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Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study
Lancet neurology, 2023-05, Vol.22 (5), p.395-406
2023
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Autor(en) / Beteiligte
Titel
Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study
Ist Teil von
  • Lancet neurology, 2023-05, Vol.22 (5), p.395-406
Ort / Verlag
England: Elsevier Ltd
Erscheinungsjahr
2023
Quelle
Access via ScienceDirect (Elsevier)
Beschreibungen/Notizen
  • Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18–74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II–IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change −4·39 [95% CI –5·28 to –3·50] vs −2·30 [–3·17 to –1·43]; least squares mean difference −2·09 [−3·24 to −0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. UCB Pharma.
Sprache
Englisch
Identifikatoren
ISSN: 1474-4422
eISSN: 1474-4465
DOI: 10.1016/S1474-4422(23)00080-7
Titel-ID: cdi_proquest_miscellaneous_2801980858
Format
–
Schlagworte
Acetylcholine receptors, Activities of Daily Living, Apheresis, Autoantibodies, Complement C5 - therapeutic use, Complement component C5, COVID-19, Dosage, Double-Blind Method, Double-blind studies, Drug dosages, Hemorrhage, Humans, Immunoglobulins, Immunologic Factors - therapeutic use, Immunosuppressive agents, Immunotherapy, Infections, Myasthenia, Myasthenia gravis, Myasthenia Gravis - drug therapy, Neuromuscular junctions, Peptides, Placebos, Safety, Serology, Steroids, Treatment Outcome

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