Clinical trial NCT05269667: A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention
Official title: SAkuraBonsai: Clinical, Imaging And Biomarker Open-Label Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Neuromyelitis Optica Spectrum Disorder
NMOSD
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical Co.
First posted: 2022-03-08
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objective of the trial is to describe the efficacy and safety of satralizumab in patients with aquaporin-4 (AQP4) antibody seropositive NMOSD, either treatment naive or inadequate responders to previous treatment with rituximab (RTX) (or its biosimilar)

Detailed description: Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are severe demyelinating inflammatory autoimmune neurological disorders. The estimated global pooled prevalence of NMOSD is 1.82 per 100 000 people (Etemadifar et al. 2015). The disorder is characterized by inflammatory lesions in the optic nerve, spinal cord, brainstem, and cerebrum; and clinically by optic neuritis (ON) and/or transverse myelitis causing potentially severe motor and sensory impairment, bladder dysfunction, vision loss, pain, and other debilitating symptoms (Wingerchuk et al. 2015). Recovery is variable, and inflammatory attacks often result in permanent disability. Untreated, the risks of severe disability or death are substantial (Jarius et al. 2014).

NMOSD is radiologically and prognostically distinct from multiple sclerosis (MS), and has a pathophysiology unresponsive to typical MS treatment (Weinshenker 2007; Oh, and Levy et al. 2012).

Eligibility criteria: Inclusion criteria

* 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-naïve 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

Exclusion criteria 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 MS or progressive multifocal leukoencephalopathy (PML)
* 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-naïve 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

Primary outcomes:
measure: Percentage of Relapse-Free Participants
timeFrame: Up to 14 months
measure: Annualized Relapse Rate (ARR)
timeFrame: Up to 14 months
measure: Time to First Relapse (TFR)
timeFrame: Up to 14 months
measure: Percentage of Participants Hospitalized Due to Relapse
timeFrame: Up to 14 months
measure: Percentage of Participants Using Corticosteroids Due to Relapse
timeFrame: Up to 14 months
measure: Percentage of Participants in Need of Rescue Therapy Due to Relapse
timeFrame: Up to 14 months
measure: Percentage of Participants in Need of Plasma Exchange Due to Relapse
timeFrame: Up to 14 months
measure: Percentage of Participants With Residual Disability Due to Relapse
timeFrame: Up to 14 months
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Score
timeFrame: Up to Week 36
measure: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks
timeFrame: Up to 12 weeks
measure: Change From Baseline in the Symbol Digital Modalities Test (SDMT)
timeFrame: Baseline, Week 24
measure: Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts
timeFrame: Baseline and Week 24
measure: Change in Visual Functioning Questionnaire -25 (VFQ-25)
timeFrame: At Week 24
measure: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans
timeFrame: Weeks 4, 8, 12 and 24
measure: Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans
timeFrame: Baseline, Week 12
measure: Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans
timeFrame: Basline, Weeks 4, and 12
measure: Number of Participants With Diffusion Abnormalities, Microbleeds and Cerebral Perfusion Alterations Assessed Using MRI Scans
timeFrame: Up to 14 Months
measure: Number of Participants With Global and Regional Brain Volume Loss Assessed Using MRI Scans
timeFrame: Up to 14 Months
measure: Number of Participants With New and Persisting Short T1 Inversion Recovery (STIR)/ Proton Density (PD) Hyperintense Lesions and T1-weighted Contrast Enhancement Assessed Using MRI Scans
timeFrame: Up to 14 months
measure: Quantitative T1 Mapping (Magnetization Prepared Rapid Gradient Echo Sequence [MP2RAGE]) Assessed Using MRI Scans
timeFrame: Up to 14 months
measure: T2*/R* Ratio for Iron Concentration Estimation Assessed Using MRI Scans
timeFrame: Up to 14 months
measure: Quantitative Diffusion/ Diffusion Tensor Imaging (DTI) Assessed Using MRI Scans
timeFrame: Up to 14 months
measure: Change in the Retinal Nerve Fiber Layer (RNFL) Thickness Assessed Using Optical Coherence Tomography (OCT)
timeFrame: Up to 14 months
measure: Change in the Ganglion Cell Plus Inner Plexiform (GCIP) Layer Thickness Assessed Using OCT
timeFrame: Up to 14 months
measure: Concentration of Satralizumab in Cerebrospinal Fluid (CSF) and Serum
timeFrame: Baseline and Week 12
measure: Number of Participants With Anti-satralizumab Antibodies
timeFrame: Up to 14 months
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to 14 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Samsun
country: Turkey
facility: Ondokuz Mayis University School of Medicine
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: