ENFLONSIA Solution for injection Ref.[116536] Active ingredients: Clesrovimab

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 including anaphylaxis

If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, appropriate treatment and/or supportive therapy should be initiated.

Individuals with thrombocytopenia and coagulation disorders

As with any other intramuscular injections, clesrovimab should be given with caution to infants with thrombocytopenia or any coagulation disorder, because bleeding or bruising may occur following an intramuscular administration in these individuals.

Excipients with known effect

This medicinal product contains 0.14 mg of polysorbate 80 per dose. Polysorbates may cause allergic reactions.

No interaction studies have been performed. Monoclonal antibodies do not typically have significant interaction potential, as they do not directly affect cytochrome P450 enzymes and are not substrates of hepatic or renal transporters. Indirect effects on cytochrome P450 enzymes are unlikely as the target of clesrovimab is an exogenous virus.

Clesrovimab does not interfere with reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen detection RSV diagnostic assays that employ commercially available antibodies targeting antigenic site 0, I, II, III, or V on the RSV fusion (F) protein. For rapid antigen detection RSV diagnostic assay results which are negative when clinical observations are consistent with RSV infection, it is recommended to confirm using an RT-PCR-based assay.

Concomitant administration with childhood vaccines

Since clesrovimab is a monoclonal antibody, a passive immunisation specific for RSV, it is not expected to interfere with the active immune response to co-administered vaccines.

There is limited experience of co-administration with vaccines. In clinical studies, when clesrovimab was given concomitantly with routine childhood vaccines, the safety profile of the co-administered regimen was similar to the safety profile when clesrovimab and childhood vaccines were administered alone. Clesrovimab can be given concomitantly with childhood vaccines.

When clesrovimab is administered concomitantly with injectable vaccines, it should be given using a separate syringe and at a different injection-site. It should not be mixed with any vaccines or medications in the same syringe or vial (see section 6.2).

There are no data regarding substitution of clesrovimab for palivizumab once prophylaxis treatment is initiated with palivizumab for the RSV season.

Not relevant.

Not relevant.

Summary of the safety profile

The most frequent adverse reactions were injection-site pain (6.5%), injection-site erythema (4.4%), injection-site swelling (3.2%) and rash (2.3%). Most (>96%) of the adverse reactions were mild or moderate.

Tabulated list of adverse reactions

Safety was evaluated in 2 854 infants who received clesrovimab in phase 2b/3 and phase 3 clinical studies (Study 004 and Study 007, respectively) (see section 5.1). Table 1 presents the adverse reactions reported in 2 409 preterm and full-term infants (GA ≥29 weeks) who received clesrovimab.

Adverse reactions reported with clesrovimab are listed by MedDRA system organ class and in decreasing order of frequency. Frequencies are defined as 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), and very rare (<1/10 000) and not known (cannot be estimated from available data).

Table 1. Adverse reactions:

^* Rash was defined by the following grouped preferred terms occurring within 14 days post-dose: rash, rash erythematous, rash papular, rash maculo-papular, rash vesicular, dermatitis allergic, and drug eruption
^† Solicited on Day 1 through Day 5 post-dose

The safety profile of clesrovimab in 445 infants at increased risk of severe RSV disease entering their first season (Study 007, see section 5.1) was similar to palivizumab (450 infants) and consistent with the safety profile of clesrovimab in infants in Study 004.

Serious adverse events reported in early preterm infants GA <29 weeks were similar in number and pattern between recipients of clesrovimab (21/97 participants) and palivizumab (31/108 participants).

Subgroup analyses by age groups at randomisation (<3 months; ≥3 to ≤6 months and >6 months) in Study 004 and Study 007 showed similar safety results in the clesrovimab and control arms (see section 5.1) across the age-groups in each study.

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.

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