Summary of the safety profile PNH The most commonly reported adverse reactions in patients with PNH treated with pegcetacoplan were injection site reactions: injection site erythema, injection site pruritus, injection site swelling, injection site pain, injection site bruising.
Other adverse reactions reported in more than 10% of patients during clinical studies were upper respiratory tract infection, diarrhoea, haemolysis, abdominal pain, headache, fatigue, pyrexia, cough, urinary tract infection, vaccination complication, pain in extremity, dizziness, arthralgia, and back pain.
The most commonly reported serious adverse reactions were haemolysis and sepsis. C3G and primary IC-MPGN The most commonly reported adverse drug reactions in patients with C3G or primary IC-MPGN treated with pegcetacoplan were infusion site reactions and upper respiratory tract infections.
The most commonly reported serious adverse reactions were acute kidney injury and pneumonia. Tabulated list of adverse reactions Table 1 gives the adverse reactions observed from clinical studies and postmarketing experience with pegcetacoplan in patients with PNH, C3G and primary IC-MPGN.
Adverse reactions are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100) or rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), and not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1:
Adverse reactions from clinical trials1 and postmarketing experience MedDRA System Organ Class Adverse reaction Frequency in PNH Frequency in C3G or primary IC- MPGN Infections and infestations Influenza Very common Upper respiratory tract infections2 Very common Very common Urinary tract infection Very common Common Sepsis Common3 Opportunistic infections Common4 COVID-19, Gastrointestinal infection, Fungal infection, Skin infection, Oral infection Common Ear infection Common Common Infection, Respiratory tract infection5, Viral infection, Bacterial infection, Vaginal infection, Eye infection Common Cervicitis, Groin infection Uncommon Pneumonia Uncommon Common Nasal abscess, Tuberculosis, Oesophageal candidiasis, COVID-19 pneumonia, Anal abscess Uncommon Immune system disorders Hypersensitivity reaction Very common6 Anaphylactic reaction7 Anaphylactic shock7 Uncommon Blood and lymphatic system disorders Haemolysis Very common Thrombocytopenia Common Common8 Neutropenia Common Common Metabolism and nutrition disorders Hypokalaemia Common Common Nervous system disorders Headache Very common Very common Dizziness Very common Vascular disorders Hypertension Common Respiratory, thoracic and mediastinal disorders Cough Very common Common Dyspnoea, Oropharyngeal pain, Nasal congestion Common Epistaxis Common Common Gastrointestinal disorders Abdominal pain Very common Diarrhoea Very common Very common Nausea Common Very common Skin and subcutaneous tissue disorders Erythema, Rash, Urticaria Common Musculoskeletal and connective tissue disorders Arthralgia, Back pain Very common Pain in extremity Very common Common Myalgia Common Common Muscle spasms Common Renal and urinary disorders Acute kidney injury Common Very common Chromaturia Common General disorders and administration site conditions Pyrexia Very common Very common Fatigue Very common Common Infusion site reactions9 Very common Very common Investigations Alanine aminotransferase increased, Bilirubin increased Common Injury, poisoning and procedural complications Vaccination complication Very common 1 Studies APL2-308, APL2-302, APL2-202, APL2-CP-PNH-204, and APL-CP0514 in PNH patients and Study APL2-C3G-310, APL2-C3G-314, APL2-201 and APL2-C3G-204 in C3G and primary IC-MPGN patients.
Medically similar terms are grouped, where appropriate, on the basis of similar medical concept. 2 Include nasopharyngitis, upper respiratory tract infection, pharyngitis, rhinitis and sinusitis. 3 Sepsis includes one case of septic shock and one case with non-encapsulated Neisseria meningitidis.
4Herpes zoster (including Herpes zoster meningoencephalitis), and Pneumocystis jirovecii infection. 5Include respiratory tract infection and respiratory tract infection viral. ’ 7 Estimated from postmarketing experience. 8Includes platelet count decreased.
9PTs included in Infusion site reactions: infusion site erythema, infusion site pruritus, infusion site swelling, infusion site bruising, infusion site pain, infusion site induration. Description of selected adverse reactions Infections No serious infection caused by encapsulated bacteria was reported during PNH Study APL2-302.
Forty-eight patients experienced an infection during the study. The most frequent infections in patients treated with pegcetacoplan during PNH Study APL2-302 were upper respiratory tract infection (28 cases, 35%). Most infections reported in patients treated with pegcetacoplan during PNH study APL2-302 were non-serious, and predominantly mild in intensity.
Ten patients developed infections reported as serious including one patient who died due to COVID-19. The most frequent serious infections were sepsis (3 cases) (leading to discontinuation of pegcetacoplan in one patient) and gastroenteritis (3 cases); all of which resolved.
In C3G and primary IC-MPGN clinical studies, four serious respiratory tract infections caused by encapsulated bacteria were reported in patients treated with pegcetacoplan: an epiglottitis, a pneumococcal pneumonia and an atypical pneumonia that led to drug interruption, and a pneumonia Haemophilus with no dose adjustment.
Events recovered and resolved except for the events of pneumonia Haemophilus and the atypical pneumonia that resolved with sequelae. In addition, one serious Escherichia urinary tract infection was reported, the event recovered and resolved with no dose adjustment.
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