SAKURABONSAI: CLINICAL, IMAGING AND BIOMARKER OPEN-LABEL STUDY IN NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD) WITH SATRALIZUMAB AS AN INTERVENTION
A Clinical, Imaging and Biomarker Study in Neuromyelitis Optica Spectrum Disorder (NMOSD) with Satralizumab as an Intervention
Regine Buffels
F. Hoffmann-La Roche Ltd
1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo
+81-120-189-706
clinical-trials@chugai-pharm.co.jp
Clinical trials information
Chugai Pharmaceutical Co., Ltd.
1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo
+81-120-189-706
clinical-trials@chugai-pharm.co.jp
Complete
July. 01, 2022
100
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Age 18 to 74 years, inclusive, at the time of informed consent
Have a diagnosis of AQP4 antibody seropositive NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria
For women of childbearing potential: agreement to either remain abstinent (refrain from heterosexual intercourse) or to use reliable means of contraception (physical barrier [patient or partner] in conjunction with a spermicidal product, contraceptive pill, patch, injectables, intrauterine device or intrauterine system) during the treatment period and for at least 3 months after the last dose of study drug
Cohort 1 (treatment-naive NMOSD patients)
Confirmation of NMOSD diagnosis with AQP4+ antibodies
Have clinical evidence of at least 1 documented attack or relapse (including first attack) in the last year prior to screening
Naive to maintenance therapy (disease-modifying therapy [DMT] or immunosuppressive therapy [IST])
Cohort 2 (NMOSD patients with inadequate response to RTX [or its biosimilar])
Confirmation of NMOSD diagnosis and AQP4+ antibodies in the disease history of the patient
Have a length of disease duration from first symptom of =5 years
History of ongoing treatment with RTX (or its biosimilar) (at least 2 infusions) for NMOSD with a maximum duration of 6 months since last administration prior to enrolment in the study
Ongoing disease activity after last RTX (or its biosimilar) infusion i.e., relapse and/or any new inflammatory event, confirmed by magnetic resonance imaging (MRI) or ophthalmological assessment
Count, volume and regional distribution of T2-weighted fluid-attenuated inversion-recovery (FLAIR) hyperintense lesions
Including new and enlarging lesions of the cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum; Fazekas scoring
Global and regional brain volume loss including basal ganglia, cerebellum and upper cervical spinal cord.
New and persisting short T1 inversion recovery (STIR)/Proton Density (PD) hyperintense lesions and T1-weighted contrast enhancement
Quantitative T1 mapping
Quantitative diffusion/diffusion tensor imaging (DTI)
Change in the retinal nerve fiber layer (RNFL) thickness
Change in the ganglion cell plus inner plexiform (GCIP) layer thickness
Incidence and severity of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs)
Exclusion criteria for both the cohorts
Inability to complete an MRI
Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of satralizumab
Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
Evidence of other demyelinating disease, including multiple sclerosis or progressive multifocal leukoencephalopathy
Evidence of serious uncontrolled concomitant diseases that may preclude patient participation
Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection or other infection (excluding fungal infections of nail beds or caries dentium) at baseline
Infection requiring hospitalization or treatment with intravenous (IV) anti-infective agents within 4 weeks prior to baseline visit
Evidence of chronic active hepatitis B
Evidence of active tuberculosis (TB)
History or laboratory evidence of coagulation disorders
Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline
Presence or history of malignancy
History of drug or alcohol abuse within 1 year prior to baseline History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation
History of severe allergic reaction to a biologic agent
Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
Treatment with any investigational agent within 6 months prior to baseline or 5 drug elimination half-lives of the investigational agent (whichever is longer)
Cohort 1 (treatment-naive NMOSD patients)
Any previous treatment with IL-6 inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, stem-cell therapy, or bone marrow transplantation
Any previous treatment with eculizumab, belimumab, natalizumab, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, siponimod, or ozanimod
Any previous treatment with anti-CD4, cladribine or mitoxantrone
Any previous treatment with B-cell depleting agents
Any previous treatment with immunosuppressants
Cohort 2 (NMOSD patients with inadequate response to RTX)
Discontinued RTX (or biosimilar) treatment due to any other reason than inadequate response to treatment
18age old over
74age old under
Both
Neuromyelitis Optica Spectrum Disorder (NMOSD)
Satralizumab: 120 mg SC injection every 4 weeks (Q4W)
Efficacy
Proportion of relapse-free patients
Annualized relapse rate (ARR)
Time to first relapse (TFR)
Mean change from baseline in Expanded Disability Status Scale (EDSS) score over the course of the study
The Expanded Disability Status Scale ranges from 0 to 10 in 0.5 unit increments. Higher results represent higher levels of disability.
Time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks and 24 weeks
Change from baseline in the Symbol Digital Modalities Test (SDMT) over the course of the study
Change in high-contrast (100%) and lowcontrast (2.5%) visual acuity using appropriate high-and low-contrast letter acuity (LCLA) charts over the course of the study
Proportion of participants hospitalized due to relapse
Proportion of participants using corticosteroids due to relapse
Proportion of participants in need of rescue therapy due to relapse
Proportion of participants in need of plasma exchange due to relapse
Proportion of participants with disability due to relapse
Safety, Other
Count, volume and regional distribution of T2-weighted fluid-attenuated inversion-recovery (FLAIR) hyperintense lesions
Including new and enlarging lesions of the cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum; Fazekas scoring
Global and regional brain volume loss including basal ganglia, cerebellum and upper cervical spinal cord.
New and persisting short T1 inversion recovery (STIR)/Proton Density (PD) hyperintense lesions and T1-weighted contrast enhancement
Quantitative T1 mapping (magnetizationprepared rapid gradient echo sequence [MP2RAGE])
Quantitative diffusion/diffusion tensor imaging (DTI)
Change in the retinal nerve fiber layer (RNFL) thickness
Change in the ganglion cell plus inner plexiform (GCIP) layer thickness
Incidence and severity of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs)
Chugai Pharmaceutical Co., Ltd.
F. Hoffmann-La Roche Ltd
Southern TOHOKU General Hospital Institutional Review Board
7-115 Yatsuyamada, Koriyama-shi, Fukushima
+81-24-934-5322
Approval
May. 13, 2022
Yes
Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).
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