Tjalf Ziemssen1, Olaf Hoffmann2, Luisa Klotz3, Herbert Schreiber4, Martin Weber5, Benedict Rauser6. 1. Department of Neurology, Center of Clinical Neuroscience, Carl Gustav Carus University Clinic, University Hospital of Dresden, Fetscherstr. 74, Dresden, DE. 2. Department of Neurology, St. Josefs-Krankenhaus, Potsdam, DE. 3. University Hospital Muenster, Department of Neurology with Institute of Translational Neurology, Muenster, DE. 4. Neurological Practice Center Ulm, Ulm, DE. 5. Institute of Neuropathology, University Medical Center Goettingen, Goettingen, DE. 6. Novartis Pharma GmbH, Nuremberg, DE.
Abstract
BACKGROUND: A high proportion of patients with relapsing remitting multiple sclerosis (RRMS) convert to secondary progressive multiple sclerosis (SPMS) characterized by irreversibly progressing disability and cognitive decline. Siponimod (Mayzent®), a selective sphingosine-1-phosphate receptor modulator, has been recently approved by the EMA for the treatment of adult SPMS patients with active disease, as evidenced by relapses or magnetic resonance imaging features of ongoing inflammatory activity. Approval by the FDA covers a broader range of indications, comprising clinically isolated syndrome, RRMS, and active SPMS. However, treatment effects of siponimod have not been assessed in a structured setting in clinical routine so far. OBJECTIVE: The objectives of AMASIA (ImpAct of Mayzent® (siponimod) on secondAry progressive multiple Sclerosis patients in a long-term non-Interventional study in GermAny), a prospective non-interventional study (NIS), are to assess long-term effectiveness and safety of siponimod in clinical routine, and to evaluate the impact of disease burden on quality of life and socioeconomic conditions. Here, we report the study design of AMASIA. METHODS: Treatment effects of siponimod will be evaluated in 1500 SPMS patients during a 3-year observational phase. According to the genetic polymorphism of CYP2C9, the initial dose will be titrated to the maintenance dose of 1 mg (CYP2C9*1*3 and *2*3) or 2 mg (all other polymorphisms of CYP2C9 except *3*3 which is contraindicated) taken orally once daily. Primary endpoint is the 6-month confirmed disability progression, as assessed by a functional composite endpoint comprising the expanded disability status scale (EDSS) and the symbol digit modalities test (SDMT) to take appropriate account of cognitive changes and to increase sensitivity. Further measures including MS activity data, assessments of functional domains, questionnaires addressing the patient's, physician's, and relatives' perspectives of disability progression, cognitive worsening, and quality of life as well as socioeconomic aspects will be documented by the MSDS3D system. RESULTS: AMASIA is being conducted between February 2020 and February 2025 in up to 250 neurological centers in Germany. CONCLUSIONS: AMASIA will complement the pivotal phase-III-derived efficacy and safety profile of siponimod by real-world data and will further evaluate several individual treatment aspects such as quality of life and socioeconomic conditions of patients and care givers. It might help to establish siponimod as promising option for the treatment of SPMS patients in clinical routine.
BACKGROUND: A high proportion of patients with relapsing remitting multiple sclerosis (RRMS) convert to secondary progressive multiple sclerosis (SPMS) characterized by irreversibly progressing disability and cognitive decline. Siponimod (Mayzent®), a selective sphingosine-1-phosphate receptor modulator, has been recently approved by the EMA for the treatment of adult SPMS patients with active disease, as evidenced by relapses or magnetic resonance imaging features of ongoing inflammatory activity. Approval by the FDA covers a broader range of indications, comprising clinically isolated syndrome, RRMS, and active SPMS. However, treatment effects of siponimod have not been assessed in a structured setting in clinical routine so far. OBJECTIVE: The objectives of AMASIA (ImpAct of Mayzent® (siponimod) on secondAry progressive multiple Sclerosispatients in a long-term non-Interventional study in GermAny), a prospective non-interventional study (NIS), are to assess long-term effectiveness and safety of siponimod in clinical routine, and to evaluate the impact of disease burden on quality of life and socioeconomic conditions. Here, we report the study design of AMASIA. METHODS: Treatment effects of siponimod will be evaluated in 1500 SPMS patients during a 3-year observational phase. According to the genetic polymorphism of CYP2C9, the initial dose will be titrated to the maintenance dose of 1 mg (CYP2C9*1*3 and *2*3) or 2 mg (all other polymorphisms of CYP2C9 except *3*3 which is contraindicated) taken orally once daily. Primary endpoint is the 6-month confirmed disability progression, as assessed by a functional composite endpoint comprising the expanded disability status scale (EDSS) and the symbol digit modalities test (SDMT) to take appropriate account of cognitive changes and to increase sensitivity. Further measures including MS activity data, assessments of functional domains, questionnaires addressing the patient's, physician's, and relatives' perspectives of disability progression, cognitive worsening, and quality of life as well as socioeconomic aspects will be documented by the MSDS3D system. RESULTS: AMASIA is being conducted between February 2020 and February 2025 in up to 250 neurological centers in Germany. CONCLUSIONS: AMASIA will complement the pivotal phase-III-derived efficacy and safety profile of siponimod by real-world data and will further evaluate several individual treatment aspects such as quality of life and socioeconomic conditions of patients and care givers. It might help to establish siponimod as promising option for the treatment of SPMS patients in clinical routine.