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Merck Sharp & Dohme B.V.

Waarderweg 392031 BN Haarlem

The Netherlands

EU/1/25/1913/001

EU/1/25/1913/002

EU/1/25/1913/003

EU/1/25/1913/004

EU/1/25/1913/005

EU/1/25/1913/006

Date of first authorisation: 24 March 2025

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.